Cover for No Agenda Show 1352: Race Norming
June 3rd, 2021 • 3h 2m

1352: Race Norming

Shownotes

Every new episode of No Agenda is accompanied by a comprehensive list of shownotes curated by Adam while preparing for the show. Clips played by the hosts during the show can also be found here.

Fauci Emails
TL;DR: Fauci's Response to Physicist Who Warned China Was Covering Up COVID '' Summit News
Wed, 02 Jun 2021 23:05
A coalition of liberties rights groups has warned that people in the UK are being convicted of breaking coronavirus ''laws'' without being provided the means to plead innocent.
The London Independent reports that cases are being processed under a system known as the 'Single Justice Procedure' where one magistrate decides the outcome of a case based solely on evidence supplied by police.
This means that anyone accused of breaching lockdown restrictions could be found guilty and notified by letter without even getting a court hearing.
The watchdog groups have penned a letter to the justice secretary outlining how ''likely thousands'' of people have been subject to miscarriages of justice, and calling for the practice to stop.
The Single Justice Procedure means people are being convicted + fined under confusing Covid laws in secretive 'trials' without meaningful oversight or review.It is likely that hundreds of people have been wrongly convicted under this process.
READ'¬‡¸
https://t.co/qrf6gu8ghL
'-- Big Brother Watch (@BigBrotherWatch) June 1, 2021The letter states that ''Hundreds of people have been wrongly charged and prosecuted under the Health Protection Regulations and the Coronavirus Act 2020 and we are concerned that many more unlawful charges brought via the Single Justice Procedure remain unchallenged.''
It continues, ''These charges and prosecutions are being brought without sufficient oversight, without any meaningful review process, and are resulting in guilty pleas and convictions for offences people have not committed, in a process they may also not be aware of. The current situation is unjust and the current process is unfit for purpose.''
The Independent notes that so far a third of prosecutions in England and Wales under coronavirus laws have been proven to to be wrongful, according to a review that is still ongoing.
Ministry of Justice figures reveal that 4,400 defendants were prosecuted and 3,500 convicted under such laws in 2020 alone. It is thought that close to half of those cases fell under the Single Justice Procedure.
Most cases are believed to relate to fines that have been issued by police and not paid. However, there is currently no way of appealing the fines other than to not pay them.
Human rights lawyer Kirsty Brimelow QC told the newspaper that the ''opaque'' Single Justice Procedure has since its introduction in 2015 been ''not easily accessible to the public''.
''It is a failing of the justice system that this has been allowed to continue when the consistent misuse and misunderstanding of the Covid laws is well known,'' Brimelow urged, adding ''People likely are paying financial penalties that they cannot afford in order to avoid prosecution of offences which do not exist.''
The Ministry of Justice has claimed that the Single Justice Procedure is only used for ''low level, non-imprisonable crimes'' and that people are able to ''request an open hearing''.
As we previously highlighted, a plethora of accounts and videos have surfaced highlighting how police in the UK are enforcing lockdown rules in an increasingly draconian manner. In one incident, a man was interrogated and arrested for refusing to provide his name, while another was hauled away for giving soup to homeless people.
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fauciemail.com
fauciemail.com now points to noagendashow.net!
Sir CAH
Fauci BillG Email
Feel like this email leak seems suspiciously designed to humanize him. But I did find this one little excerpt from a Gaurdian article funny.
Among the most revealing emails are those from wealthy or influential correspondents. In one dated 3 April last year, Fauci refers to a conversation with the Microsoft founder, Bill Gates, about a “collaborative and hopefully synergistic approach to Covid-19” with Gates’s charitable foundation.
Gates’s foundation director, Emilio Emini, says he is “seriously worried” about the health of Fauci, then 79, given his busy schedule. Fauci thanks Emini for his concern and says: “I will try to engage as much as I can given my current circumstances.”
When the Bill Gates foundation is saying they are 'worried about your health' I take it very differently LOL sounds Epstein esque to me. Especially when you reply not by saying thanks but, by saying you'll try to do something seemingly unrelated to being healthy.
FOIA email Fauci about man made virus
Lab vs Bat
Investigate the origins of COVID-19 | Science
Wed, 02 Jun 2021 19:11
On 30 December 2019, the Program for Monitoring Emerging Diseases notified the world about a pneumonia of unknown cause in Wuhan, China (1). Since then, scientists have made remarkable progress in understanding the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its transmission, pathogenesis, and mitigation by vaccines, therapeutics, and non-pharmaceutical interventions. Yet more investigation is still needed to determine the origin of the pandemic. Theories of accidental release from a lab and zoonotic spillover both remain viable. Knowing how COVID-19 emerged is critical for informing global strategies to mitigate the risk of future outbreaks.
In May 2020, the World Health Assembly requested that the World Health Organization (WHO) director-general work closely with partners to determine the origins of SARS-CoV-2 (2). In November, the Terms of Reference for a China''WHO joint study were released (3). The information, data, and samples for the study's first phase were collected and summarized by the Chinese half of the team; the rest of the team built on this analysis. Although there were no findings in clear support of either a natural spillover or a lab accident, the team assessed a zoonotic spillover from an intermediate host as ''likely to very likely,'' and a laboratory incident as ''extremely unlikely'' [(4), p. 9]. Furthermore, the two theories were not given balanced consideration. Only 4 of the 313 pages of the report and its annexes addressed the possibility of a laboratory accident (4). Notably, WHO Director-General Tedros Ghebreyesus commented that the report's consideration of evidence supporting a laboratory accident was insufficient and offered to provide additional resources to fully evaluate the possibility (5).
As scientists with relevant expertise, we agree with the WHO director-general (5), the United States and 13 other countries (6), and the European Union (7) that greater clarity about the origins of this pandemic is necessary and feasible to achieve. We must take hypotheses about both natural and laboratory spillovers seriously until we have sufficient data. A proper investigation should be transparent, objective, data-driven, inclusive of broad expertise, subject to independent oversight, and responsibly managed to minimize the impact of conflicts of interest. Public health agencies and research laboratories alike need to open their records to the public. Investigators should document the veracity and provenance of data from which analyses are conducted and conclusions drawn, so that analyses are reproducible by independent experts.
Finally, in this time of unfortunate anti-Asian sentiment in some countries, we note that at the beginning of the pandemic, it was Chinese doctors, scientists, journalists, and citizens who shared with the world crucial information about the spread of the virus'--often at great personal cost (8, 9). We should show the same determination in promoting a dispassionate science-based discourse on this difficult but important issue.
Nicholas Wade - Wikipedia
Wed, 02 Jun 2021 19:14
This article is about the science journalist. For the psychologist and academic, see
Nicholas J. Wade.
Nicholas Wade (born 17 May 1942) is a British author and journalist.[1]
He is the author of numerous books, and has served as staff writer and editor for Nature, Science, and the science section of The New York Times.[2][3]
His 2014 book A Troublesome Inheritance: Genes, Race and Human History was widely denounced by the scientific community for misrepresenting research into human population genetics.[4][5][6]
Early life and education [ edit ] Wade was born in Aylesbury, England[1] and educated at Eton College.[7] He earned a Bachelor of Arts degree in Natural Sciences from King's College, Cambridge in 1964.[1]
Wade immigrated to the United States in 1970.[1]
Career [ edit ] Wade was a science writer and editor for the journals Nature, from 1967 to 1971, and Science, from 1972 to 1982.[8] He joined The New York Times in 1982 and retired in 2012,[1] but he freelances occasionally for his former employer.[9] At the Times he served as an editorial writer covering science, environment and defence, and then as an editor of the science section.
His 1980 book, The Nobel Duel: Two Scientists' Twenty-one Year Race to Win the World's Most Coveted Research Prize, described the competition between Andrew Schally and Roger Guillemin, whose discoveries regarding the peptide hormone led to them sharing the 1977 Nobel Prize in Physiology or Medicine. According to the Washington Post Book World, it "may be the most unflattering description of scientists ever written." Betrayers of the Truth: Fraud and Deceit in the Halls of Science (1982), co-authored with William J. Broad, discusses historical and contemporary examples of scientific fraud.
In the 2000s, Wade's books began to focus on human evolution. He released Before the Dawn: Recovering the Lost History of Our Ancestors in 2006, which is about what Wade referred to as "two vanished periods" in human development, and The Faith Instinct in 2009, about the evolution of religious behavior.[10][11]
In 2014, Wade released A Troublesome Inheritance: Genes, Race and Human History, in which he argued that human evolution has been "recent, copious, and regional" and that genes may have influenced a variety of behaviours that underpin differing forms of human society.[12] The book has been widely denounced by scientists, including many of those upon whose work the book was based.[13][4][5][6] On 8 August 2014, The New York Times Book Review published an open letter signed by 139 faculty members in population genetics and evolutionary biology.[4][5] After publication, the letter was signed by 4 more faculty members.[6] The letter read:[13]
Wade juxtaposes an incomplete and inaccurate account of our research on human genetic differences with speculation that recent natural selection has led to worldwide differences in I.Q. test results, political institutions and economic development. We reject Wade's implication that our findings substantiate his guesswork. They do not.
We are in full agreement that there is no support from the field of population genetics for Wade's conjectures.
Wade issued a statement in response, saying that these scientists had misunderstood his intent.[4][5]
The book was further criticized in a series of five reviews by Agust­n Fuentes, Jonathan M. Marks, Jennifer Raff, Charles C. Roseman and Laura R. Stein. which were published together in the scientific journal Human Biology.[14] Marks, for instance, described the book as "entirely derivative, an argument made from selective citations, misrepresentations, and speculative pseudoscience."[15] Other reviews were more moderate in their criticism, such as that of H. Allen Orr, who wrote in The New York Review of Books that "Wade's survey of human population genomics is lively and generally serviceable. It is not, however, without error. He exaggerates, for example, the percentage of the human genome that shows evidence of recent natural selection."[16]
In May of 2021, Wade published an article which advanced the claim that COVID-19 originated from a leak at the Wuhan Institute of Virology.[17][18] This claim is at odds with the current scientific consensus that the virus most likely has a zoonotic origin.[19][20][21][22]
References [ edit ] ^ a b c d e "Nicholas Wade." Contemporary Authors Online. Detroit: Gale, 2011. Biography in Context. Web. 8 July 2014. ^ Amos Esty (25 May 2006). "The Bookshelf talks with Nicholas Wade". American Scientist. Archived from the original on 25 October 2007. ^ Gitschier, Jane (2005). "Turning the Tables'--An Interview with Nicholas Wade". PLOS Genetics. 1 (3): e45. doi:10.1371/journal.pgen.0010045. ISSN 1553-7390. PMC 1239940 . PMID 16205791. ^ a b c d Balter, Michael, "Geneticists decry book on race and evolution", Science, 8 August 2014 ^ a b c d Callaway, Ewen (8 August 2013). "Geneticists say popular book misrepresents research on human evolution". Nature. ^ a b c Michael Hiltzik (12 August 2014). "Racism, the Misuse of Genetics and a Huge Scientific Protest". Los Angeles Times. ^ "Spirit level". The Economist. 17 December 2009 . Retrieved 14 February 2018 . ^ "Nicholas Wade: Journalist & Science Author, Speaker | PRH Speakers Bureau". www.prhspeakers.com . Retrieved 9 December 2017 . ^ "Nicholas Wade". The New York Times. ^ Salevouris, Michael J. (2015). The methods and skills of history : a practical guide. Conal Furay (4 ed.). Chichester, West Sussex, UK. p. 273. ISBN 978-1-118-74544-1. OCLC 885229353. ^ Shulevitz, Judith (24 December 2009). "The God Gene". The New York Times. ISSN 0362-4331 . Retrieved 15 May 2021 . ^ Wade, Nicholas (2014). A Troublesome Inheritance: Genes, Race and Human History. New York: Penguin Publishing Group. ISBN 0698163796. ^ a b Coop, Graham; Eisen, Michael; Nielsen, Rasmus; Przeworski, Molly; Rosenberg, Noah (8 August 2014). "Letter to the Editor of The New York Times Book Review (Letter from Population Geneticists)" . Retrieved 25 September 2014 . We are in full agreement that there is no support from the field of population genetics for Wade's conjectures. ^ Human Biology 2014; 86 (3). ^ Marks, Jonathan M. (1 July 2014). "Review of a Troublesome inheritance by Nicholas Wade". Human Biology . Retrieved 15 May 2021 . ^ Orr, H. Allen (5 June 2014). "Stretch Genes". New York Review of Books . Retrieved 17 May 2014 . ^ Wade, Nicolas (5 May 2021). "The origin of COVID: Did people or nature open Pandora's box at Wuhan?". Bulletin of the Atomic Scientists. ^ Mukunth, Vasudevan (12 May 2021). "In COVID Origins Storm, Fauci Denies US Funded Controversial Study in Wuhan". The Wire Science. ^ Beaumont, Peter (27 May 2021). "Did Covid come from a Wuhan lab? What we know so far". The Guardian. ^ Hakim, Mohamad S. (14 February 2021). "SARS-CoV-2, Covid-19, and the debunking of conspiracy theories". Reviews in Medical Virology: e2222. doi:10.1002/rmv.2222. ISSN 1099-1654. PMC 7995093 . PMID 33586302. ^ Frutos, Roger; Gavotte, Laurent; Devaux, Christian A. (18 March 2021). "Understanding the origin of COVID-19 requires to change the paradigm on zoonotic emergence from the spillover model to the viral circulation model". Infection, Genetics and Evolution. doi:10.1016/j.meegid.2021.104812. ISSN 1567-1348. PMC 7969828 . ^ "COVID-19 Virtual Press conference transcript - 9 February 2021". www.who.int . Retrieved 13 February 2021 .
Apollo Capital Leon Black NBA Gates
Apollo NBA Links
Josh Harris, billionaire governor of the Philadelphia 76ers, co-founded Apollo.
Tony Ressler, billionaire governor of the Atlanta Hawks, co-founded Apollo.
Tony Ressler’s sister, Debra, is married to Leon Black, Apollo’s founder, chairman, and—until recently—CEO.
NBA commissioner Adam Silver’s college roommate at Duke, Jim Zelter, is the co-president of Apollo.
Paul Allen - Blazers
Steve Balmer - Clippers
Apollo United Banana
It didn’t take long for Eli Black to become chairman, CEO, and president of the very same United Fruit that had worked hand-in-glove with intelligence agencies. (In Part 2, we dug into United Fruit’s decades of intelligence connections.) Much has been written about the ensuing years. It’s something of a business whodunnit. United Fruit was suspected of paying a bribe, in some reports—which seems like a misdemeanor compared to a lot of what United Fruit did in its earlier days. In another telling, United Fruit was simply short of cash, and bedeviled by storms in the Caribbean, and the cost of fuel to bring bananas to North America.
Whatever happened, it ended badly. Eli’s son, Leon Black, a student at Harvard Business School, visited home for a weekend in 1975. Peter T. Kilborn writes in The New York Times:
“On Saturday, I took him to get a haircut, and he took me to a store and bought me a sweater,” Leon said. “We all went out to dinner that night. Dad ate a big steak. Then we went to see the ‘Orient Express.’ On Sunday, I cooked him an omelet for breakfast.
On Monday, Eli Black tumbled from the 44th floor window of his office building.
The NBA's most important source of cash - TrueHoop
Wed, 02 Jun 2021 11:32
This kicks off an ongoing TrueHoop series on Apollo Global, the NBA, and Jeffrey Epstein.
PART 2 PART 3 PART 4 PART 5 PART 6
PART 7 PART 8 PART 9 PART 10 PART 11 PART 12
BY HENRY ABBOTTTo the top executives of the NBA, Apollo Global is arguably the most important source of money on planet Earth. The billionaires who run the 76ers and Hawks made fortunes at Apollo. Apollo was born out of Drexel Burnham Lambert, whose alumni are a who's who of the billionaire set. The banker who raised money for Tilman Fertitta to buy the Rockets worked with Apollo's founders at Drexel. Apollo is around the corner from league headquarters; NBA commissioner Adam Silver is still close to his college roommate from Duke, who is Apollo's co-president.
Anyone who cares about the ''behind the curtain'' NBA should care about Apollo's recent crisis: According to an outside investigation, Apollo's founder, longtime CEO, and chairman, Leon Black, paid Jeffrey Epstein $158 million. Black was possibly Epstein's main source of cash over the last decade.
There's a mountain of evidence that Epstein was not only a predator and a pedophile, but also a schemer of a more profound variety, who'--according to depositions'--trafficked underaged women to powerful men and bragged about the leverage that resulted. There were compromising photos, compromising anecdotes, reportedly hidden cameras staffed by men in a secret room, and a trove of photos and video that has yet to see the light of day.
Epstein could pull the levers of power like no one else. In the mid-2000s, when Palm Beach police identified dozens of women telling similar stories of abuse, Epstein seemed destined for a long prison sentence. But a legal team befitting a president'--Alan Dershowitz, Ken Starr, Roy Black, Gerald Lefcourt'--rushed to Epstein's aid and negotiated a sweetheart deal from the U.S. Attorney, who himself went on to be a U.S. cabinet secretary.
Imagine what a guy like Epstein, who'd had powerbrokers like Bill Clinton and Prince Andrew on his private jet, could do in return for $158 million.
Why did Leon Black pay Epstein so much? For what?
It's a giant and profound question in understanding how the world of NBA billionaires works.
Apollo's three-member conflicts committee commissioned an outside investigation that found Black paid all those millions for ''legitimate advice on trust and estate planning, tax issues, issues relating to artwork, Black's airplane, Black's yacht, and other similar matters.''
The New York Times talked to experts in tax and estate matters, one of whom said ''you could be the best lawyer in Manhattan working on the most complicated trusts and estates and it would never come anywhere close to that kind of money,'' he said. Others pointed out that for $158 million you could purchase an entire law firm.
Largely, though, the media seems to accept the report's conclusions'--The Times notes the report, from the law firm Dechert, ''cleared Mr. Black of any wrongdoing.'' Apollo's stock has bounced back nicely since. Black's Apollo co-founders, like 76ers governor Josh Harris'--have been largely insulated from the fallout.
But looking deeper, that report raises as many questions as it answers. At TrueHoop, we are dissatisfied:
The Dechert attorney who led the investigation has reportedly known Epstein since the 1980s.
The report makes conclusions based on evidence (interviews, documents, and Black's text messages) which is not included.
Leon Black was exonerated, as far as the report goes, but nevertheless stepped down as Apollo's CEO. Why?
Epstein, the report notes, was fixated on using Black to reach others at Apollo, including co-founders like Josh Harris. How far did that go?
And then there's the Hollywood-esque character of A.B. ''Buzzy'' Krongard. He's married to a former Apollo executive, sits on Apollo's three-person conflicts committee which commissioned the Dechert report, and is fascinating:
The 9/11 commission looked into unusual investments that may have profited from 9/11. No evidence of wrongdoing was found, but Krongard's name was in the middle of it all.
He's the investment banker who took Microsoft public (which made Bill Gates, Clippers billionaire Steve Ballmer, and deceased Blazers billionaire Paul Allen rich).
''He would subscribe to these magazines which basically sold armaments,'' a colleague told the Baltimore Sun. ''If you wanted to get a shoulder-fired ground-to-air missile, you could order them through these magazines.'' He trained with SWAT teams on the weekend, reportedly had ''dangerous fish'' in his basement, and a bucket of rice'--to jam his fingers into to make them tougher.
And here's where it gets very Hollywood: He's CIA. Or at least sometimes. Was he working with the Agency all through the decades when he was ostensibly a banker? Perhaps. His banking colleagues joke about it. In a move that reportedly pissed off the CIA, a banker named Edwin F. Hale Sr. said Buzzy recruited him to the CIA in 1992.
But Hale and Krongard are birds of a feather: A few years apart, both Hale and Krongard were caught trying to carry loaded guns onto planes at Baltimore Washington International Airport. Krongard's was a 9mm. Hale had a .38.
A.B. ''Buzzy'' Krongard is a master of secrecy. As executive director of the CIA after 9/11, he gave a 2001 presentation to investors, broadcast on C-SPAN about the war on terror. ''I believe it will be won,'' he explained, ''in large part by forces you will not see deploy, fighting engagements you will not witness, and things occurring which you do not want to know about.''At times, Krongard has had prominent CIA jobs, and he is amazing at tough-guy talk. After 9/11, he said things like:
''We at CIA have been restricted from talking to people in the world other than Mother Teresa.''
''Certainly the rules have changed and today there's only one rule, and that's: there are no rules.''
''How do we resolve the tension between between prevention and protection vs. traditional civil liberties? Will racial profiling be re-examined? Will a national identification system be implemented? Will wiretap and other fourth amendment rights be revisited?''
As executive director he reportedly helped set up ''black sites'' where terrorism suspects were taken.
And his work at the CIA includes a famously ''outrageous'' (in the words of an elected official) episode of conflicted interest.
Buzzy had been instrumental in setting up CIA work for the private military contractor Blackwater, and at one point served on a Blackwater advisory panel. Blackwater came to be embroiled in scandal, accused of everything from mass murder to arms smuggling. A State Department inspector general took up multiple investigations. But his subordinates grew frustrated that their boss, the inspector general, may have in fact been stymying their Blackwater research.
It turns out their supervisor, the inspector general, the man accused of going soft investigating Blackwater'--was Buzzy's brother, Howard ''Cookie'' Krongard. Cookie would ultimately resign. (Headline: ''The cookie crumbles.'')
It's a longer story we'll explore, but fast forward to 2021 and Buzzy, who's 84 now, owns a chunk of Apollo Global, where he is on the board. And as of 2016, Apollo owns Blackwater, which has been through several iterations and is now called Constellis.
The Apollo conflicts committee was charged with exploring the well-hidden secrets of the extremely wealthy and powerful, especially Leon Black and Jeffrey Epstein. Is a master of secrecy, a former CIA executive with evident active current conflicts (equity in Apollo, ties to Blackwater), and a history of ''outrageous'' apparent conflicted interest, the person you'd pick if you actually wanted to unearth and disseminate the truth?
Epstein's story is the most troubling. It raises every question, tweaks every fear. Why do so many characters in that story have ties to intelligence, which is supposed to be about keeping us safe? Why do so many characters in that story have ties to the NBA, which is supposed to be about basketball?
READ PART 2 NOW.
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Ex-Apollo CEO Leon Black raped and harassed Russian model, lawsuit alleges
Wed, 02 Jun 2021 05:19
Leon Black, the former chief executive of Apollo Global Management, has been hit with a lawsuit claiming that he raped and harassed a young Russian model before manipulating her with promises of money and sham job interviews at Goldman Sachs.
The claims, which come weeks after Black stepped down from Apollo following scrutiny of his ties to the late paedophile Jeffrey Epstein, contradict Black's account of what he has characterised as a ''consensual affair'' with a woman who he claims later extorted him.
Guzel Ganieva was in her early 20s when she says Black picked her out of a crowd at a New York event marking International Women's Day, and invited her to discuss her future over dinner at the upscale restaurant La Grenouille.
She alleges that soon after that 2008 encounter, the Apollo Global Management founder took her to a bare studio apartment where, on a mattress on the floor, he subjected her to ''forced sadistic sexual acts''.
Black ''derived pleasure from humiliating and debasing'' Ganieva and intentionally caused her physical pain, according to a civil complaint filed in New York state supreme court on Tuesday.
But when Ganieva indicated she was cutting off contact, she says Black turned conciliatory '-- offering to finance a movie that she could produce, and to use his contacts to facilitate an application at Harvard Business School.
''This frivolous lawsuit is riddled with lies, and is nothing more than a wholesale fiction,'' a spokesperson for Black said on Tuesday, adding that Ganieva ''had a wholly consensual relationship with [Black] for six years'' and that her allegations of ''harassment and other inappropriate behaviour'' were ''categorically untrue''.
Black resigned from Apollo in March, citing ''relentless public attention and media scrutiny'' of his professional ties to Epstein, to whom he paid $158m for tax advice and art transaction services. An investigation by Dechert, the international law firm, found no evidence that Black had done anything wrong.
Ganieva's lawsuit claims that Black harmed her reputation by making false and malicious statements in response to news reports detailing some of her allegations of sexual harassment.
''The truth is that I have been extorted by Ms Ganieva for many years,'' Black said in an April statement that Ganieva's lawyers say was ''false and defamatory''.
''I made substantial monetary payments to her, based on her threats to go public concerning our relationship, in an attempt to spare my family from public embarrassment,'' the statement added.
Ganieva's lawsuit offers a different version of events surrounding the money she received from Black, beginning with a $480,000 loan that she says he offered in June 2011 to help her resume her college studies.
A photograph of a one-page ''loan agreement'' attached to the lawsuit appears to bear Black's flowing signature alongside Ganieva's, and arranges for her to receive $60,000 every three months for the subsequent two years.
''The principal loan will be repaid in full on June 1 2016 and will carry a simple interest rate of 5 per cent per annum,'' the document states, without calculating the amount to be repaid. Ganieva says she signed another, nearly identical ''loan agreement'' in 2013.
With her mathematics degree finished, Ganieva began looking for work, and she says Black offered help, arranging for her to meet top executives at Goldman Sachs. Among them was Alison Mass, who now chairs the investment banking division.
A person familiar with the 2014 meetings said the bank had not interviewed Ganieva for any specific position, and that it was not uncommon to enter into open-ended conversations about potential job openings at the request of a client. Goldman declined to comment.
In the end, no job materialised. ''Given the macro environment, there are no open jobs at Goldman Sachs right now that work for/are a fit for you,'' a Goldman banker wrote to Ganieva in an email, adding that a colleague ''would keep his eyes open'' for job openings with clients in Moscow.
''In hindsight Ms Ganieva knows that none of these arranged interviews were meant to be legitimate,'' her lawyers wrote in a court filing.
A year after the meetings at Goldman Sachs, Ganieva says she asked Black ''to leave her and her child alone, for good''.
At a meeting at New York's Four Seasons hotel, she says Black agreed to forgive her loans, and ordered her to sign two documents without allowing her to keep a copy. She says she now understands that she signed a non-disclosure agreement.
Afterwards, Ganieva says she began receiving regular payments from Black, but that the money stopped arriving in April. Weeks earlier Ganieva posted on Twitter that Black was a ''predator'' who had ''sexually harassed and abused'' her for many years.
Through a spokesperson, Black has acknowledged making payments to Ganieva and said he had ''advised the criminal authorities'' of her activities.
In Tuesday's legal filing, Ganieva's lawyers contended that Black was making a ''pre-emptive claim of extortion'' to make it harder for her to pursue legal action.
They wrote: ''He said many times to her, 'If you do not take the money, I will put you in prison.'''
CopyrightThe Financial Times Limited . All rights reserved. Please don't copy articles from FT.com and redistribute by email or post to the web.
Apollo announces that cofounder Josh Harris is stepping down, 2 months after former CEO Leon Black quit - Business Insider India
Wed, 02 Jun 2021 05:21
Kate Duffy May 20, 2021, 19:32 IST
Business Insider Josh Harris of Apollo Global Management speaks at the 2019 Delivering Alpha conference hosted by CNBC Heidi Gutman/CNBC Josh Harris, one of the cofounders of Apollo Global Management, is stepping down, the firm said Thursday. Harris would remain on the board of directors and executive committee, Apollo said. Leon Block, the Apollo cofounder who was investigated for ties to Jeffrey Epstein, quit the firm in March.Investment firm Apollo Global Management on Thursday announced that cofounder Josh Harris would step down as managing director.
He would step down once Apollo merges with its insurance affiliate Athene, the company said in a statement. Apollo's acquisition of Athene, which is set to create a $29 billion conglomerate, is expected to complete in the first quarter of 2022.
Harris would remain on the Apollo board of directors and executive committee, the firm said.
Harris said in the statement: "After nearly 31 years at Apollo, it is time for me to start the next chapter of my career, where I will focus full-time on the platforms I've created outside of the firm as well as deepen my commitment to philanthropy and social impact."
Read more: We talked to billionaires, business titans and an NBA star about the Apollo cofounder who wants to buy the New York Mets. Here's how he can apply his private equity turnaround playbook to a team that haven't won a World Series since 1986.
Fellow cofounder Leon Black, former CEO and chairman of Apollo, quit the firm in March. Black's departure followed an independent investigation into his relationship with the convicted sex offender Jeffrey Epstein, which showed Black paid $158 million to the disgraced financier between 2012 to 2017.
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The investigation found that neither Black nor Apollo employees were involved in Epstein's criminal activities.
MoMA Braces For a Showdown Over Epstein Pal Leon Black
Wed, 02 Jun 2021 05:27
Pressure is building on private-equity billionaire Leon Black to resign as chairman of the Museum of Modern Art ahead of a crucial board meeting next week as his ties to deceased sex trafficker Jeffrey Epstein continue to haunt him.
Fevered discussion about Black's possible departure from MoMA comes a day after Black quit Apollo Global Management, the $455 billion firm he co-founded in 1990. An internal review revealed Black paid the sex offender more than $150 million from 2012 to 2017'--three times higher than what was initially reported. The report found no evidence that Black knew of or participated in Epstein's sexual abuse of girls and young women.
But that same review found that Black and Epstein were unusually close, bound by a series of personal and professional connections stretching back decades. Black loaned Epstein $30 million in early 2017, only $10 million of which was paid back. Black once flew on Epstein's private plane, the so-called ''Lolita Express,'' and visited Epstein's ranch in Stanley, New Mexico and his private Caribbean island, where Epstein's victims were trafficked and abused. He also spent time with Epstein in Florida and in France, and they socialized in New York, often over breakfast. Black funded Epstein's favorite researchers at MIT and Harvard, and gave $10 million to Epstein's secret charity. ''Black confided in Epstein on personal matters, and Black introduced Epstein to his family,'' the report found, adding: ''Black stated that he was repulsed by the details of Epstein's crimes that were published in late 2018...'' By then, those crimes were well and widely known. Epstein's pyramid abuse scheme had been the stuff of headlines since 2010. The legal battles between Epstein's associates, his victims, and Epstein himself had dragged on, in public view, for years.
Black denies any involvement in Epstein's trafficking ring. In October, he told shareholders on an earnings call that palling around with Epstein after his 2008 conviction for soliciting a minor in Florida was a ''terrible mistake.''
''Let me be clear,'' Black said. ''There has never been an allegation by anyone that I engaged in any wrongdoing, because I did not. And any suggestion of blackmail or any other connection to Epstein's reprehensible conduct is categorically untrue.''
Black previously announced he was stepping down as CEO of Apollo and said he'd hand the reins to co-founder Marc Rowan on or before July 31. But on Monday, Apollo said the 69-year-old Wall Street mogul and art collector quit earlier than scheduled and had also relinquished his role as chairman. In a statement, Black said he planned to spend more time with his family and focus on his health and other passions like art. ''And time is precious,'' Black said. ''My wife, Debra, lost a close family member to the pandemic and faces considerable health challenges. I intend to address my own health issues, and take some personal time to pursue my many interests away from Apollo'--including the arts, culture, medical research, and philanthropy.''
Now Black may also lose one of his high-profile positions in the art world: the MoMA chairmanship he's held since 2018. That year, Black donated $40 million to the museum and had two floors of its film center named after him and his wife.
A rep for Black declined to comment. MoMA did not respond to multiple requests for comment.
Still, the museum looks likely to address Black's future on the board at its next meeting scheduled for March 30.
None of MoMA's nearly 80 officers and trustees would speak about Black on the record, though several said they supported him and viewed his relationship to Epstein strictly as business: Black was among a litany of high-powered people to associate with Epstein. One member told The Daily Beast, ''It's obvious to me people used [Epstein], not the least of which as ways to meet other people. And people did do business with him, ergo Leon.''
Another trustee, however, told The Daily Beast that they were troubled by Black's decades-long friendship and ties with a sexual predator. ''There's people who feel strongly, but there has not been a forum for people to express their thoughts yet,'' the person said, referring to the museum's decision to twice postpone its board meeting since February. Asked if they were bothered by the chairman's association with Epstein, the trustee added, ''Of course it disturbs me. I have a conscience and I have children.''
Last week, the New York Post revealed ''a number of MoMA trustees'' had contacted Black about resigning once his term ends on July 1. The report indicated the billionaire could rescind the museum's access to his vast art holdings'--including Edvard Munch's The Scream'--should he leave the board altogether. ''Remember, if MoMA kicks out Black, they lose a chance at his personal art collection,'' one source told the Post.
The Blacks' collection, said to be valued at $1 billion, also includes Head of a Young Apostle, a chalk drawing by Raphael purchased for $48 million; the $106-million Picasso sculpture Bust of a Woman; and the $27-million Constantin BrncuÈi sculpture Bird in Space, which is on display at MoMA.
Calls for Black's ouster have included a petition signed by a phalanx of prominent artists including Nan Goldin and Xaviera Simmons, who demanded MoMA boot Black over his links to Epstein. ''We, as artists and art workers, support the removal of Leon Black from the board of MoMA for reasons that have already been stated by many others. However, this should be considered the bare minimum,'' the group said in a statement. One of the signatories, Guerrilla Girls, the anonymous feminist art collective, said it terminated its book contract with Phaidon Press in 2019 because it's owned by Black. They said MoMA should axe not only Black but fellow trustee Glenn Dubin, a billionaire whose family has longstanding ties to Epstein and whom Virginia Roberts Giuffre, a survivor of Epstein's sex ring, accused of abuse.
Giuffre says Epstein and his alleged accomplice Ghislaine Maxwell kept her as a ''sex slave'' and sent her to powerful men including Britain's Prince Andrew, Dubin, and former New Mexico Gov. Bill Richardson. (All three of the men have denied Giuffre's accusations.)
''We were outraged by Black's silence about his relationship to a known pedophile,'' Guerrilla Girls said in a prior statement. ''So we put up a message outside MoMA demanding the museum kick Black off its Board, along with Epstein pal Glenn Dubin, and tell the world why. It was the least MoMA could do for victims of sexual assault everywhere.''
The art group said: ''How could Black, a shrewd businessman and guy around town, not have known his money subsidized Epstein's elaborate lifestyle, enabling Epstein to continue abusing and trafficking underage girls right up to his suspicious death in 2019? Was Black complicit in Epstein's crimes?''
''Why does MoMA tolerate people like Black and Dubin on its Board?'' Guerrilla Girls added. ''If we're stuck with a system where our tax-exempt, educational institutions have to depend on money from the superrich, they should at least choose donors who make the world a better, not a worse place.''
Black has been under fire in the press for his ties to Epstein since July 2019, when Manhattan federal prosecutors charged the 66-year-old financier with exploiting girls as young as 14 from 2002 to 2005. And the media firestorm didn't fade after Epstein killed himself in jail one month later.
Their relationship is also being investigated by at least one government official: Denise N. George, the attorney general for the U.S. Virgin Islands, who subpoenaed Black as part of her civil racketeering lawsuit against Epstein's estate and companies. (George has also subpoenaed Dubin for all communications relating to Epstein and Dubin's three children, along with records relating to a Swedish girl who traveled with Epstein.)
Shortly after Epstein's New York indictment, Black sent an email to Apollo employees addressing concerns about his relationship with the money manager. ''I was completely unaware of, and am deeply troubled by, the conduct that is now the subject of the federal criminal charges brought against him,'' Black wrote.
''There's people who feel strongly, but there has not been a forum for people to express their thoughts yet.''
At the same time, reports surfaced that Black had donated $10 million to the financier's secret foundation, Gratitude America Ltd., in 2015 using a shell company called BV70 LLC. ''Black felt comfortable making this donation because he understood that Epstein was a strong proponent of scientific innovation,'' Apollo's internal review said. Black also used BV70 to make $30.5 million in loans to Epstein ''in connection with an art transaction involving'' the perverted hedge funder, who repaid only $10 million despite Black's demands for repayment throughout 2018.
Their friendship dissolved, the report says, in October 2018 because of a long-running dispute over Epstein's fees. About a month later, Epstein became a household name after the Miami Herald published a three-part expos(C) into his Palm Beach trafficking ring and the lenient 2008 plea deal he negotiated with Miami federal prosecutors.
Apollo's internal report said Black and Epstein met through an unnamed mutual friend in the mid-1990s and ''developed a personal relationship.''
''While Black and Epstein discussed estate planning, philanthropy, and related issues over the years, Black did not engage Epstein to provide him with any services until 2012,'' the report claims. ''Initially, Black viewed Epstein as someone who was very intelligent and knowledgeable regarding issues relating to estate planning and taxation. Black also was impressed by Epstein's connections to many prominent figures in business, politics, and science. Epstein spoke knowledgeably about scientific innovation and technology. He introduced Black to well-regarded researchers at Harvard University and the Massachusetts Institute of Technology and encouraged Black to donate to charitable causes that supported scientific development.''
Indeed, Black's name has surfaced in multiple reports on Epstein's companies and donations'--including internal reviews by Harvard University and the Massachusetts Institute of Technology, as well as Deutsche Bank.
An MIT report said Epstein claimed to have set up anonymous donations for the school's Media Lab from Black and Microsoft co-founder Bill Gates. ''Black has publicly acknowledged donating to charities 'affiliated' with Epstein, but has not specifically addressed whether he donated to MIT or whether Epstein asked him to donate to MIT,'' the document concluded. ''Notably, we did not find any evidence that the money donated by Gates or Black actually was Epstein's money'--that is, there is no evidence that Gates and Black acted to 'launder' Epstein's money.'' The backlash over Epstein's donations to the MIT Media Lab caused director Joi Ito to resign in 2019.
For its part, Harvard noted that Epstein helped two professors obtain millions in donations from Black: Martin Nowak, who helmed the university's Program in Evolutionary Dynamics, and Harvard Medical School geneticist George Church. ''Jeffrey Epstein introduced Mr. Black to the research that was being undertaken by Professors Church and Nowak,'' a representative for Black told Harvard counsel for the university's own report. ''Mr. Black met with Professors Nowak and Church to discuss their research in Cambridge, Massachusetts and, in the case of Professor Church, also at Mr. Black's New York office. The gifts made in support of Professor Church's and Professor Nowak's research were made by Mr. Black. None of the funds were provided by Mr. Epstein and no attempt was made to conceal the source of these gifts.''
''Black viewed Epstein as a friend worthy of his trust.''
The Apollo report further illustrated the social and financial ties that bound Epstein and Black. In 1997, Black named Epstein a director of his family foundation, whose only other officers were himself and spouse Debra. While Black claims Epstein left this position in mid-2007'--when the FBI was investigating him in Palm Beach for abusing minors'--the foundation's tax forms continued to list Epstein through 2012.
And Black continued to socialize with Epstein and pay him for estate and tax planning, among other services, even after his 2008 conviction in Florida.
''Following Epstein's prison sentence, Black believed that Epstein had served his time and that it would not be inappropriate to maintain a personal and professional relationship with Epstein,'' the report notes. At the time, Black thought Epstein's crimes were ''limited to a single instance of soliciting a 17 year old prostitute that Black believed Epstein had mistakenly understood was older.'' The report also says Black ''believes in rehabilitation, and in giving people second chances.''
According to the report, ''Black viewed Epstein as a friend worthy of his trust.'' The billionaire regularly visited Epstein in New York, including at events with other prominent guests, and ''confided in Epstein on personal matters.'' Black and his wife visited Epstein at his residences in France, Florida, the Caribbean, and New Mexico but never spent the night, the report claims. ''At Epstein's request, Black and his wife provided transportation from Santa Fe to California on Black's plane to two or more of Epstein's adult guests in Santa Fe,'' a footnote in the report states.
''Black viewed Epstein as a confirmed bachelor with eclectic tastes, who often employed attractive women,'' the review says. ''However, Black did not believe that any of the women in Epstein's employ were underage. Black has no recollection of ever seeing Epstein with an underage woman at any time.''
The internal report says that for years, Epstein managed Black's art collection and counseled him on forming a new art partnership and ''obtaining a potential advisory opinion from the New York State Department of Taxation and Finance regarding a contemplated transaction involving Black's art.'' Epstein was also ''fairly involved in assisting Black in connection with the sale of certain pieces of artwork'' and advised him on ''the contested ownership of a Picasso sculpture.''
In 2015, Black purchased Bust of a Woman from the artist's daughter, Maya Widmaier Picasso, for $106 million. The Qatari royal family and their agents, however, challenged the transaction; they said they'd already reached a deal with Widmaier Picasso to buy the sculpture for about $42 million two years before. Both sides reached a settlement in 2016, with Black the winner of the piece.
Around the same time, Black and Epstein's relationship started to unravel. Epstein began demanding tens of millions in fees for supposedly coming up with a tax-planning transaction that saved Black $600 million. He emailed Black throughout 2016 and 2017 to pressure him to pay more for the expertise. ''Epstein also would invoke his friendship with Black in those emails,'' the Apollo report states, ''including by referencing personal matters that Black had shared with Epstein in confidence, although there is no evidence that those matters had any relationship to any of Epstein's criminal activity or to any of Black's payments to Epstein.''
Black, per the report, ''was shocked'' when Epstein's sex crimes made news in late 2018. ''Some witnesses noted specifically that they did not believe Black would have allowed Epstein to be introduced to Black's wife and children if Black had had any suspicion that Epstein had done anything inappropriate or illegal with girls or young women,'' the review says.
But at least one guest who attended a swanky pool party at Black's Hamptons property in 2015 was surprised to see Epstein among the swimsuit-clad revelers.
''Leon had a personal relationship with Jeffrey, and I found it odd,'' one witness told the Post. ''Why was what Jeffrey did not that bad?''
Apollo announces that cofounder Josh Harris is stepping down, 2 months after former CEO Leon Black quit | Business Insider India
Wed, 02 Jun 2021 17:44
Josh Harris of Apollo Global Management speaks at the 2019 Delivering Alpha conference hosted by CNBC Heidi Gutman/CNBC
Josh Harris, one of the cofounders of Apollo Global Management, is stepping down, the firm said Thursday. Harris would remain on the board of directors and executive committee, Apollo said. Leon Block, the Apollo cofounder who was investigated for ties to Jeffrey Epstein, quit the firm in March.Investment firm Apollo Global Management on Thursday announced that cofounder Josh Harris would step down as managing director.
He would step down once Apollo merges with its insurance affiliate Athene, the company said in a statement. Apollo's acquisition of Athene, which is set to create a $29 billion conglomerate, is expected to complete in the first quarter of 2022.
Harris would remain on the Apollo board of directors and executive committee, the firm said.
Harris said in the statement: "After nearly 31 years at Apollo, it is time for me to start the next chapter of my career, where I will focus full-time on the platforms I've created outside of the firm as well as deepen my commitment to philanthropy and social impact."
Read more: We talked to billionaires, business titans and an NBA star about the Apollo cofounder who wants to buy the New York Mets. Here's how he can apply his private equity turnaround playbook to a team that haven't won a World Series since 1986.
Fellow cofounder
Leon Black, former CEO and chairman of Apollo,
quit the firm in March. Black's departure followed an independent investigation into his relationship with the convicted sex offender Jeffrey Epstein, which showed
Black paid $158 million to the disgraced financier between 2012 to 2017.
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The investigation found that neither Black nor Apollo employees were involved in Epstein's criminal activities.
{{}}
Bill Gates and Jeffrey Epstein - TrueHoop
Wed, 02 Jun 2021 11:30
BY HENRY ABBOTTBill Gates is in the news because earlier this week, after 27 years of marriage, his wife Melinda filed for divorce.
The news got all kinds of people talking about Bill Gates. To my surprise, his name has popped up again and again in TrueHoop's ongoing investigation of Epstein's ties to Apollo Global and the NBA. Rooted in Drexel Burnham Lambert, Apollo has become the NBA's most important source of cash.
Of particular interest: Epstein and Gates both have had ties to the current leaders of the United Arab Emirates and Saudi Arabia.
A timeline:
1986Microsoft's IPO made Bill Gates one of the richest Americans. One of the main banks with which he did this is Alex. Brown, whose then head was A.B. ''Buzzy'' Krongard. Buzzy later became an executive at the CIA, and is now on the board of Apollo Global, "which is undergoing profound change following the revelation of its founder's relationship with sex trafficker Jeffrey Epstein."
1993A Seattle Times story describes the convicted felon, Robert Evans, who, at the time, invested much of Bill Gates' portfolio. It's a story of leverage: Evans reportedly got to decide which large bank handled Gates' routine sales'--reportedly about a million shares per quarter'--of Microsoft stock. In exchange, he expected to get in on the hottest initial public offerings the banks have to offer. ''Buzzy'' Krongard's Alex. Brown was one of Evans' most frequent partners.
1994A New Yorker profile of Gates includes a quote from an unnamed competitor: ''I think the guy is truly dangerous. Bill is the most surprisingly conscience-free individual I've ever met, and that amount of power in the hands of a guy without a conscience is dangerous.''
Bill and Melinda Gates were married in Hawaii.
2000Melanie Walker reportedly met Jeffrey Epstein in the early 1990s, when he offered to get her a Victoria's Secret audition. Later she became a neuroscientist and a scientific advisor to first Epstein and later the Bill and Melinda Gates Foundation. In 2000, Walker reportedly attended Prince Andrew's 40th birthday party, thrown by the Queen at Windsor Castle, with Jeffrey Epstein and Ghislaine Maxwell.
Later, London tabloids fixated on relations between Andrew and a young neuroscientist, who evidently spent a few days together at Epstein's New Mexico property. The Daily Beast's Tom Sykes:
Deidre Stratton worked at Epstein's notorious Zorro Ranch, and she told a podcast, Epstein: Devil in the Darkness, that Andrew was ''kept company'' by the woman for three days when he stayed at the ranch on his own. '... Epstein was not there, but he arranged for Andrew to be accompanied by the young medic, according to the former housekeeper. Stratton said: ''At the time, Jeffrey had this, she supposedly was a neurosurgeon, quite young, beautiful, young and brilliant, and she stayed in the home with him... At one point we had all these different teas and you could pick the teas that you wanted and she asked me to find one that would make Andrew more horny.''
2001Nigel Rosser of the Evening Standard wrote about Prince Andrew's fascination with Ghislaine Maxwell, and Maxwell's unusual partnership with Jeffrey Epstein. Rosser reported that Epstein ''has made many millions out of his business links with the likes of Bill Gates'':
Epstein was a guest at the Queen's birthday party at Windsor and travelled with Ghislaine to Andrew's country weekend at Sandringham before Christmas. He has made many millions out of his business links with the likes of Bill Gates, Donald Trump and Ohio billionaire Leslie Wexner, whose trust he runs.
Prince Andrew's friends can only speculate what Epstein gains from his association with British royals but clearly it can do no harm to his business reputation in New York.
(This report has evidently gone missing from the Evening Standard's website.)
2006In 2006 Melanie Walker joined the faculty of the University of Washington. As of May, 2021, she is reportedly married to one of Bill Gates' longtime, most trusted Microsoft colleagues, Steven Sinofsky. It's unclear when the wedding was, but some reports attach her moving to Seattle to her relationship with Sinofsky.
2008Bill Gates founded a ''mysterious'' new entity which at one point was called BCG3, and later Gates Ventures.
In June, Epstein began to serve about a year in prison after a plea agreement stemming from an investigation based on the testimony of many underaged girls in Florida.
2009 and 2010Gates was photographed at Edge Foundation events (''the billionaires dinner''). Epstein was the foundation's biggest backer, and he attended many years, including 2009 and 2010.
2011As reported in The New York Times, Gates visited Epstein's residence in New York City on January 31. ''His lifestyle is very different,'' Gates writes of Epstein in an email to colleagues, ''and kind of intriguing although it would not work for me.'' Later a Gates spokesperson claims Gates was referring to the house's decor. Dr. Eva Andersson-Dubin and her 15-year-old daughter were at dinner. ''A very attractive Swedish woman and her daughter dropped by and I ended up staying there quite late,'' added Gates.
Shortly thereafter, Epstein and Gates were reportedly deep in conversation at TED Long Beach.
On May 3, Gates was photographed at Epstein's mansion with JP Morgan executive James E. Staley, former Treasury Secretary Lawrence Summers, Jeffrey Epstein, and Boris Nikolic. Nikolic, at the time, was a science advisor to the Bill and Melinda Gates foundation who had reportedly become friends with Epstein after being introduced by Walker.
Following that, Gates Foundation teams reportedly visited Epstein's mansion twice more, to discuss a potential Global Health Investment Fund.
2012''Microsoft staff stunned'' that Steven Sinofsky, expected to be Microsoft's next CEO, stepped down.
2013Gates flew from Teterboro to Palm Beach on Jeffrey Epstein's plane in March.
In September, Gates and Nikolic were in New York to visit a medical company Gates had invested in. Gates and Epstein reportedly had dinner.
Mohammed bin Salman'--then a local official'--has his MiSK Foundation launch the Tweeps Forum, an annual networking event that includes Ivanka Trump, top officials from the United Arab Emirates, and Twitter executives.
2014BCG3 donated $2 million to the MIT Media Lab. The New Yorker's Ronan Farrow reports:
Epstein appeared to serve as an intermediary between the lab and other wealthy donors, soliciting millions of dollars in donations from individuals and organizations, including the technologist and philanthropist Bill Gates and the investor Leon Black. According to the records obtained by The New Yorker and accounts from current and former faculty and staff of the media lab, Epstein was credited with securing at least $7.5 million in donations for the lab, including two million dollars from Gates and $5.5 million from Black, gifts the e-mails describe as ''directed'' by Epstein or made at his behest. '...
In October, 2014, the Media Lab received a two-million-dollar donation from Bill Gates; Ito wrote in an internal e-mail, ''This is a $2M gift from Bill Gates directed by Jeffrey Epstein.'' Cohen replied, ''For gift recording purposes, we will not be mentioning Jeffrey's name as the impetus for this gift.''
Bill Gates reportedly rented the super yacht ''Serene,'' off the coast of Sardinia, for $5 million a week.
2015Saudi Prince Mohammed bin Salman purchased Serene.
U.S. investigators notify Twitter that some of its employees have been cultivated as agents of the Saudi government, for instance supplying personal information of Saudi dissidents. As Twitter investigates, one of the employees moves to Saudi Arabia and begins work at the MiSK Foundation. The New York Times:
According to court documents, the Saudi official who developed the Twitter employees was the ''secretary general'' of a charitable organization owned by a member of Saudi Arabia's royal family. That description pointed to the MiSK Foundation, a technology-focused nonprofit founded by Prince Mohammed.
2016Donald Trump was elected. His first visit would be to Saudi Arabia, where he touted enormous defense contracts with the kingdom.
2017Bill Gates visited Prince Mohammed bin Salman in Saudi Arabia, and gave a speech that said: ''I'm excited about this initiative because I love challenging young people to solve very tough problems, and pursue their dreams. I know that's an aspiration I share with the Crown Prince.''
Mohammed bin Salman's foundation becomes a member of the MIT Media Lab consortium'--which will soon undergo changes because of Epstein ties. In a press release MiSK says ''By becoming a MIT Media Lab member, the MiSK Foundation joins a network of over 80 member companies and organizations '... these include MiSK's partners such as Bill & Melinda Gates Foundation'...''
2018Mohammed bin Salman visited Gates' home in Washington. In the book MBS, by Ben Hubbard, MBS is quoted saying he wants to be a disruptive leader like Steve Jobs, Mark Zuckerberg, or Bill Gates.
Also that year, journalist James B. Stewart visited Jeffrey Epstein at his house in Manhattan, and wrote:
Before we left the room [Epstein] took me to a wall covered with framed photographs. He pointed to a full-length shot of a man in traditional Arab dress. ''That's MBS,'' he said, referring to Mohammed bin Salman, the crown prince of Saudi Arabia. The crown prince had visited him many times, and they spoke often, Epstein said.
In November, journalist Jamal Khashoggi was captured, assassinated, and carved to pieces in Istanbul. In November the CIA would report that MBS had ordered the assassination, a conclusion that was affirmed by a four-page report released by the Director of National Intelligence in 2021. Two of those reportedly responsible for the murder were among MBS's personal security detail.
Later, Donald Trump reportedly bragged that MBS was going to get in trouble for the episode but Trump ''saved his ass.''
U.S. Senator Tim Kaine suggested the killers may have been trained by a U.S. private military contractor called Tier One, whose main investor is Trump intelligence appointee and donor Stephen Feinberg. Feinberg worked at Drexel Burnham Lambert with the founders of Apollo Global.
The Bill and Melinda Gates Foundation reveals that it has suspended future work with the MiSK Foundation because of the killing of Jamal Khashoggi.
2019Jeffrey Epstein was arrested.
Joi Ito, head of the MIT Media Lab, resigned from MIT and a number of other boards and positions over his ties to Epstein.
Kobe Bryant, the NBA, and Madison Square Garden reportedly met with sports officials from Saudi Arabia. The Guardian's Karim Zidan:
More recently, Saudi Arabia's sports-centric lobbying offensive has been the result of an urgent need for the kingdom to rebrand itself following the murder of Jamal Khashoggi, a US-based Washington Post columnist and Saudi dissident who was last seen entering the Saudi consulate in Istanbul, where he was reportedly killed and dismembered with a bone-saw. Saudi's attorney general later stated that the murder was premeditated, and the CIA concluded that Prince Mohammed bin Salman ordered Khashoggi's murder.In light of Saudi's recent diplomatic controversy, the kingdom has doubled down on its lobbying strategy, which, according to recently released documents, included meetings and business calls with all the leading commissioners and sports bodies in the United States.
Town & Country magazine's Ben Widdicombe explored the role of Ghislaine Maxwell, and Gates' Microsoft co-founder'--and then Trail Blazers owner'--Paul Allen came up.
''She was a big part of the jet-set,'' said one person who has known her for 15 years. "I would see her in St. Barth's, on Paul Allen's yacht"'--the Octopus, an infamous 414-foot floating pleasure palace then owned by the late Microsoft co-founder'--''and at Heidi Klum's Halloween party in New York.'' '... Much like Epstein, her social circle also encompassed Britain's Prince Andrew; a Palm Beach set which included Donald Trump; and the Clinton family'--she even attended Chelsea Clinton's 2010 wedding. ''But the thing is, to hang around those billionaire guys, you either have to be sleeping with them or you're finding them girls. There is no in-between when you're in that crowd,'' said the friend, referring not to Ghislaine individually but the dark habits and rituals common at the highest echelons of power.
Jeffrey Epstein died in custody, days after reportedly changing his will and naming Boris Nikolic'--a longtime Gates confidante'--as his backup executor. Nikolic, who shared a private JP Morgan banker with Epstein and had other business ties, reportedly rejected the assignment.
2020Gates left the Microsoft board.
2021Melinda Gates filed for divorce, saying her marriage is ''irretrievably broken.'' The New York Times reports:
The couple deployed their connections last year in response to the pandemic, calling leaders like Chancellor Angela Merkel of Germany and Crown Prince Mohammed bin Zayed of Abu Dhabi to drum up support for their plans. The foundation has committed $1.75 billion so far to its Covid-19 response, and played a key role in shaping the global deal to bring vaccines to poor countries.
That prominence has also brought a fair share of scrutiny, throwing a spotlight on Mr. Gates's robust defense of intellectual property rights '-- in this case, specific to vaccine patents '-- even in a time of extreme crisis, as well as the larger question of how unelected wealthy individuals can play such an outsize part on the global stage.
Thank you for reading TrueHoop!
Jeffrey Epstein net worth: Did he try to marry Glenn Dubin's daughter? '' Film Daily
Wed, 02 Jun 2021 11:18
The case against Jeffrey Epstein is still afoot and new documents reveal U.S. Virgin Islands prosecutors are now exploring Epstein's ties with billionaire Glenn Dubin & his family. While the Dubins claim they are ''outraged'' by the allegations against them, the Dubins history with Epstein has made many suspicious of the Dubins' activities with the registered sex offender.
Epstein died shortly after his arrest, but prosecutors are continuing their investigations. Epstein's alleged madam Ghislaine Maxwell was also arrested for enticement & sex trafficking minors in July 2020. Depositions revealed the Dubins may have more to do with Epstein's alleged sex ring than they claim, but Epstein's relationship with their daughter, Celina, has also faced scrutiny, especially after the recent subpoena.
The Virgin Islands prosecutors have been investigating Epstein's alleged sex trafficking ring & alleged racketeering. Epstein owned a private island in the Virgin Islands where he allegedly groomed, sexually abused, & sex trafficked young women & girls. Here's why Epstein could have been interested in Glenn Dubin's daughter and what this latest subpoena has to do with the investigation.
Newest subpoena According to the Washington Examiner , U.S. Virgin Islands prosecutors issued a subpoena in September requesting Dubin to turn over any & all communications, including documents & messages, related to his three children & Epstein. Dubin & his wife, Dr. Eva Andersson, have three children together: two daughters, Maye & Celina, and one son, Jordan.
The Washington Examiner reported Epstein wanted to marry Celina. Epstein met Celina when she was twelve years old and the two had ''an especially close relationship'', according to the Washington Examiner , though there is no evidence of a romantic relationship. The paper stated Epstein possibly wanted to marry Celina only for ''financial incentives'' due to her inheritance, which could boost his net worth.
The subpoena also requested financial records between Dubin & Epstein and communication between Epstein and ''a Swedish female'' he traveled with & his former butler Rinaldo Rizzo, according to the Washington Examiner . The girl in question, who was fifteen at the time, was allegedly held against her will at Epstein's island, according to testimony by Rizzo, according to the Daily Mail .
Epstein & Dubin Even before Epstein met Glenn Dubin, Epstein dated Dubin's wife, Eva Andersson-Dubin, for eleven years, according to the Washington Examiner . Dubin has been personally connected to Epstein since July 2019, when it was revealed Epstein invested millions in Dubin's hedge fund & helped negotiate the acquisition of Dubin's firm with JPMorgan, according to Vanity Fair .
Even more, unsealed documents revealed Virginia Roberts Giuffre, one of the most significant Epstein survivors, accused Epstein & associate Ghislaine Maxwell of pressuring her to have sex with Dubin. Dubin is one of many Giuffre has alleged of being sex trafficked to. Giuffre has also alleged Maxwell of grooming her for Epstein. Maxwell is now facing sex trafficking charges and is awaiting her trial after pleading not guilty.
In addition, Dubin's aforementioned former butler Rinaldo Rizzo said in his deposition how he found a saw a Swedish girl who looked like the girls he had seen on Epstein's island. The girl was hired as a nanny Dubin & Eva Andersson-Dubin. Rizzo had asked the girl about her association with Epstein when the girl revealed how she was forced to have sex, according to The Daily Beast . The Dubins have maintained their innocence.
The Dubins' billionaire lifestyle Glenn Dubin grew his net worth by being a hedge fund manager & the co-founder of Highbridge Capital Management; however, he announced his retirement earlier this year, saying he would focus on his private investments, according to Reuters . He's amassed a net worth of $2 billion.
Glenn Dubin & Eva Andersson-Dubin have been married since 1994. They've been involved with philanthropy over the years, though they've faced plenty of controversies since their connection with Epstein was revealed. Even after Epstein was deemed a sex offender, Andersson-Dubin wrote a letter to Epstein's probation officer she was ''100% comfortable'' with Epstein around her children.
While the Dubins' have dialed back their association with Epstein, he was nevertheless a seemingly large part of their lives. According to the Daily Mail , Dubin told his friends in 2014 he would likely marry Celina. She was nineteen years old at the time. According to the tabloid, Epstein allegedly wanted to give Celina some of his net worth and named Celina as the beneficiary of a $50 million trust. She was subsequently removed in 2015.
Apollo Global Management - Wikipedia
Wed, 02 Jun 2021 05:23
Apollo Global Management, Inc., is a global alternative investment manager firm. It was founded in 1990 by Leon Black, Josh Harris,[4] and Marc Rowan.[5] Apollo is headquartered in New York City, with offices across North America, Europe and Asia.[6] The company's stock is publicly traded on the NYSE under the symbol 'APO'.
Apollo Global Management, Inc.TypePublicNYSE: APOISIN US0376123065 IndustryAsset managementFounded1990 ; 31 years ago ( 1990 ) FoundersLeon Black, John Hannan, Josh Harris, Marc Rowan, Craig Cogut, Arthur Bilger, Antony ResslerHeadquartersSolow Building,New York City
,U.S.
Key people
ProductsPrivate equity funds, credit funds, real estate funds, alternative investment, leveraged buyouts, growth capital, venture capitalRevenue US$2.931 billion (2019)[1] US$ 1.407 billion (2019)[1] US$ 1.536 billion (2019)[1]AUM US$ 414 billion (June 2020[2] Total assets US$8.542 billion (2019)[1] Total equity US$ 3.038 billion (2019)[1]Number of employees
1,600 (2020)[3]Website www.apollo.com The firm specializes in investing across credit, private equity, and real assets.[7][8]
Apollo Global Management reported $414B of assets under management at the end of June 2020. Around 72% of assets are in the credit business ($300.4B as of last quarter close). Around 18% of assets ($73.3B as of last quarter close) are in private equity. The remaining 10% of assets are in real assets ($39.9B as of last quarter close).[9] Around 66% of assets are in the credit business ($209.7B as of last quarter close). Around 21% of assets ($67.7B as of last quarter close) are in private equity. The remaining assets are in real assets ($39.9B as of last quarter close).[9][failed verification ]
Among the most notable companies Apollo has an investment in are ADT, CareerBuilder, Cox Media Group, Intrado, Rackspace, Redbox, Shutterfly, Smart & Final, and University of Phoenix.
In March 2021, Apollo Global Management announced plans to merge with Athene Holding, the life insurance company. The merger values Athene at $11 billion. Since it was founded in 2009, Athene has been backed by Apollo.[10] Athene went public in 2016 and had a market capitalization of just over $10 billion. Prior to the merger announcement, Apollo already owned 35% of Athene.[11] The deal is expected to close in January 2022.[12] The combined entity will have a market cap of $29 billion, making it eligible for inclusion in the S&P 500 index.[13]
In March 2021, Apollo announced that Leon Black had stepped down as CEO and chairman after revelations that he paid Jeffrey Epstein $158 million for personal tax-related advice over the period from 2012 to 2017.[14][15] Marc Rowan became CEO after Black stepped down.[16]
History Edit Apollo, originally referred to as Apollo Advisors, was founded in 1990, on the heels of the collapse of Drexel Burnham Lambert in February 1990, by Leon Black, the former head of Drexel's mergers and acquisitions department, along with other Drexel alumni.[17] Among the most notable founders are John Hannan, Drexel's former co-director of international finance; Craig Cogut, a lawyer who worked with Drexel's high-yield division in Los Angeles; and Arthur Bilger, the former head of the corporate finance department. Other founding partners included Marc Rowan, Josh Harris, and Michael Gross, who both worked under Black in the mergers and acquisitions department, and Antony Ressler, who worked as a senior vice president in Drexel's high yield department with responsibility for the new issue/syndicate desk.[18][19][20]
Less than six months after the collapse of Drexel, the founders of Apollo had already begun a series of ventures. Apollo Investment Fund L.P., the first of its private equity investment funds, was formed to make investments in distressed companies. Apollo's first fundraised approximately $400 million of investor commitments on the strength of Black's reputation as a prominent lieutenant of Michael Milken and a key player in the buyout boom of the 1980s.[18] Lion Advisors was set up to provide investment services to Credit Lyonnais, which was seeking to profit from depressed prices in the high yield market.[21]
1990s Edit At the time of Apollo's founding, there was little financing for new leveraged buyouts and Apollo turned instead to a strategy of distressed-to-control takeovers.[22][23] Apollo would purchase distressed securities which could be converted into a controlling interest in the equity of the company through a bankruptcy reorganization or other restructuring. Apollo used distressed debt as an entry point, enabling the firm to invest in such firms as Vail Resorts,[24] Walter Industries,[25][26] Culligan, and Samsonite.[27]
Early on, Apollo made a name for itself by acquiring interests in companies that Drexel had helped finance by purchasing high-yield bonds from failed savings and loans and insurance companies. Apollo acquired several large portfolios of assets from the U.S. government's Resolution Trust Corporation.[28] One of Apollo's earliest and most successful deals involved the acquisition of Executive Life Insurance Company's bond portfolio. Using this vehicle, Apollo would purchase the Executive Life portfolio, generating tremendous profits[clarification needed ] when the value of high yield bonds recovered, but also resulting in a variety of state regulatory issues for Apollo and Credit Lyonnais over the purchase.[29] More than a decade after the purchase, in 2002, California Attorney General Bill Lockyer accused Apollo, Leon Black, and an investor group led by French bank Credit Lyonnais of illegally acquiring the assets and bond portfolio of Executive Life Insurance Co. in 1991. According to the State of California, Credit Lyonnais allegedly violated a California law that prohibited foreign government-owned banks from owning California insurance companies.[30]
AREA Property Partners logo
In 1993, Apollo Real Estate Advisers was founded in collaboration with William Mack to seek opportunities in the U.S. property markets.[31] Apollo Real Estate Investment Fund, L.P., the first in a family of real estate "opportunity funds", was closed in April 1993 with $500 million of investor commitments. In 2000, Apollo exited the partnership, which continued to operate as Apollo Real Estate Advisers until changing its name to AREA Property Partners, effective January 15, 2009. That firm is owned and controlled by its remaining principals, who include William Mack, Lee Neibart, William Benjamin, John Jacobsson, Stuart Koenig, and Richard Mack.[32] As of 2008, the firm was investing out of three funds: Apollo Real Estate Investment Fund V, Apollo European Real Estate Fund II, and Apollo Value Enhancement Fund VII. In 2004, Apollo Real Estate acquired the Value Enhancement Funds family of investment vehicles to broaden its offerings in the "value-added" segment of the real estate investment spectrum. Apollo also operates a real estate mezzanine lending program and real estate securities hedge fund called Claros Real Estate Securities Fund, L.P.[33]
In 1995, Apollo raised its third private equity fund, Apollo Investment Fund III, with $1.5 billion of investor commitments from investors that included CalPERS and the General Motors pension fund.[34][35] Unlike its first two funds and later funds, Fund III would ultimately prove only an average performer for private equity funds of its vintage. Among the investments made in Fund III (invested through 1998) were: Alliance Imaging, Allied Waste Industries, Breuners Home Furnishings, Levitz Furniture,[36] Communications Corporation of America,[37] Dominick's, Ralphs (acquired Apollo's Food-4-Less),[38] Move.com, NRT Incorporated,[39] Pillowtex Corporation,[40] Telemundo,[41] and WMC Mortgage Corporation.[42]
Apollo invested in
AMC in 2001 and would buy out the company in 2004
Also in 1995, Apollo founding partner Craig Cogut left the firm to found a smaller competitor Pegasus Capital Advisors. Since inception Pegasus has raised $1.8 billion in four private equity funds focused on investments in middle-market companies in financial distress. In 1997, Apollo co-founder Tony Ressler founded Ares Management as the successor to its Lion Advisors business which would manage collateralized debt obligation vehicles.[43]
In 1998, Apollo raised its fourth private equity fund, Apollo Investment Fund IV, with $3.6 billion of investor commitments.[34] Among the investments made in Fund IV (invested through 2001) were: Allied Waste Industries,[44] AMC Entertainment,[45] Berlitz International,[46] Clark Retail Enterprises,[47] Corporate Express (Buhrmann), Encompass Services Corporation, National Financial Partners, Pacer International,[48] Rent-A-Center, Resolution Performance Products, Resolution Specialty Materials, Sirius Satellite Radio, SkyTerra Communications, United Rentals, and Wyndham Worldwide.[49]
2000''2005 Edit Apollo deployed its fourth fund during the booming markets of the late 1990s, only to experience difficulties with the collapse of the Internet bubble and the onset of the recession. Amid the turmoil of collapsing markets, Apollo was able to raise its fifth private equity fund in 2001, Apollo Investment Fund V, with $3.7 billion of investor commitments.[citation needed ] Among the investments made in Fund V (invested through 2006) were Affinion Group, AMC Entertainment, Berry Plastics, Cablecom, Compass Minerals, General Nutrition Centers (GNC), Goodman Global, Hexion Specialty Chemicals (Borden), Intelsat, Linens 'n Things, Metals USA, Nalco Investment Holdings, Sourcecorp, Spectrasite Communications, and Unity Media.
Meanwhile, Ares profited significantly from investments made after the collapse of the high yield market in 2000 and 2001.[citation needed ] Although the founders of Ares had completed a spin-out with the formation of the firm in 1997, they had initially maintained a close relationship with Apollo and operated as the West Coast affiliate of Apollo.[50][citation needed ] By 2002, when Ares raised its first corporate opportunities fund, the firm announced that it would separate from its former parent company. The timing of this separation also coincided with Apollo's legal difficulties with the State of California over its purchase of Executive Life Insurance Company in 1991.[51]
Following the spin-off of Ares in 2002, Apollo developed two new affiliates to continue its investment activities in the capital markets. The first of these new affiliates, founded in 2003, was Apollo Distressed Investment Fund (DIF) Management a credit opportunity investment vehicle.[52] The following year, in April 2004, Apollo raised $930 million through an initial public offering (IPO) for a listed business development company, Apollo Investment Corporation (Nasdaq: AINV)). Apollo Investment Corporation was formed to invest primarily in middle-market companies in the form of mezzanine debt and senior secured loans, as well as by making certain direct equity investments in companies. The company also invests in the securities of public companies.[53][54]
2005''2010 Edit Between 2005 and 2007 the private equity market was booming, with new "largest buyout" records set and surpassed several times in an 18-month window.[55] Although Apollo was involved in a number of notable and large buyouts, the firm avoided the very largest transactions during the time. Among Apollo's most notable investments during this period included Harrah's Entertainment, a leading US gaming and casino company; Norwegian Cruise Line, the cruise line operator; Claire's Stores, the retailer of costume jewelry; and Realogy, the real estate franchisor.[56]
In August 2006, Apollo launched a $2 billion publicly traded private equity vehicle in Europe, AP Alternative Assets (ENXTAM:AAA).[54] The IPO of this new vehicle followed in the footsteps of Kohlberg Kravis Roberts, which raised $5 billion for its KKR Private Equity Investors vehicle in May 2006.[57] Apollo initially attempted to raise $2.5 billion for the public vehicle but fell short when it offered the shares in June, raising only $1.5 billion. Apollo raised an additional $500 million via private placements in the weeks following that sale.[58]
Between 2006 and 2007, as the private equity industry expanded, several of the largest private equity firms, most notably The Blackstone Group and Kohlberg Kravis Roberts, announced plans to realize value from their firms through the sale of shares in the public equity markets. Apollo Management chose a different path and completed a private placement of shares in its management company in July 2007. By pursuing a private placement rather than a public offering, Apollo was able to avoid much of the public scrutiny applied to Blackstone and KKR.[54][59] In November 2007, Apollo was able to realize additional value from the sale of a 9% ownership interest in its management company to the Abu Dhabi Investment Authority (ADIA).[60] Ultimately, in April 2008, Apollo filed with the U.S. Securities and Exchange Commission (SEC)[61] to permit some holders of its privately traded stock to sell their shares on the New York Stock Exchange. That same year, the firm opened an office in India, marking their first push into Asia.[62]
As the deterioration of the financial markets worsened into 2008, Apollo saw several of its investments come under pressure. Apollo's 2005 investment in the struggling US retailer Linens 'n Things suffered from a significant debt burden and softening consumer demand. In May 2008, Linens filed for bankruptcy protection, costing Apollo all of its $365 million investment in the company.[63][64] At the same time, Apollo's investment in Claire's, Realogy and Harrah's Entertainment came under pressure.[56] Apollo responded to its investment difficulties by seeking to exchange a portion of the existing debt at Harrah's and Realogy to more favorable securities.[65] At Claire's, Apollo exercised its "PIK toggle" option to shut off cash interest payments to its bondholders and instead issue more debt, in order to provide the company with additional financial flexibility.[66]
In December 2008, Apollo completed fundraising for its latest fund, Apollo Investment Fund VII, with approximately $14.7 billion of investor commitments.[67] Apollo had been targeting $15 billion, but had been in fundraising for more than 16 months, with the bulk of the capital raised in 2007.[68]
In December 2009, it was announced that Apollo would acquire Cedar Fair Entertainment Company shares and the company would become private underneath the management group.[69] The deal includes a cash payment of $635 million and assumed debt which gives the transaction a value of $2.4 billion.[70] It was later announced in April 2010 that the deal was pulled due to poor shareholder response.[71]
2011''2017 Edit In January 2011, Apollo acquired 51% of Alcan Engineered Products from Rio Tinto.[72]
In March 2011, Apollo completed its initial public offering (NYSE: APO).[73]
In March 2012, Apollo made a second attempt to acquire an amusement park operator with a $225.7 million offer for Great Wolf Resorts.[74] In November 2012, Apollo acquired The McGraw-Hill Companies' education division ("McGraw-Hill Education") in a deal totaling $2.5 billion.[75]
On March 11, 2013, Apollo Global Management made the only bid for the snacks business of Hostess Brands, including Twinkies, for $410 million.[76] Apollo bought a portfolio of Irish home loans from Lloyds Bank in December 2013 for '‚¬307m, less than half their nominal £610m ('‚¬367m) value.[clarification needed ] The shares were bought by an Apollo Global Management subsidiary, Tanager Limited. The portfolio made a £33m loss last year.[77]
In January 2014, Apollo and CEC Entertainment, the parent company of Chuck E. Cheese's, announced that Apollo bought the company and its brand for about $1 billion.[78]
In October 2014, Apollo finalized the merger of its Endemol television studio with 21st Century Fox's Shine Group. The merged company became Endemol Shine Group, with AGM and Fox each owning half of the studio.[79]
On March 24, 2015, Centerbridge Partners reached an agreement with Apollo to acquire the Great Wolf chain from them for $1.35 billion.[80] The acquisition was finalized on May 12, 2015.[81]
In June 2015, Apollo Global Management made a successful offer of around $1.03 billion in cash to privatize OM Group.[82] Also that month, Apollo won the bidding during an auction for Saint-Gobain's Verallia glass bottle manufacturing unit for a rumored fee of around 2.95 billion.[83]
In February 2016, ADT Corporation agreed to be acquired by Apollo Global Management.[84] Apollo Education Group[85] shareholders approved a merger with Apollo Global Management in May 2016. Apollo Education is the parent company of the University of Phoenix. In June 2016, Apollo Global Management made a successful offer to purchase Diamond Resorts International.[86] Apollo made a successful offer to purchase Rackspace in August 2016.[87]
In May 2017, Apollo announced that it had entered into an agreement to acquire West Corp for approximately $2 billion.[88] In December, Apollo agreed to acquire Mexican restaurant chain Qdoba from Jack in the Box.[89]
In November 2017, Apollo Global Management loaned $184 million to Kushner Companies.[90]
2018''2019 Edit AGM was in talks to buy Nexstar Media Group for over $1 billion.[91] However, on February 14, 2019, Cox Media Group announced that it was selling its 14 television stations to AGM.[92] In March 2019 filings with the Federal Communications Commission (FCC), Apollo disclosed that, through the newly formed Terrier Media, the Cox stations would be acquired for $3.1 billion (to be reduced by the value of a minority equity stake in Terrier that will be retained by Cox Enterprises); Terrier will also concurrently acquire Northwest Broadcasting, giving the company 25 television stations.[93] On June 26, 2019, Cox announced that its 60 radio stations, as well as its national advertising business CoxReps, and local OTT advertising agency Gamut, would also be acquired by the new company, which concurrently announced that it would retain the Cox Media Group name instead of Terrier Media.[94] On February 10, 2020, Cox Enterprises bought back the Ohio newspapers it sold to AGM. The FCC required Apollo to reduce the daily newspapers to three days or sell them.[95]
On April 16, 2019, AGM announced that it would once again acquire Smart & Final for $1.1 billion.[96] On June 10, 2019, AGM announced that it would acquire Shutterfly for $2.7 billion, as well as its competitor Snapfish in a separate transaction valued at around $300 million. Apollo plans to merge both companies into a single entity, with Snapfish parent company District Photo as a minority stakeholder.[97] In August, AGM agreed to provide approximately $1.8 billion of debt financing to support New Media Investment Group Inc.'s acquisition of Gannett.[98] On October 23, 2019, AGM announced it signed agreements to take a 48.6% stake in Italian gambling group Gamenet SPA.[99][100] On October 26, 2019, Apollo and The Walt Disney Company agreed to sell Endemol Shine Group to French studio Banijay Group.[101] The sale was completed on July 3, 2020.[102]
2020''present Edit At the end of March 2020, Apollo Global Managed reported $315.5 billion of assets under management.[103][104] In April 2020, AGM announced that it would invest $300 million in Cimpress, an Irish-domiciled printing group that owns Vistaprint.[105] In May, AGM announced the purchase of $1.75 billion of preferred stock in Albertsons Companies.[106] In July 2020, it was reported that the company totalled around $100 billion in investments for war chest in the second quarter of 2020. The sum was double the company's previous record despite the effects of the COVID-19 pandemic.[107]
In March 2021, Apollo managed a $110 million mezzanine credit facility between LendingPoint and MidCap Financial Trust.[108]
On May 3, 2021, Apollo announced its intention to acquire Verizon Media (which includes AOL, Yahoo!, and Verizon Digital Media Services properties) from Verizon for $5 billion. Verizon will retain a 10% stake in the new company, which will be named Yahoo.[109]
Operations Edit Apollo is operated by its managing partners, Leon Black, Joshua Harris, and Marc Rowan and a team of more than 400 investment professionals, as of June 30, 2019. The firm's headquarters are located in the Solow Building at 9 West 57th Street[110] in New York City, with offices in Purchase, New York, Los Angeles, San Diego, El Segundo, Woodland Hills, Houston, Bethesda, London, Frankfurt, Luxembourg, Madrid, Singapore, Hong Kong, New Delhi, Powai, Shanghai, Tokyo, and Mumbai.[6]
Apollo's executive committee includes: Leon Black, chairman, and chief executive officer; Josh Harris, Co-Founder and Senior Managing Director; Marc Rowan, Co-Founder, and Senior Managing Director; Scott Kleinman, Co-President and Lead Partner, Private Equity; James Zelter, Co-President and Chief Investment Officer, Credit; and Gary Parr, Senior Managing Director.[111]
Apollo operates three business lines in an integrated manner:
Private equity: The private equity business is the cornerstone of Apollo's investment activities. Apollo invests through a variety of private equity strategies, most notably leveraged buyouts and distressed buyouts and debt investments. This business operates primarily through the firm's family of private equity investment funds (See: Investment funds).[61]Credit: Apollo invests through a variety of credit strategies to complement its core private equity business. Apollo invests through a variety of investment vehicles including mezzanine funds, hedge funds, European non-performing loan funds and senior credit opportunity funds.[112]Real Estate: Apollo Global Real Estate (AGRE) was established in 2008 to build upon Apollo's history of investing in real estate-related sectors such as hotels and lodging, leisure and logistics. AGRE manages a number of debt and equity-oriented real estate investment funds.[112]Investment vehicles Edit Private equity funds Edit Apollo has historically relied primarily on private equity funds, pools of committed capital from pension funds, insurance companies, endowments, fund of funds, high-net-worth individuals, family offices, sovereign wealth funds and other institutional investors. Since 2014, Apollo has begun investing its eighth private equity fund, Apollo Investment Fund VIII, which raised approximately $18 billion of investor commitments. In 2017, Apollo raised $24.6 billion for its ninth flagship private equity fund, making it the largest in history.[113] Since its inception in 1990, Apollo has raised a total of nine private equity funds, including:[34]
FundVintageYearCommittedCapital ($m)Apollo Investment Fund IX2017$24,600Apollo Investment Fund VIII2014$18,400Apollo Investment Fund VII[68]2008$14,700Apollo Investment Fund VI2005$10,200Apollo Investment Fund V2001$3,700Apollo Investment Fund IV1998$3,600Apollo Investment Fund III1995$1,500Apollo Investment Fund II1992$500Apollo Investment Fund I1990$400Apollo Investment Corporation Edit Apollo Investment Corporation is a US-domiciled publicly traded private equity closed-end fund and an affiliate of Apollo. AIC was formed to invest primarily in middle-market companies in the form of mezzanine debt and senior secured loans, as well as by making certain direct equity investments in companies. The company also invests in the securities of public companies.[53][54]
AIC is structured as a business development company, a type of publicly traded private equity vehicle that is designed to generate interest income and long-term capital appreciation. AIC historically has not invested in companies controlled by Apollo's private equity funds.[116]
AP Alternative Assets Edit AP Alternative Assets (Euronext: AAA) is a Guernsey-domiciled publicly traded private equity closed-end limited partnership, managed by Apollo Alternative Assets, an affiliate of Apollo Management. AAA was formed to invest alongside Apollo's main private equity funds and hedge funds.[53][54]
AAA was launched in August 2006, shortly after Kohlberg Kravis Roberts completed a $5 billion initial public offering for its KKR Private Equity Investors vehicle in May 2006.[54][57] Apollo raised a total of $2 billion for AAA including the vehicle's $1.5 billion IPO and a subsequent private placement.[58]
AAA's investment portfolio is made up of a mix of private equity and capital markets investments.[117]
Portfolio investments Edit Apollo has been an active private equity investor through the mid-2000s buyout boom. The following is a list of Apollo's most recent and currently active private equity investments. The bulk of these investments are held in Apollo Investment Fund V, VI, and VII.
InvestmentYearCompany DescriptionRef.Cox Media Group2019In December 2019, it was announced that Apollo closed the $3 billion deal which acquired the majority share of Cox Media Group. This deal entails Cox's 13 television stations, 54 radio stations, 3 newspapers, national television advertising business '' CoxReps, and local OTT advertising business '' Gamut. Smart Media from Cox.[118][119][120][121]Tech Data Corp.2019In November 2019, it was announced that Apollo acquired Florida-based Tech Data Corp. in a deal worth $5.4 billion, snatching it from Warren Buffett's Berkshire Hathaway.[122][123]GE Capital Energy Financial Services2018In October 2018, Apollo announced to have acquired a portfolio of $1 billion in energy investments of GE Capital's Energy Financial Services unit.[124]Apollo Education Group2017In February 2017, Apollo announced the acquisition of Apollo Education, the parent company of University of Phoenix, for $1.14 billion.[125][126]Diamond Resorts2016On June 29, 2016, Apollo Global Management made a successful offer to purchase Diamond Resorts International.[127]Berry Plastics2006In June 2006, Apollo and Graham Partners announced the acquisition of Berry Plastics Corporation, a maker of plastic containers, for $2.25 billion from Goldman Sachs Capital Partners and JPMorgan Partners.[128]Chuck E. Cheese's2014In 2014, Apollo bought CEC Entertainment, the parent of Chuck E. Cheese's Restaurants.Claire's2007In March 2007, Apollo announced the $3.1 billion leveraged buyouts of costume jewelry retailer, Claire's Stores. In 2008, Claire's experienced financial difficulty amid the slump in consumer spending.[129][130]Constellis2016Apollo bought Constellis Holdings in 2016 for $1 billion. Constellis is a private military contractor that was created as a result of a merger between rival contractors Triple Canopy and Academi in 2014. Academi, founded by Erik Prince and formerly known as Blackwater USA, is best known for its role in the Nisour Square Massacre, where Blackwater guards killed 17 Iraqi civilians and injured 20.[131][132][133][134]Countrywide plc2007In May 2007, Apollo acquired Countrywide plc, the leading provider of residential property related services in the UK, formerly known as Hambro Countrywide (1988) and Countrywide Assured Group (1998) for $1.05 billion (not related to Countrywide Financial).[135]CEVA Logistics2006In August 2006, TNT N.V. announced that it had agreed to the sale of its logistics division to Apollo for $1.9 billion. The business was re-branded as CEVA in November 2007.[136]Debt investments2008''2009Since the beginning of 2008, Apollo has been a significant acquirer of senior secured loans from investment banks and other financial institutions. In April 2008, Apollo, TPG Capital, and The Blackstone Group completed the acquisition of $12.5 billion of bank loans from Citigroup. The portfolio comprised primarily senior secured leveraged loans that had been made to finance leveraged buyout transactions at the peak of the market. Citigroup had been unable to syndicate the loans before the onset of the credit crunch. The loans were reported to have been sold in the "mid-80 cents on the dollar" relative to face value. In late 2008, it was reported that Apollo had received margin calls associated with the financing of its purchase of certain loan portfolios as the price of the loans decreased.[137][138][139]Great Wolf Resorts2012In March 2012 Apollo announced plans to acquire the resort's chain for $703 million. Reports indicated the chain had not turned a profit since 2008.[140]Harrah's Entertainment2006On December 19, 2006, Apollo and TPG Capital announced an agreement to acquire the gaming company for $27.4 billion, including the assumption of existing debt.[141]Hexion Specialty Chemicals2005Hexion was formed in 2005 through the merger of Borden Chemical, Inc., Resolution Performance Products LLC, and Resolution Specialty Materials LLC, and the acquisition of Bakelite AG. Hexion announced in July 2007 that it was acquiring Huntsman Corporation, a major specialty chemicals company, in a $6.5 billion leveraged buyout. Hexion announced in June 2008 it would refuse to close the deal, prompting a series of legal actions. The transaction was officially terminated on December 14 after a settlement between Hexion and Huntsman, wherein they were required to pay Huntsman $1 billion to drop fraud charges that would have potentially sent the CEO of Apollo to prison.[142][143]Jacuzzi Brands2006In October 2006, Apollo announced a $990 million leveraged buyout of Jacuzzi Brands, the manufacturer of whirlpool baths.[144]McGraw-Hill Education2012In November 2012, McGraw Hill announced that it had agreed to the sale of its education division to Apollo for $2.5 billion.[145]Momentive Performance Materials2006In June 2006, Apollo acquired General Electric's Advanced Materials (Silicones & Quartz) business in a deal valued at approximately $3.8 billion.[146]Noranda Aluminum2007In April 2007, Apollo acquired the US aluminum business of the mining company Xstrata for $1.15 billion. The aluminum business, Noranda Aluminum, includes a primary smelter and three rolling mills in Tennessee, North Carolina, and Arkansas along with other operations.[147]Norwegian Cruise Line2008In January 2008, Apollo completed a $1 billion investment in the cruise line operator to support a recapitalization of the company's balance sheet.[148]Novitex Enterprise Solutions2013In 2013, Apollo acquired Pitney Bowes Management Services (PBMS) for $400 million. From PBMS, Apollo formed Novitex Enterprise Solutions. Novitex is a document outsourcing provider that manages business-critical services for over 500 companies across ten industries. Many of its clients are Fortune 500 companies.[149][150]Oceania Cruises2007In February 2007, Apollo acquired the luxury cruise line and provided additional capital to fund the expansion of the company with the purchase of two new cruise ships.[151][152]Philips Lumileds2017In June 2017, Apollo bought 80.1% of Philips Lumileds division for $1.5 billion.[153][154]Realogy:Coldwell BankerSotheby's International RealtyCentury 21 Real Estate2006In December 2006, Apollo announced an $8.5 billion buyout of the real estate franchisor that owns Coldwell Banker, Century 21 and Sotheby's International Realty. The transaction closed in April 2007 and was delisted from the New York Stock Exchange. As the housing market crash accelerated in 2008, Realogy faced financial pressures relating to its debt load. In November 2008, Realogy launched an exchange offer for a portion of its debt to provide additional flexibility, prompting a lawsuit from Carl Icahn.[65][155][156][157]Regent Seven Seas Cruises2008In February 2008, Apollo purchased the luxury cruise line from Carlson Companies for $1 billion. Following the purchase, Apollo made public its plans to order a new ship for Regent.[158]Rexnord Corporation2006In May 2006, Apollo announced the acquisition of the manufacturer of precision motion technology products, primarily focused on power transmission, from private equity firm The Carlyle Group for $1.825 billion.[144][159]Smart & FinalHenry's MarketplaceSprouts Farmers Market2007In February 2007, Apollo announced the acquisition of the Smart & Final chain of warehouse-style food and supply stores. In June 2007, Smart & Final completed the acquisition of the Henry's Marketplace chain of "farmers market" style food retailers from Wild Oats Markets as part of that company's acquisition by Whole Foods Market. In 2011, the Henry's chain was merged with Sprouts Farmers Market, which, like the Henry's markets, had been founded by Henry Boney.[160][161][162][163]
Thai Ornament Resorts2016In January 2016, Apollo announced the acquisition of Thai Ornament Resorts, an upscale destination resort developing firm, for $75.8 million from Tri-Cities Partnership and The Pool Trust.[164]Vantium Management2008In May 2008, Apollo invested in Vantium, a company that buys residential mortgage assets as part of a strategy to profit from the housing market crash.[165]Verso Paper2006In 2006, Apollo acquired International Paper's coated and supercalendered paper business for $1.4 billion, renaming the business, Verso Paper. Verso has been the second-largest producer for the North American magazine publishing and catalog/commercial print markets. In May 2008, Verso was able to complete an initial public offering of stock.[166][167]Other investments include Connections Academy and Unity Media GMBH.
Affiliated businesses Edit From its inception, Apollo was built as part of a network of affiliated businesses focusing on private equity and a variety of distressed investment strategies.
Lion Advisors Edit Lion Advisors (or Lion Capital), which was founded at the same time as Apollo in 1990, focused on investment management and consulting services to foreign institutional accounts targeting investments in public and private high yield debt securities in the US. In 1992, Lion entered into a more formal arrangement to manage the $3 billion high-yield portfolio for Credit Lyonnais which together with a consortium of other international investors provided the capital for Lion's investment activities. The Lion business would ultimately be replaced by Ares Management.[168]
Ares Management Edit Ares Management, founded in 1997, was initially established to manage a $1.2 billion market value collateralized debt obligation vehicle. Ares would grow to manage a family of collateralized loan obligation (CLO) vehicles that would invest in capital markets-based securities including senior bank loans and high-yield and mezzanine debt. Ares was founded by Antony Ressler and John H. Kissick, both partners at Apollo as well as Bennett Rosenthal, who joined the group from the global leveraged finance group at Merrill Lynch.[169]
Ares I and II which were raised were structured as market value CLOs. Ares III though Ares X was structured as cash flow CLOs. In 2002, Ares completed a spinout from Apollo management. Although technically, the founders of Ares had completed a spinout with the formation of the firm in 1997, they had maintained a close relationship with Apollo over its first five years and operated as the West Coast affiliate of Apollo. Shortly thereafter, Ares completed fundraising for Ares Corporate Opportunities Fund, a special situations investment fund with $750 million of capital under management.[168][169]
In 2004, Ares debuted a publicly traded business development company, Ares Capital Corporation (NASDAQ:ARCC).[170] In 2006, Ares raised a $2.1 billion successor special situations fund (Ares Corporate Opportunities Fund II).[169]
References Edit ^ a b c d e "Apollo Global Management Form 10-K". Securities and Exchange Commission . Retrieved February 21, 2020 . ^ Oguh, Chibuike (October 29, 2020). "Apollo third-quarter earnings drop as CEO faces heat from investors" '' via www.reuters.com. ^ "About Apollo Global Management". www.apollo.com. ^ Idzelis, Christine (September 19, 2019). "Apollo's Josh Harris Talks Private Markets at Delivering Alpha". Institutional Investor. As capital floods private markets, Apollo Global Management co-founder Joshua Harris believes investors are finally taking steps toward properly valuing publicly-traded private equity firms. ^ Gordon, Amanda L (October 2, 2018). "Apollo's Marc Rowan Gives Wharton $50 Million for Professorships". Bloomberg. Marc Rowan, a co-founder of Apollo Global Management LLC, gave $50 million to the Wharton School at the University of Pennsylvania, the largest single gift in Wharton's history. ^ a b "Contact". apollo.com . Retrieved October 21, 2019 . ^ Mendon§a, Elisngela (February 7, 2020). "Apollo buys drugmaker Covis from Cerberus". Private Equity News. Apollo has $331bn in assets under management in credit, private equity, and real assets funds. ^ Oguh, Chibuike (January 30, 2020). "Apollo Global's fourth-quarter profit soars on strong asset sales". Reuters. ...driven by growth in its credit and private equity divisions that offset a decline in its real estate unit. ^ a b "Apollo Global Management, Inc. Reports Second Quarter 2020 Results" (PDF) . Apollo. July 30, 2020 . Retrieved August 3, 2020 . ^ Scism, Miriam Gottfried and Leslie (March 8, 2021). "Apollo Reabsorbs Athene in All-Stock Deal That Values Firm at $11 Billion". Wall Street Journal. ISSN 0099-9660 . Retrieved March 9, 2021 . ^ "Apollo Reabsorbs Athene in All-Stock Deal That Values Firm at $11 Billion". The Wall Street Journal. March 8, 2021 . 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Los Angeles Business Journal, August 22, 1994 Archived October 29, 2007, at the Wayback Machine ^ HFS-Apollo in Real Estate Brokerage Venture. New York Times, August 13, 1997 ^ Pillowtex to Acquire Fieldcrest for $400 Million. New York Times, September 12, 1997 ^ Telemundo Plan Backed. New York Times, July 21, 1994 ^ Weyerhaeuser Mortgage Company sale closes. Business Wire, May 22, 1997 ^ Pegasus Capital Advisors > Craig Cogut Profile Archived July 30, 2012, at the Wayback Machine (company website). Also: Craig Cogut's Professional Profile (Founder of Pegasus Capital Advisors) [dead link ] . ^ A trash hauler is buying a much bigger rival, a type of deal that makes Wall Street a bit nervous. The New York Times, March 9, 1999 ^ For a Theater Chain, A Revival May Be Near. New York Times, January 27, 2002 ^ Apollo Takes 20% Stake In Berlitz For $100 Million. New York Times, October 8, 1998 ^ Apollo Affiliate Is Acquiring Clark's Store Operations. New York Times, May 14, 1999 ^ Neptune Orient To Sell North American Train Network. New York Times, March 18, 1999 ^ Wyndham Receives $1 Billion From Investor Group. The New York Times, July 1, 1999 ^ Karmin, Craig (May 9, 2013). "Ares Management to Buy AREA Property Partners". WSJ . Retrieved May 14, 2020 . ^ "Private equity: the generational feud that rocked Apollo". Financial Times . Retrieved May 14, 2020 . ^ Apollo raising distressed-debt fund [dead link ] . The Deal, June 5, 2003 ^ a b c Fabrikant, Geraldine. "Private Firms Use Closed-End Funds To Tap the Market." The New York Times, April 17, 2004. ^ a b c d e f Sorkin, Andrew Ross. "Equity Firm Is Seen Ready to Sell a Stake to Investors." The New York Times, April 5, 2007. ^ Samuelson, Robert J. "The Private Equity Boom". The Washington Post, March 15, 2007. ^ a b In Private Equity, the Limits of Apollo's Power. New York Times, December 7, 2008 ^ a b Timmons, Heather. "Opening Private Equity's Door, at Least a Crack, to Public Investors." The New York Times, May 4, 2006. ^ a b Apollo equity fund IPO falls short of its target. International Herald Tribune, June 9, 2006 ^ Sorkin, Andrew Ross and De La Merced, Michael J. "Buyout Firm Said to Seek a Private Market Offering." The New York Times, July 18, 2007. ^ Apollo chief says sold nine percent of firm to Abu Dhabi. Reuters, November 7, 2007 ^ a b Apollo Global Management, LLC, Form S-1, Securities And Exchange Commission, April 8, 2008 ^ Forget slowdown, PEs still heading to India. The Economic Times, August 8, 2008 ^ a b Bankruptcy Protection for Retailer. New York Times, May 3, 2008 ^ Apollo Struggles to Keep Debt From Sinking Linens 'n Things. The New York Times, April 14, 2008 ^ a b An End Run Around Realogy's Lenders. The New York Times, November 27, 2008 ^ PIK and Roll: Companies Seize On Perks of Loose Lending. Wall Street Journal, May 19, 2008 ^ "Apollo First-Quarter Profit Rises 76% as Holdings Gain". Bloomberg. ^ a b Apollo Closes Buyout Fund Near $15 Billion Target. Wall Street Journal, January 23, 2009. Most recently, Apollo acquired Cedar Fair L.P. for about $650 million dollars cash. The company had seen profits plummet in the recent recession. Net income dropped more than $45 million from last year, and Cedar Fair was forced to sell. Apollo acquired more than 1.5 billion dollars of debt. ^ "Press Releases :: Cedar Fair Entertainment Company". Archived from the original on December 21, 2009. ^ "Coastal Business: Charleston Port activity studied". The Sun News. December 31, 2009 . Retrieved January 1, 2010 . [dead link ] ^ "Cedar Fair: Takeover not happening". The Seattle Times. April 6, 2010. Archived from the original on January 30, 2013 . 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"Exclusive: Centerbridge in $1.35 billion deal for Great Wolf Resorts: sources". Reuters . Retrieved June 9, 2015 . ^ Schuyler, David (May 12, 2015). "New owner pledges to grow Great Wolf Lodge chain". Milwaukee Business Journal . Retrieved June 9, 2015 . ^ Ankit Ajmera (June 1, 2015). "OM Group to be taken private by Apollo Global in $1.03 billion deal". Reuters . Retrieved June 2, 2015 . ^ Andrew Callus (June 7, 2015). "Apollo wins auction for St-Gobain's Verallia". Reuters . Retrieved June 8, 2015 . ^ Picker, Leslie (February 16, 2016). "ADT in $6.9 Billion Deal to Sell Itself to Apollo Buyout Firm". The New York Times. ISSN 0362-4331 . Retrieved July 21, 2017 . ^ "Apollo Education Group shareholders approve merger agreement". Rueters. May 6, 2016 . Retrieved August 18, 2016 . ^ Jarzemsky, Matt; Mattioli, Dana (June 29, 2016). "Apollo Global to Buy Diamond Resorts for $2.2 Billion" . Retrieved July 4, 2016 '' via Wall Street Journal. ^ "Rackspace to Go Private in $4.3 Billion Deal". August 26, 2016 . Retrieved August 26, 2016 '' via Wall Street Journal. ^ "Apollo Global to buy West Corp for about $2 billion". Reuters. May 10, 2017 . Retrieved November 25, 2019 . ^ "Apollo to buy Qdoba in $305M deal". Nation's Restaurant News. December 19, 2017 . Retrieved December 5, 2019 . ^ Drucker, Jesse; Kelly, Kate; Protess, Ben (February 28, 2018). "Kushner's Family Business Received Loans After White House Meetings" . Retrieved January 13, 2019 '' via NYTimes.com. ^ "Apollo is said to be nearing deal for group of Nexstar stations". Crain's New York Business. February 13, 2019 . Retrieved February 15, 2019 . ^ "Apollo Global Management Acquires Cox's Television Stations Plus Radio & Newspapers In Dayton". RadioInsight. February 15, 2019 . Retrieved February 15, 2019 . ^ Jessell, Harry A. (March 6, 2019). "Cox TV Valued At $3.1 Billion In Apollo Acquisition". TV News Check . Retrieved March 6, 2019 . ^ Jacobson, Adam (June 26, 2019). "It's Official: Cox Radio, Gamut, CoxReps Going To Apollo". Radio & Television Business Report . Retrieved June 26, 2019 . ^ "Cox Enterprises buys back Ohio newspapers; 7-day publication continues". daytondailynews . Retrieved February 10, 2020 . ^ Brumpton, Harry; Roumeliotis, Greg (April 16, 2019). "Buyout firm Apollo to buy Smart & Final Stores for $1.1 billion". Reuters . Retrieved April 21, 2019 . ^ Newburger, Emma (June 10, 2019). "Shutterfly strikes take-private deal with Apollo Global, valuing company at $2.7 billion". CNBC . Retrieved June 27, 2019 . ^ Scigliuzzo, Davide; Ahmed, Nabila (August 5, 2019). "Apollo Takes on Wall Street With Massive Newspaper Loan Deal". Bloomberg. ^ "Apollo PE takes majority stake in Gamenet Italia". SBC News. October 23, 2019 . Retrieved October 23, 2019 . ^ "Apollo Global Management buys 48.67% stake in Italy's Gamenet". Reuters. October 23, 2019 . Retrieved October 23, 2019 . ^ "France's Banijay to acquire rival Endemol Shine Group, producer of 'Black Mirror ' ". Los Angeles Times. October 26, 2019 . Retrieved December 5, 2019 . ^ Kanter, Jake (July 3, 2020). "Sophie Turner Laing To Leave Endemol Shine Group As Banijay Group Completes $2.2BN Takeover". Deadline . Retrieved August 12, 2020 . ^ Oguh, Chibuike (May 1, 2020). "Apollo's first-quarter profit falls 20% as virus weighs on asset sales". Reuters . Retrieved July 30, 2020 . The New York-based firm said it had $315.5 billion of assets under management at the end of March ^ "Apollo Global Management, Inc. Reports First Quarter 2020 Results" (PDF) . Apollo. May 1, 2020 . Retrieved July 30, 2020 . ^ Taylor, Charlie. "Apollo to invest $300m in Irish-domiciled Cimpress". The Irish Times . Retrieved May 14, 2020 . ^ Franklin, Joshua (May 20, 2020). "Apollo Global invests $1.75 billion in U.S. supermarket operator Albertsons". Reuters . Retrieved July 1, 2020 . ^ Vandevelde, Mark (July 30, 2020). "Apollo adds $100bn to war chest in second quarter". Financial Times . Retrieved July 30, 2020 . ^ "LendingPoint Closes $110MM Mezzanine Facility with Midcap Financial Trust and Apollo". ABL Advisor. March 10, 2021. ^ "Verizon offloads Yahoo and AOL in $5 billion deal". CNN. May 3, 2021. ^ Business People; Taking Tyco's View. The New York Times, February 29, 2004 ^ "About Apollo Global Management". www.apollo.com . Retrieved January 13, 2019 . ^ a b Amendment No. 8 to Form S-1 ^ Dasha Afanasieva (July 27, 2017). "Apollo raises $24.6 billion for largest private equity fund ever". Reuters. ^ a b Apollo Investment (AINV) annual SEC income statement filing via Wikinvest. ^ a b Apollo Investment (AINV) annual SEC balance sheet filing via Wikinvest. ^ Apollo Investment Corporation: Portfolio Companies Archived February 27, 2009, at the Wayback Machine (company website) ^ Apollo Alternative Assets: Investment Strategy (company website) Archived January 29, 2009, at the Wayback Machine ^ "Cox Enterprises Announces Close of Cox Media Group Sale to Affialiates of Apollo Global Management". PR NEWSWIRE . Retrieved May 26, 2020 . ^ "Cox Enterprises to Sell Majority Stake in TV Stations to Apollo". The Atlanta Journal Constitution . Retrieved May 26, 2020 . ^ "It's Official: Cox Radio, Gamut, CoxReps Going to Apollo". Radio+Television Business Report . Retrieved May 26, 2020 . ^ "It's Official: Cox, Apollo Agree to Private Company". Dayton Daily News . Retrieved May 26, 2020 . ^ Coffey, Lauren (November 13, 2019). "Tech Data acquired in $5.4 billion deal". Tampa Bay Business Journal . Retrieved December 5, 2019 . ^ "Warren Buffett Failed to Spend His $128 Billion Cash Pile in Unusual Bid". Observer. December 3, 2019 . Retrieved December 5, 2019 . ^ "Apollo Global to acquire $1bn energy investments portfolio of GE" . Retrieved December 5, 2019 . ^ News, The PIE. "Apollo Education Group acquired for $1.14bn". thepienews.com . Retrieved December 5, 2019 . ^ Wiles, Russ. "Apollo Education starts new chapter as private firm". azcentral . Retrieved December 5, 2019 . ^ Jarzemsky, Matt; Mattioli, Dana (June 29, 2016). "Apollo Global to Buy Diamond Resorts for $2.2 Billion". The Wall Street Journal. ^ Berry Plastics to Be Sold Again. Reuters, June 29, 2006 ^ Costume Jewelry Retailer Agrees to a Takeover. The New York Times, March 21, 2007 ^ Wave of Bankruptcy Filings Expected From Retailers in Wake of Holidays. Wall Street Journal, January 12, 2009 ^ U.S. defense spending bonanza puts niche acquisitions in play. CNBC, February 13, 2018 ^ Woolf, Nicky (April 14, 2015). "Former Blackwater guards sentenced for massacre of unarmed Iraqi civilians". The Guardian . Retrieved August 17, 2018 . ^ "Blackwater's Descendants Are Doing Just Fine". Foreign Policy . Retrieved August 17, 2018 . ^ Franklin, Joshua. "Apollo pauses plans to sell security firm Constellis: sources". U.S . Retrieved August 17, 2018 . ^ Apollo Sweetens Countrywide PLC Bid. Wall Street Journal, April 13, 2007 ^ Dutch Postal Deal. Associated Press, August 24, 2006 ^ Citi Is Said to Be Near Deal to Sell $12.5 Billion of Loans. The New York Times, April 9, 2008 ^ Apollo, GSO Debt Funds Have Faced Margin Call Issues. Wall Street Journal, November 12, 2008 ^ Black: Apollo's debt bets were 'a little early' Archived July 15, 2011, at the Wayback Machine. Private Equity Online, January 23, 2009 ^ Ahmed, Azam (March 13, 2012). "Apollo to Acquire Water Park Operator for $703 Million". The New York Times. ^ Sorkin, Andrew Ross. "Harrah's Is Said to Be in Talks to Accept $16.7 Billion Buyout." The New York Times, December 18, 2006. ^ Manufacturer of Chemicals Agrees to Bid From Apollo. The New York Times, July 13, 2007 ^ Huntsman Settles With Apollo, The New York Times, December 14, 2008 ^ a b Jacuzzi Brands Is Going Private. Reuters, October 12, 2006 ^ "McGraw-Hill to Sell Education Unit to Apollo for $2.5 Billion". The New York Times. November 26, 2012. ^ Apollo Management to buy GE Advanced Materials Business. AltAssets, September 18, 2006 Archived June 8, 2008, at the Wayback Machine ^ Mine Company Sells U.S. Unit. The New York Times, April 12, 2007 ^ Closes $1 Billion Investment by Apollo Archived February 26, 2009, at the Wayback Machine. Reuters, January 7, 2008 ^ Apollo Global Management to Acquire Management Services Business from Pitney Bowes. Pitney Bowes Inc, July 30, 2013 ^ "News & Insights '' Document Outsourcing '' Novitex" (PDF) . Archived from the original on June 17, 2014 . Retrieved July 4, 2016 . ^ Oceania Cruises sold to new owners. USA Today, February 27, 2007 Archived September 5, 2007, at the Wayback Machine ^ Oceania Cruises Closes A Transaction With Apollo Management: Completes $850 Million Strategic Partnership. Oceania Cruises press release, April 30, 2007 Archived December 5, 2008, at the Wayback Machine ^ "Philips completes sale of 80.1% interest in Lumileds to funds managed by affiliates of Apollo Global Management". August 10, 2017. [permanent dead link ] ^ "Philips to Sell Lumileds to Apollo". Bloomberg Technology . Retrieved August 10, 2017 . ^ Latest Deal in Real Estate for $9 Billion. The New York Times, December 18, 2006 ^ "Apollo Management, L.P. Completes Acquisition Of Realogy Corporation". Realogy. Archived from the original on September 27, 2007 . Retrieved June 5, 2007 . ^ Icahn Sues Real Estate Company Over Debt. The New York Times, December 2, 2008 ^ Apollo to buy cruise company Regent Seven Seas Cruises. AltAssets, December 12, 2007 Archived December 2, 2008, at the Wayback Machine ^ Carlyle to sell Rexnord Corporation to Apollo for $1.8bn. AltAssets, May 25, 2006 Archived March 7, 2008, at the Wayback Machine ^ Smart & Final sells to Apollo Management affiliate in $813.9M deal. Los Angeles Business, February 20, 2007 ^ Whole Foods Deal. Bloomberg, June 21, 2007 ^ Hamstra, Mark (February 16, 2011). "Apollo Combines Sprouts, Henry's". Supermarket News. Penton Media, Inc . Retrieved December 4, 2011 . ^ Crabtree, Penni (February 27, 2011). "Merger of Henry's, Sprouts is latest in Boney family's retail saga". SignOn San Diego. The San Diego Union-Tribune . Retrieved December 4, 2011 . ^ "Cotton ornaments, 'Happy Thai Horses' (set of 4)" . Retrieved July 4, 2016 . ^ Apollo Management Invests in Buyer of Mortgage Assets. The New York Times, May 28, 2008 ^ Verso Paper turns a page with IPO; President & CEO Mike Jackson credits a foundation document, focused strategies, and talented employees for company's success. Paper360, Oct 2008 ^ Verso Paper Sets I.P.O. Range. The New York Times, April 29, 2008 ^ a b Ares Enhanced Loan Investment Strategy IR, Ltd. Prospectus. September 22, 2008 [dead link ] ^ a b c Ares Management to Take New Fund Public. Los Angeles Times, April 22, 2004 ^ Ares Capital IPO Raises $165 Million. Los Angeles Times, October 6, 2004 External links Edit Media related to Apollo Global Management at Wikimedia Commons Official website Cox Media GroupGamut. Smart Media from Cox.McGraw-Hill EducationQdoba Mexican EatsADT Inc.Business data for Apollo Global Management, LLC:
Who is Boris Nikolic? Epstein-named executor is former Bill Gates adviser | Fox Business
Wed, 02 Jun 2021 17:38
One of the men named in Jeffrey Epstein's will as potentially being responsible for carrying it out says he was unaware he was included.
Epstein, the financier and convicted sex offender, signed a will detailing nearly $600 million in assets just two days before he killed himself in a Manhattan jail cell. In the will, he named biotech venture capitalist Boris Nikolic as ''successor executor,'' the person who would take control of the estate if the two named executors are unable or unwilling to.
Nikolic, 49, said in a statement that he was ''shocked'' that he was included.
A spokesperson for Nikolic confirmed to FOX Business that he "was never consulted on these matters and has no intent to fulfill these duties, whatsoever."
Court records show the two executors, Darren K. Indyke and Richard D. Kahn, each signed an oath confirming their willingness to serve as executor. But no such oath was filed by Nikolic.
Nikolic is a physician who completed postdoctoral training at Harvard Medical School, where he also served as an assistant professor. He previously served as chief advisor for science and technology to Bill Gates.
WASHINGTON, DC - JULY 21: Bill Gates and Boris Nikolic attend Together To End AIDS: An Evening To Benefit amfAR and GBCHealth at John F. Kennedy Center for the Performing Arts on July 21, 2012 in Washington, DC. (Photo by Paul Morigi/Getty Images)
As co-founder and managing director of health care and life sciences venture investing firm Biomatics Capital, Nikolic sits on the boards of directors for several of its portfolio companies.
A spokesperson for Nikolic told FOX Business that he and Epstein had no business ties. Nikolic has a broad network in the scientific world that overlapped with Epstein's at points.
Both men were clients of the private bank at JPMorgan Chase & Co., where several people familiar with the matter told Bloomberg Epstein helped bankers attract lucrative new clients.
FILE - This March 28, 2017, file photo, provided by the New York State Sex Offender Registry shows Jeffrey Epstein. A judge denied bail for jailed financier Jeffrey Epstein on sex trafficking charges Thursday, July 18, 2019, saying the danger to the
The executors of Epstein's will receive $250,000. The document tallies cash and investments he said he had just before his death, which were then organized into a trust. The only potential beneficiary named is Epstein's brother, Mark.
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For Billionaire Glenn Dubin, the Epstein Saga Isn't Over | Vanity Fair
Wed, 02 Jun 2021 17:32
Many secrets died with Jeffrey Epstein, the high-society pedophile, philanthropist, and financier whose inner circle included princes, a former prime minister, and a former president. But the search for answers continues in New York, where Epstein held court for years before hanging himself in federal prison. One of Epstein's more puzzling relationships was the one he had with Glenn Dubin, the billionaire hedge fund manager, and his wife, Dr. Eva Andersson-Dubin, the founder of the Dubin Breast Center of the Tisch Cancer Institute at the Mount Sinai Medical Center. Could one of Manhattan's most prominent power couples know more about the Epstein mystery?
The three were close, after all. Andersson-Dubin, a former Miss Sweden, dated Epstein for years before she and Dubin married in 1994. Even after Epstein's conviction in 2008, the couple stayed in contact with the registered sex offender, inviting him to Thanksgiving dinner at their home in Palm Beach the following year. Andersson-Dubin also wrote an email to Epstein's probation officer, asserting that she was ''100% comfortable with Jeffrey Epstein around my children,'' who were then all minors. Multiple sources told me last month that Epstein was the godfather to the Dubins' three children, although a spokesman for Dubin disputed that assertion. (''The Dubins are Jewish and Jewish people do not typically do godparents,'' he said.)
Epstein and Dubin had business ties as well. Epstein introduced Dubin to Jes Staley, then a senior executive at JPMorganChase & Co. and now the CEO of Barclays, the big British bank. After JPMorganChase bought control of Highbridge Capital, Dubin's hedge fund, in stages, starting in 2004, Epstein reportedly received a $15 million fee. Dubin also directed some of Epstein's money, for which Epstein was a fiduciary, to at least two hedge fund managers'--Dan Zwirn and Joseph Kusnan'--who once worked at Highbridge before starting their own firms. ''Glenn Dubin introduced me to Epstein as a new manager that he was familiar with and thought highly of,'' Kusnan wrote me in an email, though he and Epstein met only once, he said, and never communicated again beyond Kusnan delivering ''a good rate of return on his modest investment.''
The relationship between Epstein and Dubin also ventured into more controversial realms, if one believes the depositions recently unsealed in an old court case between one of Epstein's alleged victims, Virginia Giuffre, and Epstein's longtime companion and alleged madam, Ghislaine Maxwell. According to Giuffre's May 2016 deposition, Dubin was the ''first'' powerful person that Maxwell sent her to have sex with ''after my training.'' She also said that she was instructed by Maxwell to have sex with, among others, Alan Dershowitz, the Harvard Law professor; George Mitchell, the former U.S. senator; Bill Richardson, the former New Mexico governor; and Jean-Luc Brunel, a French model scout. ''My whole life revolved around just pleasing these men and keeping Ghislaine and Jeffrey happy,'' Giuffre said in her deposition. ''[Maxwell and Epstein's] whole entire lives revolved around sex. They call massages sex. They call modeling sex.'' She said Maxwell told her to give Dubin ''a massage.'' (The Dubins categorically deny Giuffre's allegations. Their spokesperson also provided evidence they say disproves Giuffre's account. Dershowitz, Mitchell, Richardson, and Brunel have also denied her allegations.)
Then there is Rinaldo Rizzo's June 2016 deposition, which was also recently unsealed. Rizzo and his wife, Debra, worked for the Dubins, primarily as their full-time chefs, but they did other work for the Dubins too, such as tagging their luggage for the private jet trips and generally being helpful with travel to and between the Dubins' various homes in Palm Beach; Westchester County; Gothenburg, Sweden; Manhattan; and a sprawling ranch in Gunnison, Colorado. According to the deposition, Rizzo and his wife were preparing dinner for the Dubins in the kitchen of one of their homes when Andersson-Dubin brought in a 15-year-old Swedish girl who had accompanied Epstein and Maxwell on this visit to the Dubins' home.
Rizzo testified that in late 2004 or early 2005, Andersson-Dubin told the unnamed girl to sit on a barstool in the kitchen. She seemed to be ''distraught'' and ''upset,'' Rizzo said, ''and she was shaking.'' She didn't want to talk, her head was down, and Rizzo thought she was ''on the verge of crying.'' According to the deposition, the girl told him and his wife that she worked for Epstein as his ''executive personal assistant,'' and when Rizzo expressed shock that such a young girl could have that job, ''she just breaks down hysterically.'' Rizzo stated that the girl told him she was involved in some forced sexual activity at Epstein's Caribbean island and was told by Maxwell and Epstein not to discuss it. Rizzo said he and his wife were dumbfounded. ''We hear people approach and she just shuts up,'' Rizzo testified. ''Eva comes in and tells her that she will be working for Eva in the city as a nanny.''
But about a month later, according to Rizzo, the Dubins, along with the girl and the Rizzos, were on Dubin's private jet back to Sweden and the girl was returned home. ''We flew to Sweden,'' Rizzo said in his deposition, ''we stopped at an airport we didn't usually stop at and she got off the plane.'' The Rizzos left the Dubins' employ in October 2005, following those events, he said in his deposition. ''My wife and I had discussed these incidents, and this last one was just, we couldn't deal with it,'' he said.
The Dubins vehemently deny that any such incident had taken place. ''There was never a 15-year-old Swedish nanny in the Dubins' home and flight records for trips to Sweden on the Dubins' plane do not include any minors other than family members,'' said the spokesperson, who shared the records. The Dubins also provided the testimony of their longtime live-in nanny, who attested ''with certainty'' that the couple had never employed an underage nanny. (Attempts to reach the Rizzos were unsuccessful.)
The spokesperson did confirm, however, that Dubin and his family traveled with Epstein on his private jet. Flight records show that Dubin and his family occasionally flew on Epstein's planes, often between Palm Beach and New York, where they both had homes. Ghislaine Maxwell also hitched a ride on Dubin's plane, twice, alongside Dubin's children, on that same route'--once in 2004 and again in 2010, after Epstein was a convicted sex offender. ''Epstein was not on either flight,'' Dubin's spokesman said. Jim Dowd, who piloted jets for both Dubin and Epstein, told me the men were ''friends'' and liked ''vacationing together.'' (The Dubin spokesperson disputed that characterization.) The private jets, Dowd said, gave the two men a way to avoid the delays and tedium of commercial travel. ''The only thing money cannot buy is time,'' he explained. ''These planes are time machines. They save lots of time.''
The Dubins' social circle overlapped with Epstein in New York, too. A source with knowledge of the matter said that Andersson-Dubin was ''friendly'' with Lana Pozhidaeva, the Russian model who was recently in the news for having received a $55,000 donation from Epstein for her New York-based nonprofit, Education Advance. (The Dubin spokesperson insisted the Dubins don't know her.) Pozhidaeva worked for Brunel's modeling agency, MC2 Model Management, and appeared to live in an Upper East Side apartment building where Epstein had been accused of housing underage models. (Pozhidaeva did not respond to multiple emailed requests for comment.)
And then there is the Dubins' link to Leslie Wexner, the billionaire founder and CEO of L Brands'--a retail empire that includes Victoria's Secret'--who was Epstein's only known financial client. It's not unusual, of course, for billionaires to flock together. Wexner's infamous ties to Epstein have been well documented by now, although his friendship with the Dubins has never before been reported. Yes, it was true, Dubin's spokesman told me, that Wexner had allowed the Dubins and their three children the exclusive use of Limitless, Wexner's $100 million, 316-foot private yacht, for a Mediterranean vacation. (Wexner's wife, Abigail, ''graciously invited the Dubins to use their boat for four days while Eva Dubin was recovering from breast cancer surgery,'' Dubin's spokesperson explained.) But according to one source, it was quite unusual for Wexner to let anyone use Limitless when he was not on board.
The source recalled talking to Debra Rizzo, the Dubins' onetime chef, about the trip. ''She was telling me how magnificent this thing was,'' this person said, ''and she said that the captain came over to her and she said he goes, 'I've got to ask you, what does your boss do? Who is he?' And she's like, 'Well, it's Glenn Dubin. He runs a hedge fund.' He's like, 'Oh. I'm just baffled because nobody is allowed on this boat. Nobody. We've never had anybody on this boat other than the owner.' So she said it was like a really, really big deal to them and they were shocked that Dubin was on this thing.'' (A spokesperson for Wexner declined to comment.)
Spike Protein
The Spike Protein is the weapon - Peter McCullough
Zombie Preparedness | CDC
Tue, 01 Jun 2021 14:51
Wonder why zombies, zombie apocalypse, and zombie preparedness continue to live or walk dead on a CDC web site? As it turns out what first began as a tongue-in-cheek campaign to engage new audiences with preparedness messages has proven to be a very effective platform. We continue to reach and engage a wide variety of audiences on all hazards preparedness via ''zombie preparedness''.
Zombie Preparedness BlogThere are all kinds of emergencies out there that we can prepare for.Take a zombie apocalypse for example.
Zombie Preparedness for EducatorsLooking to teach preparedness in the classroom?We've got full lesson plans and activities for you to use or adapt with your students.
Zombie Preparedness Graphic NovelLooking for an entertaining way to introduce emergency preparedness?Check out our graphic novella which uses the idea of a zombie apocalypse to demonstrate the importance of preparedness.Included is a personal preparedness checklist so you can take action once you're done reading.
SCIENCE!
NACI recommends mixing AstraZeneca, Pfizer, Moderna COVID-19 vaccines - National | Globalnews.ca
Tue, 01 Jun 2021 18:56
WATCH: NACI recommends mixing AstraZeneca, Pfizer, Moderna COVID-19 vaccines, Tam says
Canada's National Advisory Committee on Immunization (NACI) has updated its guidance, recommending that approved COVID-19 vaccines can be safely mixed and matched in most scenarios.
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Under the new recommendations released June 1, people who received a first dose of the AstraZeneca vaccine may receive an mRNA vaccine '-- Pfizer-BioNTech or Moderna '-- for their second dose, unless contraindicated.
But it is not recommending AstraZeneca after a first shot of Pfizer or Moderna.
Read more: 2nd COVID-19 shots should be offered 'as soon as possible': NACI
People who have received a first dose of an mRNA vaccine should be offered the same vaccine for their second dose, NACI said. But mRNA vaccines can be interchangeable if the same product is not readily available for the second dose, it added.
In either case, the previous dose should be counted, and the series need not be restarted, the guidance stated.
Advice on mixing vaccine shots based on goal of not wanting vaccine doses to go to waste
The non-binding recommendations were based on a range of factors '-- from safety concerns to vaccine supply, Theresa Tam, Canada's chief public health officer, said during a news conference Tuesday.
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''The interchangeability of vaccines means that you can receive one vaccine product for your first dose and then safely receive a different vaccine for your second dose to complete your two-dose vaccine series for optimal protection from COVID-19,'' Tam said.
''This advice provides provinces and territories with effective options to manage their vaccine programs,'' she added.
''It is good news that people now have the choice.''
Will B.C.'mix and match' COVID-19 vaccines?
Early data from studies in Europe suggests that mixing doses of COVID-19 vaccines is safe and effective.
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Preliminary results from a University of Oxford study published on May 12 found that mixing the Pfizer-BioNtech and AstraZeneca COVID-19 vaccines may increase the frequency of mild to moderate side effects. But these symptoms were short-lived '-- lasting no longer than a few days '-- and there were no hospitalizations or other safety concerns.
Trending Stories
Read more: Mixing COVID-19 vaccines appears safe '-- but no data on whether it works, U.K. study says
Meanwhile, a Spanish study released on May 18 showed that the presence of neutralizing antibodies rose sevenfold after people who already received a first shot of AstraZeneca vaccine were given the Pfizer dose, significantly more than the doubling effect observed after a second AstraZeneca shot.
A nationwide study was also launched in Canada last month to look at the safety and effectiveness of mixing and matching different types of shots.
Albertans being sought for national study on mixing COVID-19 vaccines '' May 20, 2021
Amid concerns of reports of rare blood clots linked with the AstraZeneca vaccine, NACI said several European countries had begun offering an mRNA vaccine as the second dose to those who received a first shot of AstraZeneca.
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The risk of the new blood-clotting syndrome, known as vaccine-induced thrombotic thrombocytopenia, or VITT, was among the considerations for NACI's updated guidance.
''This is not a new concept,'' NACI said.
''Similar vaccines from different manufacturers are used when vaccine supply or public health programs change.''
Read more: 'No A, B list of COVID vaccines': Experts weigh in on NACI's 'mixed messages'
Tania Watts, an immunologist and professor at the University of Toronto, said NACI's new recommendation was ''great news,'' making it easier to get the second dose into people's arms.
While NACI makes recommendations for the use of vaccines approved for use by Health Canada, it is ultimately up to the provinces and territories to implement that advice.
The National advisory Committee on immunization changes to vaccine mixing and matching
Some experts fear that this could lead to wastage of Canada's AstraZeneca supply.
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''It may now be more challenging to get a second dose of the AstraZeneca vaccine into people who remain overly concerned about side effects, despite the fact that VITT, which is quite uncommon, is even less common amongst second-dose recipients,'' said Gerald Evans, an infectious disease specialist at Queen's University in Kingston, Ont.
Study shows COVID-19 vaccine mixing produces 'robust immune response': Dr. Tam
Tam said it remains to be seen what the actual uptake of AstraZeneca will be following the new guidance.
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''We don't want to be ordering vaccines if we're not using it, but it can only be ascertained in a more granular way when we see what the vaccine uptake looks like in the coming days,'' she said.
'-- With files from Global News' Abigail Bimman
(C) 2021 Global News, a division of Corus Entertainment Inc.
Gary Chappell on Twitter: "Indian Bar Association serves legal notice on WHO Chief Scientist Dr Soumya Swaminathan. They claim she "deliberately suppressed the data regarding effectiveness of the drug Ivermectin, with an intent to dissuade the people of I
Mon, 31 May 2021 11:47
Gary Chappell : Indian Bar Association serves legal notice on WHO Chief Scientist Dr Soumya Swaminathan. They claim she "deliberate'... https://t.co/fWjyFImW9s
Sun May 30 19:05:56 +0000 2021
🌸🌸🌸MULUC9🇬🇧🌸🌸 : @GaryChappellDE @pepelep48542643 Good on them!!!
Mon May 31 09:21:22 +0000 2021
Bill Sadler : @GaryChappellDE @MainPerth Bloody awesome the truth is coming out
Mon May 31 09:13:59 +0000 2021
Alan Leonard : @GaryChappellDE @JoHamLew This could be the first 'real' nail in the coffin of this virus.
Mon May 31 09:10:59 +0000 2021
Catherine 🇬🇧 : @GaryChappellDE Good, hopefully many more to come!
Mon May 31 07:45:29 +0000 2021
avcobe : @GaryChappellDE @SharpieDj This has been a part of the active and intense suppression of treatment alternatives to'... https://t.co/IZ7coUmZMe
Mon May 31 07:34:51 +0000 2021
Tim and the Hidden People : @GaryChappellDE https://t.co/Zx3ClBOmyZ
Mon May 31 06:26:19 +0000 2021
VAERS
CDC caught removing Covid vaccine injury reports from VAERS '' NaturalNews.com
Thu, 03 Jun 2021 13:45
(Natural News) Last month, Great Game India published a report about a two-year-old child who died after receiving a Wuhan coronavirus (Covid-19) ''vaccine'' from Pfizer. The case was reported in the Vaccine Adverse Event Reporting System (VAERS), only to later be removed by the U.S. Centers for Disease Control and Prevention (CDC).
Since only children between the ages of five and 11 are ''authorized'' to receive a Chinese Virus injection from Pfizer, Great Game India wanted to know why a two-year-old baby received it, calling on the CDC to fully investigate the situation. Instead, the CDC ignored the request and proceeded to remove the VAERS entry without explanation.
The two-year-old girl in question passed almost immediately after receiving her second dose of Pfizer's experimental mRNA (messenger RNA) injection, instantly developing severe reactions. She ended up dead within just a few days.
News started to spread and many were calling on the CDC to take action, seeing as how it is supposed to act in the best interests of public health. Since the CDC is actually a private corporation that works for Big Pharma, however, nothing was done and the girl's death was quickly scrubbed from the government database.
The fake news media quickly swooped in to defend Big Pharma as well, falsely claiming that children under the age of five were not receiving Wuhan Flu shots at the time. Three ''fact checkers'' from Newsweek all made this patently false claim.
''Vaccine trials for babies as young as six months are underway at least since March,'' reported Great Game India about the facts.
CDC says removal of young girl's death entry was an oopsieMore than 10,000 babies as young as six months old, in fact, were receiving mRNA injections from Pfizer and Moderna as far back as mid-March, which is right around the time the two-year-old girl died from her injection.
Pfizer itself admits this to be true, which makes the Newsweek ''fact check'' laughable. In what way and using what evidence did these ''fact checkers'' come to the conclusion that babies were not yet receiving Pfizer injections as of mid-March, we would like to know?
Right on their website, Pfizer and BioNTech admit that the first doses of Chinese Virus injection administered to children as young as six months old began in March 2021, constituting a three-phase continuous study to learn how the shots are tolerated by babies.
Once the ''fact checkers'' were challenged with the actual facts, they moved on to blaming VAERS for the ''error,'' as the entry showing that a baby had died was removed by the CDC.
Newsweek actually reported on the entry's removal, claiming that the CDC took a ''rare step'' in axing it from the VAERS system. Hilariously, Newsweek's excuse for the CDC action is that the entry must have been '' since the CDC never lies, according to the fake news media '' because it was ''completely made up.''
No further details were provided by Newsweek about how it was determined that the entry was ''made up.'' Somehow, we are all just supposed to believe whatever the fake news and fake science says on any given day about a matter, even if it makes no sense and contradicts itself.
The latest claim is that VAERS is ''unreliable'' and ''noisy,'' and is not to be trusted '' even though it is supposed to be monitored by the federal government. These ''errors'' are to be expected, the establishment claims, because technology is just too hard to get right.
''The good news for a very rare event is it will pop up on VAERS,'' stated Dr. Jesse Goodman, a former chief scientist at the U.S. Food and Drug Administration (FDA), attempting to provide cover for the CDC.
More related news about the mass genocide being invoked by Chinese Virus injections can be found at ChemicalViolence.com.
Sources for this article include:
GreatGameIndia.com
GreatGameIndia.com
NaturalNews.com
The Purge
Russia Monitoring Biden's "Persecution" Of Capitol Hill Rioters & Their "Opposition Rights" | ZeroHedge
Wed, 02 Jun 2021 22:28
Moscow had some stinging words for Washington which were also hilariously ironic on Monday, as both Putin and Biden look ahead to their in-person summit set for June 16 in Geneva. Warning of "uncomfortable" signals to come, the Kremlin indicated that high on the agenda would be a range of human rights and free speech issues in the United States, particularly the "persecution" of those behind the January 6 Capitol riot by the Biden administration.
The words appear Moscow's ultimate trolling response to Biden remarks on Sunday wherein he vowed to confront Putin on egregious human rights abuses: "Of course, we will be ready to discuss everything, including problems that exist in the United States," Lavrov told reporters Monday following Biden's statements. According to AFP:
He said Russia was monitoring the "persecution" of those behind the January 6 riot at the US Capitol.
How an American reacts to something like this is a superb Rorschach Test to measure so many important attributes: https://t.co/lQyTry3VcF
'-- Glenn Greenwald (@ggreenwald) May 31, 2021Lavrov then sarcastically adopted the language and tone of US officials when they frequently lecture foreign adversaries around the world from Russia to Syria to China to Venezuela to Iran, or to any country the US doesn't like. This included Lavrov talking about the US "opposition" and their "rights" while referencing the prior pro-Trump protests and unrest inundating the Capitol.
Lavrov continued:
"A lot of interesting things are happening there," he said, adding that Russia wanted to discuss "protection of opposition rights" in the United States.
The Biden administration has over the past two months heavily focused scathing criticism on the Alexei Navalny saga - frequently holding up the now jailed anti-Kremlin activist (stemming from a prior parole violation and embezzlement case) as leading the "democratic opposition" to Putin's rule, despite before last August's alleged 'nerve agent poisoning' ordeal not having much name recognition at all inside Russia.
Here's what Biden had said in his speech ahead of Memorial Day:
In a speech marking the Memorial Day holiday, Biden said: "I'm meeting with President Putin in a couple weeks in Geneva, making it clear we will not stand by and let him abuse those rights."
He also said that the moment was right to show the world, and namely China, that the US was ready to lead again after four years of a largely inward-looking foreign policy under Donald Trump.
"It's time to remind everybody who we are," he said.
So it appears Russia is ready to punch bad just as hard with its own criticisms, focusing heavily on US double standards and hypocrisy (the Snowden and Assange situations topping the list lately).
The US has also of late focused heavy criticism on Belarus' Lukeshenko and his apparently close relationship with Putin in the wake of the Ryanair incident. The Kremlin has dismissed the West's reaction (which has included expanded sanctions against Belarus) as more "fits of hysteria" - with Putin days ago telling his Belarusian counterpart directly that this is nothing but the latest "emotional outburst" coming from the West.
Great Reset
JBS Ransomware - Cyber - Bitcoin - War on meat
Dean Banks resigns as Tyson Foods president and CEO; Donnie King named successor (UPDATED) - Talk Business & Politics
Wed, 02 Jun 2021 17:50
Springdale-based Tyson Foods said Wednesday (June 2) that president and CEO Dean Banks has resigned from the company and board for personal reasons. Donnie King, the company's chief operating officer, has been named as his successor, effective immediately.
''The board and I know that Donnie has a deep understanding of our business, values and culture and the solid leadership skills needed to continue to implement our strategy and deliver strong results,'' John H. Tyson, chairman of the board, said in a company news release. ''We want to express our appreciation to Dean for his contributions as a board member and executive.''
Banks joined the company as president in 2017 and added the CEO title in October 2020.
''Upon deep personal reflection, and discussions with my family, the board, and my colleagues, I believe that stepping down and concentrating on my family is the right decision at this time,'' Banks said in a statement.
King has more than 36 years of experience in the protein business, holding a variety of executive leadership positions involving virtually all facets of the company including poultry, beef, pork, prepared foods and international. He has also provided executive oversight of other important areas, such as food safety and quality assurance, health and safety, continuous improvement, engineering, and supply chain.
King was promoted to COO earlier this year.
''I'm humbled but excited about leading Tyson Foods, a company that feeds millions of people and means so much to me personally,'' King said in a statement. ''I believe we need to be sharply focused on operating with excellence, executing our strategies, and continuing to innovate across our businesses throughout the world. With our strong leadership team, we are committed to winning with our customers and delivering an outstanding team member experience.''
ANALYSTS REACTTyson Foods' leadership change was unexpected, but Stephens Inc. analyst Ben Bienvenu said King is well suited to fill the role given his industry experience and company knowledge.
''King is very well regarded among investors and has more than three decades of experience in the protein business, having held executive leadership positions in poultry, beef, pork, prepared foods and international. He has increasingly become more visible in the public markets with his responsibilities as COO, and we expect the company's strategic and operational priorities will remain the same following this transition,'' Bienvenu said.
Bienvenu expects to see steady improving results at Tyson Foods in the coming months. Stephens Inc. reiterated its ''buy'' rating on the shares with a price target of $90.
Analysts with Bank of America are not surprised to see Donnie King selected to replace Banks as CEO. The firm thinks King's priority remains a chicken turnaround, as Tyson's chicken segment profitability lags the industry. King recently told Wall Street that the performance in the chicken segment has not been acceptable. His goal is to restore the profits by better serving customers and resolving the hatch issues of last year after a new male used in breeding resulted in less supply.
Peter Galbo at Bank of America said King has a successful track record in the past by improving chicken margins. As a result, Bank of America remains neutral on Tyson Foods, with a target price of $84.
Tyson Foods plans to host an investor meeting this fall, and the company will release more details later.
Shares of Tyson Foods (NYSE: TSN) were unfazed Wednesday morning by the leadership transition, trading at $80.31 up 11 cents. For the past 52 weeks, shares of Tyson Foods have traded between $55.28 and $81.79. The share value is up about 25% year to date.
Talk Business & Politics senior analyst Kim Souza contributed to this report.
The latest magnetic theory
Dr Pierre Gilbert
Le Gouvernement Mondial (Conference 1995)
English translation
In the biological destruction there are the organized tempests on the magentic fields. What will follow is the contamination of the bloodstreams of mankind creating intentional infections. This will be enforced via laws that will make vaccination mandatory. And these vaccines will make it possible to control people. The vaccines will have liquid crystals that will become hosted in the brain cells, which will become micro receivers of electromagnetic fields where waves of very very low frequencies will be sent. And through these low frequency waves people will be unable to think. You'll be turned into a zombie. Don't think of this as an hypothesis... this has been done. Think of Ruanda.
Ship Carrying Auto Parts Sinks Off Japan Coast | ZeroHedge
Tue, 01 Jun 2021 15:27
By Kim Link-Wills of American Shipper
A search is ongoing for three crew members reported missing from a roll-on/roll-off (ro/ro) vessel that sank off the coast of Japan early Friday morning. The MV Byakko sank at about 2:40 a.m. local time after colliding with the chemical tanker Ulsan Pioneer just before midnight in the Seto Inland Sea, Reuters reported. The Byakko reportedly sank about 2.5 miles off the coast of Imabari.
Nine of the Byakko's 12 crew members were said to have been rescued by the Japanese coast guard and nearby ships.
Built just last year, the roll-on/roll-off vessel Byakko sank off the coast of Japan on FridayKyodo News reported that the ship's captain, 66-year-old Tamotsu Sato, was among the missing. Responders also are searching for two of the Byakko's engineers, Japanese men in their 20s.
The 557-foot-long Byakko is operated by Kobe, Japan-based Prince Kaiun Co. According to Kyodo News, the Byakko was carrying auto parts and left Kobe at 4:30 p.m. Thursday bound for Kanda, Japan. The Ulsan Pioneer reportedly departed a port in China on Tuesday and was scheduled to arrive in Osaka, Japan, on Friday afternoon.
There was no word on what types of auto parts the Byakko was carrying. Denso is the largest automotive parts manufacturer in Japan and specializes in electronic systems and powertrain control modules, according to Japan Industry News, which lists the other major suppliers in the country as Aisin Seiki, Yazaki, JTEKT and Hitachi Automotive Systems.
Sebastian Blanco, who follows the automotive industry for FreightWaves, said Toyota has a plant in Kanda and Nissan has one in the region.
On its website, Prince Kaiun lists its primary clients as Nissan Motor Co., Mitsubishi Logistics, Vantec Corp., Sea Link, Tatsumi Shokai, Zero Co. and Koshin Shoun.
The website says the 11,454-ton Byakko was built just last year and that it can carry ''809 commercial vehicles, 113 trailer chassis.'' Byakko is the Japanese word for white tiger.The Ulsan Pioneer, which flies under the flag of the Marshall Islands, was built in 2016.
A cause of the collision has not been reported. According to FreightWaves meteorologist Nick Austin, there were no indications of unusual weather at the time of the accident.
From ''Event 201'' to ''Cyber Polygon'': The WEF's Simulation of a Coming ''Cyber Pandemic'' - unlimitedhangout.com
Mon, 31 May 2021 11:46
On Wednesday, the World Economic Forum (WEF), along with Russia's Sberbank and its cybersecurity subsidiary BI.ZONE announced that a new global cyberattack simulation would take place this coming July to instruct participants in ''developing secure ecosystems'' by simulating a supply-chain cyberattack similar to the recent SolarWinds hack that would ''assess the cyber resilience'' of the exercise's participants. On the newly updated event website, the simulation, called Cyber Polygon 2021, ominously warns that, given the digitalization trends largely spurred by the COVID-19 crisis, ''a single vulnerable link is enough to bring down the entire system, just like the domino effect,'' adding that ''a secure approach to digital development today will determine the future of humanity for decades to come.''
The exercise comes several months after the WEF, the ''international organization for public-private cooperation'' that counts the world's richest elite among its members, formally announced its movement for a Great Reset, which would involve the coordinated transition to a Fourth Industrial Revolution global economy in which human workers become increasingly irrelevant. This revolution, including its biggest proponent, WEF founder Klaus Schwab, has previously presented a major problem for WEF members and member organizations in terms of what will happen to the masses of people left unemployed by the increasing automation and digitalization in the workplace.
New economic systems that are digitally based and either partnered with or run by central banks are a key part of the WEF's Great Reset, and such systems would be part of the answer to controlling the masses of the recently unemployed. As others have noted, these digital monopolies, not just financial services, would allow those who control them to ''turn off'' a person's money and access to services if that individual does not comply with certain laws, mandates and regulations.
The WEF has been actively promoting and creating such systems and has most recently taken to calling its preferred model ''stakeholder capitalism.'' Though advertised as a more ''inclusive'' form of capitalism, stakeholder capitalism would essentially fuse the public and private sectors, creating a system much more like Mussolini's corporatist style of fascism than anything else.
Yet, to usher in this new and radically different system, the current corrupt system must somehow collapse in its entirety, and its replacement must be successfully marketed to the masses as somehow better than its predecessor. When the world's most powerful people, such as members of the WEF, desire to make radical changes, crises conveniently emerge'--whether a war, a plague, or economic collapse'--that enable a ''reset'' of the system, which is frequently accompanied by a massive upward transfer of wealth.
In recent decades, such events have often been preceded by simulations that come thick and fast before the very event they were meant to ''prevent'' takes place. Recent examples include the 2020 US election and COVID-19. One of these, Event 201, was cohosted by the World Economic Forum in October 2019 and simulated a novel coronavirus pandemic that spreads around the world and causes major disruptions to the global economy'--just a few weeks before the first case of COVID-19 appeared. Cyber Polygon 2021 is merely the latest such simulation, cosponsored by the World Economic Forum. The forum's current agenda and its past track record of hosting prophetic simulations demands that the exercise be scrutinized.
Though Cyber Polygon 2021 is months off, it was preceded by Cyber Polygon 2020, a similar WEF-sponsored simulation that took place last July in which speakers warned of a coming deadly ''pandemic'' of cyberattacks that would largely target two economic sectors, healthcare and finance. Cyber Polygon 2020 was officially described as ''international online training for raising global cyber resilience'' and involved many of the world's biggest tech companies and international authorities, from IBM to INTERPOL. There were also many surprising participants at the event, some of whom have been traditionally seen as opposed to Western imperial interests. For example, the person chosen to open the Cyber Polygon event was the prime minister of the Russian Federation, Mikhail Mishustin, and its main host, BI.ZONE, was a subsidiary of the Russian-government-controlled Sberbank. This suggests that the overused ''Russian hacker'' narrative may be coming to an end or will soon be switched out for another boogeyman more suitable in light of current political realities.
Aside from Mishustin, WEF executive director Klaus Schwab and former UK prime minister Tony Blair participated in the Cyber Polygon 2020 event, which is due to be repeated annually and bears many similarities to 2019's Event 201. Rather than preparing for a potential medical pandemic, Cyber Polygon 2020 focused on preparing for a ''cyberpandemic,'' one that mainstream media outlets like the New Yorker claim is ''already underway.'' Given the WEF's recent simulations, powerful billionaire business owners and bankers appear to be poised to use both physical and digital pandemics to reform our societies according to their own design and for their own benefit.
The Architects of Cyber Polygon According to Russian cybersecurity firm BI.ZONE, 120 organizations spread over twenty-nine countries took part in the two scenarios that were simulated at Cyber Polygon 2020, with as many as five million people allegedly having watched the livestream in over fifty-seven countries. Like many events that took place in 2020, the Cyber Polygon simulations were conducted online due to COVID-19 restrictions. Together with the World Economic Forum, BI.ZONE, a subsidiary of Sberbank, manages the Cyber Polygon project. Sberbank's largest shareholder, as of last year, is the Russian government, and it is thus often described by English-language media outlets as a state-controlled bank.
The 2020 event was launched with an address from the prime minister of the Russian Federation Mishustin, who has a history of courting Western tech companies prior to entering politics. In 1989, Mishustin graduated from Moscow State Technological University (generally known as Stankin) with a qualification in systems engineering. During the 1990s, he worked at the International Computer Club, a nonprofit organization with the goal of ''attracting Western advanced information technologies'' to Russia. Between 1996 and 1998, Mishustin was the chairman of the board of the ICC, but the company was liquidated in 2016. Between 2010 and 2020, he served as head of the Federal Taxation Service of the Russian Federation. Even though he had never shown any previous political ambitions, on January 16, 2020, he was appointed prime minister of the Russian Federation by an executive order issued by President Putin.
During Mishustin's welcoming remarks at the WEF's Cyber Polygon 2020, the Russian PM warned of the need to create public policy to ''strengthen the digital security of critical activities without undermining the benefits from digital transformation in critical sectors that would unnecessarily restrict the use and openness of digital technology.'' The statement suggests that ''unnecessary restrictions'' could become seen as necessary in time.
Mishustin goes on to explain that Russia's post-COVID economic recovery will be based on the ''increasing digitalization of that economy and government,'' adding that ''we will drastically increase the number of available digital public services and introduce fundamentally new support measures for digital businesses.'' He also stated that ''Russia has developed a common national system for identification and the prevention of cyberattacks with the government agency's information systems linked in the system.'' He also addressed the Cyber Polygon audience about the international community needing to come together to prevent a ''global cyberfraud pandemic.''
Sberbank, the largest Russian banking institution and former Soviet savings monopoly, which was originally founded by Nicholas I, was an official host of the Cyber Polygon 2020 event alongside the World Economic Forum. As reported in the Economist in January 2021, the Russian banking giant has begun to reimagine its business in an effort to become a consumer-technology giant. Sberbank has spent around $2 billion on technology and acquisitions, including the acquisition of internet media group Rambler, which it fully acquired in 2020. As late as December 30, 2020, Sberbank acquired Doma.ai, which describes itself as ''a convenient real estate management platform.'' On June 15, 2020, Sberbank bought 2GIS, a map, navigator, and business directory with over 42 million monthly active users. Sberbank's twenty-two investments, eleven as the lead investor, include some of the most used services in Russia, and its clear intention is to become a one-stop digital shop for all services. The bank also became the owner of one of the largest data-processing centers in Europe when the South Port data-processing center opened in November 2011, replacing the existing thirty-six regional data centers. Sberbank is set to be the world's first bank to launch its own cryptocurrency, Sbercoin, and digital finance ''ecosystem'' this March. It notably announced the coming Sbercoin, a ''stablecoin'' tied to the Russian ruble, just a few weeks after the Cyber Polygon 2020 exercise.
Sberbank's alliance with the WEF and prominence at Cyber Polygon 2020 was underscored at the event during the welcoming remarks delivered by Klaus Schwab. Schwab gave special thanks to Herman Gref, a member of the board of trustees of the World Economic Forum and Sberbank's CEO and also issued the following dire warning:
We all know, but still pay insufficient attention to, the frightening scenario of a comprehensive cyberattack which would bring to a complete halt to the power supply, transportation, hospital services, our society as a whole. The COVID-19 crisis would be seen in this respect as a small disturbance in comparison to a major cyberattack. We have to ask ourselves, in such a situation, how could we let this happen despite the fact we had all the information about the possibility and seriousness of a risk attack. Cybercrime and global cooperation should be on the forefront of the global agenda.
Similar warnings were heard at a 2019 simulation that was also cosponsored by the World Economic Forum, Event 201. Event 201, which simulated a global pandemic just months before the COVID-19 crisis, presciently warned in its official documentation: ''The next severe pandemic will not only cause great illness and loss of life but could also trigger major cascading economic and societal consequences that could contribute greatly to global impact and suffering.'' In contrast to similar simulations conducted in the past, Event 201 championed a ''public-private partnership'' approach to combatting pandemics, with a focus on engaging ''the private sector in epidemic and outbreak preparedness at the national or regional level.'' The WEF is, among other things, a major evangelist for the merging of the public and private sectors globally, describing itself as the ''international organization for private-public cooperation.'' It is thus unsurprising that their latest disaster simulation, which focuses on cyberattacks, would promote this same agenda.
The Speakers at Cyber Polygon 2020Aside from Schwab and Mishustin, twenty others took part in Cyber Polygon 2020, including some big names from the top echelons of the political elite. First off, Herman Gref engaged in discussion with former UK prime minister Tony Blair, who has been pushing for digital identity systems for decades. Blair straightforwardly told the CEO of Sberbank that biometric digital identity systems will ''inevitably'' be the tools that most governments will use to deal with future pandemics. Blair, discussing the coronavirus pandemic with Gref, advocated the harshest of lockdown measures, saying the only alternative to biometric digital identities is to ''lockdown the economy.''
Next, Sebastian Tolstoy, Ericsson's general director for Eastern Europe, Central Asia, and Russia and current chairman of the Tolstoy Family Foundation in Sweden, dialogued with Alexey Kornya. Kornya is president, CEO, and chairman of the management board of Mobile TeleSystems. He previously worked for PricewaterhouseCoopers and AIG-Brunswick Capital Management at North-West Telecom. Tolstoy and Kornya presented a segment at Cyber Polygon 2020 entitled ''Building a Secure Interconnected World: What Is the Role of the Telecom Sector?'' in which they discussed the importance of digital communication and connectivity to our modern way of living.
In the next segment, Nik Gowing, BBC World News presenter between 1996 and 2014 and founder and director of Thinking the Unthinkable, spoke with Vladimir Pozner, journalist and broadcaster, on the subject of ''fake news'' in a conversation that was actually somewhat refreshing in its arguments and approach.
St(C)phane Duguin, the CEO of the CyberPeace Institute, a Geneva-based company that describes itself as ''citizens who seek peace and justice in cyberspace,'' then gave a talk to the millions of viewers watching the simulation. The CyberPeace Institute, funded by Microsoft, Facebook, Mastercard, and the Hewlett Foundation, among others, claims to help their customers ''increase digital resilience and the capacity to respond to and recover from cyberattacks.'' The core backers of the CyberPeace Institute are also among the top backers of the Global Cyber Alliance, which unites the public sectors of the US, UK, and France with multinational corporations and intelligence-linked cybersecurity firms, employing ''a coordinated approach and nontraditional collaboration'' to ''reduce cyber risk.''
Duguin, who is also on the advisory board of the Global Forum on Cyber Expertise, recently launched the Cyber4Healthcare initiative, a ''free'' cybersecurity service to healthcare providers fighting the COVID-19 pandemic. The Cyber4Healthcare initiative includes as its main partners BI.ZONE as well as Microsoft and the Global Cyber Alliance. This is yet another suspicious Microsoft-linked free cybersecurity service currently being pitched to and adopted by healthcare providers around the world at a time when warnings of a coming cyberattack on healthcare systems globally are becoming more public.
Dhanya Thakkar, senior vice president of AMEA at Trend Micro, who advertises himself online as a top ASEAN LinkedIn ''cybersecurity influencer,'' and Wendi Whitmore, vice president of IBM X-Force Threat Intelligence, next discussed the topic ''Know Your Enemy: How Is the Crisis Changing the Cyberthreat Landscape?'' IBM's presence is notable due to the company's longstanding relationship with the CIA, dating back to the early Cold War. The company has become so entrenched that the CIA recently recruited their chief information officer directly from IBM Federal. Before joining IBM, Whitmore held executive positions at California-based cybersecurity technology companies CrowdStrike and Mandiant, the latter acquired by FireEye in a stock and cash deal worth in excess of $1 billion. Whitmore was responsible for ''professional services.'' Notably, both CrowdStrike and Mandiant/FireEye are the key organizations leading the investigation into the recent SolarWinds hack, which US intelligence has blamed on a ''Russian hacker'' without providing any evidence. Whitmore began her career as a special agent conducting computer crime investigations with the Air Force Office of Special Investigations.
Jacqueline Kernot, the Australian ''partner in cybersecurity'' for Ernst and Young, and Hector Rodriguez, senior vice president and regional risk officer for Visa, next discussed how to prepare for cyberattacks. Kernot worked for over twenty-five years as a military officer for the Australian Intelligence Corps and spent two years working at IBM's Defence|Space|Intelligence for Tivoli Software in the UK with ''international responsibilities within the UK Ministry of Defence, Defence Primes, and NATO.'' Ernst and Young and Visa, alongside other WEF-linked corporations such as Salesforce, are well represented on the Vatican's exclusive Council for Inclusive Capitalism. The Council, like the WEF, calls for the reconstruction of the economic system to be more ''sustainable,'' ''inclusive,'' and ''dynamic'' by ''harnessing the power of the private sector.''
Troels rting J¸rgensen , chairman of the advisory board of the World Economic Forum's Centre for Cybersecurity, and J¼rgen Stock, the Danish secretary general of INTERPOL, also spoke together at Cyber Polygon regarding the changes in global cybercrime over the course of the previous year. A few months after appearing at Cyber Polygon, the Danish Financial Supervisory Authority announced in an official statement that ''Troels rting has notified the Ministry of Business Affairs that he is resigning from the Danish Financial Supervisory Authority's board.'' Citing unnamed sources, Danish financial news service FinansWatch reported that during the time between 2015 and 2018, when he was employed as head of security at Barclays bank, rting had been a key figure in the hunt for a whistleblower who had exposed the same criminal activity rting railed against at Cyber Polygon.
The man speaking alongside rting, J¼rgen Stock, is a former German police officer, criminologist, and lawyer. He was elected for a second term as secretary general of INTERPOL in 2019, a term that generally lasts for five years. Craig Jones, the cybercrime director at INTERPOL, also joined the discussion at Cyber Polygon 2020. The New Zealander spent twenty-seven years in law enforcement and is considered an expert in cybercrime investigations. He previously held several senior-management positions in UK law enforcement, most recently at the National Crime Agency.
Petr Gorodov and John Crain were briefly interviewed at the Cyber Polygon 2020 event. Gorodov is head of the General Directorate for International Relations and Legal Assistance of the Prosecutor General's Office of the Russian Federation and also sits on the Commission for the Control of INTERPOL's files. He is on the Requests Chamber of INTERPOL, which examines and decides on requests for access to data as well as requests for correction and/or deletion of data processed in the INTERPOL information system. John Crain is chief security, stability, and resiliency officer at ICANN, the nonprofit internet security corporation. He is currently responsible for the management of the L-Root server, one of the internet's thirteen root servers, making his inclusion at the simulation particularly notable. At Cyber Polygon 2020 he promoted a ''long-term solution of working together in the cybersecurity community.''
The final word at Cyber Polygon 2020 was delivered by Stanislav Kuznetsov, deputy chairman of the executive board at Sberbank. He is also a board member for the Sberbank charity foundation Contribution to the Future, a project that seeks to get Russian schoolchildren from grades seven through eleven interested in AI (artificial intelligence), machine learning, and data analysis and to help them develop math and programming skills. Kuznetsov studied at the Law Institute of the Ministry of Internal Affairs of the Russian Federation.
The Main Event: Enter the PolygonParticipants in the Cyber Polygon 2020 event, Source: https://cyberpolygon.com/The simulation component of Cyber Polygon 2020 saw 120 teams from twenty-nine countries take part in the cybersecurity technical simulation. During the online event, participants ''exercise[d] the actions of the response team in a targeted attack aimed at stealing confidential data and thus resulting in damage to the company reputation.'' Two teams, the Red and the Blue, went head-to-head in the simulations where the Red Team, made up of the training organizers from BI.ZONE, simulated cyberattacks and the Blue Team members attempted to protect their segments of the training infrastructure. The actual simulation was made up of two scenarios in which the various subgroups making up the teams could gain points.
The first scenario, called Defence, made the Cyber Polygon participants practice repelling an active APT (advanced persistent threat) cyberattack. The scenario's objective was stated as being to ''develop skills for repelling targeted cyberattacks on a business-critical system.'' The simulation's fictional organization's virtual infrastructure included a service that processes confidential client information. This service became the subject of interest to an APT group that planned to steal confidential user data and resell it on the ''darknet'' to financially benefit and damage the company's reputation. The APT group studied the target system in advance and discovered several critical vulnerabilities. In the scenario, the cyber ''gang'' plans to attack on the day of the exercise. The participants involved were judged on their ability to cope with the attack as fast as possible, to minimize the amount of information stolen, and to maintain service availability. Blue Team participants could apply any applications and tools to protect the infrastructure and were also allowed to fix system vulnerabilities by improving the service code.
In the second scenario, called Response, the teams had to investigate the incident using ''classic forensics and threat hunting techniques.'' Based on the information gathered, participants had to compose a dossier that would help law enforcement agencies locate the criminals. The second scenario's objective was to develop skills in incident investigation using the scenario in which cybercriminals gained access to a privileged account through a successful phishing attack.
When the BI.ZONE team released the results of the simulation they intentionally avoided using the real names of the organizations so as not to ''set off a competition between the participants and keep their results confidential.'' However, the teams could later compare their results with the others by using a basic scoreboard, and the hosts could analyse the crucial data showing various organizational weaknesses of each of the participating teams/institutions.
The final report states that the results showed that ''banks and companies from the IT industry demonstrated the highest resilience. Security assessment expertise in these sectors is quite well developed, with classic forensics and threat hunting widely applied.'' In lay terms, the teams from banks and the IT industry seemed to be better prepared than most other sectors for investigating and hunting down threats. However, all the teams involved proved to be less than able when it came to the initial defense from a cyberattack, with the BI.ZONE report stating that ''27% of the teams had difficulties earning points for the first scenario, which allows us to conclude that some of the team members lack or have insufficient expertise in security assessment and protection of web applications.'' On the subject of threat hunting, the report goes on to say that ''21% of the teams could not earn a single point for the second round of the second scenario. This was attributed to 'Threat Hunting' being a relatively novel approach and the majority of organisations lacking experience of applying its techniques in practice.''
The Cyber Polygon 2020 event revealed the weakness in human-led defensive response and resilience as it relates cyberdefense. This outcome is convenient for hi-tech cybersecurity companies like BI.ZONE that wish to highlight the superiority of AI-driven cybersecurity products in comparison to ''inefficient'' human workers. Also, it should be noted that BI.ZONE's gaining knowledge of global institutional weaknesses through cyberdefense training could be useful intelligence for their parent company, Sberbank, and in turn the largest shareholder of Sberbank, the Russian government.
Bringing Russia in from the Cold?Although Russian Federation authorities are quite used to being out in the cold both politically and physically, there appears to be a change in the usual order of nations. Russia's inclusion as the leader in such an important global cybersecurity initiative is a bit surprising, especially after Russia has been the scapegoat of choice for any cyberattack committed against any Western power for several years, most recently with the SolarWinds hack in the US. Yet, there was no outcry in the West over Cyber Polygon 2020, in which a company that is majority owned by the Russian government was able to gain direct knowledge of the cyberdefense weaknesses of major global institutions, banks, and corporations through their hosting of the exercise.
The complete absence of the ''Russian hacker'' narrative at Cyber Polygon as well as Russia's leadership role at the event suggests either that a geopolitical shift has taken place or that the Russian hacker narrative commonly deployed by intelligence agencies in the US and Europe is mainly meant for the general public and not for the elite figures and policymakers in attendance at Cyber Polygon.
Another possibility for Russia no longer being treated as the perpetual enemy of cyberspace is that it is entirely on board with both the official coronavirus narrative and the allegedly imminent cyberpandemic. Cyber Polygon 2020 appeared, in part, to be a Russian charm offensive that was welcomed by the powerful elite. Tony Blair, who once held out the hand of false reconciliation on behalf of the international community to Colonel Gaddafi, has often been involved in these exercises of international diplomacy on behalf of the elites in the years since he left public office. His involvement in the exercise may have been meant to facilitate support among Western WEF-aligned governments for even greater Russian inclusion in the Great Reset. Part of this is due to the WEF-led effort to bring BRICS nations like China and Russia into the Great Reset fold because it is essential for their agenda's success on a global scale. Now, Russia is pioneering this new model of supposedly national finance systems that the WEF supports through Sberbank's creation of a digital monopoly not only of financial services but all services within the Russian Federation.
Cyber Polygon 2020 was both an ad for pro-Russian relations and a promotional exercise for Klaus Schwab and the World Economic Forum's Great Reset. Some of the people who took part and supported the Cyber Polygon event are involved at the highest levels of cyber intelligence; some may have even been unofficial representatives of their national state intelligence apparatus. The decisions of several national governments to participate directly in the WEF-led Great Reset is no ''conspiracy theory.'' For instance, the incoming Biden administration sent its climate envoy, John Kerry, to the WEF annual meeting last month, where Kerry underscored the US commitment to the Great Reset agenda and the associated Fourth Industrial Revolution that seeks to automate most jobs being currently performed by humans. With the governments of Russia, China, the US, the UK, Israel, Canada, and India, among others, on board with this transnational agenda, it becomes deeply unsettling that high-ranking operatives in both the public and private sectors joined the WEF to conduct a simulation of a crisis that would clearly benefit the Great Reset agenda.
As previously mentioned, the WEF cosponsored a simulation of a coronavirus pandemic just months before the actual event. Soon after the COVID-19 crisis began in earnest last March, Schwab noted that the pandemic crisis was just what was needed to launch the Great Reset as it served as a convenient catalyst to begin overhauling economies, governance, and social society on a global scale. If the destabilizing events simulated at Cyber Polygon do come to pass, it will likely be similarly welcomed by the WEF, given that a critical failure in the current global financial system would allow the introduction of new public-private ''digital ecosystem'' monopolies such as those being built in Russia by Sberbank.
This effort by Sberbank to both digitize and monopolize access to all services, both private and public, may be appealing to some because of its apparent convenience. However, it will also be emblematic of what we can expect from Schwab's Great Reset'--monopolies of fused public- and private-sector entities disguised by the term ''stakeholder capitalism.'' What the general public does not realize yet is that they themselves will not be included among these ''stakeholders,'' as the Great Reset has been designed by the bankers and wealthy elite for the bankers and the wealthy elite.
As for the Cyber Polygon 2020 event, the coming cyberpandemic is being prophetically thrown in our faces just as the pandemic exercise was prior to the actual disease's appearance. Such prophetic warnings are coming not only from the WEF, however. For instance, the head of Israel's National Cyber Directorate, Yigal Unna, warned last year that a ''cyber winter'' of cyberattacks ''is coming and coming faster than even I suspected.'' In the cyber directorate, Unna works closely with Israeli intelligence agencies, including the infamous Unit 8200, which has a long history of electronic espionage targeting the US and other countries and which has been responsible for several devastating hacks, including the Stuxnet virus that damaged Iran's nuclear program. Israeli intelligence is also poised to be among the greatest beneficiaries of the Great Reset due to the strength of the nation's hi-tech sector. In addition, last month saw the UAE's central bank following Cyber Polygon's lead by conducting its first-ever cyberattack simulation in coordination with the Emirati private-finance sector. Corporate media outlets, for their part, began this year by claiming that ''cyberattacks may trigger the next crisis for banks'' and, as of February 1, that ''the next cyberattack is already underway.''
Some will say that a ''cyberpandemic'' is an inevitable consequence of the quickly developing hi-tech world in which we live, but it still fair to point out that 2021 is the year that many have been predicting for the financial destruction of big institutions that will lead to new economic systems that align with the Great Reset. The inevitable collapse of the global banking system, resulting from the off-the-charts corruption and fraud that has run rampant for decades, is likely to be conducted through a controlled collapse, one that would allow wealthy bankers and elites, such as those that participated in Cyber Polygon, to avoid responsibility for their economic pillaging and criminal activity.
This is especially true for Cyber Polygon participant Deutsche Bank, whose inevitable collapse has been openly discussed for years due to the bank's extreme corruption, fraud, and massive exposure to derivatives. In late 2019, months before the COVID-19 crisis began, the CEO of Deutsche Bank warned that central banks no longer had tools that could adequately respond to the next ''economic crisis.'' It is certainly telling that entirely new banking systems, such as Sberbank's soon-to-be-launched digital monetary monopoly, began to be developed just as it began to be publicly acknowledged that central banks' traditional means of responding to economic calamities were no longer viable.
A massive cyberattack, such as that simulated at Cyber Polygon 2020, would allow faceless hackers to be blamed for economic collapse, thus absolving the real financial criminals of responsibility. Furthermore, due to the difficult nature of investigating hacks and the ability of intelligence agencies to frame other nation states for hacks they in fact committed themselves, any boogeyman of choice can be blamed, whether a ''domestic terror'' group or a country unaligned with the WEF (for now, at least) like Iran or North Korea. Between the well-placed warnings, simulations, and the clear benefit for the global elite intent on a Great Reset, Cyber Polygon 2020 appears to have served not only its publicly stated purpose but its own ulterior motives.
Statement from the U.S. Department of Agriculture on JBS USA Ransomware Attack | USDA
Wed, 02 Jun 2021 05:08
Skip to main content Release & Contact InfoStatement
Release No. 0120.21
Contact: USDA PressEmail: press@usda.gov
WASHINGTON, June 1, 2021 '-- As noted earlier today by the White House, USDA is aware of the ransomware attack against JBS, which is affecting the company's operations, including its facilities in the United States. USDA continues to work closely with the White House, Department of Homeland Security, JBS USA and others to monitor this situation closely and offer help and assistance to mitigate any potential supply or price issues. As part of that effort, USDA has reached out to several major meat processors in the United States to ensure they are aware of the situation, encouraging them to accommodate additional capacity where possible, and to stress the importance of keeping supply moving.
USDA has also been in contact with several food, agriculture and retail organizations to underscore the importance of maintaining close communication and working together to ensure a stable, plentiful food supply. USDA will continue to encourage food and agriculture companies with operations in the United States to take necessary steps to protect their IT and supply chain infrastructure so that it is more durable, distributed and better able to withstand modern challenges, including cybersecurity threats and disruptions.
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Biden to suspend oil leases in Alaska Arctic refuge...
Tue, 01 Jun 2021 23:52
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Battle Brews Over Banning Natural Gas to Homes
Battle Brews Over Banning Natural Gas to Homes - WSJ
Mon, 31 May 2021 12:44
A growing fight is unfolding across America as cities concerned about climate change consider phasing out natural gas for home cooking and heating.
Major cities including San Francisco, Seattle, Denver and New York have either enacted or proposed measures to ban or discourage the use of the fossil fuel in new homes and buildings, two years after Berkeley, Calif., passed the first such prohibition in the U.S. in 2019.
The bans in turn have led Arizona, Texas, Oklahoma, Tennessee, Kansas and Louisiana to enact laws outlawing such municipal prohibitions in their states before they can spread. Ohio is considering a similar measure.
The outcome of the battle has the potential to reshape the future of the utility industry, and demand for natural gas, which the U.S. produces more of than any other country.
Proponents of phasing out natural gas say their aim is to reduce planet-warming emissions over time by fully electrifying new homes and buildings as wind and solar farms proliferate throughout the country, making the power grid cleaner.
Homes and businesses account for about 13% of the nation's annual greenhouse gas emissions, according to the Environmental Protection Agency, mostly because natural gas is used in cooking, heating, and washers and dryers. Climate activists say reducing that percentage is critical for states with goals to slash carbon emissions in the coming decades.
Opponents in the gas industry counter by citing the higher costs of making many homes fully electric, and pointing to the added security of having a second home energy source to heat and cook with during extreme weather events. They also highlight the preference many home and professional chefs have for using gas-fired stoves.
New all-electric homes are cost-competitive with those that use gas in many parts of the country, but retrofits can be considerably more expensive, depending on the existing heating and cooking systems and the cost of effectively converting them. A recent study by San Francisco found that retrofitting all housing units that now use natural gas would cost between $3.4 billion and $5.9 billion, costs that would fall on residents, the city or both.
Induction ranges, which use magnets to heat pots and pans directly, can be more expensive to buy than gas ranges, especially in professional kitchens. Restaurant associations across the nation have raised concerns about going electric.
Utilities that supply both electricity and natural gas could face more muted impacts if the shift accelerates. But those that supply only natural gas face the prospect of slower growth or even a reversal of demand, especially if momentum builds to electrify both new and existing homes.
Greater reliance on electricity raises the possibility that parts of the natural-gas delivery system will become stranded assets, facilities that retire before they pay for themselves. The Environmental Defense Fund, a nonprofit environmental advocacy group, in 2019 warned that in California, where gas utilities spend billions of dollars on their systems each year, stranded assets could complicate efforts to move away from gas by saddling customers with higher costs over time.
President Biden's $1.7 trillion infrastructure plan calls for greater adoption of all-electric heat pumps and induction stoves, giving proponents hope that the government will do more to incentivize their adoption.
Panama Bartholomy, director of the Building Decarbonization Coalition, which supports efforts to electrify buildings throughout California, said the organization is pushing for the state to cut emissions from homes and businesses by 40% by 2030, and to adopt zero-emission building codes for each within the next few years.
''All of a sudden there's a conversation happening that wasn't happening two years ago,'' Mr. Bartholomy said. ''It's the fastest-growing trend we've ever seen.''
Industry pushback has been swift, with many utilities and businesses voicing opposition to local gas bans.
Arizona last year became the first state to pass pre-emptive legislation barring municipalities from banning new gas hookups. The Arizona Chamber of Commerce helped lead a coalition of businesses that pushed for the legislation, even though no bans were under consideration in the state at the time. Garrick Taylor, the chamber's interim chief executive, said the legislation was born of concerns that bans would result in higher electricity costs and reduced energy choices for residents and businesses.
''If you see something next door in California, there's a chance that a municipality in your state is likely going to consider it,'' Mr. Taylor said.
The American Gas Association, a national lobbying group, has been pushing for state laws prohibiting local bans. President Karen Harbert said an indiscriminate approach to widespread electrification could put strain on the grid, resulting in either higher electricity prices or greater reliance on gas-fired power plants.
''You have to do the math,'' she said. ''We can't just say if we electrify everything, we're going to solve the challenge of climate change.''
State agencies in California, Colorado, Massachusetts and New York have launched efforts to assess how the role of gas utilities may change in the coming years if demand plateaus or declines. Utilities across the country are beginning to ask the same question as they consider new gas investments.
Jan Berman, director of energy strategy and innovation at PG&E Corp. , which serves 16 million people in Northern and Central California, said it may eventually shrink its gas distribution system, if more homes are retrofitted to run entirely on electricity.
''We welcome the opportunity to avoid investments in new gas assets that might later prove to be underutilized as decarbonization efforts progress here in California,'' she said.
Southern California Gas Co., a unit of Sempra Energy that is the nation's largest gas utility, opposes bans on new hookups, arguing that customers should have the right to choose. The California Public Utilities Commission recently determined that SoCalGas misused ratepayer money to advocate against such bans and other energy efficiency measures, and ordered the company to refund customers for those efforts.
SoCalGas said it appreciates the agency's finding that no violations, fines or penalties are warranted.
SoCalGas recently set a goal to achieve net-zero emissions by 2045. The utility is working to expand its use of renewable natural gas made from landfill waste and green hydrogen, which is produced using electricity from renewable energy sources. CEO Scott Drury said he envisions a future where the company's existing infrastructure is used to augment wind and solar power, especially during periods of peak demand.
''What is flowing through those pipes will be different in 2045 than it is today,'' he said. ''How do you take the infrastructure that's there, and use it in the most thoughtful way as a tool to enable what we're collectively trying to pursue?''
Write to Katherine Blunt at Katherine.Blunt@wsj.com
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Tue, 01 Jun 2021 14:09
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Dog are People too
The hidden reason processed pet foods are so addictive - BBC Future
Thu, 03 Jun 2021 13:52
The hidden reason processed pet foods are so addictive
(Image credit: ; Getty Images)
From potently smelly additives to offal concentrates, pet food companies turn to some surprising ingredients in the quest to make kibble delicious.
T
The cue might be a hand in a pocket, the opening of a cupboard door, or even a word said carelessly aloud '' "dinner". Before you know it, you're tripping over a pet excitedly awaiting a portion of... dull-brown dried pellets. What's in these mysterious morsels, that makes them as delectable as roasted chicken, wild salmon, or bundles of fresh herbs?
Take my flatmate, a small black rabbit. For a large part of every day, he can be found sitting attentively with his paws on his empty food bowl, awaiting his next portion of kibble '' even though it looks like his droppings and smells equally unappetising. He used to have an automatic dispenser with a timer, but he learnt to throw it across the room to access its contents prematurely. No matter what delicacies I place before him '' home-grown parsley, soft-cut hay, fresh carrot-tops, organic kale '' he would always rather eat processed pet food.
It seems that this is not unusual. Anecdotes abound about pets whose thoughts are largely preoccupied with kibble, such as the cat that has a daily panic attack when it realises it has eaten all its pellets and the pragmatic German shepherd found carrying a bag of dog food around the streets of Houston after Hurricane Harvey.
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How changing our food may have changed usThe food that lasts 2,000 yearsThe hidden risks of cooking your foodAs it happens, this addictive quality is carefully engineered. Big Pet Food is a multi-billion-dollar industry which invests heavily in research into "palatants" '' ingredients that make our pets want to eat their products. And from potently smelly chemicals usually found in rotting meat to an additive commonly added to potatoes to stop them discolouring, the quest to make the most scrumptious pet food has led to some surprising insights.
"Big [pet food] companies have huge departments that make palatants," says Darren Logan, head of research at the Waltham Petcare Science Institute, part of the company Mars Petcare. "Just like we make them for humans, we make them for pets as well."
Upper-class dogs
The first pet food was invented in 1860 by James Spratt, an enterprising lightning-rod salesman from the US state of Ohio. Legend has it that he had travelled to England for his business, and was looking out over the docks of Liverpool one day when he noticed stray dogs knocking back leftover hardtack biscuits.
This was a revelation for two reasons.
Rabbits eat fresh vegetables in the wild, but many kept as pets feast instead on processed pellets (Credit: Getty Images)
Firstly, hardtack were famously unappealing '' loathed by generations of the soldiers and sailors who ate them, these simple slabs of baked flour and water were tougher than wood and sometimes hard enough to break your teeth. Their nicknames included "sheet iron" and "worm castles", the latter because of the high proportion that were infested with maggots and weevils. The oldest piece of surviving hardtack was baked just nine years before Spratt's dock visit, and still looks suspiciously well-preserved 170 years later.
Secondly, until that moment it hadn't occurred to anyone to check what their pets would like to eat '' or that this could be monetised. For as long as we had kept domesticated animals, they had been fed more or less the same food as humans, or expected to fend for themselves.
One striking example is the husky. In their native territory of Arctic Greenland, Canada and Alaska, Inuit hunter-gatherers have traditionally fed these dogs on seal meat, which comprises the majority of their own diet. Sled-dogs are so well-adapted to this that when the British Antarctic Survey brought them to Antarctica as a form of transport in 1945, they found that they struggled to digest commercial dog food. In the end, they had to kill a number of local seals each year, just to feed the dogs, before they were largely replaced with skidoos in the 1960s and 70s.
Meanwhile in Victorian London, dogs that were lucky enough to be looked after were either given table scraps or gruel. Even specialist exotic animals were fed everyday human food '' the 20,000 or tortoises imported from Morocco each year were mostly expected to survive on ordinary garden vegetables or bread soaked in water. Cats were considered street animals and rarely fed.
But Spratt had hit upon something entirely new. Over the coming months he developed the "Meat Fibrine Dog Cake", a biscuit-like concoction of beetroot, vegetables, grains and beef of dubious origins that claimed to meet all the nutritional needs of his customers' hounds. (While its packaging implied that it was the finest prairie beef, what it was actually made from was a secret he took to his grave.)
Spratt's innovation coincided with a cultural revolution in the way people saw their pets '' dogs and cats went from being viewed as mere utility animals or borderline-vermin to beloved family members to be coddled. Consequently, the Meat Fibrine Dog Cake was marketed as a luxury food for aristocratic pets.
The husky dogs taken on early Antarctic voyages had to be fed with freshly killed seals (Credit: Ozge Elif Kizil/Anadolu Agency/Getty Images)
The adverts labelled them "Dog's Delight" and included gushing testimonials from wealthy customers. Ironically, Spratt's also promoted the fact that they were chosen to feed the sled dogs on Captain Scott's 1901 trip to the Antarctic, though we now know they would much rather have eaten seal.
Eventually the company branched out into cat food '' "Spratt's puts pussy into fine form!", they said '' and the rest is history. However, the science of pet food palatants still had some way to go.
Disgusting smells
Today it's possible to buy specialised kibble for almost any kind of pet, from frogs to sugar gliders (a small marsupial). Most follow roughly the same formula '' they usually contain some kind of base carbohydrate, assorted proteins and fats, sugars, a source of fibre, antioxidants or other preservatives, emulsifiers (which keep the fat in the food and prevent it from separating), vitamins and minerals, and colouring agents.
More sophisticated versions may also contain probiotics or digestibility enhancers '' such as chicory, which is often added to dog food '' as well as enzymes, anti-parasitic compounds and minerals to prevent the build-up of tartar on teeth.
To turn these ingredients into a dry pet food, it's formed into a paste and "extruded" via a process that involves heating it up and forcing it through a plate with holes in it, to form an aerated product that matches the shape of the holes. It's the same process that's used to make puffed snack foods, with flavourings added in the final step '' in the case of pet food, they're either sprayed on or added as a powder.
Oddly, there is very little relationship between how healthy a pet food is and its inherent deliciousness. That's because in the US, the EU and many other parts of the world, in order to describe one as "complete" '' containing everything the body needs to be healthy '' it must meet certain nutritional standards. These set out acceptable ranges for most ingredients, so manufacturers can't just load up on sugar and fat to make it compelling.
"From my standpoint as a nutritionist, all pet foods are the same," says Marion Nestle, professor emerita of nutrition, food studies, and public health at New York University.
The first processed dog foods were luxury products which ushered in the idea of the "pampered pet" (Credit: Kirn Vintage Stock/Corbis via Getty Images)
Instead, companies turn to chemistry.
Many animals rely heavily on smell to navigate the world around them, and this is often the main sense that's targeted. While human noses contain around 50 million olfactory receptors, cats have 67 million, rabbits have 100 million and dogs have around 220 million. On the other hand, their sense of taste is generally less discriminating than ours '' our relatively high density of taste receptors is thought to have evolved to help us cope with our diverse omnivorous diets.
The catch is that appealing to animals that find the smell of roadkill, sweaty socks, and vomit utterly enchanting '' as carnivorous pets often do '' while not making their human companions feel violently ill, is extremely tricky. "There is a slight paradox there, because the smells that cats particularly but also dogs seem to like are often the opposite of what humans like," says Logan.
Nestle puts it more bluntly '' "animals eat faeces", she says. "They like strong animal odours and pet food manufacturers have a really difficult time, because they have to make it disgusting enough so that the animal will eat it, but not so disgusting that the owners won't buy it."
Examples include putrescine and cadaverine, colourless chemicals produced naturally by the breakdown of proteins. They're largely responsible for the revolting smell of rotting flesh '' and cats love them. While in human food, their levels are sometimes closely monitored as a way of ensuring the freshness and safety of meat, they're often actively added to cat and dog food, either as offal extracts or lab-made additives.
In the case of naturally vegan animals, such as rabbits and guinea pigs, irresistible smells such as mint and oregano are sometimes added in the form of concentrates.
Japanese-inspired cuisine
Other insights are arguably more surprising. A recent study identified nine volatile compounds in common pet food flavourings that are linked to how delicious they are to dogs, including heptanal, nonanal, and octanal, which all have strong, fruity odours.
However, taste is also important '' and here the preferences of carnivorous pets are not so different from ours.
One of the most popular additives in human food is the enigmatic "hydrolysed protein", which is formed by breaking down the long strands of proteins into their constituent amino acids, usually using enzymes or hydrochloric acid. It imparts a flavour similar to that achieved by meat or vegetable stock, and often comes with MSG, which is produced as a by-product of the same reaction and is responsible for the savoury taste of tomatoes, cheese and Iberico ham.
Though hydrolysed proteins are produced artificially, the process is similar to what happens when you cook food for a long period of time '' it's a kind of pre-digestion, and is thought to contribute to the enticing smell of many brands of kibble.
Early processed dog food resembled the tooth-challenging hard-tack biscuits often taken on long sea voyages (Credit: Getty Images)
"The understanding of cat palatability is very similar to Japanese or Asian cuisine, where there's a lot of focus on umami and another taste modality called kokumi," says Logan.
Kokumi was discovered in Japan in 1989, and has been proposed as the sixth taste in humans, after sweetness, saltiness, bitterness, sourness and umami. It's described as a kind of mouth-feel rather than a flavour per se '' a texture that imparts richness and "thickness" to foods. Unlike the others, kokumi hasn't yet been linked to a specific set of compounds, but foods that conjure this sensory experience include scallops, soy sauce, shrimp paste, yeast and beer.
The sixth taste is thought to be particularly popular with carnivorous animals, which may discern it via receptors in their mouths that evolved to detect calcium. And as you would expect, pet food companies have already begun targeting it with cocktails of flavour-enhancing chemicals.
But there are some flavours that you will never find in certain pet foods.
For example, most wild carnivorous animals lack the receptors for tasting sugar or carbohydrates. And unlike dogs, which have been living around humans and feasted off our scraps for up to 40,000 years, domestic cats have only been around for about 4,300. For the majority of that time, they were considered a kind of free pest-control that could fend for themselves.
So, while cats are particularly drawn to Japanese food, which is rich in meat and seafood, you're unlikely to find them stealing ice-creams or doughnuts '' unlike dogs, they simply haven't been around humans for long enough to have evolved the ability to taste sugar.
Cats are irresistibly drawn to the chemical compounds found in rotting fish (Credit: Getty Images)
On the other hand, because vegan animals eat exclusively vegetable matter, which is often rich in fibre and carbohydrates, they tend to prefer sweeter pet food.
Finally, no list of palatants would be complete without pyrophosphate, described in Popular Science as "cat crack". This common additive performs a number of roles in human food, such as preventing potato products from going dark after they're cooked '' none of which involve improving its taste. Nevertheless, cats go nuts for it, possibly because it intensifies the flavour of amino acids.
Pet food companies are now so successful at making food delicious that they're increasingly encountering a dilemma '' it's almost too good. "The danger for cats and dogs today is the same as for people, it's overconsumption," says Andrew Knight, a professor of animal welfare and ethics at the University of Winchester.
Pet obesity is a growing problem in the developed world, with one survey of veterinary professionals at a vet show in London suggesting that around 51% of dogs, 44% of cats and 29% of small mammals are now overweight or obese.
According to Logan, this is not down to the way pet food is formulated, but humans succumbing to their beloved pets' pleading gazes. "The reason we make pet food palatable is that if they don't eat all the food that we give them, it won't meet the nutritional needs that they require," he says. "The real problem is owners feeding them too much '' pets can't open the packets themselves."
However, there is an upside. There are mounting concerns about the environmental impact of pet food, too '' in 2009, two New Zealand scientists estimated the planetary cost of keeping a dog as roughly twice that of having a medium-sized SUV.
Pets given too much calorific processed food may, just like humans, put on extra weight (Credit: Getty Images)
This is where palatants come in. Because most pet foods comprise a fairly tasteless base that is spruced up with delicious flavourings and smells, pet foods made from more sustainable ingredients such as insects or soya are generally just as acceptable to carnivorous pets as the real deal. (Though cats cannot be fed a diet that is meat free.)
"According to this really large-scale study that we've just finished, the animals on vegan pet foods seem to be just as happy as animals on meat ones," says Knight, who is hopeful about their future potential.
"There is a broad recognition that the need to be more sustainable will have a big impact on the pet food business," says Logan, who explains that the pet food company he works for has just released its own brand of insect-based pet food.
So, why do our pets find pet food so addictive? Well, because it's been made that way. Just like us, our pets find it hard to say no to the food we have designed to be tasty.
* Zaria Gorvett is a senior journalist for BBC Future and tweets at @ZariaGorvett
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Freedom Passpoert
The passports will be used to identify the VAXXED!!
Big Pharma
Viagra for young men - ADD and SSRI's
I just wanted to throw this into the conversation. I heard about this a few years back from my buddy who was recently married to a beautiful woman who he couldn't get hard for. He is under 30. His doctor found out it was due to his hormone levels out of whack from 20+ years of prescribed adderall use.
I bet we could do a study and see how many ADHD kids are also heavy into porn. Chicken or the egg? Do they watch so much porn because they can't get hard/get off because they are hopped up on meds that numb them? Or can they not get hard/get off because they watch too much porn?
PCR
Netherlands Drops Negative PCR-RT Test Requirement From Transit Passengers Effective Today (June 1, 2021) - LoyaltyLobby
Thu, 03 Jun 2021 13:16
Netherlands was one of the first countries to introduce PCR-RT test requirements for transit passengers (often you needed two) that some other countries followed with less time-consuming and cheaper tests.
The Netherlands has removed the negative test requirement from transit passengers effective today. However, you need to ensure that you fulfill the destination country's entry requirements, including possible test(s).
You can access the Netherlands page for Covid-19 and travel here.
Here's the information (Google translate from English):
As a traveler, you must be able to show a negative COVID-19 test result before traveling or returning to the Netherlands. This applies to most countries and to anyone aged 13 or older. The test result is mandatory for departures by plane, ship, international train and international bus. From 1 June, the negative test result is also mandatory for travelers with their own transport, such as the car or motorcycle.
Changes from June 1:
Negative NAAT(PCR) test result also mandatory for travelers with a car or motorcycle unless the travelers have been in the Netherlands for less than 12 hours . Transfer passengers except for the mandatory tests Rapid test only mandatory for travelers from countries with a worrying virus variantAND
Negative COVID-19 test result: rules when switching
As a traveler, you must be able to show a negative COVID-19 test result before traveling or returning to the Netherlands. The rules for switching differ per situation.
You start your journey in a safe country and you have a transfer in a high-risk area
If you stayed at the airport, you do not need a negative COVID-19 test result.If you leave the airport during the transfer, this counts as a new journey. In that case, the obligation applies to the negative COVID-19 test result .You start your journey in a high-risk area and you have a transfer in a non-high-risk area
The rules for the negative COVID-19 test result from a high-risk area also apply to you.You present a negative NAAT(PCR) test result of up to 72 hours old upon boarding;The test result remains valid during the transfer and possible delay. You start your journey in a high-risk area and you have a transfer in the Netherlands
You do not need to be able to show a negative NAAT(PCR) test result or rapid test result upon arrival in the Netherlands. A transfer is understood to mean: traveling on directly, within a few hours, but no later than 1 day, without leaving the transfer point. Conclusion
This is a welcomed change, and it has been rather unusual that the transit point may have required you to have a PCR-RT test when the destination country doesn't, and this has even included intra-Schengen and EU/EEA travel.
Now that the EU is opening up for first internal travel and later for more widespread international visitors, having a PCR-RT test requirement for merely a transit would have disadvantaged Netherlands, Schiphol, and KLM over other countries and airlines.
I had to take an unnecessary PCR-RT test in Barcelona last month (read more here) when I was transiting the Netherlands to Mexico City. I am back at Schiphol in four weeks and need to check a couple of days before the entry requirements to Spain and Greece and whether I need another test or two.
Trump
Are the Military and Trump in control? '' News With Views
Wed, 02 Jun 2021 13:20
Dr. Laurie Roth, Ph.D
I just got off the phone with a high up and trusted, military source I know. He comfirmed a few things for me.
Regarding, the speculation/confusion as to whether President Trump signed the Insurrection Act or not, he did. He signed it on Jan 14th, 2021. The act of signing it immediately gave him 2 more months as President according to the very directives of the Act itself. I was then told that the military gave him 2 more months as President. The second extension was over on May 20th and most likely extended again by the military who is now in control per the signed Insurrection Act.
Now, with Manhattan Attorney Cy Vance convening a Grand Jury against President Trump, regarding his taxes and business practices, the Trump which hunt continues. The only problem they may have is that they cannot arrest a sitting President and I am assured that he still is President. Once again, the liberal, legal crazies are desperately trying all they can to stop Trump.
It was confirmed today that many Generals approached Trump to run for office to take out the deep state, criminal cabal. They have been making arrests since the Biden '' fake inauguration. The military support is all around Trump and continues under the Insurrection Act.
I was told that the military goes through the FISA court and already did their own investigation, determining that there was international and domestic voter fraud They have long known the real election and voting numbers and have acted accordingly.
Our military is bound by the constitution, their duty and the signed insurrection act to be in control, do what they have to do, make arrests and make things right. They are supporting a new election in August and the return of President Trump . I am told he will be returning very soon.
My source shared much more with me that gave me real hope that justice was unfolding in a big way and the truth would soon come out in spite of the sellout media and ego-laden politicians.
Hold on to your hat. Pray for President Trump and our military as the truth really comes out.
God bless America.
(C) 2021 Laurie Roth '' All Rights Reserved
E-Mail Laurie Roth: drljroth@aol.com
Dr. Laurie Roth earned a black belt in Tae Kwon Do. In the late 90's, Laurie hosted and produced a successful PBS television show called "CD Highway" that aired nationally on 130 TV stations.Tune in to The Roth Show, Weeknights from 7:00 to 10:00 pm PAC and find out for yourself! You can listen live on cable radio network (live on the internet) channel 6 or visit The Roth Show web site and click on "where to listen" www.therothshow.com Call the Roth Show at: 1-866-388-9093 E-Mail: Rsintaro@aol.com
Insurrection Act of 1807 - Wikipedia
Wed, 02 Jun 2021 13:19
United States law
The Insurrection Act of 1807 is a United States federal law[1] that empowers the President of the United States to deploy U.S. military and federalized National Guard troops within the United States in particular circumstances, such as to suppress civil disorder, insurrection, or rebellion.
The act provides a "statutory exception" to the Posse Comitatus Act of 1878, which limits the use of military personnel under federal command for law enforcement purposes within the United States.[2][3]
Before invoking the powers under the Act, 10 U.S.C. § 254 requires the President to first publish a proclamation ordering the insurgents to disperse. As part of the Posse Comitatus Act of 1878, these provisions are now codified as amended.
There are Constitutional exceptions to Posse Comitatus restrictions rooted in the President's own constitutional authority. Defense Department guidelines describe "homeland defense" as a "constitutional exception" to Posse Comitatus restriction, meaning that measures necessary to guarantee National Security from external threats are not subject to the same limitations.
Purpose and content [ edit ] The Act empowers the U.S. president to call into service the U.S. Armed Forces and the National Guard:
when requested by a state's legislature, or governor if the legislature cannot be convened, to address an insurrection against that state (§ 251),to address an insurrection, in any state, which makes it impracticable to enforce the law (§ 252), orto address an insurrection, domestic violence, unlawful combination or conspiracy, in any state, which results in the deprivation of constitutionally secured rights, and where the state is unable, fails, or refuses to protect said rights (§ 253).The 1807 Act replaced the earlier Calling Forth Act of 1792, which had allowed for federalization of state militias, with similar language that allowed either for federalization of state militias or use of the regular armed forces in the case of rebellion against a state government.[4]: 60
The 1807 Act has been modified twice. In 1861, a new section was added allowing the federal government to use the National Guard and armed forces against the will of the state government in the case of "rebellion against the authority of the government of the United States," in anticipation of continued unrest after the Civil War.[5] In 1871, the Third Enforcement Act revised this section (§ 253) to protect Black Americans from attacks by the Ku Klux Klan. The language added at that time allows the federal government to use the act to enforce the Equal Protection Clause of the Fourteenth Amendment to the United States Constitution.[4]: 63''64 This section of the act was invoked during the Reconstruction era, and again during desegregation fights during the Civil Rights Era.[6]
The chief clause of the Insurrection Act, in its original 1807 wording (which has been thoroughly updated since to reflect modern legalese), reads:[7]
An Act authorizing the employment of the land and naval forces of the United States, in cases of insurrectionsBe it enacted by the Senate and House of Representatives of the United States of America in Congress assembled, That in all cases of insurrection, or obstruction to the laws, either of the United States, or of any individual state or territory, where it is lawful for the President of the United States to call forth the militia for the purpose of suppressing such insurrection, or of causing the laws to be duly executed, it shall be lawful for him to employ, for the same purposes, such part of the land or naval force of the United States, as shall be judged necessary, having first observed all the pre-requisites of the law in that respect.[8][9]
In 2016, Public Law 114-328 was amended to include Guam and the US Virgin Islands under Ch. 13 jurisdiction. §252: "Use of militia and armed forces to enforce Federal authority" currently reads:
Whenever the President considers that unlawful obstructions, combinations, or assemblages, or rebellion against the authority of the United States, make it impracticable to enforce the laws of the United States in any State by the ordinary course of judicial proceedings, he may call into Federal service such of the militia of any State, and use such of the armed forces, as he considers necessary to enforce those laws or to suppress the rebellion.[10][7]
Application [ edit ] The Insurrection Act has been invoked throughout American history. In the 19th century, it was invoked during conflicts with Native Americans. In the late 19th and early 20th centuries, it was invoked during labor conflicts. Later in the 20th century, it was used to enforce federally mandated desegregation,[11] with Presidents Dwight D. Eisenhower and John F. Kennedy invoking the Act in opposition to the affected states' political leaders to enforce court-ordered desegregation.[12] More recently, governors have requested and received support following looting in the aftermath of Hurricane Hugo in 1989 and during the 1992 Los Angeles riots.[13]
In 2006, the George W. Bush administration considered intervening in the state of Louisiana's response to Hurricane Katrina despite the refusal from Louisiana's governor, but this was inconsistent with past precedent, politically difficult, and potentially unconstitutional.[4]: 73''75 A provision of the John Warner National Defense Authorization Act for Fiscal Year 2007, added by an unidentified sponsor, amended the Insurrection act to permit military intervention without state consent, in case of an emergency that hindered the enforcement of laws.[2] Bush signed this amendment into law, but some months after it was enacted, all fifty state governors issued a joint statement against it, and the changes were repealed in January 2008.[2]
On June 1, 2020, President Donald Trump warned that he would invoke the Act in response to the George Floyd protests following the murder of George Floyd.[14][15][16] In his official statement, Trump urged "every governor to deploy the National Guard in sufficient numbers" to re-establish civil law and order "until the violence has been quelled".[17]
Invocations [ edit ] Date of invocationInvoking PresidentState requested?Affected areaOccasionApril 19, 1808Thomas JeffersonLake ChamplainEmbargo Act violations[12]August 23, 1831Andrew JacksonYesNorfolk, VirginiaNat Turner's slave rebellion[18]January 28, 1834Andrew JacksonYesWilliamsport, MarylandLabor dispute by workers on Chesapeake and Ohio Canal[19]April 15, 1861Abraham LincolnSouth Carolina, Georgia, Alabama, Florida, Mississippi, Louisiana, Texas, Virginia, North Carolina, Tennessee, and ArkansasCivil war[20]October 17, 1871Ulysses S. GrantNoSouth CarolinaSuppression of Ku Klux Klan[21]September 15, 1872Ulysses S. GrantNoNew Orleans, LouisianaUnrest following 1872 Louisiana gubernatorial election[22]May 13, 1874Ulysses S. GrantYesLittle Rock, ArkansasBrooks''Baxter War [23]October 7, 1878Rutherford B. HayesYesLincoln County, New Mexico TerritoryLincoln County War[24]July 7, 1894Grover ClevelandYesChicago, IllinoisPullman Strike[25][26]April 28, 1914Woodrow WilsonYesColoradoColorado Coalfield War[27]July 28, 1932Herbert HooverYesWashington, D.C.Conflict with Bonus Army[28]July 22, 1943Franklin D. RooseveltYesDetroit, Michigan1943 Detroit race riot[29]September 24, 1957Dwight D. EisenhowerNoLittle Rock, ArkansasTo protect Little Rock Nine[30]September 30, 1962John F. KennedyNoOxford, MississippiOle Miss riot of 1962[12]: 13 June 11, 1963John F. KennedyNoTuscaloosa, AlabamaStand in the Schoolhouse Door[31]September 10, 1963John F. KennedyNoAlabamaEnforce desegregation orders on Alabama public schools[12]March 20, 1965Lyndon B. JohnsonYesAlabamaProvide protection to marchers during the Selma to Montgomery Marches[32] [33]July 24, 1967Lyndon B. JohnsonYesDetroit, Michigan1967 Detroit riot[34]April 5, 1968Lyndon B. JohnsonYesWashington, D.C.1968 Washington, D.C., riots[35]April 7, 1968Lyndon B. JohnsonYesBaltimore, MarylandBaltimore riot of 1968[36]April 7, 1968Lyndon B. JohnsonYesChicago, Illinois1968 Chicago riots[37]September 20, 1989George H. W. BushYesSaint Croix, United States Virgin IslandsDisorder following Hurricane Hugo[38]May 1, 1992George H. W. BushYesLos Angeles County, California1992 Los Angeles riots[39]See also [ edit ] Martial law in the United StatesList of national emergencies in the United StatesReferences [ edit ] ^ (10 U.S.C. §§ 251''255; prior to 2016, 10 U.S.C. §§ 331''335; amended 2006, 2007) ^ a b c Hoffmeister, Thaddeus (2010). "An Insurrection Act for the Twenty-First Century". Stetson Law Review. 39: 898. Once finalized, the Enforcement Act was quietly tucked into a large defense authorization bill: the John Warner Defense Authorization Act of 2007. Very few people, including many members of Congress who voted on the larger defense bill, actually knew they were also voting to modify the Insurrection Act. The secrecy surrounding the Enforcement Act was so pervasive that the actual sponsor of the new legislation remains unknown to this day. ^ Magsamen, Kelly (June 12, 2020). "4 Ways Congress Can Amend the Insurrection Act". Center for American Progress . Retrieved June 18, 2020 . ^ a b c Banks, William C. (2009). "Providing Supplemental Security '' The Insurrection Act and the Military Role in Responding to Domestic Crises" (PDF) . Journal of National Security Law & Policy. 3. Archived (PDF) from the original on August 8, 2017 . Retrieved June 2, 2020 . ^ Coakley, Robert (1988). The role of federal military forces in domestic disorders: 1789''1878. Washington: Center of Military History, US Army. p. 228. ^ "The Posse Comitatus Act and Related Matters: The Use of the Military to Execute Civilian Law" (PDF) . Congressional Research Service. 2018. Archived (PDF) from the original on June 2, 2020 . Retrieved June 2, 2020 . ^ a b Moore, Cortney (June 1, 2020). "What is the Insurrection Act?". FOXBusiness . Retrieved June 18, 2020 . ^ Ninth Congress. Sees. H. Ch. 37, 39, 40, 41. 1807. ^ "What Is The Insurrection Act That Trump Is Threatening To Invoke?". NPR.org . Retrieved June 18, 2020 . ^ "[USC02] 10 USC Ch. 13: Insurrection". uscode.house.gov . Retrieved June 18, 2020 . ^ Hauser, Christine (June 2, 2020). "What Is the Insurrection Act of 1807, the Law Behind Trump's Threat to States?". The New York Times. ISSN 0362-4331. Archived from the original on June 3, 2020 . Retrieved June 3, 2020 . ^ a b c d Beckler, Mark M. (2008). Insurrection Act Restored: States Likely to Maintain Authority Over National Guard in Domestic Emergencies (PDF) . Fort Leavenworth, Kansas: School of Advanced Military Studies United States Army Command and General Staff College. Archived (PDF) from the original on June 2, 2020 . Retrieved June 2, 2020 . ^ Elsea, Jennifer K. (August 14, 2006). "The Use of Federal Troops for Disaster Assistance: Legal Issues" (PDF) . Congressional Research Service. Archived (PDF) from the original on June 2, 2020 . Retrieved June 1, 2020 . ^ "Trump says he will deploy military if state officials can't contain protest violence". NBC News. Archived from the original on June 3, 2020 . Retrieved June 2, 2020 . ^ Carney, Jordain (June 1, 2020). "Cotton: Trump should use Insurrection Act to deploy active-duty military to cities". The Hill. Archived from the original on June 3, 2020 . Retrieved June 2, 2020 . ^ MDParadis (June 3, 2020). "Can Trump Use the Insurrection Act to Deploy Troops to American Streets?". Lawfare . Retrieved June 18, 2020 . ^ "Statement by the President". whitehouse.gov . Retrieved June 18, 2020 '' via National Archives. ^ Coakley, Robert (1988). The role of federal military forces in domestic disorders : 1789''1878. Washington: Center of Military History, US Army. p. 93. ^ Coakley, Robert (1988). The role of federal military forces in domestic disorders : 1789''1878. Washington: Center of Military History, US Army. p. 93. ^ "A Proclamation" (PDF) . ^ Coakley, Robert (1988). The role of federal military forces in domestic disorders : 1789''1878. Washington: Center of Military History, US Army. p. 312. ^ Coakley, Robert (1988). The role of federal military forces in domestic disorders : 1789''1878. Washington: Center of Military History, US Army. p. 326. ^ Coakley, Robert (1988). The role of federal military forces in domestic disorders : 1789''1878. Washington: Center of Military History, US Army. p. 333. ^ Laurie; Cole (1997). The Role of Federal Military Forces in Domestic Disorders, 1877''1945. Washington: Center of Military History, United States Army. p. 68. ^ Eric Arnesen (2004). The Human Tradition in American Labor History. Rowman & Littlefield. p. 96. ISBN 978-0842029872. Archived from the original on April 24, 2016. ^ Laurie; Cole (1997). The Role of Federal Military Forces in Domestic Disorders, 1877''1945. Washington: Center of Military History, United States Army. p. 138. ^ Laurie; Cole (1997). The Role of Federal Military Forces in Domestic Disorders, 1877''1945. Washington: Center of Military History, United States Army. p. 208. ^ Laurie; Cole (1997). The Role of Federal Military Forces in Domestic Disorders, 1877''1945. Washington: Center of Military History, United States Army. p. 374. ^ Laurie; Cole (1997). The Role of Federal Military Forces in Domestic Disorders, 1877''1945. Washington: Center of Military History, United States Army. p. 414. ^ Scheips (2012). The Role of Federal Military Forces in Domestic Disorders, 1945''1992. Washington: Center of Military History. p. 46. ^ Scheips (2012). The Role of Federal Military Forces in Domestic Disorders, 1945''1992. Washington: Center of Military History. p. 150. ^ "Executive Order 11207 '' Providing Federal Assistance in the State of Alabama | The American Presidency Project". www.presidency.ucsb.edu . Retrieved July 28, 2020 . ^ Scheips, Paul (2012). The Role of Federal Military Forces in Domestic Disorders, 1945''1992. Center of Military History, U.S. Army. p. 163. ^ Scheips (2012). The Role of Federal Military Forces in Domestic Disorders, 1945''1992. Washington: Center of Military History. p. 46. ^ Scheips (2012). The Role of Federal Military Forces in Domestic Disorders, 1945''1992. Washington: Center of Military History. p. 284. ^ Scheips. The role of Federal Military Forces in Domestic Disorders, 1945''1992. United States Army Center of Military History. p. 333. ^ Janson, Donald (April 7, 1968). "MORE SOLDIERS SENT TO CONTROL WASHINGTON AND CHICAGO RIOTS;; 5,000 Troops Are Flown To Chicago for Riot Duty 5,000 U.S. Troops Sent as Chicago Riots Spread; Death Toll Is 9, and 300 Are Hurt A YOUTH CURFEW ORDERED BY DALEY 7,500 Guard Troops Help to Patrol the City '' 800 Persons Seized". The New York Times. Archived from the original on June 3, 2020 . Retrieved June 1, 2020 . ^ Scheips (2012). The Role of Federal Military Forces in Domestic Disorders, 1945''1992. Washington: Center of Military History. p. 441. ^ "Operation Garden Plot, JTF-LA Joint Task Force Los Angeles". GlobalSecurity.org. Archived from the original on December 28, 2019 . Retrieved June 1, 2020 . External links [ edit ] Proclamation 157 '' Declaring that Peace, Order, Tranquillity, and Civil Authority Now Exists in and Throughout the Whole of the United States of America (20 August 1866)Proclamation On The Embargo '' President Thomas Jefferson (19 April 1808)Proclamation 3204 '' Obstruction of Justice in the State of Arkansas, President Dwight Eisenhower (invoking the Insurrection Act to send troops to Little Rock, Arkansas, to enforce school desegregation orders)(23 September 1957)Executive Order 11,053 '' Providing Assistance for the Removal of Unlawful Obstructions of Justice in the State of Mississippi, President John F. Kennedy (September 30, 1962)"The Posse Comitatus Act and Related Matters: The Use of the Military to Execute Civilian Law," Updated November 6, 2018, Congressional Research Service. https://fas.org/sgp/crs/natsec/R42659.pdf
Noodle Gun
Bill gates common core
AGENDER - A Guide to Understanding Gender Identity and Pronouns : NPR
Thu, 03 Jun 2021 11:47
"Pronouns are basically how we identify ourselves apart from our name. It's how someone refers to you in conversation," says Mary Emily O'Hara, a communications officer at GLAAD. "And when you're speaking to people, it's a really simple way to affirm their identity." Kaz Fantone for NPR hide caption
toggle caption Kaz Fantone for NPR "Pronouns are basically how we identify ourselves apart from our name. It's how someone refers to you in conversation," says Mary Emily O'Hara, a communications officer at GLAAD. "And when you're speaking to people, it's a really simple way to affirm their identity."
Kaz Fantone for NPR Issues of equality and acceptance of transgender and nonbinary people '-- along with challenges to their rights '-- have become a major topic in the headlines. These issues can involve words and ideas and identities that are new to some.
That's why we've put together a glossary of terms relating to gender identity. Our goal is to help people communicate accurately and respectfully with one another.
Proper use of gender identity terms, including pronouns, is a crucial way to signal courtesy and acceptance. Alex Schmider, associate director of transgender representation at GLAAD, compares using someone's correct pronouns to pronouncing their name correctly '' "a way of respecting them and referring to them in a way that's consistent and true to who they are."
Glossary of gender identity termsThis guide was created with help from GLAAD. We also referenced resources from the National Center for Transgender Equality, the Trans Journalists Association, NLGJA: The Association of LGBTQ Journalists, Human Rights Campaign, InterAct and the American Psychological Association. This guide is not exhaustive, and is Western and U.S.-centric. Other cultures may use different labels and have other conceptions of gender.
One thing to note: Language changes. Some of the terms now in common usage are different from those used in the past to describe similar ideas, identities and experiences. Some people may continue to use terms that are less commonly used now to describe themselves, and some people may use different terms entirely. What's important is recognizing and respecting people as individuals.
Jump to a term: Sex, gender, gender identity, gender expression, cisgender, transgender, nonbinary, agender, gender-expansive, gender transition, gender dysphoria, sexual orientation, intersex
Jump to Pronouns: questions and answers
Sex refers to a person's biological status and is typically assigned at birth, usually on the basis of external anatomy. Sex is typically categorized as male, female or intersex.
Gender is often defined as a social construct of norms, behaviors and roles that varies between societies and over time. Gender is often categorized as male, female or nonbinary.
Gender identity is one's own internal sense of self and their gender, whether that is man, woman, neither or both. Unlike gender expression, gender identity is not outwardly visible to others.
For most people, gender identity aligns with the sex assigned at birth, the American Psychological Association notes. For transgender people, gender identity differs in varying degrees from the sex assigned at birth.
Gender expression is how a person presents gender outwardly, through behavior, clothing, voice or other perceived characteristics. Society identifies these cues as masculine or feminine, although what is considered masculine or feminine changes over time and varies by culture.
Cisgender, or simply cis, is an adjective that describes a person whose gender identity aligns with the sex they were assigned at birth.
Transgender, or simply trans, is an adjective used to describe someone whose gender identity differs from the sex assigned at birth. A transgender man, for example, is someone who was listed as female at birth but whose gender identity is male.
Cisgender and transgender have their origins in Latin-derived prefixes of "cis" and "trans" '-- cis, meaning "on this side of" and trans, meaning "across from" or "on the other side of." Both adjectives are used to describe experiences of someone's gender identity.
Nonbinary is a term that can be used by people who do not describe themselves or their genders as fitting into the categories of man or woman. A range of terms are used to refer to these experiences; nonbinary and genderqueer are among the terms that are sometimes used.
Agender is an adjective that can describe a person who does not identify as any gender.
Gender-expansive is an adjective that can describe someone with a more flexible gender identity than might be associated with a typical gender binary.
Gender transition is a process a person may take to bring themselves and/or their bodies into alignment with their gender identity. It's not just one step. Transitioning can include any, none or all of the following: telling one's friends, family and co-workers; changing one's name and pronouns; updating legal documents; medical interventions such as hormone therapy; or surgical intervention, often called gender confirmation surgery.
Gender dysphoria refers to psychological distress that results from an incongruence between one's sex assigned at birth and one's gender identity. Not all trans people experience dysphoria, and those who do may experience it at varying levels of intensity.
Gender dysphoria is a diagnosis listed in the Diagnostic and Statistical Manual of Mental Disorders. Some argue that such a diagnosis inappropriately pathologizes gender incongruence, while others contend that a diagnosis makes it easier for transgender people to access necessary medical treatment.
Sexual orientation refers to the enduring physical, romantic and/or emotional attraction to members of the same and/or other genders, including lesbian, gay, bisexual and straight orientations.
People don't need to have had specific sexual experiences to know their own sexual orientation. They need not have had any sexual experience at all. They need not be in a relationship, dating or partnered with anyone for their sexual orientation to be validated. For example, if a bisexual woman is partnered with a man, that does not mean she is not still bisexual.
Sexual orientation is separate from gender identity. As GLAAD notes, "Transgender people may be straight, lesbian, gay, bisexual or queer. For example, a person who transitions from male to female and is attracted solely to men would typically identify as a straight woman. A person who transitions from female to male and is attracted solely to men would typically identify as a gay man."
Intersex is an umbrella term used to describe people with differences in reproductive anatomy, chromosomes or hormones that don't fit typical definitions of male and female.
Intersex can refer to a number of natural variations, some of them laid out by InterAct. Being intersex is not the same as being nonbinary or transgender, which are terms typically related to gender identity.
Pronouns: questions and answersWhat is the role of pronouns in acknowledging someone's gender identity?
Everyone has pronouns that are used when referring to them '' and getting those pronouns right is not exclusively a transgender issue.
"Pronouns are basically how we identify ourselves apart from our name. It's how someone refers to you in conversation," says Mary Emily O'Hara, a communications officer at GLAAD. "And when you're speaking to people, it's a really simple way to affirm their identity."
"So, for example, using the correct pronouns for trans and nonbinary youth is a way to let them know that you see them, you affirm them, you accept them and to let them know that they're loved during a time when they're really being targeted by so many discriminatory anti-trans state laws and policies," O'Hara says.
"It's really just about letting someone know that you accept their identity. And it's as simple as that."
Getting the words right is about respect and accuracy, says Rodrigo Heng-Lehtinen, deputy executive director of the National Center for Transgender Equality. Kaz Fantone for NPR hide caption
toggle caption Kaz Fantone for NPR Getting the words right is about respect and accuracy, says Rodrigo Heng-Lehtinen, deputy executive director of the National Center for Transgender Equality.
Kaz Fantone for NPR What's the right way to find out a person's pronouns?
Start by giving your own '' for example, "My pronouns are she/her."
"If I was introducing myself to someone, I would say, 'I'm Rodrigo. I use him pronouns. What about you?' " says Rodrigo Heng-Lehtinen, deputy executive director of the National Center for Transgender Equality.
O'Hara says, "It may feel awkward at first, but eventually it just becomes another one of those get-to-know-you questions."
Should people be asking everyone their pronouns? Or does it depend on the setting?
Knowing each other's pronouns helps you be sure you have accurate information about another person.
How a person appears in terms of gender expression "doesn't indicate anything about what their gender identity is," GLAAD's Schmider says. By sharing pronouns, "you're going to get to know someone a little better."
And while it can be awkward at first, it can quickly become routine.
Heng-Lehtinen notes that the practice of stating one's pronouns at the bottom of an email or during introductions at a meeting can also relieve some headaches for people whose first names are less common or gender ambiguous.
"Sometimes Americans look at a name and are like, 'I have no idea if I'm supposed to say he or she for this name' '-- not because the person's trans, but just because the name is of a culture that you don't recognize and you genuinely do not know. So having the pronouns listed saves everyone the headache," Heng-Lehtinen says. "It can be really, really quick once you make a habit of it. And I think it saves a lot of embarrassment for everybody."
Might some people be uncomfortable sharing their pronouns in a public setting?
Schmider says for cisgender people, sharing their pronouns is generally pretty easy '' so long as they recognize that they have pronouns and know what they are. For others, it could be more difficult to share their pronouns in places where they don't know people.
But there are still benefits in sharing pronouns, he says. "It's an indication that they understand that gender expression does not equal gender identity, that you're not judging people just based on the way they look and making assumptions about their gender beyond what you actually know about them."
How is "they" used as a singular pronoun?
"They" is already commonly used as a singular pronoun when we are talking about someone, and we don't know who they are, O'Hara notes. Using they/them pronouns for someone you do know simply represents "just a little bit of a switch."
"You're just asking someone to not act as if they don't know you, but to remove gendered language from their vocabulary when they're talking about you," O'Hara says.
"I identify as nonbinary myself and I appear feminine. People often assume that my pronouns are she/her. So they will use those. And I'll just gently correct them and say, hey, you know what, my pronouns are they/them just FYI, for future reference or something like that," they say.
O'Hara says their family and friends still struggle with getting the pronouns right '-- and sometimes O'Hara struggles to remember others' pronouns, too.
"In my community, in the queer community, with a lot of trans and nonbinary people, we all frequently remind each other or remind ourselves. It's a sort of constant mindfulness where you are always catching up a little bit," they say.
"You might know someone for 10 years, and then they let you know their pronouns have changed. It's going to take you a little while to adjust, and that's fine. It's OK to make those mistakes and correct yourself, and it's OK to gently correct someone else."
What if I make a mistake and misgender someone, or use the wrong words?
Simply apologize and move on.
"I think it's perfectly natural to not know the right words to use at first. We're only human. It takes any of us some time to get to know a new concept," Heng-Lehtinen says. "The important thing is to just be interested in continuing to learn. So if you mess up some language, you just say, 'Oh, I'm so sorry,' correct yourself and move forward. No need to make it any more complicated than that. Doing that really simple gesture of apologizing quickly and moving on shows the other person that you care. And that makes a really big difference."
Why are pronouns typically given in the format "she/her" or "they/them" rather than just "she" or "they"?
The different iterations reflect that pronouns change based on how they're used in a sentence. And the "he/him" format is actually shorter than the previously common "he/him/his" format.
"People used to say all three and then it got down to two," Heng-Lehtinen laughs. He says staff at his organization was recently wondering if the custom will eventually shorten to just one pronoun. "There's no real rule about it. It's absolutely just been habit," he says.
But he notes a benefit of using he/his and she/her: He and she rhyme. "If somebody just says he or she, I could very easily mishear that and then still get it wrong."
What does it mean if a person uses the pronouns "he/they" or "she/they"?
"That means that the person uses both pronouns, and you can alternate between those when referring to them. So either pronoun would be fine '-- and ideally mix it up, use both. It just means that they use both pronouns that they're listing," Heng-Lehtinen says.
Schmider says it depends on the person: "For some people, they don't mind those pronouns being interchanged for them. And for some people, they are using one specific pronoun in one context and another set of pronouns in another, dependent on maybe safety or comfortability."
The best approach, Schmider says, is to listen to how people refer to themselves.
Why might someone's name be different than what's listed on their ID?
Heng-Lehtinen notes that there's a perception when a person comes out as transgender, they change their name and that's that. But the reality is a lot more complicated and expensive when it comes to updating your name on government documents.
"It is not the same process as changing your last name when you get married. There is bizarrely a separate set of rules for when you are changing your name in marriage versus changing your name for any other reason. And it's more difficult in the latter," he says.
"When you're transgender, you might not be able to update all of your government IDs, even though you want to," he says. "I've been out for over a decade. I still have not been able to update all of my documents because the policies are so onerous. I've been able to update my driver's license, Social Security card and passport, but I cannot update my birth certificate."
"Just because a transgender person doesn't have their authentic name on their ID doesn't mean it's not the name that they really use every day," he advises. "So just be mindful to refer to people by the name they really use regardless of their driver's license."
NPR's Danny Nett contributed to this report.
Rijksmuseum Slavery Exhibit Revisits 'Golden Age' | Smart News | Smithsonian Magazine
Wed, 02 Jun 2021 20:57
Smart News Keeping you current A Rijksmuseum exhibition explores the legacy of colonialism and misleading nature of the term ''Dutch Golden Age'' Anonymous, Enslaved Men Digging Trenches, c. 1850 (Courtesy of the Rijksmuseum) smithsonianmag.com June 1, 2021
Historians studying the Netherlands' history sometimes refer to the 17th century as the ''Dutch Golden Age.'' The term refers to an era of unprecedented wealth in the Dutch Republic, when artists such as Rembrandt van Rijn and Johannes Vermeer painted masterpieces and intellectual life flourished in cities like Amsterdam and Delft.
But this glittery phrase obscures a dark truth: Many of the republic's wealthiest residents made their fortunes through the enslavement, sale and exploitation of African people. The dissonance between the ''Golden Age'' descriptor and this horrific reality is such that in 2019, the Amsterdam Museum announced plans to remove the term from its galleries'--a major step in nationwide efforts to explain and contextualize Dutch citizens' role in the transatlantic slave trade.
Now, a major exhibition at the Rijksmuseum in Amsterdam is examining this period in all its brutality. ''Slavery,'' which debuted online last month and is set to welcome in-person visitors when the museum reopens this summer, traces the global history of colonialism through the stories of ten individuals, including those who suffered enslavement and those who profited from it.
All told, reports Daniel Boffey for the Guardian, Dutch traders enslaved and forcibly transported some 600,000 African people to the Americas and between 660,000 and 1.1 million people around the Indian Ocean during the so-called ''Golden Age.''
As Valika Smeulders, head of the museum's history department, tells Mike Corder of the Associated Press (AP), organizers aimed to create a show that emphasizes how this legacy has shaped the lives of all Dutch residents'--not just the descendants of the enslaved.
''We wanted to make the case, that this is a history that speaks to anybody in the Netherlands,'' she says. ''It belongs to all of us, so that's why we chose a personal approach.''
Speaking with Emi Eleode of the Art Newspaper, Smeulders adds that the museum also revised the wall text for about 70 objects with previously undisclosed relationships to the slave trade.
For the exhibition, curators united more than 140 artifacts that trace the history of Dutch involvement in the slave trade between the early 1600s and 1863, when the practice was outlawed in Suriname and the Antilles, per the Guardian. (At the time, the former was a Dutch plantation colony known as Surinam; the latter refers to a group of Caribbean islands, some of which were then under Dutch control.) These include items cherished by enslaved people, such as blue sparkling glass beads that were once used as currency on the Dutch island of Sint Eustatius. Local legend holds that at the moment of emancipation, people threw these beads into the ocean in an expression of joy, reports the Art Newspaper.
Curators also included works that are rarely explicitly linked to slavery: For instance, two Rembrandt portraits in the exhibition depict wealthy elites who profited from enslavement. Another display case holds a richly decorated brass collar that researchers once thought belonged to a family dog. As it turns out, the collar was actually designed to be worn by enslaved Black people who worked in some of the Netherland's wealthiest households, according to the Guardian.
Ten individual narratives anchor the show. One is the story of Wally, an enslaved man who was forced to work on a sugar plantation in Suriname in the early 18th century. In 1707, Wally fled captivity after arguing with his enslavers; later, he was recaptured, tortured and burned to death for attempting to escape.
An audio guide for the show includes the rarely heard oral history of Ma Chichi, a woman born into slavery in 1853. In the recording, which was made when she was 105 years old in 1958, Chichi relates her grandmothers' experiences living as an enslaved woman in 18th-century Cura§ao, notes the Guardian.
The show also features the story of Oopjen Coppit, the wealthy Dutch widow of Marten Soolmans, whose family owned the largest sugar refinery in Amsterdam. Per the AP, men and women enslaved in South America harvested the crops processed at the refinery under brutal conditions. In 1634, Oopjen sat for a portrait by Rembrandt, who rendered the material evidence of her slave-derived wealth in sharp detail: Pearls, lace, gold jewelry and other finery abound.
Though the exhibition focuses on individual narratives specific to Dutch colonial history, curators hope that its major themes resonate far and wide.
''Colonial history is international history that binds Europe, the transatlantic world and the world around the Indian Ocean together,'' Smeulders tells the Art Newspaper.
'' Slavery '' will be on view at the Rijksmuseum in Amsterdam through August 29. Materials from the show are available to peruse online.
Editor of JAMA Leaves After Outcry Over Colleague's Remarks on Racism - The New York Times
Wed, 02 Jun 2021 20:53
Dr. Howard Bauchner will step down after another editor suggested ''taking racism out of the conversation'' on a journal podcast.
Dr. Howard Bauchner during a C-Span appearance in September. He will step down from JAMA at the end of June. Credit... C-Span.org June 1, 2021
Following an outcry over comments about racism made by an editor at JAMA, the influential medical journal, the top editor, Dr. Howard Bauchner, will step down from his post effective June 30.
The move was announced on Tuesday by the American Medical Association, which oversees the journal. Dr. Bauchner, who had led JAMA since 2011, had been on administrative leave since March because of an ongoing investigation into comments made on the journal's podcast.
Dr. Edward Livingston, another editor at JAMA, had claimed that socioeconomic factors, not structural racism, held back communities of color. A tweet promoting the podcast had said that no physician could be racist. It was later deleted.
''I remain profoundly disappointed in myself for the lapses that led to the publishing of the tweet and podcast,'' Dr. Bauchner said in a statement. ''Although I did not write or even see the tweet, or create the podcast, as editor in chief, I am ultimately responsible for them.''
Last month, the A.M.A.'s leaders admitted to serious missteps and proposed a three-year plan to ''dismantle structural racism'' within the organization and in medicine. The announcement on Tuesday did not mention the status of the investigation at JAMA. The journal declined further comment.
''This is a real moment for JAMA and the A.M.A. to recreate themselves from a founding history that was based in segregation and racism to one that is now based on racial equity,'' said Dr. Stella Safo, a Black primary care physician at the Icahn School of Medicine at Mount Sinai in New York.
Dr. Safo and her colleagues started a petition, now signed by more than 9,000 people, that had called on JAMA to restructure its staff and hold a series of town hall conversations about racism in medicine. ''I think that this is a step in the right direction,'' she said of the announcement.
But other critics said they were withholding judgment to see how the organization addressed what they saw as pervasive neglect of covering racism's impact on health in its journals.
''In the entire history of all the JAMA network journals, there's only been one non-white editor,'' noted Dr. Raymond Givens, a cardiologist at Columbia University in New York. In October, Dr. Givens wrote to Dr. Bauchner, noting that editors at the JAMA journals were overwhelmingly white and male. Dr. Bauchner did not respond, according to Dr. Givens.
''This is not cause to celebrate,'' he said of the announcement, adding that he had not intended to jeopardize Dr. Bauchner's job. Nor will appointing a top editor of color resolve the issues, Dr. Givens said.
''Looking for just a person of color misses the point,'' he added. ''I'm more interested in a bold voice. I want somebody who is willing to take a stand, push to move things forward.''
The podcast that set the events in motion aired on Feb. 24 and did not include any Black researchers or experts on racism in medicine.
''Structural racism is an unfortunate term,'' Dr. Livingston, who is white, said on the podcast. ''Personally, I think taking racism out of the conversation will help. Many people like myself are offended by the implication that we are somehow racist.''
The podcast was promoted with a tweet from the journal that said, ''No physician is racist, so how can there be structural racism in health care?'' Following widespread protest in the medical community, the journal took down the podcast and deleted the tweet.
''Comments made in the podcast were inaccurate, offensive, hurtful and inconsistent with the standards of JAMA,'' Dr. Bauchner said in a statement released a week later. ''We are instituting changes that will address and prevent such failures from happening again.''
Dr. Livingston later resigned, and the A.M.A. placed Dr. Bauchner on administrative leave on March 25.
The JAMA family of journals added four new titles under Dr. Bauchner's leadership, and expanded to include podcasts, videos and new, shorter article types. But critics noted that the journals rarely addressed structural racism in medicine, and more often published papers linking health disparities to socioeconomic or biological factors.
Dr. Bauchner's exit offered the journals a chance to improve, said Dr. Mary Bassett, professor of the practice of health and human rights at Harvard University.
''Medical journals have helped build the racist idea that races have intrinsic differences that have a bearing on health,'' Dr. Bassett said. Journals are ''challenged to embrace, not only accept, racism as a health issue.''
Dr. Bauchner told The New York Times last month that JAMA had published ''more than 100 articles on issues such as social determinants of health, health care disparities and structural racism over just the last five years.'' He also noted that JAMA accepted only a tiny fraction of the manuscripts it had received.
He said in the statement on Tuesday that the journal would be better served by his resignation. ''The best path forward for the JAMA Network, and for me personally, is to create an opportunity for new leadership at JAMA,'' he said.
In an editorial published in JAMA on Tuesday, colleagues at the journal lauded Dr. Bauchner's leadership, saying he ''has left an indelible legacy of progress, innovation and excellence in medical journalism.''
The A.M.A. said it has begun a search for Dr. Bauchner's replacement. The journal's executive editor, Dr. Phil Fontanarosa, will serve as interim editor in chief.
Whoever the new editor may be, he or she will need to acknowledge the profound impact of structural racism on health outcomes for communities of color, Dr. Bassett said.
''Racism works in ways that are structural and not simply as the result of ignorant, misguided or even racist individuals,'' she added. ''As a new editor in chief is sought, there will be a chance for JAMA to lead in dismantling this idea. I hope they grab it.''
BTC
AMC, GameStop Bets Put Short Sellers Down More Than $3 Billion on Wednesday | Barron's
Thu, 03 Jun 2021 11:13
AMC Entertainment's market capitalization eclipsed GameStop, its peer in the so-called meme stock trade, on Wednesday. But any way you slice the incredible rallies in these stocks, short sellers betting against them are down big.
AMC stock climbed 95% to $62.55 on Wednesday, bringing its market cap to $28.17 billion. GameStop jumped 13% to $282.24, hitting a $19.97 billion market cap. Shares of both companies have rallied amid heightened short interest, options volume, and enthusiasm from retail traders.
Ihor...
AMC Entertainment 's market capitalization eclipsed GameStop , its peer in the so-called meme stock trade, on Wednesday. But any way you slice the incredible rallies in these stocks, short sellers betting against them are down big.
AMC stock climbed 95% to $62.55 on Wednesday, bringing its market cap to $28.17 billion. GameStop jumped 13% to $282.24, hitting a $19.97 billion market cap. Shares of both companies have rallied amid heightened short interest, options volume, and enthusiasm from retail traders.
Ihor Dusaniwsky, managing director at the short selling analytics firm S3 Partners, told Barron's he estimates AMC's short interest was recently at 90.87 million shares, or about 18% of shares available for trading. He pegs GameStop's short interest at 11.31 million shares or 19.8% of the float.
Dusaniwsky said short sellers betting against AMC were down $2.77 billion on Wednesday alone, bringing year-to-date losses to more than $5.22 billion. For GameStop, he estimates a loss of $375.7 million on Wednesday, and $7.15 billion in 2021.
Other meme stocks, including Bed Bath & Beyond (BBBY) and BlackBerry (BB), surged on Wednesday too.
The recent resurgence of meme stocks has once again brought mainstream attention to Wall Street. On Reddit investing forums such as WallStreetBets and AMCStock, the recent action has been celebrated as a win for the average person. But not everyone has been so enthused.
''I never would have believed it, but the recklessness of a segment of retail investors appears to have no bounds in this market,'' Whitney Tilson of Empire Financial Research wrote in a note Wednesday. ''This type of short-term rally is to be expected, and for stocks like these, this is an opportunity to add to a short or put position because it's clearly a dead-cat bounce.''
David Trainer, CEO of investment research firm New Constructs, wrote that AMC's business was trending in the wrong direction before the pandemic. Since then, he noted that AMC has diluted existing shares via millions in stock sales, adding that the stock is worthless considering its debt load and weak earnings prospects.
''The surge in shares of AMC Entertainment is yet another sign of the reckless meme stock-driven investing landscape that we find ourselves in today,'' Trainer said. ''Wall Street insiders are preying on the naivete of retail meme stock traders. There is no fundamental reason to be buying shares of AMC Entertainment.''
What's ahead for investors is anyone's guess. Calling a top for meme stocks has been a fool's errand this year. But eventually, the fundamentals will need to catch up to the valuation.
Write to Connor Smith at connor.smith@barrons.com
COVID-20-26
Explainer: So far, low risk of human spread of H10N3 bird flu | Reuters
Thu, 03 Jun 2021 11:03
Workers vaccinate chicks with the H9 bird flu vaccine at a farm in Changfeng county, Anhui province, April 14, 2013. REUTERS/Stringer/File Photo
A 41-year-old man in China's eastern province of Jiangsu has been confirmed as the first human case of infection with a rare strain of bird flu known as H10N3, Beijing's National Health Commission (NHC) has said.
The man, a resident of the city of Zhenjiang, was hospitalized on April 28 and diagnosed with H10N3 on May 28, the health commission said on Tuesday, adding that his condition is stable.
It did not give details on how the man was infected but said investigation of his close contacts found no other cases and the risk of spread was very low.
WHAT DO WE KNOW ABOUT H10N3?
Little is known about the virus, which appears to be rare in birds, according to the Food and Agriculture Organisation (FAO), and does not cause severe disease.
The World Health Organization (WHO) said while the source of the patient's exposure to the H10N3 virus was not known and no other cases were found among the local population, there was no indication of human-to-human transmission yet.
Yet avian influenza viruses that have little impact on birds can be much more serious in people, such as the H7N9 strain that killed almost 300 people in China during the winter of 2016-2017. The WHO has said there had been only rare instances of person-to-person spread of the H7N9 virus.
WHAT ARE THE RISKS?
The risk of further infection with H10N3 is currently believed to be very low, with experts describing the case as "sporadic".
Such cases occur occasionally in China which has huge populations of both farmed and wild birds of many species.
And with growing surveillance of avian influenza in the human population, more infections with bird flu viruses are being picked up.
In February, Russia reported the first human infection with the H5N8 virus that caused huge damage on poultry farms across Europe, Russia and East Asia last winter.
Seven people infected with the virus were asymptomatic, authorities said.
Experts will be on alert for any clusters of H10N3 cases, but for now, a single case is not much of a concern.
"As long as avian influenza viruses circulate in poultry, sporadic infection of avian influenza in humans is not surprising, which is a vivid reminder that the threat of an influenza pandemic is persistent," the WHO told Reuters in a statement.
The strain is "not a very common virus," and only around 160 isolates of the virus were reported in the 40 years to 2018, according to Filip Claes, regional laboratory coordinator of the FAO's Emergency Centre for Transboundary Animal Diseases at the regional office for Asia and the Pacific.
Still, flu viruses can mutate rapidly and mix with other strains circulating on farms or among migratory birds, known as "reassortment," meaning they could make genetic changes that pose a transmission threat to humans.
WHAT DO WE STILL NEED TO KNOW?
The genetic sequence of the virus that infected the patient has not yet been published, and will be needed to fully assess its risk.
Scientists will want to know how easily H10N3 can infect human cells to determine if it could become a greater risk.
For example, the H5N1 variant that first infected people in 1997 has been the most deadly, killing 455 people globally so far.
It would only take a few mutations before the H5N1 variant gains the ability to spread easily from person-to-person, said Ben Cowling, professor at the School of Public Health at the University of Hong Kong, making it a high priority for surveillance.
Having the genetic information for the H10N3 variant would help assess if it was "close to being the type of virus we should be worried about", he said.
Our Standards: The Thomson Reuters Trust Principles.
Israel
Netanyahu opponents reach coalition deal to oust Israeli PM
Thu, 03 Jun 2021 11:04
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VIDEO - Joshua Kop ðŸ‡...🇺 ðŸ‡"🇱 on Twitter: "@altern8ending ooohhh another for the collection @adamcurry" / Twitter
Thu, 03 Jun 2021 11:00
Joshua Kop ðŸ‡...🇺 ðŸ‡"🇱 : @altern8ending ooohhh another for the collection @adamcurry
Thu Jun 03 10:04:41 +0000 2021
VIDEO - Roberto Wakerell-Cruz '''¸ on Twitter: "Trudeau describes the euphoria of getting a COVID vaccine, tells Canadians to shame their ''crusty uncle who resists'' into getting their shots. What a lunatic. https://t.co/LaXhaQlyT7" / Twitter
Thu, 03 Jun 2021 04:03
Roberto Wakerell-Cruz '''¸ : Trudeau describes the euphoria of getting a COVID vaccine, tells Canadians to shame their ''crusty uncle who resists'... https://t.co/q5XfxHiZdX
Wed Jun 02 15:37:57 +0000 2021
Maverick-Visionaries : @Robertopedia Sophie Trudeau pulled a Melania Trump and refused to hold Justin's hand during the covid 19 vaccinati'... https://t.co/DnjaunNgVv
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A : @Robertopedia Can't believe these are the people who run countries
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The Immortal 🇨ðŸ‡... Christus Vincit : @Robertopedia He's taking Fentanyl for his frisbee injury.
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Jesse : @Robertopedia @TheLastRefuge2 COVID VAX SPIKE PROTEIN TOXIChttps://t.co/dOpJtCn8Lehttps://t.co/lvhIjX4UGh
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Star : @Robertopedia Vote him out already, would ya
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Dave Doleman 🇨ðŸ‡...🇨ðŸ‡...🇨ðŸ‡... : @Robertopedia Looks more like the euphoria of a nice little sativa buzz.
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BajasKSmith : @Robertopedia GFY @JustinTrudeau
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sub_commandante : @Robertopedia @TheLastRefuge2 https://t.co/rKbmaWSekI
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Vaccine Passports Are the Gateway to Fascism : @Robertopedia @TheLastRefuge2 He's a good marionette for his Davos, WEF, CoFR puppetmasters
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VIDEO - razorback1111 on Twitter: "Acting premier @JamesMerlinoMP finally speaks the truth, ''The vaccine is our Enemy '' https://t.co/U0F2e76AG6" / Twitter
Thu, 03 Jun 2021 04:02
razorback1111 : Acting premier @JamesMerlinoMP finally speaks the truth, ''The vaccine is our Enemy '' https://t.co/U0F2e76AG6
Thu Jun 03 02:31:48 +0000 2021
caterina catzella : @razorback11111 @JamesMerlinoMP so what happens when Covaxxed people start testing positive! Do these morons even t'... https://t.co/KWlYH8q6a7
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Thu Jun 03 03:07:12 +0000 2021
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Thu Jun 03 03:05:07 +0000 2021
Laura G : @razorback11111 @JamesMerlinoMP When you're continuously lying, sometimes the subconscious can rise up without warning. What a fuck up 🤣ðŸ‚
Thu Jun 03 02:56:07 +0000 2021
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Land cruiser : @razorback11111 @JamesMerlinoMP https://t.co/dKfPFvBGP8
Thu Jun 03 02:48:51 +0000 2021
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Thu Jun 03 02:47:29 +0000 2021
Aaron Ashley : @razorback11111 @JamesMerlinoMP Sucking agenda here.Incompence to think 'theres' only 1 way out of this pandemic''... https://t.co/XYajKbZGPG
Thu Jun 03 02:41:37 +0000 2021
something's fu''Œky in victoria, australia : @razorback11111 @JamesMerlinoMP Is he referring to supply, rollout or other?
Thu Jun 03 02:38:49 +0000 2021
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Thu Jun 03 02:37:12 +0000 2021
VIDEO - Sackler Family, Owner Of Purdue Pharma, Set To Win Immunity From Opioid Lawsuits : NPR
Thu, 03 Jun 2021 00:02
Members of the Sackler family who own Purdue Pharma, the maker of Oxycontin, moved a step closer to winning immunity from opioid lawsuits. Erik McGregor/LightRocket via Getty Images hide caption
toggle caption Erik McGregor/LightRocket via Getty Images Members of the Sackler family who own Purdue Pharma, the maker of Oxycontin, moved a step closer to winning immunity from opioid lawsuits.
Erik McGregor/LightRocket via Getty Images After more than a year of high stakes negotiations with billions of dollars on the line, a bankruptcy plan for Purdue Pharma, the maker of Oxycontin, cleared a major hurdle late Wednesday.
Federal Judge Robert Drain in White Plains, N.Y., moved the controversial deal forward despite objections from dozens of state attorneys general, setting the stage for a final vote by the company's creditors expected this summer.
The drug maker filed for Chapter 11 protection in 2019 facing an avalanche of lawsuits tied to its aggressive opioid sales practices.
Public health experts and many government officials say the introduction of Oxycontin fueled the nation's deadly opioid epidemic.
This development brings members of the Sackler family, some of whom own Purdue Pharma and served on the company's board of directors, a step closer to winning immunity from future opioid lawsuits.
According to legal documents filed as part of the case, that immunity would extend to dozens of family members, more than 160 financial trusts, and at least 170 companies, consultants and other entities associated with the Sacklers.
"The Sacklers are paying $4.275 billion and they very much plan and expect to be done with this chapter," said Marshall Huebner, an attorney representing Purdue Pharma, during a hearing last week.
One of the firms that would secure protection from future opioid lawsuits under the deal is Luther Strange & Associates, founded by former U.S. Sen. Luther Strange (R-Alabama) who helped Purdue Pharma pitch the bankruptcy plan to Republican state attorneys general.
While Purdue Pharma has twice pleaded guilty to federal crimes relating to its opioid marketing schemes, no member of the Sackler family has faced criminal charges.
Appearing before a congressional panel last December, members of the Sackler family said they had done nothing wrong. "The family and the board acted legally and ethically," testified David Sackler, who served on Purdue Pharma's board for six years.
In addition to contributing money from their personal fortunes, the Sacklers have agreed to give up control of Purdue Pharma. They will, however, retain ownership of other companies, admit no wrongdoing and will remain one of the wealthiest families in America.
Two dozen states still oppose the bankruptcy deal that's been negotiated largely behind closed doors. They argue it would improperly strip them of authority to sue members of the family for alleged wrongdoing.
"I don't believe ... at this point the plan is confirmable," said Andrew Troop, an attorney representing a coalition of "non-consenting" states, during a hearing last week.
But Judge Drain said this stage of the bankruptcy process wasn't focused on final approval of the plan.
Instead, the court evaluated whether Purdue Pharma and the Sacklers had provided enough information and transparency to allow creditors to make an informed decision on the deal's financial merits.
Despite a significant veil of secrecy surrounding the proceedings '-- which included an expansive investigation of the Sacklers that will likely never be made public '-- Drain signaled the so-called "disclosure statement" was adequate.
"I found the disclosure statement to contain adequate information," he said Wednesday.
Attorneys representing Purdue Pharma and other parties in the bankruptcy process said negotiations continue.
"We are mediating as we speak with the non-consenting states," Huebner said on Wednesday. "We continue to be open and listen as hard as we can to all other remaining objectors between now and confirmation."
A vote and final approval expected by August
In the coming weeks, more than 600,000 individuals, companies and governments with claims against Purdue Pharma will vote on the package, described by attorneys involved in the process as one of the most complicated and controversial bankruptcies ever.
A final confirmation hearing is scheduled for Aug. 9. Judge Drain has indicated he believes this plan offers the best chance at financial relief for those harmed by Purdue Pharma's Oxycontin business.
Supporters of the bankruptcy deal say the alternative would be a chaotic scrum of risky and expensive litigation. "Billions would be spent on legal fees," Huebner said last week. "It would be years until claimants might get a recovery."
The reorganization plan also includes a detailed formula that would be used to distribute hundreds of millions of dollars each year in aid to communities and individuals harmed by opioids.
A growing number of government officials have signaled they expect to vote in favor of the deal.
But critics, including more than 20 mostly Democratic state attorneys general, say the Sacklers are improperly piggybacking on their company's bankruptcy without actually filing for bankruptcy themselves.
"The bankruptcy system should not be allowed to shield non-bankrupt billionaires," said Massachusetts Attorney General Maura Healey in an interview with NPR last month.
More and more legal scholars have also questioned whether bankruptcy court is the proper venue for a case that involves a addiction crisis that has killed hundreds of thousands of Americans.
"[T]he most socially important chapter 11 case in history will be determined through a process that does not comport with basic notions of due process," wrote Adam Levitin, who teaches law at Georgetown University, in an article published last month in the Texas Law Review.
In a legal brief filed with the bankruptcy court on Tuesday, Jonathan Lipson, a legal scholar at Temple University who also represents a client with a claim against Purdue Pharma, noted this case is complicated by allegations of criminal conduct leveled against the Sacklers by the Justice Department last October.
"These cases have been overshadowed by a single, critical question: who is responsible for [Purdue Pharma's] confessed crimes and the harm they caused?" Lipson wrote in his motion.
Lipson requested an independent examiner be appointed to review whether the Chapter 11 process has been handled appropriately.
Again, the Sacklers have denied any wrongdoing, have never been charged with crimes. As part of their settlement with the DOJ, members of the Sackler family paid $225 million while denying the allegations.
Sackler family pushes back against "false allegations"
During last week's hearing an attorney representing the Raymond Sackler branch of the family said they have created a website designed to offer a rebuttal to critics of the Sacklers.
"Raymond Sackler family members have consistently expressed their regret that OxyContin, which continues to help patients suffering from chronic pain, unexpectedly became part of the opioid crisis," the family said in a statement.
In civil lawsuits already filed against the Sacklers, government officials allege some family members had direct knowledge of the highly addictive nature of Oxycontin but continued to push Purdue Pharma's sales team to maximize profits.
The DOJ settlement with the Sacklers also included the allegation some family members engaged in "fraudulent" transfers of wealth and approved a marketing plan that focused on pushing Oxycontin sales to "extreme, high-volume prescribers."
According to the Justice Department statement, that program led "health care providers to prescribe opioids for uses that were unsafe, ineffective, and medically unnecessary, and that often led to abuse and diversion."
The Sacklers maintain they did nothing wrong and acted ethically. If this bankruptcy plan is approved and upheld on appeal, it's unlikely the allegations will ever be tested in court.
More than 400 civil cases already filed against members of the Sackler family for alleged wrongdoing would be halted.
VIDEO - FRANTIC MSNBC Cries: How Can Feds Overturn State Election Laws? | Newsbusters
Wed, 02 Jun 2021 23:26
While most Americans were enjoying their Memorial Day weekend by spending time with family and paying tribute to our brave men and women who gave their lives for our country, MSNBC decided to continue vile and vitriolic rants against its political enemies in the Republican Party.
On Monday night, MSNBC's 11th Hour anchor Brian Williams led the segment by playing a clip of President Biden's Memorial Day speech in which he claimed ''democracy itself is in peril.'' The left-wing host then brought on a panel which consisted of New York Times Correspondent Peter Baker, Texas Tribune Washington Bureau Chief Abby Livingston, and Neal Katyal, Obama's former acting Solicitor General.
Baker started off the insanity by making the preposterous claim that American democracy is under attack in much the same way as other third world countries around the world. ''I spent four years living in Moscow, where I was a correspondent for the Washington Post,'' he recalled. Baker warned that the U.S. was no better than such authoritarian regimes: ''I traveled and reported from the Middle East, I traveled from countries all around the world, and we've seen, I think, in recent times, stories here I would have only imagined we would have covered as foreign correspondents.''
That comment is laughable on its face. Especially coming from a putative reporter who claims he's been to the Middle East, which throughout its history has seen no shortages of fraudulent elections, including not allowing women to vote.
Later in the segment, Williams wailed that the federal government should be able to cancel state election laws at will: "What power does the federal government have? What power does the Department of Justice have when states, when Republicans in legislatures are working so hard, and in some cases, passing laws signed by the governor to restrict voting?"
Not to be out done by Peter Baker, Neal Katyal decided to go even lower into the leftist sewer by claiming the Republican Party is an ''anti-democracy party.'' Katyal even decided to re-write history with this eyebrow-raising quote: ''And when the Democratic Party was named and originated, I don't think anyone thought that to be controversial, to be like, in favor of democracy. Who would be against that? But now we know, you have to view this Texas vote in light of so much else that the Republican Party has been doing, like a concerted effort in Georgia and other states to roll back voting, a slavish devotion to a filibuster that bears no relationship to the filibuster our founders knew that's totally empowering of a small minority.''
It's truly startling that Katyal's knowledge of history is so poor that he would ignore the Democratic Party's dismal legacy of supporting slavery, armed insurrection, and Jim Crow-era racism.
MSNBC can't even give the political attacks a day off. Even on a solemn occasion like Memorial Day, the far-left cable channel can't help itself.
This appalling display of left-wing media bias was brought to you by Verizon and Applebee's. Contact them at the Conservatives Fight Back page here
Read the transcript below by clicking "expand:"
The 11th Hour
5/31/2021
11:05 PM
BRIAN WILLIAMS: Peter, I would like to begin with you, given the life you have led in this country and overseas, given all the stories you have chronicled as a journalist, how bracing, how striking was it to hear an American president declare our democracy in peril on this Memorial Day 2021?
PETER BAKER [NEW YORK TIMES WHITE HOUSE CORRESPONDENT]: Well, I think what we have learned in recent times, is that the democracy we all thought was pretty well cemented is in fact fragile. The institutions, the norms, the standards, the traditions that we believed were rock solid in the United States have their vulnerabilities, just as we have seen in other countries around the world. I spent four years living in Moscow, where I was a correspondent for the Washington Post, I traveled and reported from the Middle East, I traveled from countries all around the world, and we've seen, I think, in recent times, stories here I would have only imagined we would have covered as foreign correspondents, and I think that's why you're right today had a certain poignancy because the people who fought and died to protect this country, whose memories we honor today, did so with the idea that they were, you know, defending a robust and healthy democratic system, one I think we do need to continue to protect and guard, whether it be on the battlefields or in our society today. That's why I think, one thing we all focus on today no matter what party we're in, whether in journalism or in government or politics, we give thanks for those who have stood up for us and we think about the role we ourselves have to play, making this a more perfect nation, as they say.
WILLIAMS: Abby, to Peter's last point, that somehow brings this story to you because it brings the story to Texas, and the prong of this, that Republicans in that state are busy and trying to achieve. Tell us how long Democrats can stave this off, how long can the impact from a walk-out last and what power the governor and Republicans have regarding a special session.
ABBY LIVINGSTON [WASHINGTON BUREAU CHIEF, TEXAS TRIBUNE]: Well a special session is called by the governor, otherwise he, Texas actually has an incredibly weak executive. But the how long is really not the specific question. It's when. So the governor, there will be a special session in the fall almost no matter what to count for redistricting and the census delay of that. But the Lt. Governor Dan Patrick is urging him to call one in June. So it's a matter of when did they pick it up again? In June or the fall? And it's very unlikely Democrats will in the end be able to override this. In some ways this bill could get worse for them and so it's very much up in the air but I think it did inject some enthusiasm into the state party and to national Democrats to have a cause specific on this voting rights issue to jump on to.
WILLIAMS: I want to return to this topic with you in a moment after we hear from Neal, and Neal we asked 30 different versions of this question to you and the former feds who we rely on during times like this. What power does the federal government have? What power does the Department of Justice have when states, when Republicans in legislatures are working so hard, and in some cases, passing laws signed by the governor to restrict voting?
NEAL KATYAL [FMR. ACTING SOLICITOR GENERAL UNDER OBAMA]: So before getting to that Brian. I think there is a bigger point here, there is a forest and this forest I think unites a lot of what we're talking about tonight, not just Texas, and this state but the January 6th commission, Biden's remarks you just averted to, and the name of it is the Republican Party has become an anti-democracy party. And when the Democratic Party was named and originated, I don't think anyone thought that to be controversial, to be like, in favor of democracy. Who would be against that? But now we know, you have to view this Texas vote in light of so much else that the Republican Party has been doing, like a concerted effort in Georgia and other states to roll back voting, a slavish devotion to a filibuster that bears no relationship to the filibuster our founders knew that's totally empowering of a small minority. You've got a party who's scared, you know, heaven forbid to have people vote in Washington, D.C. and Puerto Rico. You've got a party who's hellbent on getting their nominees to the Supreme Court to strike down legislation that they don't like, that's been passed by a majority of people. This is an anti-majority party in the end, and it's a collapsed party. It's a party that lost its moral ground. Ah, you know, It's like the USSR in the Cold War. Yes, they've bluster and strength and insults but they don't have any purpose anymore. And to answer your question, because of the Supreme Court decision in 2013, the federal government is fairly limited in the powers it has. I argued the case in 2009 that saved that part of the Voting Rights Act, but it was reversed in 2013 by a five to four vote. And so right now, pending in Congress is the John Lewis Voting Rights Act which would restore that act. So when Texas tries to pass a bill like this, it would require pre-clearance in Washington, D.C. by a court or by the Justice Department. That's the way stuff operated since 1965 but now it isn't because of that new Supreme Court decision. So we need that law passed. Without it I do fear we will have more and more antics like this from a party that is bent on these antics.
VIDEO - (263) Watch Brianna Keilar eat dead cicadas on live TV - YouTube
Wed, 02 Jun 2021 22:31
VIDEO - (263) The Blue's Clues Pride Parade ðŸ"¸'ðŸŒ Sing-Along Ft. Nina West! - YouTube
Wed, 02 Jun 2021 22:20
VIDEO - kingbaal: "now we better understand who and why Beirut port '..." - No Agenda Social
Wed, 02 Jun 2021 21:47
@ kingbaal @ adam @ Johncdvorak Well, when I was in Lebanon, they weren't too happy that Israel was stealing their oil reserves off their coastline. So I would peg it more to Israel.
VIDEO - (262) Help kids learn that bodies are private [with Scoops & Friends] - YouTube
Wed, 02 Jun 2021 19:20
VIDEO - Dr. McCullough Sounds the Alarm on Covid Jabs: All Covid-19 Vaccines Produce the Dangerous Wuhan Spike Protein (AUDIO)
Wed, 02 Jun 2021 18:25
Dr. Peter A. McCullough sounded the alarm on the Covid-19 vaccines and explained how they all make the dangerous Wuhan spike protein.
Dr. McCullough is an Internist, Cardiologist, Epidemiologist and testified to the Senate Committee on Homeland Security and Governmental Affairs in November 2020.
''It's alarming right now '' we have had over 4400 deaths and 14,000 hospitalizations'....That is probably only the tip of the iceberg,'' Dr. McCullough said in an interview with Rose Unplugged on 1320 AM WJAS.
Dr. McCullough said people who have been infected with Covid-19 should not get the vaccine.
TRENDING: HAPPENING NOW: Pennsylvania Legislative Delegation Sits Down with Arizona Lawmakers to Discuss Election Integrity And Replicating the Audit
The doctor also said pregnant women, women of child-bearing years, children or healthy people under 50 should not get the Covid jab.
Dr. McCullough explained how all Covid-19 vaccines produce the dangerous Wuhan spike protein and what that does to a person's body.
AUDIO:
Check out Rose Unplugged on WJAS 1320 AM '' The Talk of Pittsburgh 1320 AM
DOCTOR SOUNDS THE ALARM ON COVID JABS https://t.co/75fp5szJW6
'-- roseunplugged (@roseunplugged2) June 2, 2021
VIDEO - Mark Stevens on Twitter: "Yep, this is serious. Don't touch that ball! Adelaide's Covid Sherrin crackdown. '...@7NewsMelbourne'(C) @7afl https://t.co/8BvnU0kHUB" / Twitter
Wed, 02 Jun 2021 18:24
Mark Stevens : Yep, this is serious.Don't touch that ball!Adelaide's Covid Sherrin crackdown.'...@7NewsMelbourne'(C) @7afl https://t.co/8BvnU0kHUB
Wed Jun 02 05:48:48 +0000 2021
saffyishere : @Stevo7AFL @7NewsMelbourne @7AFL I suggest if there's so much concern , don't let spectators into the ground!
Wed Jun 02 16:39:46 +0000 2021
MechaRandom42, Professional Smart-A$$🉠: @Stevo7AFL @7NewsMelbourne @7AFL Most people who go out in public have already been vaxxed or don't care about germ'... https://t.co/nq0clbm8rh
Wed Jun 02 16:26:25 +0000 2021
Praz Silva : @Stevo7AFL @7NewsMelbourne @7AFL ðŸ
Wed Jun 02 16:25:08 +0000 2021
Craig Taylor : @Stevo7AFL @7NewsMelbourne @7AFL This is the same govt thought that you could receive the coronavirus off a pizza box!
Wed Jun 02 15:28:04 +0000 2021
Footy Head : @Stevo7AFL @7NewsMelbourne @7AFL I have watched this about 10 times today and laughed just as hard every time 🂠https://t.co/t8WG0da8tn
Wed Jun 02 15:24:01 +0000 2021
KGS : @Stevo7AFL @7NewsMelbourne @7AFL The high paid brainpower making the decisions'... amazing advice'...
Wed Jun 02 15:08:05 +0000 2021
Robert Brown : @Stevo7AFL @7NewsMelbourne @7AFL The dumbest thing I've ever heard a smart person say ðŸ‚👍
Wed Jun 02 14:42:42 +0000 2021
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Wed Jun 02 14:28:10 +0000 2021
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Wed Jun 02 14:26:53 +0000 2021
Simon Phoenix : @Stevo7AFL @7NewsMelbourne @7AFL I hope the players deliberately kick as many as they can out on the full
Wed Jun 02 14:24:10 +0000 2021
Tomer Cooks : @Stevo7AFL @7NewsMelbourne @7AFL O c'mon, even satirical clips should be reliable. This one is obviously too much
Wed Jun 02 14:20:37 +0000 2021
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Wed Jun 02 14:08:35 +0000 2021
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Anthony Anf Brown : @Stevo7AFL @7NewsMelbourne @7AFL Sums up Adelaide's take on this Pandemic!
Wed Jun 02 14:04:53 +0000 2021
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Wed Jun 02 14:03:34 +0000 2021
VIDEO - CNBC on Twitter: "Leon Black will retire as CEO of Apollo Global Management by the end of July, but will remain chairman. @LesliePicker has the details. https://t.co/3EiZt5R8rn https://t.co/NDKeZv0cF0" / Twitter
Wed, 02 Jun 2021 18:13
CNBC : Leon Black will retire as CEO of Apollo Global Management by the end of July, but will remain chairman.'... https://t.co/pRCi7v0WjQ
Mon Jan 25 21:56:40 +0000 2021
VIDEO - (262) Anti-Biden flags with profanity going up in the front yards of homes in Cape Coral - YouTube
Wed, 02 Jun 2021 18:01
VIDEO - BREKKIE VON BITCOIN 2021 on Twitter: "@skwp @nntaleb It's never too late to apologize @nntaleb https://t.co/owtwByXQa4" / Twitter
Wed, 02 Jun 2021 16:58
BREKKIE VON BITCOIN 2021 : @skwp @nntaleb It's never too late to apologize @nntaleb https://t.co/owtwByXQa4
Mon May 31 05:00:28 +0000 2021
VIDEO - Shooting in Springfield, Virginia: Police searching for suspects | wusa9.com
Wed, 02 Jun 2021 13:41
Ronnie Marshall, 20, and D'Angelo Strand, 19, are both facing two counts of second-degree murder and two counts of use of a firearm in a commission of a felony.
SPRINGFIELD, Va. '-- Fairfax County Police say two suspects are now in custody in connection with the murder of a husband and wife, both military veterans, in Springfield. Fairfax County Police Chief Kevin Davis said the victims were "viciously shot and killed up close at point-blank range" on their front lawn Wednesday morning.
On Thursday, Fairfax County police released a photo of one of the men responsible: 20-year-old Ronnie Keandre Marshall. The other suspect that was arrested was later identified by authorities as 19-year-old D'Angelo Strand. Both men are facing two counts of second-degree murder along with two counts of use of a firearm in a commission of a felony.
The two men went before a Fairfax County judge Friday and were ordered held without bond.
"It is outrageous, and it is a real aberration for our community," Fairfax County Commonwealth's Attorney Steve Descano said.
Police said they believe the deaths are connected to a dispute or burglary at the house that they were called to just two days earlier.
.@FairfaxCountyPD announce two suspects arrested for murder of two veterans in Springfield yesterday morning. @wusa9 pic.twitter.com/WGZIlue7tc
'-- Tom Dempsey (@KCTomDempsey) May 27, 2021Police identified the man and woman killed as 55-year-old Edward McDaniel Jr., and his 63-year-old wife, Brenda McDaniel. Edward McDaniel was currently an active duty full-bird colonel in the U.S. Army. It is not known at this time which branch of the military Brenda McDaniel served in. Major Ed O'Carroll of Fairfax Police described both victims as "physicians" and "honorable soldiers."
The shooting happened just after 9 a.m. in the 8000 block of Flint Street, police said. There were family members inside the home when the shooting happened, Davis said. Everyone that was in the home has been relocated to a safe place.
Davis said one of the people inside the home may be the son of the victims. Investigators with the Fairfax County Police Department tell WUSA9 that the suspects and one of the victims' family members are believed to be co-workers.
The motive for the shooting remains unknown, but police said they believe both Marshall and Strand are connected to Monday's burglary at the home committed before Wednesday's double murder.
Neighbors said friends of the son have been involved in trouble in the neighborhood before.
"The teenage kids, their friends are bad people," Carlos Buendia, who lives just a few doors down from where the shooting happened, said. "They bring weapons into the neighborhood."
Neighbor Juliana Buendia said she was shocked this incident happened in her neighborhood but said she's sadly not surprised at where the crime happened.
"You never really see people coming and going," she said. "It's the only house where we don't know anybody who lives here.''
Chief Davis and @edocarroll updated the community tonight on this mornings tragic double homicide in Springfield. BOLO light colored 2018 Nissan Altima MD:1EF1479. If seen call 911. https://t.co/nR59ZVSeOb #FCPD pic.twitter.com/ltoiLACqLT
'-- Fairfax County Police (@FairfaxCountyPD) May 27, 2021Police said some neighbors witnessed the shooting, while others reported seeing the couple walking their dog right before the shooting.
"Nice people," neighbor Frank Breen said. "We used to talk every time they come around walking with the dogs.''
The murders of the McDaniels are the ninth and tenth murders of the year in Fairfax County.
A probable cause hearing is scheduled for Aug. 9, at which point prosecutors will have to detail the case against Marshall and Strand, and possibly outline what could have allegedly motivated them to murder the mother and father in the front yard of their house in the prosperous Newington Forest neighborhood.
"We are going to work non-stop until we get the person or persons to justice," Davis said.
Police are offering a $10,000 reward for information in regards to this case. If you have any additional information, please contact the Fairfax County Police Department at 1-866-411-TIPS (866-411-8477).
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VIDEO - (7) Axios on Twitter: "Biden on the anniversary of the Tulsa Race Massacre: ''Terrorism from white supremacy is the most lethal threat to the homeland today.'' https://t.co/5F7lGI7Dv6" / Twitter
Tue, 01 Jun 2021 23:43
Axios : Biden on the anniversary of the Tulsa Race Massacre: ''Terrorism from white supremacy is the most lethal threat to t'... https://t.co/tA9TxrbpAD
Tue Jun 01 21:16:30 +0000 2021
Chuck Mabbott : @axios Not sure what he is trying to prove, just pandering for votes
Tue Jun 01 23:42:37 +0000 2021
Angela Downing : @axios You mean like what you were maybe still are. I haven't heard you apologize for all your past white privilege'... https://t.co/VUwFD0hovL
Tue Jun 01 23:42:25 +0000 2021
If The Shoe Fitz.... : @axios The left will do anything to keep us divided. Power is in numbers. Cut it in half. Keep em divided, keep th'... https://t.co/7w3crSVoA0
Tue Jun 01 23:41:41 +0000 2021
Mr.Ugly : @axios Joe lies again!
Tue Jun 01 23:41:32 +0000 2021
Odds : @axios Biden living still in the 50s
Tue Jun 01 23:41:20 +0000 2021
Wes Morehead : @axios pandering again...white supremacy supporters are no significant threat to USA..we can squash in 5 minutes...'... https://t.co/IME5fAxUD5
Tue Jun 01 23:41:07 +0000 2021
walleye perch : @axios Good when will the founding party of the white supremacists/slave owners/KKK founders, be barred from servi'... https://t.co/SHCx0piFnD
Tue Jun 01 23:40:04 +0000 2021
Todd Szymanski : @axios https://t.co/uPJhYKSxra
Tue Jun 01 23:37:52 +0000 2021
kevvpanther : @axios Pedo joe really talking about blm and antifa
Tue Jun 01 23:37:37 +0000 2021
Hammers are good : @axios Does anyone really believe this? I mean I know there is a constant flow of anti-white propaganda but deep do'... https://t.co/DaE8s2IyBm
Tue Jun 01 23:37:01 +0000 2021
VIDEO - Meat Supplier JBS Shuts Down Slaughterhouses After Cyberattack - YouTube
Tue, 01 Jun 2021 20:33
VIDEO - UN Live United Nations Web TV - A Pandemic Treaty to Make the World Safer
Tue, 01 Jun 2021 20:13
A Pandemic Treaty to Make the World Safer
5 Apr 2021 - The World Health Organization (WHO) chief hailed support for an international pandemic treaty to shield the world from future health crises. Twenty-five heads of government and international agencies have endorsed the treaty, which would signal high-level political action needed to protect the world from future health crisesThe international community should work together ''towards a new international treaty for pandemic preparedness and response'' to build a more robust global health architecture that will protect future generations, world leaders said in a commentary published today in several newspapers around the world.''There will always be new pathogens with pandemic potential,'' said WHO Director-General Dr. Tedros Adhanom Ghebreyesus. ''It's not a matter of if but when.''
VIDEO - Cyberattack hits world's largest meat supplier
Tue, 01 Jun 2021 16:11
CANBERRA, Australia '-- Thousands of meat workers had no work for a second day on Tuesday after a cyberattack crippled the world's largest meat processing company. A government minister said it might be days before production resumes.
JBS is also Australia's largest meat and food processing company, with 47 facilities across the country including abattoirs, feedlots and meat processing sites. JBS employs around 11,000 people.
JBS USA said in a statement from Greeley, Colorado, on Monday that it was the target on Sunday of an ''organized cybersecurity attack'' affecting some of its servers supporting its North American and Australian IT systems.
''The company's backup servers were not affected and it is actively working with an Incident Response firm to restore its systems as soon as possible,'' the statement said.
Australian Agriculture Minister David Littleproud said the government and Australian Federal Police were working with JBS to resolve the problems and to pursue those responsible.
''Despite the fact that JBS accounts for around 20 percent of our processing production here in Australia, we're not expecting there to be significant impacts on exports so long as this isn't a protracted shutdown,'' Littleproud said on Tuesday.
''We're also working with JBS right here in Australia to make sure that we can get some limited capacity up and going in the next couple of days. JBS have been very proactive in that,'' he said.
Littleproud said it was too early to say whether it was a ransomware attack or who might be responsible.
Australian staff learned of the attack when they were turned away from their workplaces on Monday.
JBS exports about 70 percent of what it produces in Australia. But Australia and New Zealand account for only 4 percent of the company's global revenue.
Several consignments of cattle in Queensland state were canceled at short notice and cattle trucks were turned around, Australian Broadcasting Corp. reported.
''We had to send them up on Sunday afternoon and then we got the message in the morning that they'd have to cancel the train because the meat works was going to be shutting for an indefinite amount of time,'' Queensland cattle rancher Colin Baker told ABC.
''We had a wasted day . . . because mustering the cattle, sorting them out and then trucking them up there and then we had to bring them home today and let them all go again,'' Baker added.
VIDEO - IS COVID-19 A BIO-WEAPON?
Tue, 01 Jun 2021 15:29
Rumble '-- IS COVID-19 A BIO-WEAPON?
The origins of #Covid19 are becoming increasingly clear, and Dr. Richard Fleming, cardiologist and researcher walks Del through a shocking paper trail surrounding the SARS-CoV2 virus and its link to Tony Fauci and US funded gain-of-function research.
#FireFauci #GainOfFunction #GOF #FlemingProtocol #Covid19 #LabCreated #WuhanLab #CovidOrigins #TheHighwire #DelBigtree
POSTED: May 13, 2021
VIDEO - (255) THE TOMORROW WAR Official Trailer (2021) - YouTube
Tue, 01 Jun 2021 13:47
VIDEO - Reporters admit dismissing Wuhan lab leak theory in part because Republicans proposed it | Fox News
Tue, 01 Jun 2021 12:53
'Some things may be true even if Donald Trump said them,' ABC's Jonathan Karl saidJournalists continued to acknowledge Sunday that the media's longstanding dismissal of the Wuhan "lab-leak" theory was in part due to Republicans pitching it.
Once widely cast aside as a racist "conspiracy theory" and "fringe" nonsense, the possibility that the coronavirus accidentally leaked from the Wuhan Institute of Virology has gained increasing credence in recent weeks. The saga has led to yet another reckoning for mainstream media journalists about groupthink and bias in the industry. Faced with criticism that they blasted the theory last year for political reasons, some reporters have admitted its Republican origins with figures like Sen. Tom Cotton, R-Ark., former President Donald Trump, and former Secretary of State Mike Pompeo played into why they disparaged it.
ABC News Washington correspondent Jonathan Karl suggested on ABC's "This Week" Sunday that figures like Trump and Pompeo were not taken seriously by members of the media, saying "now serious people are saying it needs a serious inquiry."
REPORTERS BLAME TRUMP FOR NOT INITIALLY FINDING WUHAN LAB THEORY CREDIBLE
"Yes, I think a lot of people have egg on their face," Karl said. "This was an idea that was first put forward by Mike Pompeo, secretary of state, Donald Trump, and look some things may be true even if Donald Trump said them. Because Trump was saying so much else, that was just out of control, and because he was, you know, making a frankly racist appeal talking about Kung Flu, and the China virus, he said flatly this came from that lab, and it was widely dismissed ... but now serious people are saying it needs a serious inquiry."
New York Times reporter David Leonhardt also conceded Sunday many journalists dismissed the lab-leak theory solely because Cotton, a Trump ally and longtime critic of China, proposed it.
"I think people made this mistake. I think a lot of people on the political left and a lot of people in the media made the mistake. They said, 'wow if Tom Cotton is saying something, it can't be true.' Or they assumed that. And that's not right," he said on CNN.
CNN'S SMERCONISH COMPLAINS OF COVID LAB LEAK THEORY 'POLITICS,' DESPITE NETWORK DISMISSING IT FOR MONTHS
NBC's Chuck Todd addressed the issue on "Meet The Press" Sunday, saying that "for many," the lab leak theory got "tangled up in politics" and was conflated with one theory that the Chinese released the virus deliberately.
While interviewing former Trump Deputy National Security Adviser Matthew Pottinger, Todd repeatedly suggested anti-China rhetoric was to blame for media dismissals of the virus.
"Did in some ways, the sort of irrational attacks on China, did that slow down efforts of the intelligence community to actually do some fact-finding?" Todd asked.
"Well, look, I think what slowed down efforts more than anything else were the early statements that were published by a few scientists dismissing the idea that it could have come out of a lab," Pottinger said. "And in fact, caricaturing people who thought that it might have come out of a lab."
"Do you think your former boss' statements contributed to that a little bit?" Todd asked.
WAPO COLUMNIST ROASTS MEDIA ON COVID-19 LAB THEORY ABOUT-FACE: 'ZERO SELF AWARENESS'
"Well, you know, there are political mistakes that lead to, to, you know, trouble in government. And then there are institutional shortcomings," Pottinger said.
The language mirrored that of figures like the New York Times' Maggie Haberman and the Washington Post's Glenn Kessler last week.
"I think it is important to remember that part of the issue is when this was first being reported on and discussed back a few months after the pandemic had begun, was that then President Trump and Mike Pompeo, secretary of state, suggested they've seen evidence that this was formed in a lab and they also suggested that is was not released on purpose. But they refused to release the evidence showing what it was and so because of that made this instantly political," Haberman said on CNN last week.
In a new fact-check timeline that declared the lab theory was "suddenly" credible, Kessler wrote, "The Trump administration's messaging was often accompanied by anti-Chinese rhetoric that made it easier for skeptics to ignore its claims."
Washington Post reporter Aaron Blake wrote an analysis titled, "The vexing 'lab leak' theory on China and the coronavirus," in which he defended reporters dismissing the Trump administration claims that there was a high probability the virus originated in a lab.
FORMER STATE DEPARTMENT OFFICIAL: PROBE INTO COVID ORIGINS FOUND ALMOST NO EVIDENCE SUPPORTING NATURAL ORIGIN
"Given everything we know about how Trump handled such things, caution and skepticism were invited. That (very much warranted) caution and skepticism spilled over into some oversimplification, particularly when it came to summarizing the often more circumspect reporting," Blake wrote.
The Washington Post's Josh Rogin blasted reporters on Saturday for their sudden about-face, saying the facts on the ground had not changed out of the blue, and accusing them of bias, "general incompetence" and even "TDS," short for Trump Derangement Syndrome.
President Biden ordered the intelligence community last week to investigate the origins of the virus and report back in 90 days.
Outlets from the Washington Post and New York Times to CNN and NPR have gone from outright mockery of the idea to taking it seriously, and "fact checks" have been updated with editor's notes about why the theory is no longer necessarily "debunked." Former Centers for Disease Control and Prevention Director Robert Redfield is among the proponents of the theory, pointing to the virus' efficient transmission among humans and the "gain of function" research at the Wuhan lab.
CLICK HERE TO GET THE FOX NEWS APP
The virus' true origins are still unknown.
Fox News' Thomas Barrabi and Andrew Kugle contributed to this report.
VIDEO - TODAY on Twitter: "Naomi Osaka withdrew from the French Open on Monday, a day after she was fined $15,000 by tournament officials for skipping post-match press conferences, citing her mental health. @mollymhunter reports. https://t.co/ZYfYjXArs3"
Tue, 01 Jun 2021 12:49
TODAY : Naomi Osaka withdrew from the French Open on Monday, a day after she was fined $15,000 by tournament officials for'... https://t.co/RbG6Th6uvo
Tue Jun 01 12:07:04 +0000 2021
Zarathustra : @TODAYshow @mollymhunter Naomi Osaka doesn't want to be interviewed because she hears racist comments from Japanese journalists.
Tue Jun 01 12:37:31 +0000 2021
Michelle : @TODAYshow @mollymhunter Leave her alone!! She is asking for support with her mental health and the media is making'... https://t.co/FLgW0HVPOp
Tue Jun 01 12:32:26 +0000 2021
Dave : @TODAYshow @mollymhunter Suggestion. Use that money to get help with your anxiety. Hire a professional spokes perso'... https://t.co/j9GUgR1c5q
Tue Jun 01 12:18:35 +0000 2021
marianne kimball : @TODAYshow @mollymhunter Fined for trying to look out for her mental health? Really? Better re-think that one.
Tue Jun 01 12:18:33 +0000 2021
StikeDCicada ðŸ...—🌲 ðŸ...— : @TODAYshow @mollymhunter She made $55 million last year, maybe she could plunk down 2 grand for media training. 🤷🏽''¸
Tue Jun 01 12:15:22 +0000 2021
Christine Haller : @TODAYshow @mollymhunter I don't understand why it is mandatory to talk to the media. They shouldn't have to if the'... https://t.co/MaA1bfOP1i
Tue Jun 01 12:12:49 +0000 2021
Jenny Sampangwongse : @TODAYshow @mollymhunter Good riddance #NaomiOsaka; Quit trying to move up the intersectional oppressed hierarchy.'... https://t.co/fFnwYYCCf7
Tue Jun 01 12:11:27 +0000 2021
VIDEO - Keith Olbermann on Twitter: "NEW VIDEO: As Texas @GOP votes to end democracy and education there, it's time to take power away from such Failed States. These are bullies. Bullies stop only when THEY are hurt more than they CAN hurt. The Anti-Democ
Tue, 01 Jun 2021 12:12
Keith Olbermann : NEW VIDEO: As Texas @GOP votes to end democracy and education there, it's time to take power away from such Failed'... https://t.co/55J4L0j0Bv
Sun May 30 21:21:40 +0000 2021
MajorBear640 🇺🇲 : @KeithOlbermann @GOP You look like you're about to cry.
Tue Jun 01 12:10:42 +0000 2021
FakeXero : @KeithOlbermann @GOP I hope you're in therapy.
Tue Jun 01 12:09:54 +0000 2021
Saratoga Fan : @KeithOlbermann @GOP What do you consider a failed state?
Tue Jun 01 12:08:32 +0000 2021
A J Burton : @KeithOlbermann @GOP Keith somewhere there is a village short of an idiot the jobs yours.
Tue Jun 01 12:07:51 +0000 2021
VIDEO - TikTok: COVID-19 'Lone Survivor' Fantasy Is Anti-Vax Movement's New Myth
Mon, 31 May 2021 04:13
Unvaccinated TikTokers are fantasizing they'll be the "lone survivors" of the COVID-19 pandemic. Videos show TikTokers performing to the soundtrack from "The Transformers." Vaccine misinformation has been spreading on TikTok since the start of the pandemic. Visit Insider's homepage for more stories. Unvaccinated TikTokers are rallying together by pretending they're the "lone survivors" of the coronavirus pandemic.
In more than a dozen videos seen by Insider, TikTok users are falsely claiming those who have not been vaccinated will be the last remaining survivors on earth.
Some of the videos involve TikTokers facing away from the camera, with their hands on their hips, as audio from the 2007 "The Transformers" plays in the background.
Read more: TikTok and YouTube influencers reveal the wild gifts they've received from fans and brands, including fake thongs, spicy peppers, and antique dolls
"I am Optimus Prime," the audio says "and I send this message to any surviving Autobots taking refuge among the stars. We are here. We are waiting." The videos are accompanied by hashtags including #unvaccinated and #wearehere.
One video in this format, which shows two men standing in their garden with their hands on their hips, has almost half a million views.
Other formats of the "lone survivor" videos include people whistling to the "Hunger Games" theme song alongside the caption: "Calling out all my unvaccinated Americans."
A TikToker, who made one of these videos, told Insider: "It's not like I believe everyone will die from the vaccine but I liked this format and am a 'Transformers' fan."
The person, aged 21, also said they don't plan to get the vaccine because they believe "it can harm young people" and said they think it's "unfair that the government is making people take them." They did not want to be named for this article.
The Pfizer, Moderna, and Johnson & Johnson vaccines have all been authorized by the Food and Drug Administration (FDA) and have very good safety records.
In October last year, Insider identified more than two dozen videos in which people were pretending to experience painful or sinister side-effects after taking a COVID-19 vaccine.
Many of the videos were fictional or joking in nature, however, experts told Insider they can still help spread anti-vaccine sentiment.
The lone survivor videos also come as the demand for COVID-19 vaccinations is slowing down across the US '-- a trend that has some experts concerned.
Kolina Koltai, a postdoctoral fellow at the Center for an Informed Public at The University of Washington, told Insider she's "not a fan of the videos" because they "can encourage vaccine hesitancy."
However, Koltai believes that while they promote anti-vaccine sentiment, they are "not doing anything that would fall under vaccine misinformation ... They don't make any claims about the vaccine, like if it is dangerous or that it is unnecessary."
"Expressing your opinion or sentiment on vaccines is something that should be allowed on platforms, even at the expense that it may encourage others to be more vaccine-hesitant," she added. "The bigger issue is vaccine misinformation on social media platforms and the persistent anti-vaccination narratives being promoted."
A TikTok spokesperson told Insider: "Our Community Guidelines prohibit content that's false or misleading, including medical misinformation related to COVID-19, and anti-vaccine disinformation more broadly ... In addition to removing content, we redirect searches associated with vaccine or COVID-19 disinformation to our Community Guidelines and do not autocomplete anti-vaccine hashtags in search."
The company did not include their COVID-19 tags on any of the "lone survivor" videos.
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VIDEO - The late veteran conspiracy researcher Eustace Mullins talks vaccines & how the Rockefellers own and control the pharmaceutical industry '' great information '' David Icke
Mon, 31 May 2021 04:10
Copyright (C) 2021 David Icke Books Limited. All Rights Reserved.
VIDEO - Rabbit Hole
Sun, 30 May 2021 20:36
Zombie ApocalypseEveryone injected with zombie juice is going to become a zombie because it's the intended purpose. FEMA camps are ready to house the zombies because they're walking, talking biohazards that are breeding mutant variants. It's genocide science. The information presented here is part of an ordered sequence. Take your time with it, go in order, and be patient while the videos load.
Death is not the end of life. Souls are simply being re-organized during the Great Reset. It's also necessary for the Great Awakening so that people see they can't let others decide their fate for them. The pathogen is the path of awakening. Crisis awakens the Christ.
When we align with Truth above all else, we transcend duality and elevate our world to triality.
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The Satanic Overlords ensure the cure is always censored.
These videos were removed even from alternative platforms, but truth always prevails.Save them to your computer, and share them widely.
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The mRNA technology is turning people into walking, talking biohazards that are spawning the mutant variations and creating a zombie apocalypse for operation depopulation.
Anyone injected with mRNA technology is probably going to die very quickly. The science is simple. The pathogen is equated with self, so the body stops fighting it. No fight means no symptoms. You won't get sick. You'll die. The rationale is obvious. The clinical studies demonstrate the obvious. The real-world results prove the point.
In addition, the RNA is reverse-transcribed into the DNA turning people into mutant chimeras. The body may or may not accept the modification. If it's rejected, it will either be purged or the body will destroy itself in an attempt to get rid of it.
The science is conclusive.
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There's countless videos circulating of magnets sticking to the injection site, light bulbs illuminating at the touch of the injection site, bluetooth activating as people walk nearby.
People are being injected with classified Star Trek technology to assimilate them into a 5G network for surveillance and mind control. 5G is a Trojan Horse. It's the silent killer. 5G prevents 5D and fundamentally alters the electromagnetics of our planet leading to multiple species extinction and the gradual deteroration of all that's organic.
At the same time, they're using molecular mimicry to sterilize the population by fooling the immune system into attacking the sexual organs. This Frankenstein created by morons with power may annihilate the human race.
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Free speech is humanity's only chance of survivalIf we don't put our differences aside and come together as a people to seek win-win solutions, our civilization will fall. Just as Atlantis was destroyed by Gaia who ushered in a great flood to purge the morons with power, we're now once again at the Precipice of Evolution. We've crossed a line of no return. If we don't unite now, we self-destruct.
My title as Messiah is not ego or grandiosity. It's reality. It's cold hard mathematics. I understand that most people will react in shock and disbelief at this information. I don't need you to believe me. I request that we put our differences aside and work in partnership for the highest good of our world.
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This loveable darling who invented PCR, Kary Mullis, was murdered in 2019 to prevent the world from learning about the "number lies" that currently has everyone chasing their tails in futility.
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Excessive amplification cycles is one of the strategies of the scamdemic.The test is meaningless.
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Our legal system is owned and operated by a Satanic-Luciferian elite that doesn't care about the welfare of the people.
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Michael Yeadon, former VP of Pfizer, understands the situation. Those who can be silenced don't need to be murdered. Unfortunately, there's something wrong with this video.The important quote "not my crime" appears to be unwatchable.
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He's now working with LiberalSpring to help save humanity.
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The Age of the Black Sun fades at the dawning of Age of the Gold Sun as a stepping stone to the Age of the White Sun. I'm the new Adam Weishaupt, not by choice, but by divine inheritence. I don't seek power. It's bestowed onto me. I accept my position with grace and honor.
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EMF emissions at the injection site are from the Star Trek nanotechnology used to assimilate the world into a hive mind collective.
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Satan aka Bill Gates is a moron with power who will doom our species to extinction. After the famine depopulation backup plan, autonomous regions independent of legal oversight will implement descending spirals of hell in a new form of feudalism called technocracy. Government by science. You'll own nothing and be happy while the Satanic Overlords consolidate power by assimilating the unweary into Satan's Paradise.
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In order for Satan to maintain control over the matter realm, it's necessary to disconnect it from the spirit realm. The Corona Hoax is designed to disconnect the Crown Chakra from the Mother of God by intercepting the divine transmission in the left year and replacing it with the AI Red Wave frequency of the Dark Mother. The Vagina Crown of the Lunar Matrix prevents us from uniting with our spiritual parents. Big Brother is an abusive parent.
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Chelsea Handler found out too late. Her daemon has already been removed.
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The technology spreads throughout the body. Since the vaccinated are guinea pigs, it's possible that some people are in control groups and may have been injected with a placebo.
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In the inverted system of the Satanic hell realm, ignorance and incompetence is promoted while dissenting voices are silenced by any means necessary.
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Many of our most trusted leaders are complete lies.
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Bluetooth is just the beginning. Soon, 5G-compatible robots will be able to hunt you down and exterminate you if you think about unapproved topics.
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I've said it before, and I'll say it again. Mythology is more accurate than causality as a model for reality. Materialistic science is a dead-end road to species extinction. The era of spirit science is upon us. Klaus Schwab, the current head of the snake, replacing former head Satan (Bill Gates), is Dr Evil from Austin Powers.
Stroke your hairless cat while you still can.The powers of Austin are coming for you.
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Our emerging global society is bifurcating into two factions - Transhumanism and Enlightenment. Choose your side before you get assimilated by the Borg. Transhumanism merges man with machine in order to redirect our organic ascension process into an artificial trap. Satan's Paradise is the descending path. The Mark of the Beast is the vaccine. Deny our spiritual reality to your peril. This materialistic hologram is an illusion. Our immortal souls can be trapped for harvesting in phantom worlds.
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Medbeds are highly classified alien Star Trek technology that use electromagnetism to heal our DNA. Lucifer is hiding them because Satan wants to depopulate the planet. This husband and wife pairing is cannibalistic. Their 20 year mating cycle is finally giving birth to a third. Uranus claims the throne because this is the dawning of the Age of Aquarius.
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As our society graduates to galactic citizenship, we must educate ourselves on our new rights. Knowledge is power.
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The pathogen is the path of awakening. Crisis awakens the Christ.
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This is her final performance before being gently escorted to the slaughterhouse.
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Informed consent is the difference between penetration and violation. The former is benevolent while the latter is malevolent. If you cannot think and reason for yourself, you may not survive the New World Order.
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STORIES
FireEye selling products business and name for $1.2 billion
Thu, 03 Jun 2021 13:19
The FireEye logo is seen outside the company's offices in Milpitas, California, December 29, 2014.
Beck Diefenbach | Reuters
FireEye said Wednesday it's selling its products business, including the FireEye name, to a consortium led by private-equity firm Symphony Technology Group for $1.2 billion in cash.
The U.S. cybersecurity firm said the sale will split Mandiant Solutions, its cyber forensics unit, from its cloud security, network and email products.
Shares of FireEye were relatively flat after hours. The company said the deal is expected to close by the end of the fourth quarter.
FireEye was the subject of a cyberattack in December of last year, which it believes was state-sponsored. Microsoft in February credited the company's transparency about the breach in helping it discover that had also been attacked.
FireEye CEO Kevin Mandia said the sale will help it grow its Mandiant Solutions business.
"After closing, we will be able to concentrate exclusively on scaling our intelligence and frontline expertise through the Mandiant Advantage platform, while the FireEye Products business will be able to prioritize investment on its cloud-first security product portfolio," Mandia added.
The sale is just the latest example of a big-dollar tech deal going to private equity.
With the exception of special purpose acquisition companies, seven of the 12 largest tech acquisitions in the U.S. in 2021 have been carried out by private equity firms, according to data from FactSet.
In Wednesday's announcement, FireEye also said its board approved a share buyback program of up to $500 million.
United States Patent: 11021532
Thu, 03 Jun 2021 11:44
This disclosure provides superhuman antibodies and antigen-binding fragments that can be administered to an individual that is infected or suspected of being infected with a virus. Superhuman antibodies and antigen-binding fragments provided herein can be capable of treating or curing the virus, and which may provide protection against the virus for up to at least several weeks. Superhuman antibodies and antigen-binding fragments provided herein can be used to diagnose a SARS Cov-2 infection.
Wilson Sonsini Goodrichh & Rosati Parent Case Text CROSS-REFERENCE
This application claims the benefit of U.S. Provisional Application No. 63/014,948, filed on Apr. 24, 2020; 63/013,485, filed Apr. 21, 2020; and 62/993,630, filed Mar. 23, 2020, all of which are incorporated herein by reference in their entireties for all purposes. Claims
What is claimed is:
1. An antibody or an antigen-binding fragment that selectively binds to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that comprises a variable heavy chain(VH) complementarity determining region 1 (CDR1) having an amino acid sequence of SEQ ID NO: 214; a VH CDR2 having an amino acid sequence of SEQ ID NO: 262; a VH CDR3 having an amino acid sequence of SEQ ID NO: 310; a variable light chain (VL) CDR1having an amino acid sequence of SEQ ID NO: 46; a VL CDR2 having an amino acid sequence of SEQ ID NO: 94; and a VL CDR3 having an amino acid sequence of SEQ ID NO: 142.
2. The antibody or the antigen-binding fragment of claim 1, that comprises a VH having an amino acid sequence that is at least 90% identical to SEQ ID NO: 358 and a VL having an amino acid sequence that is at least 90% identical to SEQ ID NO:382.
3. The antibody or the antigen-binding fragment of claim 2, wherein the antibody is an IgG, an IgM, an IgE, an IgA, or an IgD, or is derived therefrom.
4. The antibody or the antigen-binding fragment of claim 2, that comprises a binding affinity of less than 70 nanomolar (nM).
5. The antibody or the antigen-binding fragment of claim 2, wherein the antigen-binding fragment comprises a Fab, a Fab', a F(ab').sub.2, a variable fragment (Fv), a triabody, a tetrabody, a minibody, a bispecific F(ab').sub.2, a trispecificF(ab').sub.2, a diabody, a bispecific diabody, a single chain variable fragment (scFv), a scFv-Fc, a Fab-Fc, a VHH, or a bispecific scFv.
6. A method of preventing or treating a SARS-CoV-2 viral infection or COVID19 in a subject in need thereof, comprising administering to the subject the antibody or the antigen-binding fragment of claim 1.
7. The method of claim 6, that further comprises administering one or more additional therapies or drugs to the subject.
8. A method of diagnosing a subject as being infected with a SARS-CoV-2 virus or suspected of being infected with a SARS-CoV-2 virus, the method comprising contacting a sample obtained from the subject with the antibody or the antigen-bindingfragment of claim 1; detecting the presence or absence of an antibody/SARS-CoV-2 virus complex or an antigen-binding fragment/SARS-CoV-2 virus complex; and diagnosing the subject as being infected with a SARS-CoV-2 virus when the presence of theantibody/SARS-CoV-2 virus complex or the antigen-binding fragment/SARS-CoV-2 virus complex is detected.
9. The method of claim 8, wherein the sample comprises a nasal swab, a tissue sample, saliva, or blood.
10. The method of claim 8, wherein detecting the presence or absence of the antibody/SARS-CoV-2 virus complex or the antigen-binding fragment/SARS-CoV-2 virus complex comprises an enzyme linked immunosorbent assay (ELISA), an immunospot assay,a lateral flow assay, flow cytometry, immunohistochemistry, or a western blot.
11. The antibody or the antigen-binding fragment of claim 2, that selectively binds to a receptor binding domain (RBD) of SARS-CoV-2, wherein the RBD comprises an amino acid sequence of SEQ ID NO: 494.
12. An antibody or an antigen-binding fragment that selectively binds to a SARS-CoV-2, that comprises: (i) a VH CDR1 having an amino acid sequence of SEQ ID NO: 200, a VH CDR2 having an amino acid sequence of SEQ ID NO: 248, a VH CDR3 having anamino acid sequence of SEQ ID NO: 296, a VL CDR1 having an amino acid sequence of SEQ ID NO: 32, a VL CDR2 having an amino acid sequence of SEQ ID NO: 80, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 128; (ii) a VH CDR1 having an amino acidsequence of SEQ ID NO: 430, a VH CDR2 having an amino acid sequence of SEQ ID NO: 431, a VH CDR3 having an amino acid sequence of SEQ ID NO: 429, a VL CDR1 having an amino acid sequence of SEQ ID NO: 432, a VL CDR2 having an amino acid sequence of SEQ IDNO: 433, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 441; or (iii) a VH CDR1 having an amino acid sequence of SEQ ID NO: 215, a VH CDR2 having an amino acid sequence of SEQ ID NO: 263, a VH CDR3 having an amino acid sequence of SEQ ID NO:311, a VL CDR1 having an amino acid sequence of SEQ ID NO: 47, a VL CDR2 having an amino acid sequence of SEQ ID NO: 95, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 143.
13. An antibody or an antigen-binding fragment that selectively binds to a SARS-CoV-2, that comprises a VH having an amino acid sequence of SEQ ID NO: 358 and a VL having an amino acid sequence of SEQ ID NO: 382.
14. The antibody or the antigen-binding fragment of claim 1, that selectively binds to a receptor binding domain (RBD) of SARS-CoV-2, wherein the RBD comprises an amino acid sequence of SEQ ID NO: 494.
15. The antibody or the antigen-binding fragment of claim 1, that comprises a binding affinity of less than 70 nanomolar (nM).
16. The antibody or the antigen-binding fragment of claim 1, wherein the antibody is an IgG, an IgM, an IgE, an IgA, or an IgD, or is derived therefrom.
17. The antibody or the antigen-binding fragment of claim 1, wherein the antigen-binding fragment comprises a Fab, a Fab', a F(ab').sub.2, a variable fragment (Fv), a triabody, a tetrabody, a minibody, a bispecific F(ab').sub.2, a trispecificF(ab').sub.2, a diabody, a bispecific diabody, a single chain variable fragment (scFv), a scFv-Fc, a Fab-Fc, a VHH, or a bispecific scFv. Description
SEQUENCE LISTING
The instant application contains a Sequence Listing which has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jun. 22, 2020, is named 44561-724_201_SL.txt and is184,726 bytes in size.
BACKGROUND OF THE INVENTION
Viruses are small infectious agents that can enter a living cell of an organism. Genetic information from a virus can be injected into the living cell, and can replicate inside the living cell, and be released. Viruses can cause disease in theorganism and can spread between organisms. The mechanism by which a virus can cause disease can vary between viruses and can include cell lysis and/or cell death.
Coronaviruses are a group of related viruses that can cause disease, for example in mammals and birds. Coronaviruses can cause respiratory tract infections, such as those causing pneumonia-like diseases, that can range from mild to lethal.
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is a coronavirus responsible for a pandemic of a respiratory disease, COVID19. An outbreak of this virus was first identified in Wuhan, Hubei, China, and a pandemic was recognized bythe World Health Organization on Mar. 11, 2020. The range of the severity of COVID19 is large, and ranges from asymptomatic to death. Approximately 20% of infected individuals can require hospitalization. The mortality rate of COVID19 appears to bebetween 1% and 4%. COVID19 is transmitted between people, for example through respiratory droplets, and can be spread by symptomatic and asymptomatic individuals, including during an extended incubation period. Social distancing has been appliedworldwide to decrease the spread of COVID19.
Currently, there is no vaccine or treatment for COVID19. There is an urgent need for new compositions that can be used for treating or preventing SARS-Cov-2 infection and for diagnosing an exposure to SARS-Cov-2 virus.
SUMMARY OF THE INVENTION
Provided herein is a superhuman (SH) antibody or antigen-binding fragment that is derived from 2dd8, 2ghw, 3bgf, 6nb6, or CR3022, and that selectively binds to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In some embodiments,the SH antibody or antigen-binding fragment has a binding affinity of less than 50 nanomolar (nM). In further embodiments, the SH antibody or antigen-binding fragment selectively binds to a receptor binding domain (RBD) of severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2). In further embodiments, the SH antibody or antigen-binding fragment comprises an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to a VH CDR3 comprising an amino acid sequence of any one ofany one of SEQ ID NOS: 293-316 and 429. In further embodiments, the SH antibody or antigen-binding fragment comprises further comprise an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to one or more of a VH CDR1 comprisingan amino acid sequence of any one of SEQ ID NOS: 197-220 and 430 and a VH CDR2 comprising an amino acid sequence of any one of SEQ ID NOS: 245-268 and 431.
Provided herein is an SH antibody or antigen-binding fragment as described herein, that comprises a VH chain that comprises: a. a VH CDR1 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to any one of SEQ IDNOS: 197-220 and 430; b. a VH CDR2 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 245-268 and 431; and c. a VH CDR3 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100%identical to any one of SEQ ID NOS: 293-316 and 429.
Provided herein is an SH antibody or antigen-binding fragment as described herein, that comprises a VL chain that comprises: a. a VL CDR1 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 29-52and 432; b. a VL CDR2 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 77-100 and 433; and
a VL CDR3 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 125-148 and 441.
Provided herein is an SH antibody or antigen-binding fragment that comprises (i) a VH CDR3 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 296; (ii) a VH CDR1 having an amino acid sequence thatis at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 200; (ii) a VH CDR2 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 248; (iv) a VL CDR1 having an amino acid sequence that is at least 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 32; (v) a VL CDR2 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 80; and (vi) a VL CDR3 having an amino acid sequence that is at least 90%, 95%, 98%, 99%,or 100% identical to SEQ ID NO: 128. Further provided herein is an SH antibody or antigen-binding fragment that comprises (i) a VH CDR3 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 310; (ii) a VHCDR1 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 214; (ii) a VH CDR2 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 262; (iv) a VL CDR1 having anamino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 46; (v) a VL CDR2 having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 94; and (vi) a VL CDR3 having an amino acidsequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 142. Further provided herein is an SH antibody or antigen-binding fragment that comprises an amino acid sequence of any one of SEQ ID NOS: 5-28, a FW-L2 comprising an aminoacid sequence of any one of SEQ ID NOS: 53-76, a FW-L3 comprising an amino acid sequence of any one of any one of SEQ ID NOS: 101-124, a FW-L4 comprising amino acid of any one of SEQ ID NOS: 149-172, 435, a FW-H1 comprising an amino acid sequence of anyone of SEQ ID NOS: 173-196, a FW-H2 comprising amino acid sequence of any one of SEQ ID NOS: 221-244, a FW-H3 comprising an amino acid sequence of any one of SEQ ID NOS: 269-292, and a FW-H4 comprising an amino acid sequence of any one of SEQ ID NOS:317-340. Further provided herein is an SH antibody or antigen-binding fragment that comprises a VH chain having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 341-364 and 436. Further providedherein is an SH antibody or antigen-binding fragment that comprises a VL chain having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 365-388 and 437. Further provided herein is an SH antibody orantigen-binding fragment that comprises a VL having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 365-388 and 437, and a VH having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or100% identical to any one of SEQ ID NOS: 341-364 and 436. Further provided herein is an SH antibody or antigen-binding fragment that comprises a VH having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 344and a VL having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 368. Further provided herein is an SH antibody or antigen-binding fragment that comprises a VH having an amino acid sequence that is at least90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 358 and a VL having an amino acid sequence that is at least 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 382. Further provided herein is an SH antibody, wherein the antibody is an IgG, an IgM,an IgE, an IgA, or an IgD, or is derived therefrom.
Provided herein is an SH antibody as described herein, wherein the binding affinity is less than 50 nM, 49 nM, 48 nM, 47 nM, 46 nM, 45 nM, 44 nM, 43 nM, 42 nM, 41 nM, 40 nM, 39 nM, 38 nM, 37 nM, 36 nM, 35 nM, 34 nM, 33 nM, 32 nM, 31 nM, 30 nM,29 nM, 28 nM, 27 nM, 26 nM, 25 nM, 24 nM, 23 nM, 22 nM, 21 nM, 20 nM, 19 nM, 18 nM, 17 nM, 16 nM, 15 nM, 14 nM, 13 nM, 12 nM, 11 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, 990 pM, 980 pM, 970 pM, 960 pM, 950 pM, 940 pM, 930 pM, 920pM, 910 pM, 900 pM, 890 pM, 880 pM, 870 pM, 860 pM, 850 pM, 840 pM, 830 pM, 820 pM, 810 pM, 800 pM, 790 pM, 780 pM, 770 pM, 760 pM, 750 pM, 740 pM, 730 pM, 720 pM, 710 pM, 700 pM, 690 pM, 680 pM, 670 pM, 660 pM, 650 pM, 640 pM, 630 6M, 620 pM, 610 pM,600 pM, 590 pM, 580 pM, 570 pM, 560 pM, 550 pM, 540 pM, 530 pM, 520 pM, 510 pM, 500 pM, 490 pM, 480 pM, 470 pM, 460 pM, 450 pM, 440 pM, 430 pM, 420 pM, 410 pM, 400 pM, 390 pM, 380 pM, 370 pM, 360 pM, 350 pM, 340 pM, 330 pM, 320 pM, 310 pM, 300 pM, 290pM, 280 pM, 270 pM, 260 pM, 250 pM, 240 pM, 230 pM, 220 pM, 210 pM, 200 pM, 190 pM, 180 pM, or any integer therebetween. Further provided herein is an SH antibody or antigen-binding fragment, wherein the antibody's antigen-binding domain or theantigen-binding fragment comprises a Fab, a Fab', a F(ab')2, a variable fragment (Fv), a triabody, a tetrabody, a minibody, a bispecific F(ab')2, a trispecific F(ab')2, a diabody, a bispecific diabody, a single chain variable fragment (scFv), a scFv-Fc,a Fab-Fc, a VHH, or a bispecific scFv.
Provided herein is a method of preventing or treating a SARS-CoV-2 viral infection or COVID19 in a subject in need thereof, comprising administering to the subject one or more of the SH antibodies or antigen-binding fragments as describedherein. Further provided herein is a method, that further comprises administering one or more additional therapies or drugs to the subject. Further provided herein is a method of diagnosing a subject as being infected with a SARS-Cov-2 virus orsuspected of being infected with a SARS-Cov-2 virus, the method comprising contacting a sample obtained from the subject with a SH antibody or antigen-binding fragment as described herein; detecting the presence or absence of the SH antibody orantigen-binding fragment; and diagnosing the subject as being infected with a SARS-CoV-2 virus when the presence of the SH antibody or antigen-binding fragment is detected. Further provided herein is a method, wherein the sample comprises a nasal swab,a tissue sample, saliva, or blood. Further provided herein is a method, wherein detecting the presence or absence of the SH antibody or antigen-binding fragment comprises an enzyme linked immunosorbent assay (ELISA), an immunospot assay, a lateral flowassay, flow cytometry, immunohistochemistry, or a western blot.
INCORPORATION BY REFERENCE
All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individuallyindicated to be incorporated by reference.
BRIEF DISCLOSURE OF THE DRAWINGS
The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed descriptionthat sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which:
FIG. 1 provides representative viral antigen sequences.
DETAILED DESCRIPTION OF THE INVENTION
In view of the ongoing pandemic, there is a great need for therapeutic and diagnostic antibodies that selectively bind to severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2).
"2dd8" is a SARS-Cov-1 spike protein receptor binding domain. A "parental clone" or a "parental clone 2dd8" as used herein refers to an antibody that selectively binds to SARS-Cov-1 and which has the following combination of complementaritydetermining regions (CDRs), or the following variable heavy chain (VH), and variable light chain (VL).
TABLE-US-00001 2dd8 Parental CDR Sequences SEQ ID NO VH CDR1 GTFSSYTIS 389 VH CDR2 MGGITPILGIANYA 390 VH CDR3 CARDTVMGGMDV 391 VL CDR1 GGNNIGSKSVH 392 VL CDR2 DDSDRPS 393 VL CDR3 QVWDSSSDYV 394
TABLE-US-00002 Clone VH/VL Parental CDR Sequences SEQ ID NO 2dd8 VH QVQLQQSGAEVKKPGSSVKVSCK 395 ASGGTFSSYTISWVRQAPGQGLEW MGGITPILGIANYAQKFQGRVTITT DESTSTAYMELSSLRSEDTAVYYC ARDTVMGGMDVWGQGTTVTVSS 2dd8 VL SYELTQPPSVSVAPGKTARITCGGN 396NIGSKSVHWYQQKPGQAPVLVVYD DSDRPSGIPERFSGSNSGNTATLTISR VEAGDEADYYCQVWDSSSDYVFGT GTKVTVL
"2ghw" is a SARS-Cov-1 spike protein receptor binding domain. A "parental clone" or a "parental clone 2ghw" as used herein refers to an antibody that selectively binds to SARS-Cov-1 and which has the following combination of CDRs, or thefollowing variable heavy chain (VH), and variable light chain (VL).
TABLE-US-00003 2ghw Parental CDR Sequences SEQ ID NO VH CDR1 FAFSSYAMH 397 VH CDR2 AVISYDGSNKYYA 398 VH CDR3 CARDRSYYLDY 399 VL CDR1 RASQSVRSNLA 400 VL CDR2 DASTRAT 401 VL CDR3 CQQRSNWPPT 402
TABLE-US-00004 Clone VH/VL Parental CDR Sequences SEQ ID NO 2ghw VH EVQLVQ SGGGVVQPGKSLRLSCAAS 403 GFAFSSYAMHWVRQAPGKGLEWVA VISYDGSNKYYADSVKGRFTISRDNS KNTLYLQMNSLRAEDTAVYYCARD RSYYLDYWGQGTLVTVSS 2ghw VL ETTLTQSPATLSLSPGERATLSCRASQ 404SVRSNLAWYQQKPGQAPRPLIYDAST RATGIPDRFSGSGSGTDFTLTISRLEPED FAVYYCQQRSNWPPTFGQGTKVEVK
"3bgf" is a Middle East Respiratory Syndrome Coronavirus (MERS) spike protein receptor binding domain. A "parental clone" or a "parental clone 3bgf" as used herein refers to an antibody that selectively binds to MERS and which has the followingcombination of CDRs, or the following variable heavy chain (VH), and variable light chain (VL).
TABLE-US-00005 3bgf Parental CDR Sequences SEQ ID NO VH CDR1 YTFTTYRMH 405 VH CDR2 GAIYPGNSDTTYN 406 VH CDR3 CTREGIPQLLRTLDY 407 VL CDR1 RASQEISGYLS 408 VL CDR2 AASTLDS 409 VL CDR3 CLQYVSYPWT 410
TABLE-US-00006 Clone VH/VL Parental CDR Sequences SEQ ID NO 3bgf VH EVQLEESGTVLARPGASVKMSCKASGYTFTTYRM 411 HWIKQRPGQGLEWIGAIYPGNSDTTYNQKFKDKA KLTAVTSTSSAYMELSSLTNEDSAVYFCTREGIPQL LRTLDYWGQGTSVTVSS 3bgf VL DILMTQSPSSLSASLGERVSLTCRASQEISGYLSWL 412QEKPDGTIKRLIYAASTLDSGVPKRFSGSRSGSDYS LTISSLESEDFADYYCLQYVSYPWTFGGGTKLEIK
"6nb6" is a SARS-Cov-1 spike protein receptor binding domain. A "parental clone" or a "parental clone 6nb6" as used herein refers to an antibody that selectively binds to SARS-Cov-1 and which has the following combination of CDRs, or thefollowing variable heavy chain (VH), and variable light chain (VL).
TABLE-US-00007 6nb6 Parental CDR Sequences SEQ ID NO VH CDR1 FTFRNYAMH 413 VH CDR2 AVITSDGRNKFYA 414 VH CDR3 CVTQRDNSRDYFPHYFHDMDV 415 VL CDR1 RSSQSLVYSDGDTYLN 416 VL CDR2 QVSNRDS 417 VL CDR3 CMQGSHWPPT 418
TABLE-US-00008 Clone VH/VL Parental CDR Sequences SEQ ID NO 6nb6 VH QVQLVESGGALVQPGRSLRLSCAASGFTFRNYAMH 419 WVRQAPATGLQWLAVITSDGRNKFYADSVKGRFTI SREDSKNTLYLQMDSLRGEDTAVYYCVTQRDNSR DYFPHYFHDMDVWGQGTLVTVSS 6nb6 VLDVVLTQSPLSLPVTLGQPASISCRSSQSLVYSDGDT 420 YLNWFQQRPGQSPRRLIYQVSNRDSGVPDRFSGSG SGTDFTLKISRVEAEDVGVYYCMQGSHWPPTFGQG TKVEIK
"CR3022" as referenced herein refers to an antibody that selectively binds to SARS-Cov-1 and which has the following combination of complementarity determining regions (CDRs), or the following variable heavy chain (VH), and variable light chain(VL).
TABLE-US-00009 CR3022 Parental CDR Sequences SEQ ID NO VH CDR1 YGFITYWIG 421 VH CDR2 GIIYPGDSETRYS 422 VH CDR3 CAGGSGISTPMDV 423 VL CDR1 KSSQSVLYSSINKNYLA 424 VL CDR2 WASTRES 425 VL CDR3 CQQYYSTPYT 426
TABLE-US-00010 Clone VH/VL Parental CDR Sequences SEQ ID NO CR3022 VH QMQVQSGTEVKKPGESLKISCKGSGYGFITYWIGW 427 VRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISA DKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDV WGQGTTVTVSS CR3022 VL DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKN428 YLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGS GTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTK VEIK
The present disclosure describes superhuman (SH) antibodies and antigen-binding fragments herein that selectively bind to SARS-Cov-2.
A SH antibody or antigen-binding fragment herein that is "derived from" these parental clones and which selectively bind to SARS-Cov-1 or MERS refers to an antibody or antigen-binding fragment that does not comprise amino acid sequences that are100% identical to the combination of CDRs of the parental clones, or that does not comprise amino acid sequences that are 100% identical to amino acid sequences of the VH and the VL sequences of the parental clones. Instead, such SH antibodies orantibody-binding fragments can have some degree of sequence identity to the parental clones.
In one instance, SH antibodies and antigen-binding fragments herein do not contain amino acid sequences that are 100% identical to the following combination of CDRs of the parental clone 2dd8 of SEQ ID NOS: 389-394, or amino acid sequences thatare 100% identical to the VH/VL combination of SEQ ID NOS: 395 and 396.
In one instance, SH antibodies and antigen-binding fragments herein do not contain amino acid sequences that are 100% identical to the following combination of CDRs of the parental clone 2ghw of the CDRs of SEQ ID NOS: 397-402, or amino acidsequences that are 100% identical to the VH/VL combination of SEQ ID NOS: 403 and 404.
In one instance, SH antibodies and antigen-binding fragments herein do not contain amino acid sequences that are 100% identical to the following combination of CDRs of the parental clone 3bgf of the CDRs of SEQ ID NOS: 405-410, or amino acidsequences that are 100% identical to the VH/VL combination of SEQ ID NOS: 411 and 412.
In one instance, SH antibodies and antigen-binding fragments herein do not contain amino acid sequences that are 100% identical to the following combination of CDRs of the parental clone 6nb6 of the CDRs of SEQ ID NOS: 413-418, or amino acidsequences that are 100% identical to the VH/VL combination of SEQ ID NOS: 419 and 420.
In one instance, SH antibodies and antigen-binding fragments herein do not contain amino acid sequences that are 100% identical to the following combination of CDRs of the parental clone CR3022 of the CDRs of SEQ ID NOS: 421-426, or amino acidsequences that are 100% identical to the VH/VL combination of SEQ ID NOS: 427 and 428.
As used herein, the terms "SH antibody or antigen-binding fragment" and "SH antibody or antigen-binding fragment herein which selectively binds to the SARS-Cov-2" are synonymous.
A SH antibody or antigen-binding fragment herein also refers to an antibody or antigen-binding fragment that selectively binds to SARS-Cov-2, and which has a greater binding affinity for SARS-Cov-2 than to SARS-Cov-1. A SH antibody orantigen-binding fragment herein that is derived from the parental clone also refers to a SH antibody or antigen-binding fragment that is capable of neutralizing the activity of SARS-Cov-2. A SH antibody or antigen-binding fragment herein can selectivelybind to the receptor binding domain (RBD) of SARS-Cov-2. In one instance, a SH antibody or antigen-binding fragment herein selectively binds solely to SARS-Cov-2, and not to SARS1, SARS2, and/or Middle East Respiratory Syndrome (MERS).
Binding affinity of a SH antibody or antigen-binding fragment herein can be determined by any suitable means including, but not limited to, high-throughput surface plasmon resonance (SPR) kinetic experiments. Briefly, a SH antibody orantigen-binding fragment herein is immobilized to a solid surface using an anti-V5 antibody. Different concentrations of antigen (SARS-Cov-2, SARS-Cov-1, SARS2, or MERS RBD proteins) are flowed over the immobilized SH antibodies or antigen-bindingfragments to characterize the interactions to the immobilized SH antibodies or antigen-binding fragments. The SPR signal originates from changes in the refractive index at the surface of a gold sensor chip. An increase in mass associated with a bindingevent between an antibody or antigen-binding fragment and the antigen causes a proportional increase in the refractive index, which is observed as a change in response. These changes are measured as changes in the resonance angle (.delta..theta.) ofrefracted light when the antigen, flowing in a microfluidic channel, binds to the immobilized antibody and increases in density at the sensor chip. For antibody-antigen interactions, the change in refractive index on the surface is linearly related tothe number of antigens bound to an immobilized antibody. The response signal (the SPR signal) is quantified in resonance units (RU). When a steady-state is achieved (all binding sites occupied), the maximum RU is determined (n: number of binding sitesin ligand). Monitoring the change in the SPR signal over time produces a sensorgram, a plot of the binding response (RU) versus time which allows different stages of a binding event to be visualized and evaluated. During the injection of an antigen,the binding response increase is due to the formation of antigen-antibody complexes at the surface and the sensorgram is dominated by the association phase. After a certain time of injection, a steady state is reached, in which binding and dissociatingmolecules are in equilibrium. The decrease in response after analyte injection is terminated is due to dissociation of the complexes, defining the dissociation phase. Depending on the dissociation rate of the tested antibody, some assays may require aregeneration step in order to reach the baseline again. Fitting the sensorgram data to an appropriate kinetic binding model allows calculation of kinetic parameters such as the association (k.sub.d) and dissociation (k.sub.d) rate constants, and thebinding affinity of the tested interactions.
Preferably, a SH antibody or antigen-binding fragment herein selectively binds to SARS-Cov-2 with a binding affinity of less than 50 nM. In one instance, a SH antibody or antigen-binding fragment herein can selectively bind to SARS-Cov-2 with abinding affinity of from about 0.26 nM (e.g., 260 pM) to about 50 nM. In one instance, a SH antibody or antigen-binding fragment herein can selectively bind to SARS-Cov-2 with a binding affinity of less than 50 nM, 49 nM, 48 nM, 47 nM, 46 nM, 45 nM, 44nM, 43 nM, 42 nM, 41 nM, 40 nM, 39 nM, 38 nM, 37 nM, 36 nM, 35 nM, 34 nM, 33 nM, 32 nM, 31 nM, 30 nM, 29 nM, 28 nM, 27 nM, 26 nM, 25 nM, 24 nM, 23 nM, 22 nM, 21 nM, 20 nM, 19 nM, 18 nM, 17 nM, 16 nM, 15 nM, 14 nM, 13 nM, 12 nM, 11 nM, 10 nM, 9 nM, 8 nM,7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, 990 pM, 980 pM, 970 pM, 960 pM, 950 pM, 940 pM, 930 pM, 920 pM, 910 pM, 900 pM, 890 pM, 880 pM, 870 pM, 860 pM, 850 pM, 840 pM, 830 pM, 820 pM, 810 pM, 800 pM, 790 pM, 780 pM, 770 pM, 760 pM, 750 pM, 740 pM, 730pM, 720 pM, 710 pM, 700 pM, 690 pM, 680 pM, 670 pM, 660 pM, 650 pM, 640 pM, 630 6M, 620 pM, 610 pM, 600 pM, 590 pM, 580 pM, 570 pM, 560 pM, 550 pM, 540 pM, 530 pM, 520 pM, 510 pM, 500 pM, 490 pM, 480 pM, 470 pM, 460 pM, 450 pM, 440 pM, 430 pM, 420 pM,410 pM, 400 pM, 390 pM, 380 pM, 370 pM, 360 pM, 350 pM, 340 pM, 330 pM, 320 pM, 310 pM, 300 pM, 290 pM, 280 pM, 270 pM, 260 pM, 250 pM, 240 pM, 230 pM, 220 pM, 210 pM, 200 pM, 190 pM, or 180 pM, or any integer therebetween.
In any of the embodiments herein, a SH antibody or antigen-binding fragment herein can neutralize the activity of SARS-Cov-2. Neutralization ability of a SH antibody or antigen-binding fragment herein can be assessed using any suitable meansincluding, but not limited to, an in vitro pseudovirus assay. For example, spike genes from a SARS-Cov-2 virus are codon-optimized for human cells and cloned into eukaryotic expression plasmids to generate envelope recombinant plasmids; mammalian cellsare then transfected with the plasmids. The transfected mammalian cells are contacted with a SH antibody or antigen-binding fragment herein and trypsinization is determined as a measure of neutralization. In some instances, a SH antibody orantigen-binding fragment herein neutralize SARS-Cov-2 by at least 5%, 10%, 15%, 20%, 25%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or more compared to a non-specific antibody, or compared to an antibody that selectively binds toSARS-Cov-1 or MERS. Neutralization ability of a SH antibody or antigen-binding fragment herein can also be assessed using, for example, an in vivo hamster animal model. For example, hamsters can be injected with either saline or a SH antibody orantigen-binding fragment herein. Body weight and viable signs (e.g., ruffled hair and movement) are recorded. Viral titers are assessed in homogenates of lung tissues and/or by immunohistochemistry of lung tissue. A SH antibody or antigen-bindingfragment herein reduces viral titers compared to controls.
Competition assay of the interaction of SARS-Cov-2 with angiotensin-converting enzyme 2 (ACE2) can be assessed using an assay including, but not limited to, a classical sandwich and premix assay format. For example, anti-V5 tag antibodies arebiotinylated and loaded onto streptavidin sensor tips. For a classical sandwich assay format, a SH antibody or antigen-binding fragment herein is loaded onto the anti-V5 sensor tips. Following establishment of a baseline, SARS-Cov-2 is added, followedby sandwiching of ACE2 or buffer. Dissociation in buffer is measured. Capture of biotinylated ACE2 is included as a self-blocking control. Alternatively, for a premix assay format, a SH antibody or antigen-binding fragment herein are loaded onto theanti-V5 sensor tips. Following establishment of a baseline, a premix complex of SARS-Cov-2+ACE2, or a SARS-Cov-2 alone are added to the antibodies or antigen-binding fragments. Dissociation in buffer is measured. Capture of biotinylated ACE2 isincluded as a self-blocking control.
Representative CDR Sequences that Selectively Bind to SARS-Cov-2
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-Cov-2 can comprise an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100%identical to a VH CDR3 comprising an amino acid sequence of any one of any one of SEQ ID NOS: 293-316 and 429-320.
In some instances, a SH antibody or antigen-binding fragment herein that selectively binds to SARS-Cov-2 can further comprise an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,98%, 99%, or 100% identical to one or more of a VH CDR1 comprising an amino acid of any one of SEQ ID NOS: 197-220 and 431-432; and a VH CDR2 comprising an amino acid sequence of any one of SEQ ID NOS: 245-268 and 433-434.
In some instances, a SH antibody or antigen-binding fragment herein that selectively binds to SARS-Cov-2 can further comprise an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,98%, 99%, or 100% identical to one or more of a VL CDR1 comprising an amino acid of any one of SEQ ID NOS: 29-52 and 435-436, a VL CDR2 comprising an amino acid sequence of any one of SEQ ID NOS: 77-100 and 437-438, and a VL CDR3 comprising an amino acidsequence of any one of SEQ ID NOS: 125-148 and 439-440.
In other instances, a SH antibody or antigen-binding fragment that specifically binds to a Sars-Cov-2 virus, that comprises an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,98%, 99%, or 100% identical to a VH CDR1, a VH CDR2, a VH CDR3, a VL CDR1, a VL CDR2, and a VL CDR3; wherein the VH CDR1 has an amino acid sequence of any one of SEQ ID NOS: 197-220 and 431-432; the VH CDR2 has an amino acid sequence of any one of SEQ IDNOS: 245-268 and 433-434; the VH CDR3 has an amino acid sequence of any one of SEQ ID NOS: 293-316 and 429-420; a VL CDR1 has an amino acid sequence of any one of SEQ ID NOS: 29-52 and 435-436; a VL CDR2 has an amino acid sequence of any one of SEQ IDNOS: 77-100 and 437-438; and a VL CDR3 has an amino acid sequence of any one of SEQ ID NOS: 125-148 and 441.
Representative VH CDR3 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00011 Clone ID VH CDR3 SEQ ID NO: COVID19_P23_F10 CAIGTTVVTPFGYW 293 COVID19_P24_H06 CARGQVRGSGPQVVVMDVW 294 COVID19_P24_F11 CAKDGTLITTTLDYW 295 COVID19_P23_G11 CARAGYSSSSGYYYYGMDVW 296 COVID19_P24_D09 CARVRGSAAIAMMDVW 297COVID19_P11_H02 CASFERFGELVPETFDYW 298 COVID19_P24_C06 CARDRGSYDTDAFDIW 299 COVID19_P12_B07 CASAHSSSWYSDWFDPW 300 COVID19_P24_H04 CAGMGMGRDGYNSRAFDIW 301 COVID19_P23_G10 CARVDYGDYGRLEDYW 302 COVID19_P24_A09 CARLEGGSYWTGYFDLW 303 COVID19_P11_D12CAKTRYGGNSRSRYYYYGMDVW 304 COVID19_P24_A11 CARDLMDIVVVPWLGGMDVW 305 COVID19_P24_C10 CARD SGVDTATLRYYYYGMDVW 306 COVID19_P11_D08 CARDSGVDTATLRYYYYGMDVW 307 COVID19_P24_E02 CAKDVQNYYGSGSSFDYW 308 COVID19_P23_H10 CARGSSGYYFGW 309 COVID19_P24_G06CTTDPVLEWFGYSIW 310 COVID19_P24_C01 CAKGAPHDYIWGSYRPDAFDIW 311 COVID19_P24_G09 CAKGAPHDYIWGSYRPDAFDIW 312 COVID19_P24_D08 CATVTPGYGMDVW 313 COVID19_P11_H07 CARGWMAYDAFDIW 314 COVID19_P11_G03 CARDRGYSYDHDQIYYYYGMDVW 315 COVID19_P24_B09 CARDRGDTIDYW 316COVID19_P23_G12 CARDRGSYDTDAFDIW 429 Representative VH CDR1 sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00012 Clone ID VH CDR1 SEQ ID NO: COVID19_P23_F10 DTFSNYGIS 197 COVID19_P24_H06 FSFSNYDMH 198 COVID19_P24_F11 FTFSGSAMH 199 COVID19_P23_G11 GTFRSTAIS 200 COVID19_P24_D09 GTFSSYAIS 201 COVID19_P11_H02 GTFTSYHMH 202 COVID19_P24_C06YIFTSYPIH 203 COVID19_P12_B07 YTFINYDIN 204 COVID19_P24_H04 YTFTDYHMH 205 COVID19_P23_G10 YTFTDYYIQ 206 COVID19_P24_A09 YTFTDYYMQ 207 COVID19_P11_D12 YTFTENEMH 208 COVID19_P24_A11 YTFTENEMH 209 COVID19_P24_C10 YTFTENEMH 210 COVID19_P11_D08 YTFTENEMH 211COVID19_P24_E02 YTFTGNYIH 212 COVID19_P23_H10 YTFTGSYAIS 213 COVID19_P24_G06 YTFTNYGIS 214 COVID19_P24_C01 YTFTRYYIH 215 COVID19_P24_G09 YTFTRYYIH 216 COVID19_P24_D08 YTFTSYDIN 217 COVID19_P11_H07 YTFTSYDIN 218 COVID19_P11_G03 YTFTSYEIN 219COVID19_P24_B09 YTFTSYGIS 220 COVID19_P23_G12 YIFTSYPIH 430
Representative VH CDR2 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a VH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00013 Clone ID VH CDR2 SEQ ID NO: COVID19_P23_F10 GWMNPNSGGTNYA 245 COVID19_P24_H06 AVISYDGGFKLYA 246 COVID19_P24_F11 SAISRNGGTTYYA 247 COVID19_P23_G11 GWMNPNSGNTGYA 248 COVID19_P24_D09 GIVNPSSGSTTYA 249 COVID19_P11_H02 GWMNPNSGNTGYA250 COVID19_P24_C06 GWMNPNSGNTGYA 251 COVID19_P12_B07 GVINPSAGSTSYA 252 COVID19_P24_H04 GWMNPNSGNTSYA 253 COVID19_P23_G10 GWINPNSGGPNYA 254 COVID19_P24_A09 GWIDPHSGATNYA 255 COVID19_P11_D12 GIINPSGGSTSYA 256 COVID19_P24_A11 GIINPSGGSTSYA 257COVID19_P24_C10 GIINPSGGSTSYA 258 COVID19_P11_D08 GIINPSGGSTSYA 259 COVID19_P24_E02 GWMNPNSGNTGYA 260 COVID19_P23_H10 GWINPKTGDTNYA 261 COVID19_P24_G06 GWISARNGNTNYA 262 COVID19_P24_C01 GIINPSGGSTTYA 263 COVID19_P24_G09 GIINPSGGSTTYA 264 COVID19_P24_D08GIIDPSGGSTSYA 265 COVID19_P11_H07 GWMNSNSGSTGYA 266 COVID19_P11_G03 GIINPSDGSSTYA 267 COVID19_P24_B09 GGIIPMFGTTNYA 268 COVID19_P23_G12 GWMNPNSGNTGYA 431
Representative VL CDR1 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a VL CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00014 Clone ID VL CDR1 SEQ ID NO: COVID19_P23_F10 RASESVSSRYLA 29 COVID19_P24_H06 QASQGIRNDLG 30 COVID19_P24_F11 RAS QSIGYYLN 31 COVID19_P23_G11 RASQGISNNLN 32 COVID19_P24_D09 RASQDIRNELG 33 COVID19_P11_H02 RASQGIRNDLA 34COVID19_P24_C06 RASQDISNYLN 35 COVID19_P12_B07 RASQSISSYLN 36 COVID19_P24_H04 RASQSISTYLN 37 COVID19_P23_G10 RASQSIYSWLA 38 COVID19_P24_A09 RASQSVSSNYLA 39 COVID19_P11_D12 RASQHISSYLN 40 COVID19_P24_A11 RASQAITNYLA 41 COVID19_P24_C10 QASQDISKYLN 42COVID19_P11_D08 QASQDISKYLN 43 COVID19_P24_E02 RASQGIRNYLA 44 COVID19_P23_H10 RASQSISSYLN 45 COVID19_P24_G06 KSSQSVFSSSNNKNYLA 46 COVID19_P24_C01 RASENIDSWLA 47 COVID19_P24_G09 RASENIDSWLA 48 COVID19_P24_D08 RASQTIYSYLN 49 COVID19_P11_H07 QASQSIYNYLN 50COVID19_P11_G03 RVSQGISSYLN 51 COVID19_P24_B09 RASQGISNNLN 52 COVID19_P23_G12 RASQDISNYLN 432
Representative VL CDR2 sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00015 Clone ID VL CDR2 SEQ ID NO: COVID19_P23_F10 GASTRAT 77 COVID19_P24_H06 DASRLQS 78 COVID19_P24_F11 AASSLQS 79 COVID19_P23_G11 AASSLQS 80 COVID19_P24_D09 AASSLQS 81 COVID19_P11_H02 AASSLQS 82 COVID19_P24_C06 AASNLQS 83COVID19_P12_B07 AASSLQS 84 COVID19_P24_H04 AASTLQS 85 COVID19_P23_G10 DASSLES 86 COVID19_P24_A09 AVSSRAT 87 COVID19_P11_D12 AASALQS 88 COVID19_P24_A11 AASSLQS 89 COVID19_P24_C10 GASTLSD 90 COVID19_P11_D08 GASTLSD 91 COVID19_P24_E02 AASTLQS 92COVID19_P23_H10 AASRLQS 93 COVID19_P24_G06 WASTRES 94 COVID19_P24_C01 EASTLES 95 COVID19_P24_G09 EASTLES 96 COVID19_P24_D08 DASNLET 97 COVID19_P11_H07 DASNLET 98 COVID19_P11_G03 AASILQS 99 COVID19_P24_B09 AASSLES 100 COVID19_P23_G12 AASNLQS 433
Representative VL CDR3 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00016 Clone ID VL CDR3 SEQ ID NO: COVID19_P23_F10 CQQGYKNPPTF 125 COVID19_P24_H06 CQQYYSTPPLTF 126 COVID19_P24_F11 CQQSYTTPLTF 127 COVID19_P23_G11 CQQYDTFPLTF 128 COVID19_P24_D09 CQQSYSTPPWTF 129 COVID19_P11_H02 CQQSYSTPPTF 130COVID19_P24_C06 CQQANSFPSTF 131 COVID19_P12_B07 CQQSYSTPLTF 132 COVID19_P24_H04 CQQSYSMPLTF 133 COVID19_P23_G10 CQQLNSYPYTF 134 COVID19_P24_A09 CQQYGSSPLTF 135 COVID19_P11_D12 CQQGYGTPYTF 136 COVID19_P24_A11 CQQYYSYPPTF 137 COVID19_P24_C10 CQQGYSTPYSF138 COVID19_P11_D08 CQQGYSTPYSF 139 COVID19_P24_E02 CQQSYSPPLTF 140 COVID19_P23_H10 CQQSYSTPLTF 141 COVID19_P24_G06 CQQYYSTPLTF 142 COVID19_P24_C01 CHQYLSSPETF 143 COVID19_P24_G09 CHQYLSSPETF 144 COVID19_P24_D08 CQQAISFPLTF 145 COVID19_P11_H07CQQAISFPLTF 146 COVID19_P11_G03 CQQGYSTPFTF 147 COVID19_P24_B09 CQQGNGFPLTF 148 COVID19_P23_G12 CQQANSFPSTF 441
Representative CDR Combinations
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 293; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 197; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 245; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 29; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 77; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 125.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 294; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 198; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 246; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 30; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 78; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 126.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 295; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 199; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 247; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 31; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 79; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 127.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 296; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 200; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 248; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 32; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 80; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 128.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 297; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 201; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 249; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 33; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 81; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 129.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 298; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 202; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 250; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 34; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 82; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 130.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 299; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 203; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 251; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 35; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 83; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 131.
In one instance, the antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 300; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 204; (ii) a VHCDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 252; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 36; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 84; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 132.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 301; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 205; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 253; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 37; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 85; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 133.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 302; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 206; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 254; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 38; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 86; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 134.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 303; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 207; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 255; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 39; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 87; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 135.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 304; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 208; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 256; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 40; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 88; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 136.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 305; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 209; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 257; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 41; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 89; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 137.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 306; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 210; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 258; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 42; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 90; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 138.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 307; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 211; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 259; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 43; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 91; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 139.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 308; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 212; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 260; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 44; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 92; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 140.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 309; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 213; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 261; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 45; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 93; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 141.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 310; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 214; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 262; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 46; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 94; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 142.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 311; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 215; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 263; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 47; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 95; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 143.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 312; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 216; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 264; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 48; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 96; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 144.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 313; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 217; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 265; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 49; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 97; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 145.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 314; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 218; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 266; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 50; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 98; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 146.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 315; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 219; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 267; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 51; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 99; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 147.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 316; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 220; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 268; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 52; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 100; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 148.
In one instance, the SH antibody or antigen-binding fragment that selectively binds to SARS-Cov-2 can comprise (i) a VH CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 429; (ii) a VH CDR1 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 430; (ii) aVH CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 431; (iv) a VL CDR1 having an amino acid sequence that is at least 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 432; (v) a VL CDR2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95%, 98%, 99%, or 100% identical to SEQ ID NO: 433; and (vi) a VL CDR3 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 441.
Representative Superhuman (SH) Frameworks (FW) of Antibodies and Antigen-Binding Fragments that Selectively Bind to SARS-CoV-2
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-Cov-2 can comprise an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100%identical to one or more of a FW-L1 comprising an amino acid sequence of any one of SEQ ID NOS: 5-28, a FW-L2 comprising an amino acid sequence of any one of SEQ ID NOS: 53-76, a FW-L3 comprising an amino acid sequence of any one of any one of SEQ IDNOS: 101-124, a FW-L4 comprising amino acid of any one of SEQ ID NOS: 149-172, 435, a FW-H1 comprising an amino acid sequence of any one of SEQ ID NOS: 173-196, a FW-H2 comprising amino acid sequence of any one of SEQ ID NOS: 221-244, a FW-H3 comprisingan amino acid sequence of any one of SEQ ID NOS: 269-292, and a FW-H4 comprising an amino acid sequence of any one of SEQ ID NOS: 317-340.
Representative FW-L1 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a (FW-L1) having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00017 Clone ID FW-L1 SEQ ID NO: COVID19_P23_F10 EIVMTQSPATLSVSPGERATLSC 5 COVID19_P24_H06 DIQMTQSPSSLSASVGDRVTITC 6 COVID19_P24_F11 DIQMTQSPSSLSASVGDRVTITC 7 COVID19_P23_G11 DIQMTQSPSSLSASVGDRVTITC 8 COVID19_P24_D09DIQMTQSPSSLSASVGDRVTITC 9 COVID19_P11_H02 DIQMTQSPSSLSASVGDRVTITC 10 COVID19_P24_C06 DIQMTQSPSSLSASVGDRVTITC 11 COVID19_P12_B07 DIQMTQSPSSLSASVGDRVTITC 12 COVID19_P24_H04 DIQMTQSPSSLSASVGDRVTITC 13 COVID19_P23_G10 DIQMTQSPSSLSASVGDRVTITC 14COVID19_P24_A09 EIVMTQSPATLSVSPGERATLSC 15 COVID19_P11_D12 DIQMTQSPSSLSASVGDRVTITC 16 COVID19_P24_A11 DIQMTQSPSSLSASVGDRVTITC 17 COVID19_P24_C10 DIQMTQSPSSLSASVGDRVTITC 18 COVID19_P11_D08 DIQMTQSPSSLSASVGDRVTITC 19 COVID19_P24_E02 DIQMTQSPSSLSASVGDRVTITC20 COVID19_P23_H10 DIQMTQSPSSLSASVGDRVTITC 21 COVID19_P24_G06 DIVMTQSPDSLAVSLGERATINC 22 COVID19_P24_C01 DIQMTQSPSSLSASVGDRVTITC 23 COVID19_P24_G09 DIQMTQSPSSLSASVGDRVTITC 24 COVID19_P24_D08 DIQMTQSPSSLSASVGDRVTITC 25 COVID19_P11_H07DIQMTQSPSSLSASVGDRVTITC 26 COVID19_P11_G03 DIQMTQSPSSLSASVGDRVTITC 27 COVID19_P24_B09 DIQMTQSPSSLSASVGDRVTITC 28 COVID19_P23_G12 DIQMTQSPSSLSASVGDRVTITC 28
Representative FW-L2 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a FW-L2 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00018 Clone ID FW-L2 SEQ ID NO: COVID19_P23_F10 WYQQKPGQAPRLLIY 53 COVID19_P24_H06 WYQQKPGKAPKLLIY 54 COVID19_P24_F11 WYQQKPGKAPKLLIY 55 COVID19_P23_G11 WYQQKPGKAPKLLIY 56 COVID19_P24_D09 WYQQKPGKAPKLLIY 57 COVID19_P11_H02WYQQKPGKAPKLLIY 58 COVID19_P24_C06 WYQQKPGKAPKLLIY 59 COVID19_P12_B07 WYQQKPGKAPKLLIY 60 COVID19_P24_H04 WYQQKPGKAPKLLIY 61 COVID19_P23_G10 WYQQKPGKAPKLLIY 62 COVID19_P24_A09 WYQQKPGQAPRLLIY 63 COVID19_P11_D12 WYQQKPGKAPKLLIY 64 COVID19_P24_A11WYQQKPGKAPKLLIY 65 COVID19_P24_C10 WYQQKPGKAPKLLIY 66 COVID19_P11_D08 WYQQKPGKAPKLLIY 67 COVID19_P24_E02 WYQQKPGKAPKLLIY 68 COVID19_P23_H10 WYQQKPGKAPKLLIY 69 COVID19_P24_G06 WYQQKPGQPPKLLIY 70 COVID19_P24_C01 WYQQKPGKAPKLLIY 71 COVID19_P24_G09WYQQKPGKAPKLLIY 72 COVID19_P24_D08 WYQQKPGKAPKLLIY 73 COVID19_P11_H07 WYQQKPGKAPKLLIY 74 COVID19_P11_G03 WYQQKPGKAPKLLIY 75 COVID19_P24_B09 WYQQKPGKAPKLLIY 76 COVID19_P23_G12 WYQQKPGKAPKLLIY 76
Representative FW-L3 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a FW-L3 having an amino acid sequence o that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00019 Clone ID FW-L3 SEQ ID NO: COVID19_P23_F10 GIPARFSGSGSGTEFTLTISSLQSEDFAVYY 101 COVID19_P24_H06 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 102 COVID19_P24_F11 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 103 COVID19_P23_G11 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY104 COVID19_P24_D09 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 105 COVID19_P11_H02 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 106 COVID19_P24_C06 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 107 COVID19_P12_B07 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 108 COVID19_P24_H04GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 109 COVID19_P23_G10 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 110 COVID19_P24_A09 GIPARFSGSGSGTEFTLTISSLQSEDFAVYY 111 COVID19_P11_D12 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 112 COVID19_P24_A11 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 113COVID19_P24_C10 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 114 COVID19_P11_D08 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 115 COVID19_P24_E02 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 116 COVID19_P23_H10 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 117 COVID19_P24_G06GVPDRFSGSGSGTDFTLTISSLQAEDVAVYY 118 COVID19_P24_C01 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 119 COVID19_P24_G09 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 120 COVID19_P24_D08 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 121 COVID19_P11_H07 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 122COVID19_P11_G03 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 123 COVID19_P24_B09 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 124 COVID19_P23_G12 GVPSRFSGSGSGTDFTLTISSLQPEDFATYY 124
Representative FW-L4 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise FW-L4 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or100% identical to any one of the following sequences:
TABLE-US-00020 Clone ID FW-L4 SEQ ID NO: COVID19_P23_F10 GQGTKVEIKR 149 COVID19_P24_H06 GQGTKVEIKR 150 COVID19_P24_F11 GGGTKVEIKR 151 COVID19_P23_G11 GQGTKLEIKR 152 COVID19_P24_D09 GQGTKLEIKR 153 COVID19_P11_H02 GQGTKLEIKR 154 COVID19_P24_C06GQGTKLEIKR 155 COVID19_P12_B07 GGGTKVEIKR 156 COVID19_P24_H04 GQGTKVEIKR 157 COVID19_P23_G10 GQGTKVEIKR 158 COVID19_P24_A09 GGGTKVEIKR 159 COVID19_P11_D12 GQGTKLEIKR 160 COVID19_P24_A11 GQGTKLEIKR 161 COVID19_P24_C10 GQGTKLEIKR 162 COVID19_P11_D08GQGTKLEIKR 163 COVID19_P24_E02 GQGTKVEIKR 164 COVID19_P23_H10 GGGTKVEIKR 165 COVID19_P24_G06 GGGTKVEIKR 166 COVID19_P24_C01 GQGTKVEIKR 167 COVID19_P24_G09 GQGTKVEIKR 168 COVID19_P24_D08 GGGTKLEIKR 169 COVID19_P11_H07 GGGTKVEIKR 170 COVID19_P11_G03GPGTKVDIKR 171 COVID19_P24_B09 GPGTKVDIKR 172 COVID19_P23_G12 GQGTKLEIKR 435
Representative FW-H1 Sequences
A SH antibody or antigen-binding fragment herein can comprise a VH framework (FW) 1 (FW-H1) having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100%identical to any one of the following sequences:
TABLE-US-00021 SEQ ID Clone ID FW-H1 NO: COVID19_P23_F10 QVQLVQSGAEVKKPGASVKVSCKASG 173 COVID19_P24_H06 EVQLLESGGGLVQPGGSLRLSCAASG 174 COVID19_P24_F11 EVQLLESGGGLVQPGGSLRLSCAASG 175 COVID19_P23_G11 QVQLVQSGAEVKKPGASVKVSCKASG 176 COVID19_P24_D09QVQLVQSGAEVKKPGASVKVSCKASG 177 COVID19_P11_H02 QVQLVQSGAEVKKPGASVKVSCKASG 178 COVID19_P24_C06 QVQLVQSGAEVKKPGASVKVSCKASG 179 COVID19_P12_B07 QVQLVQSGAEVKKPGASVKVSCKASG 180 COVID19_P24_H04 QVQLVQSGAEVKKPGASVKVSCKASG 181 COVID19_P23_G10QVQLVQSGAEVKKPGSSVKVSCKASG 182 COVID19_P24_A09 QVQLVQSGAEVKKPGASVKVSCKASG 183 COVID19_P11_D12 QVQLVQSGAEVKKPGASVKVSCKASG 184 COVID19_P24_A11 QVQLVQSGAEVKKPGASVKVSCKASG 185 COVID19_P24_C10 QVQLVQSGAEVKKPGASVKVSCKASG 186 COVID19_P11_D08QVQLVQSGAEVKKPGASVKVSCKASG 187 COVID19_P24_E02 QVQLVQSGAEVKKPGASVKVSCKASG 188 COVID19_P23_H10 QVQLVQSGAEVKKPGASVKVSCKASG 189 COVID19_P24_G06 QVQLVQSGAEVKKPGASVKVSCKASG 190 COVID19_P24_C01 QVQLVQSGAEVKKPGASVKVSCKASG 191 COVID19_P24_G09QVQLVQSGAEVKKPGASVKVSCKASG 192 COVID19_P24_D08 QVQLVQSGAEVKKPGASVKVSCKASG 193 COVID19_P11_H07 QVQLVQSGAEVKKPGASVKVSCKASG 194 COVID19_P11_G03 QVQLVQSGAEVKKPGASVKVSCKASG 195 COVID19_P24_B09 QVQLVQSGAEVKKPGSSVYVSCKASG 196 COVID19_P23_G12QVQLVQSGAEVKKPGASVKVSCKASG 194
Representative FW-H2 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a FW-112 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00022 Clone ID FW-H2 SEQ ID NO: COVID19_P23_F10 WVRQAPGQGLEWM 221 COVID19_P24_H06 WVRQAPGKGLEWV 222 COVID19_P24_F11 WVRQAPGKGLEYV 223 COVID19_P23_G11 WVRQAPGQGLEWM 224 COVID19_P24_D09 WVRQAPGQGLEWM 225 COVID19_P11_H02 WVRQAPGQGLEWM 226COVID19_P24_C06 WVRQAPGQGLEWM 227 COVID19_P12_B07 WVRQAPGQGLEWM 228 COVID19_P24_H04 WVRQAPGQGLEWM 229 COVID19_P23_G10 WVRQAPGQGLEWM 230 COVID19_P24_A09 WVRQAPGQGLEWM 231 COVID19_P11_D12 WVRQAPGQGLEWM 232 COVID19_P24_A11 WVRQAPGQGLEWM 233 COVID19_P24_C10WVRQAPGQGLEWM 234 COVID19_P11_D08 WVRQAPGQGLEWM 235 COVID19_P24_E02 WVRQAPGQGLEWM 236 COVID19_P23_H10 WVRQAPGQGLEWM 237 COVID19_P24_G06 WVRQAPGQGLEWM 238 COVID19_P24_C01 WVRQAPGQGLEWM 239 COVID19_P24_G09 WVRQAPGQGLEWM 240 COVID19_P24_D08 WVRQAPGQGLEWM241 COVID19_P11_H07 WVRQAPGQGLEWM 242 COVID19_P11_G03 WVRQAPGQGLEWM 243 COVID19_P24_B09 WVRQAPGQGLEWM 244 COVID19_P23_G12 WVRQAPGQGLEWM 244
Representative FW-H3 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a FW-113 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00023 Clone ID FW-H3 SEQ ID NO: COVID19_P23_F10 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 269 COVID19_P24_H06 DSVKGRFTISRDNAKNSLYLRMNSLRSEDTAVYY 270 COVID19_P24_F11 DSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY 271 COVID19_P23_G11QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 272 COVID19_P24_D09 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 273 COVID19_P11_H02 LKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 274 COVID19_P24_C06 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 275 COVID19_P12_B07 HKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY276 COVID19_P24_H04 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 277 COVID19_P23_G10 QKFQGRVTITADESTSTAYMELSSLRSEDTAVYY 278 COVID19_P24_A09 HSFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 279 COVID19_P11_D12 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 280 COVID19_P24_A11QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 281 COVID19_P24_C10 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 282 COVID19_P11_D08 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 283 COVID19_P24_E02 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 284 COVID19_P23_H10 QEFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY285 COVID19_P24_G06 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 286 COVID19_P24_C01 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 287 COVID19_P24_G09 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 288 COVID19_P24_D08 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 289 COVID19_P11_H07QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 290 COVID19_P11_G03 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 291 COVID19_P24_B09 QKFQGRVTITADKSTSTAYMELSSLRSEDTAVYY 292 COVID19_P23_G12 QKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYY 291
Representative FW-H4 Sequences
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise a FW-114 having an amino acid sequence that is at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%,or 100% identical to any one of the following sequences:
TABLE-US-00024 Clone ID FW-H4 SEQ ID NO: COVID19_P23_F10 GQGTLVNVSS 317 COVID19_P24_H06 GKGTTVTVSS 318 COVID19_P24_F11 GQGTLVTVSS 319 COVID19_P23_G11 GKGTTVTVSS 320 COVID19_P24_D09 GQGTTVTVSS 321 COVID19_P11_H02 GQGTLVTVSS 322 COVID19_P24_C06GQGTMVTVSS 323 COVID19_P12_B07 GQGTLVTVSS 324 COVID19_P24_H04 GQGTMVTVSS 325 COVID19_P23_G10 GQGTLVTVSS 326 COVID19_P24_A09 GRGTLVTVSS 327 COVID19_P11_D12 GQGTTVTVSS 328 COVID19_P24_A11 GQGTTVTVSS 329 COVID19_P24_C10 GQGTTVTVSS 330 COVID19_P11_D08GQGTTVTVSS 331 COVID19_P24_E02 GQGTLVTVSS 332 COVID19_P23_H10 GQGTLVTVSS 333 COVID19_P24_G06 GQGTMVTVSS 334 COVID19_P24_C01 GQGTMVTVSS 335 COVID19_P24_G09 GQGTMVTVSS 336 COVID19_P24_D08 GQGTTVTVSS 337 COVID19_P11_H07 GQGTMVTVSS 338 COVID19_P11_G03GQGTTVTVSS 339 COVID19_P24_B09 GQGTLVTVSS 340 COVID19_P23_G12 GQGTMVTVSS 338
Representative SH VH and VL Sequences that Bind to SARS-CoV-2
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise an VH amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to any one of the following sequences:
TABLE-US-00025 SEQ ID Clone ID VH NO: COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGDTFSNYGISWVRQAPGQGLEWM 341 P23_F10 GWMNPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCA IGTTVVTPFGYWGQGTLVNVSS COVID19_ EVQLLESGGGLVQPGGSLRLSCAASGFSFSNYDMHWVRQAPGKGLEWVA 342P24_H06 VISYDGGFKLYADSVKGRFTISRDNAKNSLYLRMNSLRSEDTAVYYCARG QVRGSGPQVVVMDVWGKGTTVTVSS COVID19_ EVQLLESGGGLVQPGGSLRLSCAASGFTFSGSAMHWVRQAPGKGLEYVS 343 P24_F11 AISRNGGTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKD GTLITTTLDYWGQGTLVTVSS COVID19_QVQLVQSGAEVKKPGASVKVSCKASGGTFRSTAISWVRQAPGQGLEWMG 344 P23_G11 WMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR AGYSSSSGYYYYGMDVWGKGTTVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMG 345 P24_D09IVNPSSGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARV RGSAAIAMMDVWGQGTTVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGGTFTSYHMHWVRQAPGQGLEWM 346 P11_H02 GWMNPNSGNTGYALKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCA SFERFGELVPETFDYWGQGTLVTVSS COVID19_QVQLVQSGAEVKKPGASVKVSCKASGYIFTSYPIHWVRQAPGQGLEWMG 347 P24_C06 WMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DRGSYDTDAFDIWGQGTMVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFINYDINWVRQAPGQGLEWM 348 P12_B07GVINPSAGSTSYAHKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAS AHSSSWYSDWFDPWGQGTLVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYHMHWVRQAPGQGLEW 349 P24_H04 MGWMNPNSGNTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYC AGMGMGRDGYNSRAFDIWGQGTMVTVSS COVID19_QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYYIQWVRQAPGQGLEWM 350 P23_G10 GWINPNSGGPNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR VDYGDYGRLEDYWGQGTLVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMQWVRQAPGQGLEW 351 P24_A09 MGWIDPHSGATNYAHSFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARLEGGSYWTGYFDLWGRGTLVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTENEMHWVRQAPGQGLEWM 352 P11_D12 GIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKT RYGGNSRSRYYYYGMDVWGQGTTVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTENEMHWVRQAPGQGLEWM 353 P24_A11GIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARD LMDIVVVPWLGGMDVWGQGTTVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTENEMHWVRQAPGQGLEWM 354 P24_C10 GIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARD SGVDTATLRYYYYGMDVWGQGTTVTVSS COVID19_QVQLVQSGAEVKKPGASVKVSCKASGYTFTENEMHWVRQAPGQGLEWM 355 P11_D08 GIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARD SGVDTATLRYYYYGMDVWGQGTTVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTGNYIHWVRQAPGQGLEWM 356 P24_E02GWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCA KDVQNYYGSGSSFDYWGQGTLVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTGSYAISWVRQAPGQGLEWM 357 P23_H10 GWINPKTGDTNYAQEFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCA RGSSGYYFGWGQGTLVTVSS COVID19_QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGISWVRQAPGQGLEWM 358 P24_G06 GWISARNGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCT TDPVLEWFGYSIWGQGTMVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYYIHWVRQAPGQGLEWM 359 P24_C01GIINPSGGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKG APHDYIWGSYRPDAFDIWGQGTMVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYYIHWVRQAPGQGLEWM 360 P24_G09 GIINPSGGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKG APHDYIWGSYRPDAFDIWGQGTMVTVSS COVID19_QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWM 361 P24_D08 GIIDPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATV TPGYGMDVWGQGTTVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWM 362 P11_H07 GWMNSNSGSTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGWMAYDAFDIWGQGTMVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYEINWVRQAPGQGLEWM 363 P11_G03 GIINPSDGSSTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARD RGYSYDHDQIYYYYGMDVWGQGTTVTVSS COVID19_ QVQLVQSGAEVKKPGSSVYVSCKASGYTFTSYGISWVRQAPGQGLEWMG 364 P24_B09GIIPMFGTTNYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARDR GDTIDYWGQGTLVTVSS COVID19_ QVQLVQSGAEVKKPGASVKVSCKASGYIFTSYPIHWVRQAPGQGLEWMG 436 P23_G12 WMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DRGSYDTDAFDIWGQGTMVTVSS
A SH antibody or antigen-binding fragment herein that selectively binds to SARS-CoV-2 can comprise an VL amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to any one of the following sequences
TABLE-US-00026 SEQ ID CloneID VL NO: COVID19_ EIVMTQSPATLSVSPGERATLSCRASESVSSRYLAWYQQKPGQAPRLLIYG 365 P23_F10 ASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQGYKNPPTFGQGT KVEIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCQASQGIRNDLGWYQQKPGKAPKLLIYDA 366 P24_H06SRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYSTPPLTFGQGT KVEIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQSIGYYLNWYQQKPGKAPKLLIYAA 367 P24_F11 SSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTTPLTFGGGTK VEIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKLLIYAA368 P23__G11 SSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYDTFPLTFGQZTK VEIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQDIRNELGWYQQKPGKAPKLLIYAA 369 P24_D09 SSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPWTFGQGT KLEIKR COVID19_DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLAWYQQKPGKAPKLLIYAA 370 P11_H02 SSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTFGQGTKL EIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYAA 371 P24_C06 SNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPSTFGQGTK LEIKRCOVID19_ DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAAS 372 P12_B07 SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKV EIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQKPGKAPKLLIYAAS 373 P24_H04TLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSMPLTFGQGTKV EIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQSIYSWLAWYQQKPGKAPKLLIYDA 374 P23_G10 SSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNSYPYTFGQGTK VEIKR COVID19_ EIVMTQSPATLSVSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLLIYA 375P24_A09 VSSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGSSPLTFGGGT KVEIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQHISSYLNWYQQKPGKAPKLLIYAA 376 P11_D12 SALQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYGTPYTFGZZTK VEIKR COVID19_DIQMTQSPSSLSASVGDRVTITCRASQAITNYLAWYQQKPGKAPKLLIYAA 377 P24_A11 SSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYSYPPTFGQGTK LEIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCQASQDISKYLNWYQQKPGKAPKLLIYGA 378 P24_C10 STLSDGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSTPYSFGQGTK LEIKRCOVID19_ DIQMTQSPSSLSASVGDRVTITCQASQDISKYLNWYQQKPGKAPKLLIYGA 379 P11_D08 STLSDGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSTPYSFGZGTK LEIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQGIRNYLAWYQQKPGKAPKLLIYAA 380 P24_E02STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSPPLTFGQGTK VEIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAAS 381 P23_H10 RLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKV EIKR COVID19_ DIVMTQSPDSLAVSLGERATINCKSSQSVFSSSNNKNYLAWYQQKPGQPPK382 P24_G06 LLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPL TFGGZTKVEIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASENIDSWLAWYQQKPGKAPKLLIYEA 383 P24_C01 STLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYLSSPETFGQGTK VEIKR COVID19_DIQMTQSPSSLSASVGDRVTITCRASENIDSWLAWYQQKPGKAPKLLIYEA 384 P24_G09 STLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYLSSPETFGQGTK VEIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQTIYSYLNWYQQKPGKAPKLLIYDA 385 P24_D08 SNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAISFPLTFGGGTKL EIKRCOVID19_ DIQMTQSPSSLSASVGDRVTITCQASQSIYNYLNWYQQKPGKAPKLLIYDA 386 P11_H07 SNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAISFPLTFGGGTKV EIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRVSQGISSYLNWYQQKPGKAPKLLIYAA 387 P11_G03SILQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSTPFTFGPGTKV DIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQGISNNLNWYQQKPGKAPKLLIYAA 388 P24_B09 SSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNGFPLTFGPGTK VDIKR COVID19_ DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYAA437 P23_G12 SNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPSTFGQGTK LEIKR
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 341and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 365.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 342and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 366.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 343and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 367.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 344and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 368.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 345and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 369.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 346and an VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 370.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 347and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 371.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 348and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 372.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 349and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 373.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 350and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 374.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 351and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 375.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 352and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 376.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 353and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 377.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 354and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 378.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 355and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 379.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 356and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 380.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 357and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 381.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 358and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 382.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 359and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 383.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 360and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 384.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 361and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 385.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 362and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 386.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 363and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 387.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 364and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 388.
In one instance, a SH antibody or antigen-binding fragment, herein that selectively binds to SARS-Cov-2 can comprise a VH having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 436and a VL having an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 437.
Modified Antibodies
The present disclosure provides for modified antibodies. Modified antibodies can comprise antibodies which have one or more modifications which can enhance their activity, binding, specificity, selectivity, or another feature. In one aspect,the present disclosure provides for modified antibodies (which can be heteromultimers) that comprise an anti-SARS-Cov-2 antibody as herein. Reference to a modified antibody herein also refers to a modified antigen-binding fragment.
A modified antibody can comprise a bispecific modified antibody, a trispecific modified antibody or antigen-binding fragment, or a tetraspecific modified antibody or antigen-binding fragment. A bispecific modified antibody can be able tospecifically bind to 2 targets. In some cases, one of the targets a bispecific modified antibody can specifically bind to can be a SARS-CoV-2. A trispecific modified antibody can be able to specifically bind to 3 targets. In some cases, one of thetargets a trispecific modified antibody can specifically bind to can be a SARS-CoV-2. A tetraspecific modified antibody can be able to specifically bind to 4 targets. In some cases, one of the targets a tetraspecific modified antibody can specificallybind to can be a SARS-CoV-2.
A modified antibody can comprise a human modified antibody. Also included herein are amino acid sequence variants of the modified antibody which can be prepared by introducing appropriate nucleotide changes into the modified antibody DNA, or bysynthesis of the desired modified antibody polypeptide. Such variants include, for example, deletions from, or insertions or substitutions of, residues within the amino acid sequences of the first and second polypeptides forming the modified antibody. Any combination of deletion, insertion, and substitution is made to arrive at the final construct, provided that the final construct possesses the desired antigen-binding characteristics. The amino acid changes also may alter post-translationalprocesses of the modified antibody, such as changing the number or position of glycosylation sites.
"Alanine scanning mutagenesis" can be a useful method for identification of certain residues or regions of the modified antibody polypeptides that might be preferred locations for mutagenesis. Here, a residue or group of target residues areidentified (e.g., charged residues such as Arg, Asp, His, Lys, and Glu) and replaced by a neutral or negatively charged amino acid (for example, alanine or polyalanine) to affect the interaction of the amino acids with the surrounding aqueous environmentin or outside the cell. Those domains demonstrating functional sensitivity to the substitutions then are refined by introducing further or other variants at or for the sites of substitution. Thus, while the site for introducing an amino acid sequencevariation is predetermined, the nature of the mutation per se need not be predetermined.
Normally the mutations can involve conservative amino acid replacements in non-functional regions of the modified antibody. Exemplary mutations are shown below.
TABLE-US-00027 Original Preferred Residue Exemplary Substitutions Substitutions Ala (A) Val; Leu; Ile Val Arg (R) Lys; Gln; Asn Lys Asn (N) Gln; His; Lys; Arg Gln Asp (D) Glu Glu Cys (C) Ser Ser Gln (Q) Asn Asn Glu (E) Asp Asp Gly (G) Pro; AlaAla His (H) Asn; Gln; Lys; Arg Arg Ile (I) Leu; Val; Met; Ala; Phe; Norleucine Leu Leu (L) Norleucine; Ile; Val; Met; Ala; Phe Ile Lys (K) Arg; Gln; Asn Arg Met (M) Leu; Phe; Ile Leu Phe (F) Leu; Val; Ile; Ala; Tyr Leu Pro (P) Ala Ala Ser (S) Thr Thr Thr(T) Ser Ser Trp (W) Tyr; Phe Tyr Tyr (Y) Trp; Phe; Thr; Ser Phe Val (V) Ile; Leu; Met; Phe; Ala; Norleucine Leu
Covalent modifications of antibody, antigen-binding fragment, or modified antibody polypeptides are included within the scope of this disclosure. Covalent modifications of the modified antibody can be introduced into the molecule by reactingtargeted amino acid residues of the modified antibody or fragments thereof with an organic derivatizing agent that can be capable of reacting with selected side chains or the N- or C-terminal residues. Another type of covalent modification of themodified antibody polypeptide can comprise altering the native glycosylation pattern of the polypeptide. Herein, "altering" can mean deleting one or more carbohydrate moieties found in the original modified antibody, and/or adding one or moreglycosylation sites that are not present in the original modified antibody. Addition of glycosylation sites to the modified antibody polypeptide can be accomplished by altering the amino acid sequence such that it contains one or more N-linkedglycosylation sites. The alteration may also be made by the addition of, or substitution by, one or more serine or threonine residues to the original modified antibody sequence (for O-linked glycosylation sites). For ease, the modified antibody aminoacid sequence can be altered through changes at the DNA level, particularly by mutating the DNA encoding the modified antibody polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids. Anothermeans of increasing the number of carbohydrate moieties on the modified antibody polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide. Removal of carbohydrate moieties present on the modified antibody can be accomplishedchemically or enzymatically.
Another type of covalent modification of modified antibody comprises linking the modified antibody polypeptide to one of a variety of non-proteinaceous polymers, e.g., polyethylene glycol, polypropylene glycol, or polyoxyalkylenes.
Methods for complexing binding agents or the antibody or antigen-binding fragments thereof herein with another agent are known in the art. Such methods may utilize one of several available heterobifunctional reagents used for coupling orlinking molecules.
In one instance, Fc portions of antibodies can be modified to increase half-life of the molecule in the circulation in blood when administered to a subject.
Additionally, antibodies may be produced or expressed so that they do not contain fucose on their complex N-glycoside-linked sugar chains to increase effector functions. Similarly, antibodies can be attached at their C-terminal end to all orpart of an immunoglobulin heavy chain derived from any antibody isotype, e.g., IgG, IgA, IgE, IgD, and IgM and any of the isotype subclasses, e.g., IgG1, IgG2b, IgG2a, IgG3, and IgG4.
Glycosylation of immunoglobulins has been shown to have significant effects on their effector functions, structural stability, and rate of secretion from antibody-producing cells. Antibodies and antigen-binding fragments herein may beglycosylated. Glycosylation at a variable domain framework residue can alter the binding interaction of the antibody with antigen. The present disclosure includes criteria by which a limited number of amino acids in the framework or CDRs of animmunoglobulin chain can be chosen to be mutated (e.g., by substitution, deletion, and/or addition of residues) in order to increase the affinity of an antibody.
Linkers for conjugating antibodies to other moieties are within the scope of the present disclosure. Associations (binding) between antibodies and labels include, but are not limited to, covalent and non-covalent interactions, chemicalconjugation, as well as recombinant techniques.
Antibodies, or antigen-binding fragments thereof, can be modified for various purposes such as, for example, by addition of polyethylene glycol (PEG). PEG modification (PEGylation) can lead to one or more of improved circulation time, improvedsolubility, improved resistance to proteolysis, reduced antigenicity and immunogenicity, improved bioavailability, reduced toxicity, improved stability, and easier formulation.
An antibody or antigen-binding fragment can be conjugated to, or recombinantly engineered with, an affinity tag (e.g., a purification tag). Affinity tags such as, for example, His6 tags (His-His-His-His-His-His) (SEQ ID NO: 442) have beendescribed.
Since it is often difficult to predict in advance the characteristics of a variant modified antibody, it will be appreciated that some screening of the recovered variants may be needed to select an optimal variant. Exemplary methods ofscreening the recovered variants are described below in the Examples.
Methods of Expressing Antibodies
Also provided herein are methods of making any of these antibodies or polypeptides. The polypeptides can be produced by proteolytic or other degradation of the antibodies, by recombinant methods (i.e., single or fusion polypeptides) asdescribed above, or by chemical synthesis. Polypeptides of the antibodies, especially shorter polypeptides up to about 50 amino acids, can be made by chemical synthesis. Methods of chemical synthesis are commercially available. For example, anantibody could be produced by an automated polypeptide synthesizer employing a solid phase method.
Antibodies may be made recombinantly by first isolating the antibodies and antibody producing cells from host animals, obtaining the gene sequence, and using the gene sequence to express the antibody recombinantly in host cells (e.g., CHOcells). Another method which may be employed is to express the antibody sequence in plants (e.g., tobacco) or transgenic milk. Methods for expressing antibodies recombinantly in plants or milk have been disclosed. Methods for making derivatives ofantibodies, e.g., single chain, etc. are also within the scope of the present disclosure.
As used herein, "host cell" includes an individual cell or cell culture that can be or has been a recipient for vector(s) for incorporation of polynucleotide inserts. Host cells include progeny of a single host cell, and the progeny may notnecessarily be completely identical (in morphology or in genomic DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation. A host cell includes cells transfected with a polynucleotide(s) of this disclosure.
DNA encoding an antibody may be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the monoclonalantibodies). Hybridoma cells may serve as a source of such DNA. Once isolated, the DNA may be placed into one or more expression vectors (such as expression vectors disclosed in PCT Publication No. WO 87/04462), which are then transfected into hostcells such as E. coli cells, simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also may bemodified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences, or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence fora non-immunoglobulin polypeptide. In that manner, "chimeric" or "hybrid" antibodies are prepared that have the binding specificity of an antibody herein.
Contemplated herein are vectors that encode the one or more antibodies or antigen-binding fragments herein. As used herein, "vector" means a construct, which is capable of delivering, and possibly expressing, one or more gene(s) or sequence(s)of interest in a host cell. Examples of vectors include, but are not limited to, viral vectors; naked DNA or RNA expression vectors; plasmid, cosmid, or phage vectors; DNA or RNA expression vectors associated with cationic condensing agents; DNA or RNAexpression vectors encapsulated in liposomes; and certain eukaryotic cells, such as producer cells.
As used herein, "expression control sequence" means a nucleic acid sequence that directs transcription of a nucleic acid. An expression control sequence can be a promoter, such as a constitutive or an inducible promoter, or an enhancer. Theexpression control sequence is operably linked to the nucleic acid sequence to be transcribed. An expression vector can be used to direct expression of an antibody. Expression vectors can be administered to obtain expression of an exogenous protein invivo.
For high level production, a widely used mammalian expression system is one which utilizes Lonza's GS Gene Expression System.TM.. This system uses a viral promoter and selection via glutamine metabolism to provide development of high-yieldingand stable mammalian cell lines.
For alternative high-level production, a widely used mammalian expression system is one which utilizes gene amplification by dihydrofolate reductase deficient ("dhfr") Chinese hamster ovary cells. The system is based upon the dihydrofolatereductase "dhfr" gene, which encodes the DHFR enzyme, which catalyzes conversion of dihydrofolate to tetrahydrofolate. In order to achieve high production, dhfr-CHO cells are transfected with an expression vector containing a functional DHFR gene,together with a gene that encodes a desired protein. In this case, the desired protein is recombinant antibody heavy chain and/or light chain.
By increasing the amount of the competitive DHFR inhibitor methotrexate (MTX), the recombinant cells develop resistance by amplifying the dhfr gene. In standard cases, the amplification unit employed is much larger than the size of the dhfrgene, and as a result the antibody heavy chain is co-amplified.
When large scale production of the protein, such as the antibody chain, is desired, both the expression level and the stability of the cells being employed are taken into account.
The present application provides one or more isolated polynucleotides (nucleic acids) encoding an antibody or an antigen-binding fragment herein, vectors containing such polynucleotides, and host cells and expression systems for transcribing andtranslating such polynucleotides into polypeptides.
The present application also provides constructs in the form of plasmids, vectors, transcription or expression cassettes which comprise at least one polynucleotide as above.
The present application also provides a recombinant host cell which comprises one or more constructs as above. A nucleic acid encoding any antibody herein forms an aspect of the present application, as does a method of production of theantibody, which method comprises expression from encoding nucleic acid therefrom. Expression can be achieved by culturing under appropriate conditions recombinant host cells containing the nucleic acid. Following production by expression, an antibodyor a portion thereof can be isolated and/or purified using any suitable technique, then used as appropriate. Systems for cloning and expression of a polypeptide in a variety of different host cells are contemplated for use herein.
A further aspect provides a host cell containing nucleic acid as disclosed herein using any suitable method. A still further aspect provides a method comprising introducing such nucleic acid into a host cell. The introduction can be followedby causing or allowing expression from the nucleic acid, e.g., by culturing host cells under conditions for expression of the gene.
One or more polynucleotides encoding an antibody or an antigen-binding fragment can be prepared recombinantly/synthetically in addition to, or rather than, cloned. In a further embodiment, the full DNA sequence of the recombinant DNA moleculeor cloned gene(s) of an antibody or antigen-binding fragment herein can be operatively linked to an expression control sequence which can be introduced into an appropriate host using any suitable method.
Nucleic acid sequences can be expressed by operatively linking them to an expression control sequence in an appropriate expression vector and employing that expression vector to transform an appropriate host cell. Any of a wide variety ofexpression control sequences--sequences that control the expression of a nucleic acid sequence operatively linked to it--can be used in these vectors to express the nucleic acid sequences.
A wide variety of host/expression vector combinations can be employed in expressing the nucleic acid sequences of this disclosure. It will be understood that not all vectors, expression control sequences, and hosts will function equally well toexpress the nucleic acid sequences. Neither will all hosts function equally well with the same expression system. In some embodiments, in selecting a vector, the host is considered such that the vector can function in it. The vector's copy number, theability to control that copy number, and the expression of any other proteins encoded by the vector, such as antibiotic markers, may also be considered. In certain embodiments, in selecting a vector, the host is considered such that the vector functionsin it. The vector's copy number, the ability to control that copy number, and the expression of any other proteins encoded by the vector, such as antibiotic markers, can also be considered.
The present application also provides a method which comprises using a construct as stated above in an expression system in order to express the antibodies (or portions thereof) as above. Considering these and other factors, a variety ofvector/expression control sequence/host combinations can be constructed that can express the nucleic acid sequences on fermentation or in large scale animal culture.
Simultaneous incorporation of the antibody (or portion thereof)-encoding nucleic acids and the selected amino acid position changes can be accomplished by a variety of suitable methods including, for example, recombinant and chemical synthesis.
Provided herein are methods of expressing an antibody or antigen-binding fragment antigen-binding that can selectively bind to SARS-Cov-2 in a subject comprising administering to the subject a composition comprising one or more polynucleotides(e.g., mRNA) encoding the antibody or antigen-binding fragment.
In some cases, administering the one or more polynucleotides to the subject can comprise enteral, gastroenteral, oral, transdermal, epicutaneous, intradermal, subcutaneous, nasal administration, intravenous, intraperitoneal, intraarterial,intramuscular, intraosseous infusion, transmucosal, insufflation, or sublingual administration. In some cases, a polynucleotide can be administered via more than one route.
Antibodies or antigen-binding fragments can be synthesized in the subject based at least in part on the polynucleotide encoding the antibody or antigen-binding fragment. For example, a polynucleotide can enter a cell of the subject, and theantibody or antigen-binding fragment can be synthesized at least in part by using the subject's cellular transcription and/or translation machinery. In some cases, for example where the polynucleotide is an mRNA molecule, the antibody or antigen-bindingfragment can be synthesized at least in part by using the subject's cellular translation machinery (e.g., ribosomes, tRNA, etc.). In some cases, antibody or antigen-binding fragments can be transported from a cell to the plasma of the subject aftertranslation.
Compositions
Compositions comprising a SH antibody or antigen-binding fragment herein may be prepared for storage by mixing an antibody or antigen-binding fragment having the desired degree of purity with optional pharmaceutically acceptable carriers,excipients or stabilizers (Remington, The Science and Practice of Pharmacy 20th Ed. Mack Publishing (2000)), in the form of lyophilized formulations or aqueous solutions.
As used herein, "pharmaceutically acceptable carrier" or "pharmaceutical acceptable excipient" includes any material which, when combined with an active ingredient, allows the ingredient to retain biological activity and is non-reactive with thesubject's immune system. Examples include, but are not limited to, any of the standard pharmaceutical carriers such as a phosphate buffered saline solution, water, emulsions such as oil/water emulsion, and various types of wetting agents. Preferreddiluents for aerosol or parenteral administration are phosphate buffered saline or normal (0.9%) saline. Compositions comprising such carriers are formulated by well-known conventional methods (see, for example, Remington's Pharmaceutical Sciences, 18thedition, A. Gennaro, Ed., Mack Publishing Co., Easton, Pa., 1990; and Remington, The Science and Practice of Pharmacy 20th Ed. Mack Publishing, 2000).
Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and may comprise buffers such as phosphate, citrate, and other organic acids; salts such as sodium chloride; antioxidantsincluding ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens, such as methyl or propylparaben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone;amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol,trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and/or non-ionic surfactants such as TWEEN.TM., PLURONICS.TM. or polyethylene glycol (PEG).
The compositions to be used for in vivo administration may be sterilized. This may be accomplished by, for example, filtration through sterile filtration membranes, or any other art-recognized method for sterilization. Antibody compositionsare generally placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle. Other methods for sterilization and filtration are known in the art andare contemplated herein.
In one embodiment of the present invention, the compositions are formulated to be free of pyrogens such that they are acceptable for administration to a subject.
The compositions according to the present invention may be in unit dosage forms such as solutions or suspensions, tablets, pills, capsules, powders, granules, or suppositories, etc., for intravenous, oral, parenteral or rectal administration, oradministration by inhalation or insufflation.
The phrase "pharmaceutically acceptable" refers to molecular entities and compositions that are physiologically tolerable and do not typically produce an allergic or similar untoward reaction, such as gastric upset, dizziness and the like, whenadministered to a subject.
In some instances, an antibody or antigen-binding fragment can be bound to one or more carriers. Carriers can be active and/or inert. Examples of well-known carriers include polypropylene, polystyrene, polyethylene, dextran, nylon, amylases,glass, natural and modified celluloses, polyacrylamides, agaroses and magnetite. The nature of the carrier can be either soluble or insoluble for purposes of the invention. Those skilled in the art will know of other suitable carriers for bindingantibodies, or will be able to ascertain such, using routine experimentation.
One embodiment contemplates the use of the antibodies and antigen-binding fragments to manufacture a medicament for treating a condition, disease or disorder described herein. Medicaments can be formulated based on the physical characteristicsof the subject needing treatment, and can be formulated in single or multiple formulations based on the stage of the condition, disease or disorder. Medicaments can be packaged in a suitable package with appropriate labels for the distribution tohospitals and clinics wherein the label is for the indication of treating a subject having a disease described herein. Medicaments can be packaged as a single or multiple units. Instructions for the dosage and administration of the compositions can beincluded with the packages as described below. The invention is further directed to medicaments of an antibody or antigen-binding fragment and a pharmaceutically acceptable carrier.
Kits
Provided herein are kits that comprise one or more SH antibodies or antigen-binding fragments herein. Provided herein is a container means comprising one or more SH antibodies or antigen-binding fragments herein. The container means may be anysuitable container which may house a liquid or lyophilized composition including, but not limited to, a vial, a syringe, a bottle, an intravenous (IV) bag, an ampoule, or any other suitable container. A syringe may be able to hold any volume of liquidsuitable for injection into a subject including, but not limited to, 0.5 cc, 1 cc, 2 cc, 5 cc, 10 cc or more. In some embodiments, the SH antibody or antigen-binding fragment is lyophilized, and the kit comprises one or more suitable buffers forreconstitution prior to injection.
The kit may comprise one or more instruction sheets describing the use of the one or more SH antibodies or antigen-binding fragments. The kit may include one or more labels describing the contents and use of the one or more SH antibodies.
Methods of Treatment
The present disclosure provides methods of preventing or treating a subject infected with SARS-Cov-2 (COVID) or suspected of being infected with SARS-Cov-2 in a subject in need thereof, comprising administering to the subject an antibody herein. In one instance, the subject to be treated is symptomatic prior to administration of the antibody. In another instance, the subject to be treated is asymptomatic prior to administration of the antibody.
The present disclosure provides methods of prophylactically treating (e.g., preventing) a subject having one or more co-morbidities or having an increased or high risk of infection.
A "subject" as herein, includes, but is not limited to, a human, a rodent, a primate, etc. In some instances, the subject to be treated exhibits one or more underlying conditions that exacerbate the infection such as, for example, high bloodpressure, heart problems, diabetes, immunocompromised, lung disease, cancer, clots, thrombosis, or a combination thereof.
A subject can be administered a SH antibody or antigen-binding fragment herein in an amount that achieves at least partially a partial or complete reduction of one or more symptoms. Reduction can be, for example, a decrease of one or moresymptoms by about 5% or more compared to prior to treatment. For the administration to human patients, the compositions can be formulated by methodology known by one in the art. The amount of an antibody necessary to bring about therapeutic treatmentof COVID19 is not fixed per se. The amount of antibody administered may vary with the extensiveness of the disease, and size of the human suffering from COVID19. Treatment, in one instance, lowers infection rates in a population of subjects. Treatmentmay also result in a shortened recovery time, in fewer symptoms, or in less severe symptoms, or a combination thereof compared to an untreated subject who has COVID19.
The SH antibodies and antigen-binding fragments herein may be used to treat a COVID19 infection (an infection caused by SARS-Cov-2) in a subject in need thereof, thereby reducing one or more symptoms of the infection. The one or more symptomsto be treated include, but are not limited to, a fever of over 100.4.degree. F., fatigue, coughing (e.g., a dry cough), aches, pains, runny nose, stuffy nose, sore throat, diarrhea, headaches, shortness of breath, or any combination thereof. In someinstances, treatment of a subject includes a reduction by at least 5% in 1 symptom, 2 symptoms, 3 symptoms, 4 symptoms, 5 symptoms, 6 symptoms, 7 symptoms, 8 symptoms, 9 symptoms, 10 symptoms, or 11 symptoms. During at least a portion of this timeperiod the SH antibody or antigen-binding fragment can protect the subject from infection by SARS-Cov-2. Protecting can comprise for example reducing an infection rate of SARS-Cov-2 or reducing or preventing reproduction of SARS-Cov-2. Treatment cancomprise for example reducing symptoms of COVID-19, reducing a death rate, or reducing or preventing reproduction of SARS-Cov-2.
"Administering" is referred to herein as providing one or more compositions to a patient in a manner that results in the composition being inside the patient's body. Such an administration can be by any route including, without limitation,locally, regionally, or systemically, by subcutaneous, intradermal, intravenous, intra-arterial, intraperitoneal, or intramuscular administration (e.g., injection). In one instance, administration is via intradermal injection. In another instance,administration is via subcutaneous injection. In one embodiment, a subject is administered one of the antibodies or antigen-binding fragments herein one or more times. In another embodiment, a subject is administered two of the antibodies orantigen-binding fragments herein one or more times. In another embodiment, a subject is administered three of the antibodies or antigen-binding fragments herein one or more times. In another embodiment, a subject is administered four of the antibodiesor antigen-binding fragments herein one or more times. A SH antibody or antigen-binding fragment herein to be administered to the subject exhibits a nM or a pM binding affinity, e.g., between 180 pM and 50 nM.
The present disclosure provides methods of reducing the death rate of infection by SARS-Cov-2 by administering to a subject in need thereof a composition comprising one or more polynucleotides (e.g., mRNA) encoding an antibody or antigen-bindingfragment that can specifically bind to SARS-Cov-2. Reduction in death rate can be determined for example by comparing the rate of death of subjects infected by SARS-Cov-2 between a cohort that receives the composition and a cohort that does not receivethe composition. Death rate can be determined for example by determining the number of infected subjects of a cohort wherein infection by SARS-Cov-2 results in death. In some cases, the death rate can be reduced compared with subjects not administereda composition comprising an mRNA molecule provided herein by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%. In some cases, the death rate can be reducedcompared with subjects not administered a composition comprising an mRNA molecule provided herein by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or a range between any two foregoing values.
The present disclosure also provides methods for reducing the infection rate of SARS-Cov-2 by administering to a subject non infected with SARS-Cov-2 a composition comprising one or more polynucleotides (e.g., mRNA) encoding an antibody orantigen-binding fragment that can specifically bind to SARS-CoV-2. Reduction in infection rate can be determined for example by comparing the rate of infection of subjects exposed to SARS-Cov-2 between a cohort that receives the composition and a cohortthat does not receive the composition. Infection of a subject can be determined by analyzing a sample from the subject for the presence or absence of SARS-Cov-2 after suspected or confirmed exposure to SARS-Cov-2, or after an elapsed time in whichexposure to SARS-Cov-2 is likely. In some cases, the infection rate can be reduced compared with subjects not administered a composition comprising an mRNA molecule provided herein by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%,at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%. In some cases, the infection rate can be reduced compared with subjects not administered a composition comprising an mRNA molecule provided herein by about 10%, about 20%, about30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or a range between any two foregoing values.
The present disclosure also provides methods for slowing or preventing reproduction of SARS-Cov-2 in a subject by administering to a subject infected with SARS-Cov-2 a composition comprising one or more polynucleotides (e.g., mRNA) encoding anantibody or antigen-binding fragment that can specifically bind to SARS-Cov-2. Slowing or preventing reproduction of SARS-Cov-2 can be determined for example by comparing the rate of reproduction of the virus in subjects infected SARS-Cov-2 between acohort that receives the composition and a cohort that does not receive the composition. Replication of SARS-Cov-2 can be determine for example by determining (directly or indirectly) the amount of SARS-Cov-2 in a sample acquired from the subject atdifferent time points. Assays that can be used to determine amount of SARS-Cov-2 in a sample can include a plaque assay, a focus forming assay, an endpoint dilution assay, a protein assay (e.g., a bicinchoninic acid assay or a single radialimmunodiffusion assay), transmission electron microscopy, tunable resistive pulse sensing, flow cytometry, qPCR, ELISA, or another acceptable method. An assay can be performed on a whole sample or a fraction of a sample, or SARS-Cov-2 can be isolatedfrom the sample prior to performing an assay. In some cases, the reproduction of SARS-Cov-2 can be slowed compared with subjects not administered a composition comprising an mRNA molecule provided herein by at least 5%, at least 10%, at least 20%, atleast 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%. In some cases, the reproduction of SARS-Cov-2 can be slowed compared with subjects not administered a composition comprising an mRNA molecule providedherein by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or a range between any two foregoing values.
The present disclosure also provides methods of activating T cells in a subject comprising administering to a subject a composition comprising one or more polynucleotides (e.g., mRNA) encoding an antibody or antigen-binding fragment that canspecifically bind to SARS-CoV-2. In some cases, T cell activation can be elevated compared with subjects not administered the composition. Activation of T cells can be determined for example by comparing the activation of T cells in subjects infectedSARS-Cov-2 between a cohort that receives the composition and a cohort that does not receive the composition. In one aspect, the activation of T cells in the subject can be directed to an anti-SARS-Cov-2 response in the subject. Activated T cells inthe subject can reduce severity of COVID-19 symptoms, death rate, time to recovery, or viral reproduction in the subject. Activation of T cells can be measured for example by measuring T cell proliferation, measuring cytokine production (e.g., viaenzyme-linked immunosorbent assays or enzyme-linked immunospot assays), or detection of cell-surface markers associated with T cell activation (e.g., CD69, CD40L, CD137, CD25, CD71, CD26, CD27, CD28, CD30, CD154, or CD134) for example by flow cytometry. In some cases, the T cell activation can be elevated compared with subjects not administered a composition comprising an mRNA molecule provided herein by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, atleast 70%, at least 80%, or at least 90%. In some cases, the T cell activation can be elevated compared with subjects not administered a composition comprising an mRNA molecule provided herein by about 10%, about 20%, about 30%, about 40%, about 50%,about 60%, about 70%, about 80%, about 90%, or a range between any two foregoing values.
The present disclosure also provides methods for inducing T cell proliferation in a subject comprising administering to a subject a composition comprising one or more polynucleotides (e.g., mRNA) encoding an antibody or antigen-binding fragmentthat can specifically bind to SARS-CoV-2. In some cases, T cell proliferation can be elevated compared with subjects not administered the composition. In some cases, T cell proliferation can be directed to an anti-SARS-Cov-2 response in the subject. In some cases, T cell proliferation in the subject can reduce or decrease severity of COVID-19 symptoms, death rate, time to recovery, or viral reproduction in the subject. T cell proliferation can be determined for example by cell counting, viabilitystaining, optical density assays, or detection of cell-surface markers associated with T cell activation (e.g., CD69, CD40L, CD137, CD25, CD71, CD26, CD27, CD28, CD30, CD154, or CD134) for example by flow cytometry. In some cases, T cell proliferationcan be elevated compared with subjects not administered a composition comprising an mRNA molecule provided herein by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least90%. In some cases, T cell proliferation can be elevated compared with subjects not administered a composition comprising an mRNA molecule provided herein by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about90%, or a range between any two foregoing values.
The present disclosure also provides methods for inducing a memory T cell response in a subject comprising administering to a subject a composition comprising one or more polynucleotides (e.g., mRNA) encoding an antibody or antigen-bindingfragment that can specifically bind to SARS-CoV-2. In some cases, a memory T cell response can be elevated compared with subjects not administered the composition. In some cases, a memory T cell response in the subject can reduce or decrease i severityof COVID-19 symptoms, death rate, time to recovery, or viral reproduction in the subject. A memory T cell response can be directed to an anti-SARS-Cov-2 response in the subject. A memory T cell response can be determined for example by measuring T cellmarkers associated with memory T cells, measuring local cytokine production related to memory immune response, or detecting memory T cell-surface markers for example by flow cytometry. In some cases, the memory T cell response can be elevated comparedwith subjects not administered a composition comprising an mRNA molecule provided herein by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%. In some cases, thememory T cell response can be elevated compared with subjects not administered a composition comprising an mRNA molecule provided herein by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or a rangebetween any two foregoing values.
A polynucleotide (e.g., mRNA) herein can be administered in any route available, including, but not limited to, enteral, gastroenteral, oral, transdermal, epicutaneous, intradermal, subcutaneous, nasal administration, intravenous,intraperitoneal, intraarterial, intramuscular, intraosseous infusion, transmucosal, insufflation, or sublingual administration. In some cases, mRNA of the present disclosure can be administered parenterally (e.g., includes subcutaneous, intravenous,intraperitoneal, intratumoral, intramuscular, intra-articular, intra-synovial, intrasternal, intrathecal, intrahepatic, intralesional and injection or infusion techniques), intraventricularly, orally, by inhalation spray, topically, rectally, nasally,buccally, or via an implanted reservoir.
Actual dosage levels of antibody can be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response without being toxic to the patient. The selected dosage level will depend upon avariety of factors including the activity of the particular antibody employed, the route of administration, the time of administration, the rate of excretion of the particular antibody being employed, the duration of the treatment, other drugs, compoundsand/or materials used in combination with the particular composition employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts.
The antibodies herein can be administered to a subject in various dosing amounts and over various time frames.
A physician or veterinarian can readily determine and prescribe the effective amount (ED50) of the antibody required. For example, the physician or veterinarian could start doses of the antibody employed in the composition at levels lower thanthat required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. Alternatively, a dose can remain constant.
The antibody can be administered to a patient by any convenient route such as described above. Regardless of the route of administration selected, the antibodies of the present invention, which can be used in a suitable hydrated form, and/orthe compositions, are formulated into acceptable dosage forms.
Toxicity and therapeutic efficacy of compounds can be determined by standard procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED.sub.50 (the dosetherapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50/ED50. While compounds that exhibit toxic side effects may be used, care shouldbe taken to design a delivery system that targets such compounds to the site of affected tissue in order to minimize potential damage to healthy cells and, thereby, reduce side effects.
Data obtained from cell culture assays and/or animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 withlittle or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound, a therapeutically effective dose can be estimated initially from cell culture assays. Adose can be formulated in animal models to achieve a circulating plasma concentration arrange that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition) as determined in cell culture. Levels in plasmacan be measured, for example, by high performance liquid chromatography. Such information can be used to more accurately determine useful doses in humans.
It will be understood that administration of one or more of the antibodies or antigen-binding fragments herein can be supplemented by one or more additional therapies or drugs such as, for example, respiratory therapy; one or more blood thinnersor anti-coagulants; statins, intubation; hydroxy chloroquine; one or more antibiotics (e.g., doxycycline, Azithromycin, etc.); one or more decongestants (e.g., Mucinex, Sudafed, etc.); one or more anti-histamines and/or glucocorticoids (e.g., Zyrtec,Claritin, Allegra, fluticasone luroate, etc.); one or more pain relievers (e.g., acetominophen); one or more zinc-containing medications (e.g., Zycam, etc.); Azithromycin, hydroquinolone, or a combination thereof; one or more integrase inhibitors (e.g.,Bictegravir, dolutegravir (Tivicay), elvitegravir, raltegravir, or a combination thereof); one or more nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; e.g., abacavir (Ziagen), emtricitabine (Emtriva), lamivudine (Epivir), tenofoviralafenamide fumarate (Vemlidy), tenofovir disoproxil fumarate (Viread), zidovudine (Retrovir), didanosine (Videx, Videx EC), stavudine (Zerit), or a combination thereof); a combination of NRTIs (e.g., (i) abacavir, lamivudine, and zidovudine (Trizivir),(ii) abacavir and lamivudine (Epzicom), (iii) emtricitabine and tenofovir alafenamide fumarate (Descovy), (iv) emtricitabine and tenofovir disoproxil fumarate (Truvada), (v) lamivudine and tenofovir disoproxil fumarate (Cimduo, Temixys), (vi) lamivudineand zidovudine (Combivir), etc.); a combination of Descovy and Truvada; one or more non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., doravirine (Pifeltro), efavirenz (Sustiva), etravirine (Intelence), nevirapine (Viramune, Viramune XR),rilpivirine (Edurant), delavirdine (Rescriptor), or a combination thereof); one or more Cytochrome P4503A (CYP3A) inhibitors (e.g., cobicistat (Tybost), ritonavir (Norvir), etc.); one or more protease inhibitors (PIs; e.g., atazanavir (Reyataz),darunavir (Prezista), fosamprenavir (Lexiva), lopinavir, ritonavir (Norvir), tipranavir (Aptivus), etc.); one or PIs in combination with cobicistat, ritonavir, Lopinavir, Tipranavir, Atazanavir, fosamprenavir, indinavir (Crixivan), nelfinavir (Viracept),saquinavir (Invirase), or a combination thereof; Atazanavir; fosamprenavir; a combination of Atazanavir, darunavir and cobicistat; one or more fusion inhibitors (e.g., enfuvirtide (Fuzeon); one or more post-attachment inhibitors (e.g., ibalizumab-uiyk(Trogarzo)); one or more Chemokine coreceptor antagonists (CCR5 antagonists; e.g., maraviroc (Selzentry)); and one or more viral entry inhibitors (e.g., enfuvirtide (Fuzeon), ibalizumab-uiyk (Trogarzo), maraviroc (Selzentry), etc.); or a combinationthereof.
Non-limiting examples of combinations include one or more of the antibodies or antigen-binding fragments herein to be administered with one or more of the following: (1) Azithromycin, hydroquinolone, or a combination thereof, (2) darunavir andcobicistat (Prezcobix), (3) lopinavir and ritonavir (Kaletra), (4) abacavir, lamivudine, and zidovudine (Trizivir), (5) abacavir and lamivudine (Epzicom), (6) emtricitabine and tenofovir alafenamide fumarate (Descovy), (7) emtricitabine and tenofovirdisoproxil fumarate (Truvada), (8) lamivudine and tenofovir disoproxil fumarate (Cimduo, Temixys), (9) lamivudine and zidovudine (Combivir), (10), atazanavir and cobicistat (Evotaz), (11) doravirine, lamivudine, and tenofovir disoproxil fumarate(Delstrigo), (12) efavirenz, lamivudine, and tenofovir disoproxil fumarate (Symfi), (13) efavirenz, lamivudine, and tenofovir disoproxil fumarate (Symfi Lo), (14) efavirenz, emtricitabine, and tenofovir disoproxil fumarate (Atripla), (15) emtricitabine,rilpivirine, and tenofovir alafenamide fumarate (Odefsey), (16) emtricitabine, rilpivirine, and tenofovir disoproxil fumarate (Complera), (17) elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (Stribild), (18) elvitegravir,cobicistat, emtricitabine, and tenofovir alafenamide fumarate (Genvoya), (19) abacavir, dolutegravir, and lamivudine (Triumeq), (20) bictegravir, emtricitabine, and tenofovir alafenamide fumarate (Biktarvy), (21) dolutegravir and lamivudine (Dovato),(22) dolutegravir and rilpivirine (Juluca), (23) darunavir, cobicistat, emtricitabine, and tenofovir alafenamide fumarate (Symtuza).
Non-limiting examples of combinations include one or more of the antibodies or antigen-binding fragments herein to be administered with one or more blood thinners. Blood thinners to be co-administered include, but are not limited to,anti-platelet, and anti-coagulation medications. Antiplatelet medications are those such as, for example, aspirin, clopidogrel (PLAVIX.RTM.); prasugrel (EFFIENT.RTM.); ticlopidine (TICLID.RTM.); ticagrelor (BRILINTA.RTM.); and combinations thereof. Anticoagulants include, but are not limited to, Warfarin (COUMADIN.RTM., JANTOVEN.RTM.); Heparin (e.g., FRAGMIN.RTM., INNOHEP.RTM., and LOVENOX.RTM.); Eabigatran (PRADAXA.RTM.); Epixaban (ELIQUIS.RTM.); Non-vitamin K antagonist oral anticoagulants(NOACs) such as, for example, Rivaroxaban (XARELTO.RTM.); Factor Xa inhibitors such as, for example, Edoxaban (SAVAYSA.RTM.), Fondaparinux (ARIXTRA.RTM.); and combinations thereof.
Diagnostics
Provided herein are methods of diagnosing a subject suspected of being infected with SARS-Cov-2 by contacting a sample obtained from the subject with one or more antibodies or antigen-binding fragments herein.
A "sample" from a subject to be tested utilizing one or more of the assays herein includes, but is not limited to, a nasal swab, a tissue sample, saliva, blood, etc. In some instances, the sample is treated prior to use in a diagnostic assay. For example, a nasal swab may be flushed with phosphate buffered saline (PBS); a fluid sample may be centrifuged to concentrate the sample components; blood may be treated with heparin to prevent coagulation, etc.
Samples may be tested in any suitable assay including, but not limited to, an enzyme linked immunosorbent assay (ELISA), an immunospot assay, a lateral flow assay, immunohistochemistry (IHC), western blot, flow cytometry, etc. The sample iscontacted with an antibody herein, and when the presence of the antibody bound to a SARS-CoV-2 is detected, the subject is diagnosed as being infected with SARS-Cov-2 and/or having a COVID-19 infection.
In one instance, a sample obtained from a subject is contacted with a SH antibody or antigen-binding fragment herein that selectively binds to SARS-Cov-2 and the presence or absence of the antibody or antigen-binding fragment is determined. Thesubject is diagnosed as being infected with SARS-Cov-2 when the presence of the antibody or antigen-binding fragment is detected.
Exemplary Definitions
The term "about" as used herein, generally refers to a range that is 2%, 5%, 10%, 15% greater than or less than (.+-.) a stated numerical value within the context of the particular usage. For example, "about 10" would include a range from 8.5to 11.5. As used herein, the terms "about" and "approximately," when used to modify a numeric value or numeric range, indicate that deviations of up to about 0.2%, about 0.5%, about 1%, about 2%, about 5%, about 7.5%, or about 10% (or any integerbetween about 1% and 10%) above or below the value or range remain within the intended meaning of the recited value or range.
As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, references to "a method" include one or more methods,and/or steps of the type herein and/or which will become apparent to those persons skilled in the art upon reading this disclosure.
Polypeptides (e.g., proteins) and polynucleotides (e.g., nucleic acids) herein can be isolated and/or purified from their natural environment in substantially pure or homogeneous form. Methods of purifying proteins and nucleic acids arecontemplated for use herein. "Isolated" (used interchangeably with "substantially pure") when applied to polypeptides means a polypeptide or a portion thereof which, by virtue of its origin or manipulation: (i) is present in a host cell as theexpression product of a portion of an expression vector; (ii) is linked to a protein or other chemical moiety other than that to which it is linked in nature; or (iii) does not occur in nature, for example, a protein that is chemically manipulated byappending, or adding at least one hydrophobic moiety to the protein so that the protein is in a form not found in nature. By "isolated" it is further meant a protein that is: (i) synthesized chemically or (ii) expressed in a host cell and purified awayfrom associated and contaminating proteins. The term generally means a polypeptide that has been separated from other proteins and nucleic acids with which it naturally occurs. The polypeptide may also be separated from substances such as antibodies orgel matrices (polyacrylamide) which are used to purify it. As used herein, substantially pure, isolated," or purified refers to material which is at least 50% pure (e.g., free from contaminants), at least 60% pure, at least 70% pure, at least 80% pure,at least 85% pure, at least 90% pure, at least 91% pure, at least 92% pure, at least 93% pure, at least 94% pure, at least 95% pure, at least 96% pure, at least 97% pure, at least 98% pure, or at least 99% pure.
Polypeptides can be isolated and purified from culture supernatant or ascites by saturated ammonium sulfate precipitation, an euglobulin precipitation method, a caproic acid method, a caprylic acid method, ion exchange chromatography (DEAE orDE52), or affinity chromatography using anti-Ig column or a protein A, protein G, or protein L column such as described in more detail below. In one aspect, reference to a binding agent, an antibody or an antigen-binding fragment also refers to an"isolated binding agent," an "isolated antibody," or an "isolated antigen-binding fragment." In another aspect, reference to a binding agent, an antibody, or an antigen-binding fragment also refers to a "purified binding agent," a "purified antibody," ora "purified antigen-binding fragment."
Antibodies can be "isolated" and "purified" from the culture supernatant or ascites mentioned above by saturated ammonium sulfate precipitation, euglobulin precipitation method, caproic acid method, caprylic acid method, ion exchangechromatography (DEAE or DE52), or affinity chromatography using anti-Ig column or a protein A, G or L column using art-recognized conventional methods.
As used herein, the term "antibody" refers to an immunoglobulin (Ig), polypeptide, or a protein having a binding domain which is, or is homologous to, an antigen-binding domain. The term further includes "antigen-binding fragments" and otherinterchangeable terms for similar binding fragments as described below. Native antibodies and native immunoglobulins (Igs) are generally heterotetrameric glycoproteins of about 150,000 Daltons, composed of two identical light chains and two identicalheavy chains. Each light chain is typically linked to a heavy chain by one covalent disulfide bond, while the number of disulfide linkages varies among the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularlyspaced intrachain disulfide bridges. Each heavy chain has at one end a variable domain ("VH") followed by a number of constant domains ("C.sub.H"). Each light chain has a variable domain at one end ("VL") and a constant domain ("CL") at its other end;the constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the light-chain variable domain is aligned with the variable domain of the heavy chain. Particular amino acid residues are believed to form aninterface between the light- and heavy-chain variable domains. In some instances, an antibody or an antigen-binding fragment comprises an isolated antibody or antigen-binding fragment, a purified antibody or antigen-binding fragment, a recombinantantibody or antigen-binding fragment, a modified antibody or antigen-binding fragment, or a synthetic antibody or antigen-binding fragment.
Antibodies and antigen-binding fragments herein can be partly or wholly synthetically produced. An antibody or antigen-binding fragment can be a polypeptide or protein having a binding domain which can be, or can be homologous to, anantigen-binding domain. In one instance, an antibody or an antigen-binding fragment can be produced in an appropriate in vivo animal model and then isolated and/or purified. It would be understood that the antibodies herein can be modified as describedbelow or as known in the art.
Antibodies useful in the present invention encompass, but are not limited to, monoclonal antibodies, polyclonal antibodies, antibody fragments (e.g., Fab, Fab', F(ab').sub.2, Fv, Fc, scFv, scFv-Fc, Fab-Fc, scFv-zipper, scFab, crossFab, camelids(VHH), etc.), chimeric antibodies, bispecific antibodies, multispecific antibodies, heteroconjugate antibodies, single chain (ScFv), mutants thereof, fusion proteins comprising an antibody portion (e.g., a domain antibody), humanized antibodies, humanantibodies, and any other modified configuration of the immunoglobulin molecule that comprises an antigen recognition site of the required specificity, including glycosylation variants of antibodies, amino acid sequence variants of antibodies, andcovalently modified antibodies.
Depending on the amino acid sequence of the constant domain of its heavy chains, immunoglobulins (Igs) can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these maybe further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2. An Ig or portion thereof can, in some cases, be a human Ig. In some instances, a C.sub.H3 domain can be from an immunoglobulin. In some cases, a chain or apart of an antibody or antigen-binding fragment, a modified antibody or antigen-binding fragment, or a binding agent can be from an Ig. In such cases, an Ig can be IgG, an IgA, an IgD, an IgE, or an IgM. In cases where the Ig is an IgG, it can be asubtype of IgG, wherein subtypes of IgG can include IgG1, an IgG2a, an IgG2b, an IgG3, and an IgG4. In some cases, a C.sub.H3 domain can be from an immunoglobulin selected from the group consisting of an IgG, an IgA, an IgD, an IgE, and an IgM.
The "light chains" of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa or (".kappa." or "K") and lambda or (".lamda."), based on the amino acid sequences of theirconstant domains.
As used herein, a "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, e.g., the individual antibodies comprising the population are identical except for possible naturally-occurringmutations that may be present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a singledeterminant on the antigen (epitope). The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody byany particular method. For example, the monoclonal antibodies to be used in accordance with the present invention may be made by the hybridoma method first described by Kohler and Milstein, 1975, Nature, 256:495, or may be made by recombinant DNAmethods such as described in U.S. Pat. No. 4,816,567. The monoclonal antibodies may also be isolated from phage libraries generated using the techniques described in McCafferty et al., 1990, Nature, 348:552-554, for example. Other methods are knownin the art and are contemplated for use herein.
A "variable region" of an antibody refers to the variable region of the antibody light chain or the variable region of the antibody heavy chain, either alone or in combination. The variable regions of the heavy and light chain each consist offour framework regions (FR) connected by three complementarity determining regions (CDRs) also known as hypervariable regions. The CDRs in each chain are held together in close proximity by the FRs and, with the CDRs from the other chain, contribute tothe formation of the antigen-binding site of antibodies. Amino acid residues of CDRs and framework regions are as herein for the provided sequences.
With respect to antibodies, the term "variable domain" refers to the variable domains of antibodies that are used in the binding and specificity of each particular antibody for its particular antigen. However, the variability is not evenlydistributed throughout the variable domains of antibodies. Rather, it is concentrated in three segments called hypervariable regions (also known as CDRs) in both the light chain and the heavy chain variable domains. More highly conserved portions ofvariable domains are called the "framework regions," "FWs," or "FRs." The variable domains of unmodified heavy and light chains each contain four FRs (FR1, FR2, FR3, and FR4), largely adopting a .beta.-sheet configuration interspersed with three CDRswhich form loops connecting and, in some cases, part of the .beta.-sheet structure. The CDRs in each chain are held together in close proximity by the FRs and, with the CDRs from the other chain, contribute to the formation of the antigen-binding siteof antibodies.
A "constant region" of an antibody refers to the constant region of the antibody light chain or the constant region of the antibody heavy chain, either alone or in combination.
"Epitope" refers to that portion of an antigen or other macromolecule capable of forming a binding interaction with the variable region binding pocket of an antibody. Such binding interactions can be manifested as an intermolecular contact withone or more amino acid residues of one or more CDRs. Antigen-binding can involve, for example, a CDR3 or a CDR3 pair or, in some cases, interactions of up to all six CDRs of the VH and VL chains. An epitope can be a linear peptide sequence("continuous") or can be composed of noncontiguous amino acid sequences ("conformational" or "discontinuous"). An antibody can recognize one or more amino acid sequences; therefore, an epitope can define more than one distinct amino acid sequence. Epitopes recognized by antibodies can be determined by peptide mapping and sequence analysis techniques well known to one of skill in the art. Binding interactions are manifested as intermolecular contacts between an epitope on an antigen and one ormore amino acid residues of a CDR. An epitope provided herein can refer to an amino acid sequence on a receptor binding domain or a spike domain.
An antibody selectively binds to a target if it binds with greater affinity, avidity, more readily, and/or with greater duration than it binds to other substances. For example, an antibody or antigen-binding fragment that selectively binds to aSARS-Cov-2 epitope is an antibody or antigen-binding fragment that binds this epitope with greater affinity, avidity, more readily, and/or with greater duration than it binds to SARS-Cov-1 or MERS. The term "Fc region" is used to define a C-terminalregion of an immunoglobulin heavy chain. The "Fc region" may be a native sequence Fc region or a variant Fc region. Although the boundaries of the Fc region of an immunoglobulin heavy chain might vary, the human IgG heavy chain Fc region is usuallydefined to stretch from an amino acid residue at position Cys226, or from Pro230, to the carboxyl-terminus thereof. The Fc region of an immunoglobulin generally comprises two constant domains, CH2 and CH3.
The terms "hypervariable region" and "CDR" when used herein, refer to the amino acid residues of an antibody which are responsible for antigen-binding. The CDRs comprise amino acid residues from three sequence regions which bind in acomplementary manner to an antigen and are known as CDR1, CDR2, and CDR3 for each of the VH and VL chains. It is understood that the CDRs of different antibodies may contain insertions, thus the amino acid numbering may differ. CDR sequences of theantibodies and antigen-binding fragments thereof have been provided herein below.
As used herein, "framework region" or "FR" or "FW" refers to framework amino acid residues that form a part of the antigen-binding pocket or groove. In some embodiments, the framework residues form a loop that is a part of the antigen-bindingpocket or groove and the amino acids residues in the loop may or may not contact the antigen. Framework regions generally comprise the regions between the CDRs. Framework regions of the antibodies and antigen-binding fragments thereof have beenprovided herein below.
The loop amino acids of a FR can be assessed and determined by inspection of the three-dimensional structure of an antibody heavy chain and/or antibody light chain. The three-dimensional structure can be analyzed for solvent accessible aminoacid positions as such positions are likely to form a loop and/or provide antigen contact in an antibody variable domain. Some of the solvent accessible positions can tolerate amino acid sequence diversity and others (e.g., structural positions) are,generally, less diversified. The three-dimensional structure of the antibody variable domain can be derived from a crystal structure or protein modeling.
In the present disclosure, the following abbreviations (in the parentheses) are used in accordance with the customs, as necessary: heavy chain (H chain), light chain (L chain), heavy chain variable region (VH), light chain variable region (VL),complementarity determining region (CDR), first complementarity determining region (CDR1), second complementarity determining region (CDR2), third complementarity determining region (CDR3), heavy chain first complementarity determining region (VH CDR1),heavy chain second complementarity determining region (VH CDR2), heavy chain third complementarity determining region (VH CDR3), light chain first complementarity determining region (VL CDR1), light chain second complementarity determining region (VLCDR2), and light chain third complementarity determining region (VL CDR3).
In some instances, an anti-SARS-Cov-2 antibody is a monoclonal antibody. As used herein, a "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodiescomprising the population are identical except for possible naturally-occurring mutations that may be present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against differentdeterminants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen (epitope). The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population ofantibodies and is not to be construed as requiring production of the antibody by any particular method, including the Tumbler methods described below.
In some instances, an anti-SARS-Cov-2 antibody or antigen-binding fragment is a humanized antibody or a humanized antigen-binding fragment. As used herein, "humanized" antibodies refer to forms of non-human (e.g., murine) antibodies that arespecific chimeric immunoglobulins, immunoglobulin chains, or fragments thereof that contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residuesfrom a complementarity determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and biological activity. In someinstances, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, the humanized antibody may comprise residues that are found neither in the recipient antibody nor in the imported CDRor framework sequences, but are included to further refine and optimize antibody performance. In general, a humanized antibody comprises substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDRregions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulinconstant region or domain (Fc), typically that of a human immunoglobulin. Antibodies may have Fc regions modified as described in, for example, WO 99/58572. Other forms of humanized antibodies have one or more CDRs (one, two, three, four, five, or six)which are altered with respect to the original antibody, which are also termed one or more CDRs "derived from" one or more CDRs from the original antibody.
If needed, an antibody or an antigen-binding fragment herein can be assessed for immunogenicity and, as needed, be deimmunized (i.e., the antibody is made less immunoreactive by altering one or more T cell epitopes). As used herein, a"deimmunized antibody" means that one or more T cell epitopes in an antibody sequence have been modified such that a T cell response after administration of the antibody to a subject is reduced compared to an antibody that has not been deimmunized. Analysis of immunogenicity and T-cell epitopes present in the antibodies and antigen-binding fragments herein can be carried out via the use of software and specific databases. Exemplary software and databases include iTope.TM. developed by Antitope ofCambridge, England. iTope.TM., is an in silico technology for analysis of peptide binding to human MEW class II alleles. The iTope.TM. software predicts peptide binding to human MEW class II alleles and thereby provides an initial screen for thelocation of such "potential T cell epitopes." iTope.TM. software predicts favorable interactions between amino acid side chains of a peptide and specific binding pockets within the binding grooves of 34 human MHC class II alleles. The location of keybinding residues is achieved by the in silico generation of 9mer peptides that overlap by one amino acid spanning the test antibody variable region sequence. Each 9mer peptide can be tested against each of the 34 MHC class II allotypes and scored basedon their potential "fit" and interactions with the MHC class II binding groove. Peptides that produce a high mean binding score (>0.55 in the iTope.TM. scoring function) against >50% of the MHC class II alleles are considered as potential T cellepitopes. In such regions, the core 9 amino acid sequence for peptide binding within the MHC class II groove is analyzed to determine the MHC class II pocket residues (P1, P4, P6, P7, and P9) and the possible T cell receptor (TCR) contact residues (P-1,P2, P3, P5, P8). After identification of any T-cell epitopes, amino acid residue changes, substitutions, additions, and/or deletions can be introduced to remove the identified T-cell epitope. Such changes can be made so as to preserve antibodystructure and function while still removing the identified epitope. Exemplary changes can include, but are not limited to, conservative amino acid changes.
An anti-SARS-Cov-2 antibody or antigen-binding fragment can be a human antibody or human antigen-binding fragment. As used herein, a "human antibody" means an antibody having an amino acid sequence corresponding to that of an antibody producedby a human and/or that has been made using any suitable technique for making human antibodies. This definition of a human antibody includes antibodies comprising at least one human heavy chain polypeptide or at least one human light chain polypeptide. One such example is an antibody comprising murine light chain and human heavy chain polypeptides. In one embodiment, the human antibody is selected from a phage library, where that phage library expresses human antibodies (Vaughan et al., 1996, NatureBiotechnology, 14:309-314; Sheets et al., 1998, PNAS USA, 95:6157-6162; Hoogenboom and Winter, 1991, J. Mol. Biol., 227:381; Marks et al., 1991, J. Mol. Biol., 222:581). Human antibodies can also be made by introducing human immunoglobulin loci intotransgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. This approach is described in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; and 5,661,016. Alternatively, the human antibody may be prepared by immortalizing human B lymphocytes that produce an antibody directed against a target antigen (such B lymphocytes may be recovered from an individual or may have been immunized in vitro). See, e.g.,Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boerner et al., 1991, J. Immunol., 147 (1):86-95; and U.S. Pat. No. 5,750,373.
Any of the anti-SARS-Cov-2 antibodies, or antigen-binding fragments herein can be bispecific. Bispecific antibodies are antibodies that have binding specificities for at least two different antigens or different affinities for the same antigen. Bispecific antibodies can be prepared using the antibodies or antigen-binding fragments disclosed herein. Methods for making bispecific antibodies are described (see, e.g., Suresh et al., 1986, Methods in Enzymology 121:210). Traditionally, therecombinant production of bispecific antibodies was based on the co-expression of two immunoglobulin heavy chain-light chain pairs, with the two heavy chains having different specificities (Millstein and Cuello, 1983, Nature, 305, 537-539). Bispecificantibodies can be composed of a hybrid immunoglobulin heavy chain with a first binding specificity in one arm, and a hybrid immunoglobulin heavy chain-light chain pair (providing a second binding specificity) in the other arm. This asymmetric structure,with an immunoglobulin light chain in only one half of the bispecific molecule, facilitates the separation of the desired bispecific compound from unwanted immunoglobulin chain combinations. Bispecific antibody fragments may be connected via a linker. This approach is described in PCT Publication No. WO 94/04690.
According to one approach to making bispecific antibodies, antibody variable domains with the desired binding specificities (antibody-antigen combining sites) are fused to immunoglobulin constant domain sequences. The fusion can be with animmunoglobulin heavy chain constant domain, comprising at least part of the hinge, CH2 and CH3 regions. The first heavy chain constant region (CH1), containing the site necessary for light chain binding, can be present in at least one of the fusions. DNAs encoding the immunoglobulin heavy chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. This provides for great flexibility in adjustingthe mutual proportions of the three polypeptide fragments in embodiments when unequal ratios of the three polypeptide chains used in the construction provide the optimum yields. It is, however, possible to insert the coding sequences for two or allthree polypeptide chains in one expression vector when the expression of at least two polypeptide chains in equal ratios results in high yields or when the ratios are of no particular significance.
Heteroconjugate antibodies, comprising two covalently joined antibodies, are also within the scope of the disclosure. Such antibodies have been used to target immune system cells to unwanted cells (U.S. Pat. No. 4,676,980). Heteroconjugateantibodies may be made using any suitable cross-linking methods. Suitable cross-linking agents and techniques are described, for example, in U.S. Pat. No. 4,676,980.
In some instances, an anti-SARS-Cov-2 antibody herein is a chimeric antibody. "Chimeric" forms of non-human (e.g., murine) antibodies include chimeric antibodies which contain minimal sequence derived from a non-human Ig. For the most part,chimeric antibodies are murine antibodies in which at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin, is inserted in place of the murine Fc. Chimeric or hybrid antibodies also may be prepared in vitrousing suitable methods of synthetic protein chemistry, including those involving cross-linking agents. For example, immunotoxins may be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents forthis purpose include iminothiolate and methyl-4-mercaptobutyrimidate.
Provided herein are antibodies and antigen-binding fragments thereof, modified antibodies and antigen-binding fragments thereof, and binding agents that specifically bind to one or more epitopes on one or more target antigens. In one instance,a binding agent selectively binds to an epitope on a single antigen. In another instance, a binding agent is bivalent and either selectively binds to two distinct epitopes on a single antigen or binds to two distinct epitopes on two distinct antigens. In another instance, a binding agent is multivalent (i.e., trivalent, quatravalent, etc.) and the binding agent binds to three or more distinct epitopes on a single antigen or binds to three or more distinct epitopes on two or more (multiple) antigens.
Functional fragments of any of the antibodies herein are also contemplated. The terms "antigen-binding portion of an antibody," "antigen-binding fragment," "antigen-binding domain," "antibody fragment," or a "functional fragment of an antibody"are used interchangeably herein to refer to one or more fragments of an antibody that retain the ability to specifically bind to an antigen. Representative antigen-binding fragments include, but are not limited to, a Fab, a Fab', a F(ab').sub.2, a Fv, ascFv, a dsFv, a variable heavy domain, a variable light domain, a variable NAR domain, bi-specific scFv, a bi-specific Fab.sub.2, a tri-specific Fab.sub.3, an AVIMER.RTM., a minibody, a diabody, a maxibody, a camelid, a VHH, an intrabody, fusion proteinscomprising an antibody portion (e.g., a domain antibody), a single chain binding polypeptide, a scFv-Fc, or a Fab-Fc.
"F(ab').sub.2" and "Fab'" moieties can be produced by treating an Ig with a protease such as pepsin and papain, and include antibody fragments generated by digesting immunoglobulin near the disulfide bonds existing between the hinge regions ineach of the two heavy chains. For example, papain cleaves IgG upstream of the disulfide bonds existing between the hinge regions in each of the two heavy chains to generate two homologous antibody fragments in which an light chain composed of V.sub.Land C.sub.L (light chain constant region), and a heavy chain fragment composed of V.sub.H and C.sub.H.gamma.1 (.gamma.1) region in the constant region of the heavy chain) are connected at their C terminal regions through a disulfide bond. Each of thesetwo homologous antibody fragments is called Fab'. Pepsin also cleaves IgG downstream of the disulfide bonds existing between the hinge regions in each of the two heavy chains to generate an antibody fragment slightly larger than the fragment in whichthe two above-mentioned Fab' are connected at the hinge region. This antibody fragment is called F(ab').sub.2.
The Fab fragment also contains the constant domain of the light chain and the first constant domain (C.sub.H1) of the heavy chain. Fab' fragments differ from Fab fragments by the addition of a few residues at the carboxyl terminus of the heavychain C.sub.H1 domain including one or more cysteine(s) from the antibody hinge region. Fab'-SH is the designation herein for Fab' in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab').sub.2 antibody fragmentsoriginally were produced as pairs of Fab' fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.
A "Fv" as used herein refers to an antibody fragment which contains a complete antigen-recognition and antigen-binding site. This region consists of a dimer of one heavy chain and one light chain variable domain in tight, non-covalent orcovalent association (disulfide linked Fvs have been described, see, e.g., Reiter et al. (1996) Nature Biotechnology 14:1239-1245). It is in this configuration that the three CDRs of each variable domain interact to define an antigen-binding site on thesurface of the V.sub.H-V.sub.L dimer. Collectively, a combination of one or more of the CDRs from each of the V.sub.H and V.sub.L chains confer antigen-binding specificity to the antibody. For example, it would be understood that, for example, theCDRH3 and CDRL3 could be sufficient to confer antigen-binding specificity to an antibody when transferred to V.sub.H and V.sub.L chains of a recipient antibody or antigen-binding fragment and this combination of CDRs can be tested for binding,specificity, affinity, etc. using any of the techniques herein. Even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although likely at a lower specificity oraffinity than when combined with a second variable domain. Furthermore, although the two domains of a Fv fragment (V.sub.L and V.sub.H) are coded for by separate genes, they can be joined using recombinant methods by a synthetic linker that enables themto be made as a single protein chain in which the V.sub.L and V.sub.H regions pair to form monovalent molecules (known as single chain Fv (scFv); Bird et al. (1988) Science 242:423-426; Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883;and Osbourn et al. (1998) Nat. Biotechnol. 16:778). Such scFvs are also intended to be encompassed within the term "antigen-binding portion" of an antibody. Any V.sub.H and V.sub.L sequences of specific scFv can be linked to an Fc region cDNA orgenomic sequences in order to generate expression vectors encoding complete Ig (e.g., IgG) molecules or other isotypes. V.sub.H and V.sub.L can also be used in the generation of Fab, Fv, or other fragments of Igs using either protein chemistry orrecombinant DNA technology.
"Single-chain Fv" or "sFv" antibody fragments comprise the V.sub.H and V.sub.L domains of an antibody, wherein these domains are present in a single polypeptide chain. In some embodiments, the Fv polypeptide further comprises a polypeptidelinker between the V.sub.H and V.sub.L domains which enables the sFv to form the desired structure for antigen-binding. For a review of sFvs, see, e.g., Pluckthun in The Pharmacology of Monoclonal Antibodies, Vol. 113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269-315 (1994).
The term "AVIMER.RTM." refers to a class of therapeutic proteins of human origin, which are unrelated to antibodies and antibody fragments, and are composed of several modular and reusable binding domains, referred to as A-domains (also referredto as class A module, complement type repeat, or LDL-receptor class A domain). They were developed from human extracellular receptor domains by in vitro exon shuffling and phage display (Silverman et al., 2005, Nat. Biotechnol. 23:1493-1494; Silvermanet al., 2006, Nat. Biotechnol. 24:220). The resulting proteins can contain multiple independent binding domains that can exhibit improved affinity and/or specificity compared with single-epitope binding proteins. Each of the known 217 human A-domainscomprises .about.35 amino acids (.about.4 kDa); and these domains are separated by linkers that average five amino acids in length. Native A-domains fold quickly and efficiently to a uniform, stable structure mediated primarily by calcium binding anddisulfide formation. A conserved scaffold motif of only 12 amino acids is required for this common structure. The end result is a single protein chain containing multiple domains, each of which represents a separate function. Each domain of theproteins binds independently, and the energetic contributions of each domain are additive.
Antigen-binding polypeptides also include heavy chain dimers such as, for example, antibodies from camelids and sharks. Camelid and shark antibodies comprise a homodimeric pair of two chains of V-like and C-like domains (neither has a lightchain). Since the V.sub.H region of a heavy chain dimer IgG in a camelid does not have to make hydrophobic interactions with a light chain, the region in the heavy chain that normally contacts a light chain is changed to hydrophilic amino acid residuesin a camelid. V.sub.H domains of heavy-chain dimer IgGs are called V.sub.HH domains. Shark Ig-NARs comprise a homodimer of one variable domain (termed a V-NAR domain) and five C-like constant domains (C-NAR domains). In camelids, the diversity ofantibody repertoire is determined by the CDRs 1, 2, and 3 in the V.sub.H or V.sub.HH regions. The CDR3 in the camel V.sub.HH region is characterized by its relatively long length, averaging 16 amino acids (Muyldermans et al., 1994, Protein Engineering7(9): 1129). This is in contrast to CDR3 regions of antibodies of many other species. For example, the CDR3 of mouse V.sub.H has an average of 9 amino acids. Libraries of camelid-derived antibody variable regions, which maintain the in vivo diversityof the variable regions of a camelid, can be made by, for example, the methods disclosed in U.S. Patent Application Ser. No. 20050037421.
As used herein, a "maxibody" refers to a bivalent scFv covalently attached to the Fc region of an immunoglobulin, see, e.g., Fredericks et al., Protein Engineering, Design & Selection, 17:95-106 (2004) and Powers et al., Journal of ImmunologicalMethods, 251:123-135 (2001).
As used herein, a "dsFv" can be a Fv fragment obtained by introducing a Cys residue into a suitable site in each of a heavy chain variable region and a light chain variable region, and then stabilizing the heavy chain variable region and thelight chain variable region by a disulfide bond. The site in each chain, into which the Cys residue is to be introduced, can be determined based on a conformation predicted by molecular modeling. In the present disclosure, for example, a conformationis predicted from the amino acid sequences of the heavy chain variable region and light chain variable region of the above-described antibody, and DNA encoding each of the heavy chain variable region and the light chain variable region, into which amutation has been introduced based on such prediction, is then constructed. The DNA construct is incorporated then into a suitable vector and prepared from a transformant obtained by transformation with the aforementioned vector.
Single chain variable region fragments ("scFv") of antibodies are herein. Single chain variable region fragments may be made by linking light and/or heavy chain variable regions by using a short linking peptide. Bird et al. (1988) Science242:423-426. The single chain variants can be produced either recombinantly or synthetically. For synthetic production of scFv, an automated synthesizer can be used. For recombinant production of scFv, a suitable plasmid containing polynucleotide thatencodes the scFv can be introduced into a suitable host cell, either eukaryotic, such as yeast, plant, insect, or mammalian cells, or prokaryotic, such as E. coli. Polynucleotides encoding the scFv of interest can be made by routine manipulations suchas ligation of polynucleotides. The resultant scFv can be isolated using any suitable protein purification techniques.
Diabodies can be single chain antibodies. Diabodies can be bivalent, bispecific antibodies in which VH and VL domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domainson the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen-binding sites (see, e.g., Holliger, P., et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993); and Poljak, R. J., et al.,Structure, 2:1121-1123 (1994)).
As used herein, a "minibody" refers to a scFv fused to CH3 via a peptide linker (hingeless) or via an IgG hinge has been described in Olafsen, et al., Protein Eng. Des. Sel., April 2004; 17(4):315-23.
As used herein, an "intrabody" refers to a single chain antibody which demonstrates intracellular expression and can manipulate intracellular protein function (Biocca, et al., EMBO J. 9:101-108, 1990; Colby et al., Proc Natl Acad. Sci. USA. 101:17616-21, 2004). Intrabodies, which comprise cell signal sequences which retain the antibody construct in intracellular regions, may be produced as described in Mhashilkar et al., (EMBO J., 14:1542-51, 1995) and Wheeler et al. (FASEB J. 17:1733-5. 2003). Transbodies are cell-permeable antibodies in which a protein transduction domains (PTD) is fused with single chain variable fragment (scFv) antibodies Heng et al. (Med Hypotheses. 64:1105-8, 2005).
A "scFv-Fc" fragment as herein refers to an scFv attached to an Fc domain. For example, an Fc domain may be attached to the C-terminal of the scFv. The Fc domain may follow the VH or VL, depending on the orientation of the variable domains inthe scFv (i.e., VH-VL or VL). Any suitable Fc domain known in the art or herein may be used. In some cases, the Fc domain comprises an IgG1 Fc domain or an IgG4 Fc domain. A scFv-Fc format allows for rapid characterization of candidate scFvs isolatedfrom phage display libraries before conversion into a full-length IgG. This format offers several advantages over the phage display-derived scFv, including bivalent binding, longer half-life, and Fc-mediated effector functions. Here, a detailed methodis presented, which describes the cloning, expression, and purification of an scFv-Fc fragment, starting from scFv fragments obtained from a phage display library. This method facilitates the rapid screening of candidate antibodies, prior to a moretime-consuming conversion into a full IgG format. In one instance, a single-chain Fv (scFv) includes the heavy and light chains in the Fv of an anti-SARS-Cov-2 antibody herein joined with a flexible peptide linker (e.g., of about 10, 12, 15 or moreamino acid residues) in a single peptide chain. The single chain antibody may be monovalent, if only a single VH and VL are used, bivalent, if two VH and VL are used, or polyvalent, if more than two VH and VL are used. In some instances, the entire Fcregion is attached to the scFv. In other instances, only the CH3 region of a Fc is attached to the scFv (a "scFv-CH).
A "scFab" as herein refers to an antigen-binding domain that specifically binds to SARS-Cov-2 is fused via a peptide linker to the C-terminus to one of the heavy chains.
A "scFv zipper" as herein refers to constructs of leucine zipper-based dimerization cassettes for the conversion of recombinant monomeric scFv antibody fragments to bivalent and bispecific dimers. A truncated murine IgG3 hinge region and a Fosor Jun leucine zipper are cloned into four scFv fragments. Cysteine residues flanking the zipper region are introduced to covalently link dimerized scFv fragments. The secreted fusion proteins form stable Fos Fos or Jun Jun homodimers.
A "cross-Fab fragment" or "xFab fragment" or "crossover Fab fragment" as herein refers to a Fab fragment, wherein either the variable regions or the constant regions of the heavy and light chain are exchanged. Two different chain compositionsof a crossover Fab molecule are possible and comprised within the scope of bispecific antibodies and antigen-binding fragments herein. On the one hand, the variable regions of the Fab heavy and light chain are exchanged, i.e. the crossover Fab moleculecomprises a peptide chain composed of the light chain variable region (VL) and the heavy chain constant region (CH1), and a peptide chain composed of the heavy chain variable region (VH) and the light chain constant region (CL). This crossover Fabmolecule is also referred to as CrossFab VLVH. On the other hand, when the constant regions of the Fab heavy and light chain are exchanged, the crossover Fab molecule comprises a peptide chain composed of the heavy chain variable region (VH) and thelight chain constant region (CL), and a peptide chain composed of the light chain variable region (VL) and the heavy chain constant region (CH1). This crossover Fab molecule is also referred to as CrossFab CLCH1.
A "Fab-Fc" fragment as herein refers to a Fab fragment that is attached to a CH1, CH2, and/or a CH3 region of a Fc, where the molecule does not contain all of a CH1, CH2, and CH3.
The terms "single domain antibody" and "sdAb" refer to a single-chain antibody polypeptide consisting of a single monomeric variable antibody domain. The term "VHH" as used herein refers to molecules engineered from heavy-chain antibodies foundin camelids. The terms "shark new antigen receptor", "VNAR" and "IgNAR" as used herein refer to molecules obtained from the heavy-chain antibodies of cartilaginous fish, such as sharks. Single-domain antibodies can also be obtained by splitting dimericvariable domains from common immunoglobulin G (IgG) into monomers. Single-domain antibodies are typically about 110 amino acids long and have a typical molecular weight in the region of from about 12 to about 15 kDa. As such, single-domain antibodiesare much smaller than common antibodies (150-160 kDa), and even smaller than Fab fragments (which consist of one light chain and half a heavy chain and have a molecular weight of about 50 kDa) and single-chain variable fragments (which consist of twovariable domains, one from a light and one from a heavy chain, and have a molecular weight of about 25 kDa).
Suitable linkers may be used to link various parts of recombinant or synthetic antibodies or antigen-binding fragments thereof or to multimerize binding agents. A non-limiting example of a linking peptide is (GGGGS).sub.n, where n=3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more (SEQ ID NO: 443) and which bridges approximately 3.5 nm between the carboxy terminus of one variable region and the amino terminus of the other variable region. Linkers of other sequences havebeen designed and used. Methods of producing such antibodies are described in for instance U.S. Pat. No. 4,946,778, Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269-315(1994), Bird et al., Science 242, 423-426 (1988), Huston et al., PNAS USA 85, 5879-5883 (1988) and McCafferty et al., Nature 348, 552-554 (1990). Linkers can in turn be modified for additional functions, such as attachment of drugs or attachment tosolid supports. Fab and scFab fragments may be stabilized via natural disulfide bonds between the CL domain and the CH1 domain. Antigen-binding fragments comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), such as theFab, crossFab, scFv and scFab fragments as herein might be further stabilized by introducing interchain disulfide bridges between the VH and the VL domain. Accordingly, in one embodiment, the Fab fragment(s), the crossFab fragment(s), the scFvfragment(s) and/or the scFab fragment(s) comprised in the antigen-binding receptors according to the invention might be further stabilized by generation of interchain disulfide bonds via insertion of cysteine residues. Such stabilized antigen-bindingmoieties are referred to by the term "ds". Cysteine engineered antibodies, in some embodiments, are made reactive for conjugation with linker-degrader intermediates herein, by treatment with a reducing agent such as DTT (Cleland's reagent,dithiothreitol) or TCEP (tris(2-carboxyethyl)phosphine hydrochloride; Getz et al. (1999) Anal. Biochem. Vol 273:73-80; Soltec Ventures, Beverly, Mass.) followed by re-formation of the inter-chain disulfide bonds (re-oxidation) with a mild oxidant suchas dehydroascorbic acid.
Also provided herein are affinity matured antibodies. For example, affinity matured antibodies can be produced by any suitable procedure (see, e.g., Marks et al., 1992, Bio/Technology, 10:779-783; Barbas et al., 1994, Proc Nat. Acad. Sci, USA91:3809-3813; Schier et al., 1995, Gene, 169:147-155; Yelton et al., 1995, J. Immunol., 155:1994-2004; Jackson et al., 1995, J. Immunol., 154(7):3310-9; Hawkins et al, 1992, J. Mol. Biol., 226:889-896; and WO2004/058184). The following methods may beused for adjusting the affinity of an antibody and for characterizing a CDR. One way of characterizing a CDR of an antibody and/or altering (such as improving) the binding affinity of a polypeptide, such as an antibody, is termed "library scanningmutagenesis." Generally, library scanning mutagenesis works as follows. One or more amino acid position in the CDR is replaced with two or more (such as 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids. This generatessmall libraries of clones (in some embodiments, one for every amino acid position that is analyzed), each with a complexity of two or more members (if two or more amino acids are substituted at every position). Generally, the library also includes aclone comprising the native (unsubstituted) amino acid. A small number of clones, for example, about 20-80 clones (depending on the complexity of the library), from each library can be screened for binding specificity or affinity to the targetpolypeptide (or other binding target), and candidates with increased, the same, decreased, or no binding are identified. Binding affinity may be determined using Biacore surface plasmon resonance analysis, which detects differences in binding affinityof about 2-fold or greater. Biacore can be particularly useful when the starting antibody already binds with a relatively high affinity, for example, a K.sub.D of about 10 nM or lower.
In some instances, an antibody or antigen-binding fragment is bi-specific or multi-specific and can specifically bind to more than one antigen. In some cases, such a bi-specific or multi-specific antibody or antigen-binding fragment canspecifically bind to 2 or more different antigens. In some cases, a bi-specific antibody or antigen-binding fragment can be a bivalent antibody or antigen-binding fragment. In some cases, a multi specific antibody or antigen-binding fragment can be abivalent antibody or antigen-binding fragment, a trivalent antibody or antigen-binding fragment, or a quatravalent antibody or antigen-binding fragment.
An antibody or antigen-binding fragment herein can be an isolated, purified, recombinant, or synthetic.
As used herein, the term "affinity" refers to the equilibrium constant for the reversible binding of two agents and is expressed as K.sub.D. The binding affinity (K.sub.D) of a SH antibody or antigen-binding fragment herein can be less than 50nM, 49 nM, 48 nM, 47 nM, 46 nM, 45 nM, 44 nM, 43 nM, 42 nM, 41 nM, 40 nM, 39 nM, 38 nM, 37 nM, 36 nM, 35 nM, 34 nM, 33 nM, 32 nM, 31 nM, 30 nM, 29 nM, 28 nM, 27 nM, 26 nM, 25 nM, 24 nM, 23 nM, 22 nM, 21 nM, 20 nM, 19 nM, 18 nM, 17 nM, 16 nM, 15 nM, 14nM, 13 nM, 12 nM, 11 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, 990 pM, 980 pM, 970 pM, 960 pM, 950 pM, 940 pM, 930 pM, 920 pM, 910 pM, 900 pM, 890 pM, 880 pM, 870 pM, 860 pM, 850 pM, 840 pM, 830 pM, 820 pM, 810 pM, 800 pM, 790 pM,780 pM, 770 pM, 760 pM, 750 pM, 740 pM, 730 pM, 720 pM, 710 pM, 700 pM, 690 pM, 680 pM, 670 pM, 660 pM, 650 pM, 640 pM, 630 6M, 620 pM, 610 pM, 600 pM, 590 pM, 580 pM, 570 pM, 560 pM, 550 pM, 540 pM, 530 pM, 520 pM, 510 pM, 500 pM, 490 pM, 480 pM, 470pM, 460 pM, 450 pM, 440 pM, 430 pM, 420 pM, 410 pM, 400 pM, 390 pM, 380 pM, 370 pM, 360 pM, 350 pM, 340 pM, 330 pM, 320 pM, 310 pM, 300 pM, 290 pM, 280 pM, 270 pM, 260 pM, 250 pM, 240 pM, 230 pM, 220 pM, 210 pM, 200 pM, 190 pM, 180 pM, or any integertherebetween.
Binding affinity may be determined using surface plasmon resonance (SPR), Kinexa Biocensor, scintillation proximity assays, enzyme linked immunosorbent assay (ELISA), ORIGEN immunoassay (IGEN), fluorescence quenching, fluorescence transfer,yeast display, or any combination thereof. Binding affinity may also be screened using a suitable bioassay.
As used herein, the term "avidity" refers to the resistance of a complex of two or more agents to dissociation after dilution. Apparent affinities can be determined by methods such as an enzyme linked immunosorbent assay (ELISA) or any othertechnique familiar to one of skill in the art. Avidities can be determined by methods such as a Scatchard analysis or any other technique familiar to one of skill in the art.
An antibody or antigen-binding fragment can be modified by making one or more substitutions in the amino acid sequence using a conservative or a non-conservative substitution such that the resulting modified antibody exhibits about 80% homologyto a sequence herein.
The phrase "conservative amino acid substitution" refers to grouping of amino acids on the basis of certain common properties. A functional way to define common properties between individual amino acids is to analyze the normalized frequenciesof amino acid changes between corresponding proteins of homologous organisms (Schulz, G. E. and R. H. Schirmer, Principles of Protein Structure, Springer-Verlag). According to such analyses, groups of amino acids may be defined where amino acids withina group exchange preferentially with each other, and therefore resemble each other most in their impact on the overall protein structure. Examples of amino acid groups defined in this manner include:
(i) a charged group, consisting of Glu and Asp, Lys, Arg and His;
(ii) a positively-charged group, consisting of Lys, Arg and His;
(iii) a negatively-charged group, consisting of Glu and Asp;
(iv) an aromatic group, consisting of Phe, Tyr and Trp;
(v) a nitrogen ring group, consisting of His and Trp;
(vi) a large aliphatic non-polar group, consisting of Val, Leu and Ile;
(vii) a slightly-polar group, consisting of Met and Cys;
(viii) a small-residue group, consisting of Ser, Thr, Asp, Asn, Gly, Ala, Glu, Gln and Pro;
(ix) an aliphatic group consisting of Val, Leu, Ile, Met and Cys; and
(x) a small hydroxyl group consisting of Ser and Thr.
In addition to the groups presented above, each amino acid residue may form its own group, and the group formed by an individual amino acid may be referred to simply by the one and/or three letter abbreviation for that amino acid commonly usedin the art as described above.
A "conserved residue" is an amino acid that is relatively invariant across a range of similar proteins. Often conserved residues will vary only by being replaced with a similar amino acid, as described above for "conservative amino acidsubstitution."
The letter "x" or "xaa" as used in amino acid sequences herein is intended to indicate that any of the twenty standard amino acids may be placed at this position unless specifically noted otherwise.
As used herein, "identity" means the percentage of identical nucleotide or amino acid residues at corresponding positions in two or more sequences when the sequences are aligned to maximize sequence matching, i.e., taking into account gaps andinsertions. Identity can be readily calculated by known methods, including but not limited to those described in Computational Molecular Biology, Lesk, A. M., ed., Oxford University Press, New York, 1988; Biocomputing: Informatics and Genome Projects,Smith, D. W., ed., Academic Press, New York, 1993; Computer Analysis of Sequence Data, Part I, Griffin, A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994; Sequence Analysis in Molecular Biology, von Heinje, G., Academic Press, 1987; andSequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M Stockton Press, New York, 1991; and Carillo, H., and Lipman, D., SIAM J. Applied Math., 48: 1073 (1988). Methods to determine identity are designed to give the largest match between thesequences tested. Moreover, methods to determine identity are codified in publicly available computer programs. Computer program methods to determine identity between two sequences include, but are not limited to, the GCG program package (Devereux, J.,et al., Nucleic Acids Research 12(1): 387 (1984)), BLASTP, BLASTN, and FASTA (Altschul, S. F. et al., J. Molec. Biol. 215: 403-410 (1990) and Altschul et al. Nuc. Acids Res. 25: 3389-3402 (1997)). The BLAST X program is publicly available from NCBIand other sources (BLAST Manual, Altschul, S., et al., NCBI NLM NIH Bethesda, Md. 20894; Altschul, S., et al., J. Mol. Biol. 215: 403-410 (1990). The well-known Smith Waterman algorithm may also be used to determine identity. Ranges of desireddegrees of sequence identity across a CDR, a FR, a VH, and/or a VL, a fragment, etc. are from about 80% to about 100% and integer values therebetween. In general, this disclosure encompasses sequences with about 80%, about 81%, about 82%, about 83%,about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%, sequence identity with any sequence provided herein. The letter "X" or theterm "Xaa" as used in an amino acid sequence herein is intended to indicate that any of the twenty standard amino acids may be placed at this position, unless specifically noted otherwise.
"Polynucleotide" or "nucleic acid," as used interchangeably herein, refer to polymers of nucleotides of any length, and include DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and/ortheir analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and their analogs. If present, modification to the nucleotide structuremay be imparted before or after assembly of the polymer. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component. Other types of modifications include, for example, "caps," substitution of one or more of the naturally-occurring nucleotides with an analog, internucleotide modifications such as, for example, those with uncharged linkages (e.g., methyl phosphonates,phosphotriesters, phosphoamidates, carbamates, etc.) and with charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), those containing pendant moieties, such as, for example, proteins (e.g., nucleases, toxins, antibodies, signal peptides,ply-L-lysine, etc.), those with intercalators (e.g., acridine, psoralen, etc.), those containing chelators (e.g., metals, radioactive metals, boron, oxidative metals, etc.), those containing alkylators, those with modified linkages (e.g., alpha anomericnucleic acids, etc.), as well as unmodified forms of the polynucleotide(s). Further, any of the hydroxyl groups ordinarily present in the sugars may be replaced, for example, by phosphonate groups, phosphate groups, protected by standard protectinggroups, or activated to prepare additional linkages to additional nucleotides, or may be conjugated to solid supports. The 5' and 3' terminal OH can be phosphorylated or substituted with amines or organic capping group moieties of from 1 to 20 carbonatoms. Other hydroxyls may also be derivatized to standard protecting groups. Polynucleotides can also contain analogous forms of ribose or deoxyribose sugars including, for example, 2'-O-methyl-, 2'-O-allyl, 2'-fluoro- or 2'-azido-ribose, carbocyclicsugar analogs, alpha-anomeric sugars, epimeric sugars such as arabinose, xyloses, or lyxoses, pyranose sugars, furanose sugars, sedoheptuloses, acyclic analogs, and abasic nucleoside analogs such as methyl riboside. One or more phosphodiester linkagesmay be replaced by alternative linking groups. These alternative linking groups include, but are not limited to, embodiments wherein phosphate is replaced by P(O)S ("thioate"), P(S)S ("dithioate"), (O)NR.sub.2 ("amidate"), P(O)R, P(O)OR', CO, orCH.sub.2 ("formacetal"), in which each R or R' is independently H or substituted or unsubstituted alkyl (1-20 C) optionally containing an ether (--O--) linkage, aryl, alkenyl, cycloalkyl, cycloalkenyl, or araldyl. Not all linkages in a polynucleotideneed be identical. The preceding description applies to all polynucleotides referred to herein, including RNA and DNA.
In one aspect, provided herein is one or more RNA molecules that encode one or more of the antibodies or antigen-binding fragments herein. Such one or more RNA molecules may be present in a vector for administration to a subject.
Provide herein are polynucleotides (such as RNA, for example mRNA) encoding antibodies or antigen-binding fragments that can specifically bind to SARS-CoV-2. Antibody or antigen-binding fragments encoded by polynucleotides can includeantibodies or antigen-binding fragments. Polynucleotides can be administered to a subject to prevent infection of the subject by SARS-Cov-2 or to treat a subject infected by SARS-CoV-2. In some cases, antibodies or antigen-binding fragments can beproduced in a subject that has been administered a polynucleotide herein.
Polynucleotides can comprise genetic material encoding an antibody or antigen-binding fragment (e.g., DNA or mRNA). In some cases, polynucleotides can be in a vector, such as a viral vector or an artificial chromosome such as a human artificialchromosome. In some cases, polynucleotides can additionally comprise a promoter, a terminator, a sequence encoding a tag, a sequence encoding a second antibody or antigen-binding fragment, or a sequence encoding a molecule that can aid in folding orfunction of the antibody or antigen-binding fragment.
In some cases, polynucleotides can be used to prevent and/or treat disease caused by SARS-Cov-2 or a similar virus (e.g., COVID-19); i.e., polynucleotides can have prophylactic or therapeutic uses, or both prophylactic and therapeutic uses. Accordingly, the present disclosure provides methods to prevent and/or treat infection by SARS-CoV-2. In some cases, such methods can comprise administering to a subject one or more mRNA molecules encoding a antibody or antigen-binding fragment that canspecifically bind to SARS-CoV-2.
An antibody library herein can comprise a plurality of antibodies and/or antigen-binding fragments. The plurality of antibodies and/or antigen-binding fragments can be at least 1.0.times.10.sup.6, 1.0.times.10.sup.7, 1.0.times.10.sup.8,1.0.times.10.sup.9, 1.0.times.10.sup.10, 2.0.times.10.sup.10, 3.0.times.10.sup.10, 4.0.times.10.sup.10, 5.0.times.10.sup.10, 6.0.times.10.sup.10, 7.0.times.10.sup.10, 8.0.times.10.sup.10, 9.0.times.10.sup.10, or 10.0.times.10.sup.10.
The practice of the present invention will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry and immunology, which are within the skillof the art. Such techniques are explained fully in the literature, such as, Molecular Cloning: A Laboratory Manual, second edition (Sambrook et al., 1989) Cold Spring Harbor Press; Oligonucleotide Synthesis (M. J. Gait, ed., 1984); Methods in MolecularBiology, Humana Press; Cell Biology: A Laboratory Notebook (J. E. Cellis, ed., 1998) Academic Press; Animal Cell Culture (R. I. Freshney, ed., 1987); Introduction to Cell and Tissue Culture (J. P. Mather and P. E. Roberts, 1998) Plenum Press; Cell andTissue Culture: Laboratory Procedures (A. Doyle, J. B. Griffiths, and D. G. Newell, eds., 1993-1998) J. Wiley and Sons; Methods in Enzymology (Academic Press, Inc.); Handbook of Experimental Immunology (D. M. Weir and C. C. Blackwell, eds.); GeneTransfer Vectors for Mammalian Cells (J. M. Miller and M. P. Cabs, eds., 1987); Current Protocols in Molecular Biology (F. M. Ausubel et al., eds., 1987); PCR: The Polymerase Chain Reaction, (Mullis et al., eds., 1994); Current Protocols in Immunology(J. E. Coligan et al., eds., 1991); Short Protocols in Molecular Biology (Wiley and Sons, 1999); Immunobiology (C. A. Janeway and P. Travers, 1997); Antibodies (P. Finch, 1997); Antibodies: a practical approach (D. Catty., ed., IRL Press, 1988-1989);Monoclonal antibodies: a practical approach (P. Shepherd and C. Dean, eds., Oxford University Press, 2000); Using antibodies: a laboratory manual (E. Harlow and D. Lane (Cold Spring Harbor Laboratory Press, 1999); and The Antibodies (M. Zanetti and J. D.Capra, eds., Harwood Academic Publishers, 1995).
EXAMPLES
The application may be better understood by reference to the following non-limiting examples, which are provided as exemplary embodiments of the application. The following examples are presented in order to more fully illustrate embodiments andshould in no way be construed, however, as limiting the broad scope of the application.
Example 1: Kinetics and Affinity Determination of an Anti-SARS-Cov-2scFv by Surface Plasmon Resonance
High-throughput surface plasmon resonance (SPR) kinetic experiments were performed on Carterra LSA Array SPR instrument (Carterra, Salt Lake City, Utah) equipped with HC200M sensor chip (catalog No. 4287, Carterra, Salt Lake City, Utah) at25.degree. C. Anti-SARS-Cov-2 scFv constructs were expressed with a V5 epitope tag to enable capture via immobilized anti-V5 antibody. Surfaces were prepared in HBSTE (10 mM HEPES pH 7.4, 150 mM NaCl, 3 mM EDTA, 0.01% (v/v) Tween-20) as running buffer. The capture surface was prepared by standard amine-coupling of anti-V5 tag antibody (catalog No. ab27671, Abcam, Cambridge, Mass.) on the entire chip surface as follows. The chip was activated with a 10-min injection of a freshly prepared 1:1:1 (v/v/v)mixture of 0.4 M 1-Ethyl-3-(3-Dimethylaminopropyl) carbodiimide hydrochloride (EDC)+0.1 M N-hydroxysulfosuccinimide (sNHS)+0.1 M 2-(N-morpholino) ethanesulfonic acid (MES) pH 5.5. Then, anti-V5 tag antibody was diluted to 50 .mu.g/ml in 10 mM sodiumacetate pH 4.3 and coupled for 14 min. Excess reactive esters were blocked with a 10-min injection of 1 M ethanolamine HCl pH 8.5. A library of anti-COVID-19 scFv clones was supplied as plates of crude bacterial periplasmic extracts (PPE) and diluted2-fold in running buffer. ScFv samples were flow printed for 15-min in batches of 96 PPE's in parallel using the 96 channel printhead to generate a 384-ligand array comprising 1 spot per scFv. For the interaction analysis, the running buffer HBST (10mM HEPES pH 7.4, 150 mM NaCl, 0.01% (v/v) Tween-20) was supplemented with 0.5 mg/ml BSA. Surfaces were stabilized with seven to eight buffer analyte injections. SARS-CoV-2, SARS-CoV-1, and MERS Receptor Binding Domain (RBD) proteins were prepared atconcentrations of 0, 3.7, 11.1, 33.3, 100, 37, and 300 nM and these samples were injected as analyte for 5 min, allowing a 15-min dissociation time. Samples were injected in ascending concentration without any regeneration in between them. Binding datafrom the local reference spots were subtracted from the active spots and the nearest buffer blank analyte responses were subtracted to double-reference the data. The double-referenced data were fitted to a simple 1:1 Langmuir binding model in Carterra'sKinetic Inspection Tool to give kinetics (k.sub.d, k.sub.d), affinity (K.sub.D), and R.sub.max value for each interaction.
TABLE-US-00028 Captures RL ka KD Rmax Clone ID (RU) (M-1 s-1) kd (s-1) (nM) (RU) COVID19_P23_F10 1552 9.80E+04 7.70E-04 7.86 65.79 COVID19_P24_H06 1709 1.20E+05 5.70E-05 0.5 21 COVID19_P24_F11 1531 6.16E+05 2.80E-04 0.46 18 COVID19_P23_G11 18722.94E+04 1.08E-04 3.67 20.39 COVID19_P24_D09 1825 1.14E+05 5.70E-05 0.5 19 COVID19_P11_H02 1609 3.20E+05 7.10E-04 2.2 25 COVID19_P24_C06 1514 2.28E+05 5.70E-05 0.3 31 COVID19_P12_B07 1641 1.78E+05 5.70E-05 0.32 17.8 COVID19_P24_H04 2116 1.70E+05 6.80E-044 91 COVID19_P23_G10 1629 1.54E+05 5.70E-05 0.37 8.72 COVID19_P24_A09 1432 1.52E+05 2.29E-04 1.51 51 C0V1D19_P11_D12 1756 7.90E+04 3.40E-04 4.3 74 C0V1D19_P24_A11 1435 1.58E+05 3.08E-04 1.95 20 C0V1D19_P24_C10 1356 5.53E+05 4.87E-04 0.88 48C0V1D19_P11_D08 1294 1.10E+05 5.30E-04 4.7 41 C0V1D19_P24_E02 1507 2.09E+05 8.36E-04 4.01 109 C0V1D19_P23_H10 2025 5.53E+04 5.70E-05 1.03 9.63 C0V1D19_P24_G06 1742 3.70E+05 1.92E-04 0.52 35 COVID19_P24_C01 1478 3.28E+05 3.22E-04 0.98 18 COVID19_P24_G091708 3.29E+05 5.12E-04 1.56 33 COVID19_P24_D08 1532 5.65E+05 4.10E-04 0.73 31 COVID19_P11_H07 1734 1.10E+05 5.70E-05 0.5 39 COVID19_P11_G03 1532 9.90E+04 6.40E-04 6.45 40 COVID19_P24_B09 1467 5.08E+05 1.39E-02 27.47 47.99 COVID19_P23_G12 0.37
The described clones each had a superior binding affinity of less than 50 nM. Moreover, some clones were found to not only bind to Sars-Cov-2, but also to MERS and/or SARS-Cov-1.
TABLE-US-00029 Clone ID Binding Affinity For: COVID19_P23_F10 COV2 COVID19_P24_H06 COV2 COVID19_P24_F11 COV2 COVID19_P23_G11 COV2+SARS1+SARS2 COVID19_P24_D09 COV2 COVID19_P11_H02 COV2 COVID19_P24_C06 COV2 COVID19_P12_B07 COV2 COVID19_P24_H04COV2 COVID19_P23_G10 COV2 COVID19_P24_A09 COV2 COVID19_P11_D12 COV2 COVID19_P24_A11 COV2 COVID19_P24_C10 COV2 COVID19_P11_D08 COV2 COVID19_P24_E02 COV2 COVID19_P23_H10 COV2+SARS1+SARS2 COVID19_P24_G06 COV2 COVID19_P24_C01 COV2 COVID19_P24_G09 COV2COVID19_P24_D08 COV2 COVID19_P11_H07 COV2+SARS1+SARS2+MERS COVID19_P11_G03 COV2 COVID19_P24_B09 COV2 COVID19_P23_G12
Example 2: In Vitro Neutralization Assay for Sars-Cov-2 Virus
Production and Titration of Pseudoviruses
For pseudovirus construction, spike genes from a SARS CoV-2 virus strain, a specific were codon-optimized for human cells and cloned into eukaryotic expression plasmid to generate the envelope recombinant plasmids. The pseudoviruses wereproduced and titrated using methods similar, as described previously in Nie J. et al. (Emerg Microbes Infect. 2020 December; 9(1):680-686), 293T cells were transfected with Pseudo virus vector using Lipofectamine system (ThermoFisher) following themanufacturer's instruction. Twenty-four hours later, new media was replaced and after 48 h from the beginning of transfection SARS-CoV-2 pseudoviruses containing culture supernatants were harvested, filtered (0.45-.mu.m pore size, Millipore, SLHP033RB)and stored at -80.degree. C. in aliquots until use. The 50% tissue culture infectious dose (TCID50) of SARS-CoV-2 pseudovirus was determined using a single-use aliquot from the pseudovirus bank; all stocks were used only once to avoid inconsistenciesthat could have resulted from repeated freezing-thawing cycles. For titration of the SARS-CoV-2 pseudovirus, a 2-fold initial dilution was made in triplicates wells of 96-well culture plates followed by serial 3-fold dilutions (8 dilutions in total). The last column served as the cell control without the addition of pseudovirus. Then, the 96-well plates were seeded with trypsin-treated Vero E6 mammalian transfectable cells adjusted to a pre-defined concentration. After 24 h incubation in a 5%CO.sub.2 environment at 37.degree. C., the culture supernatant was aspirated gently to leave 100 .mu.l in each well; then, 100 .mu.l of luciferase substrate was added to each well. Two min after incubation at room temperature, 150 .mu.l of lysate wastransferred to white solid 96-well plates for the detection of luminescence using a microplate luminometer (PerkinElmer). The positive well was determined as ten-fold relative luminescence unit (RLU) values higher than the cell background. The 50%tissue culture infectious dose (TCID50) was calculated using the Reed-Muench method, as described in Nie J et al. Id. In some cases the pseudovirus included a GFP reporter instead of Luciferase; in these cases, GFP fluorescence is measured by flowcytometry.
Pseudovirus Based Neutralization Assay
Neutralization is measured by the reduction in luciferase gene expression or GFP gene expression as described previously Nie J et al. Id. The 50% inhibitory dilution (EC50) is defined as the dilution of the tested antibodies at which therelative light units (RLUs) were reduced by 50% compared with the virus control wells (virus+ cells) after subtraction of the background RLUs in the control groups with cells only. In brief, pseudovirus in the TCID50 determined above is incubated withserial dilutions of the test samples (six dilutions in a 3-fold step-wise manner) in duplicate for 1 h at 37.degree. C., together with the virus control and cell control wells in triplicate. Then, freshly trypsinized cells were added to each well. Following 24 h of incubation in a 5% CO.sub.2 environment at 37.degree. C., the luminescence or fluoresce (depending on the reporter gene used) is measured as described above (relating to pseudovirus titration). The EC50 values were calculated withnon-linear regression, i.e., log (inhibitor) vs. response (four parameters), using GraphPad Prism 8 (GraphPad Software, Inc., San Diego, Calif., USA).
Results
Neutralization was observable for the clones tested: Average Tm1 (.degree. C.) and IC50 data for a subset of the clones was provided below:
TABLE-US-00030 Average IC50 IC50 [.mu.g/mL] IC50 Tm1 [.mu.g/mL] pseudotyped [.mu.g/mL] Clone ID (.degree. C.) plaque lenti neut neut COVID19_P24_H06 62 - COVID19_P24_F11 74.5 + COVID19_P23_G11 74.1 0.26 COVID19_P24_D09 62.6 + COVID19_P23_G1273.7 + 15.9 COVID19_P12_B07 73.4 + COVID19_P24_C10 59.2 + COVID19_P23_H10 63.1 COVID19_P24_G06 72.8 <3 0.16 <1:16 COVID19_P24_C01 68.5 + 0.92 COVID19_P24_D08 59.6 + 17 - COVID19_P11_H07 60.9 COVID19_P23_G10 65.9 -
Example 3: Competition of SARS-CoV-2/ACE2 Interaction with Anti-SARS-Cov-2 scFv by Biolayer Interferometry
Competition assay of the interaction of SARS-CoV-2 with ACE2 is conducted in a classical sandwich and a premix assay format using a ForteBio Octet HTX biolayer interferometry instrument (Molecular Devices ForteBio LLC, Fremont, Calif.) at25.degree. C. with running buffer HBST (10 mM HEPES pH 7.4, 150 mM NaCl, 0.01% (v/v) Tween-20, pH 7.4) supplemented with 1 mg/mL BSA.
An Anti-V5 tag antibody (catalog No. ab27671, Abcam, Cambridge, Mass.) is biotinylated with a 5:1 molar ratio of sulfo-NHS-LC-LC-biotin (catalog No. 21338, ThermoFisher Scientific, Waltham, Mass.) and buffer exchanged into PBS using ThermoFisherZeba 7K MWCO columns (catalog No. 89883, ThermoFisher Scientific, Waltham, Mass.).
Streptavidin sensor tips (catalog no. 18-5021, Molecular Devices ForteBio LLC, Fremont, Calif.) are equilibrated in buffer for 10-min before the run. Sample plates are agitated at 1000 rpm. At the start of the run, sensors are exposed tobuffer for 60 sec to establish a baseline. The biotinylated anti-V5 tag antibody at 7 .mu.g/mL are loaded onto the sensors for 5-min to prepare an anti-V5 surface. To block remaining free biotin binding sites, all sensors are exposed for 5-min with 20.mu.M amine-PEG2-biotin (catalog No. 21346, ThermoFisher Scientific, Waltham, Mass.) followed by two alternating 30-sec cycles of 10 mM glycine-HCl pH1.7 and buffer to precondition the sensors.
For the classical sandwich assay format, a baseline in buffer is established for 60-sec and anti-SARS-Cov-2 scFv clones as PPE undiluted are captured for 2-min onto the anti-V5 sensor tips. Baseline in buffer is recorded for 60-sec followed byassociation of SARS-Cov-2 at 100 nM for 2-min, a quick wash in buffer for 15-sec, and sandwiching of 500 nM ACE2 or buffer for 2-min. After each classical sandwich cycle, sensors are regenerated with two alternating 30-sec cycles of 10 mM glycine-HClpH1.7 and buffer.
For the premix assay format, a baseline in buffer is established for 60-sec and anti-SARS-Cov-2 scFv clones as PPE undiluted are captured for 2-min onto the anti-V5 sensor tips. Baseline in buffer is recorded for 60-sec followed by associationof buffer, a premixed complex of 100 nM SARS-Cov-2+500 nM ACE2, or 100 nM SARS-Cov-2. Dissociation in buffer is measured for 30-sec. After each binding cycle, sensors are regenerated with two alternating 30-sec cycles of 10 mM glycine-HCl pH1.7 andbuffer. Capture of biotinylated ACE2 at 10 .mu.g/mL is included as a self-blocking control in both assays.
Example 4: In Vivo Hamster Model for Sars-COV2 Infections
Competent 6-8 weeks old Syrian golden hamsters females (Charles River Laboratories or Harlan Laboratories) are housed three per cage in a biosafety level 3-4 animal facility in UTMB Galveston. Animals will be acclimatized in the BSL-3-4biosafety containment 3-5 days before the experiment begins. Animal will be housed and treated as recommended by Institutional Biosafety and the Institutional Animal Care and Use Committees.
Animals are injected IP with 0.5-1 mL of either saline, a therapeutic antibody at 10 mg/Kg (as disclosed herein), or an isotype control antibody at 10 mg/Kg, 24 h before viral infection. Animals are acclimatized in the ABSL-3 biosafetycontainment. On the day of infection, hamsters (5 per group) will be inoculated with PBS or 10E5 (1.times.10.sup.5) virus load via nasal cavity in a total volume of 100 .mu.L (50 .mu.L into each naris).
Hamsters' bodyweight and viable signs (such as ruffled hair and lack of movement) will be monitored and recorded twice daily for 3 days and virus titers will be measured from a nasal swab on day 2. Hamsters will be sacrificed on day 3 and virustiters in homogenates of lung tissues will be determined.
H&E-stained lung tissues will be evaluated by a suitable scientist, medical professional, or veterinary professional (e.g., trained in pathology) to determine the severity of infection and amount of protection provided by the neutralizingantibodies. To determine the TCID50 in the lungs, tissues will be homogenized and spun down and the supernatants will be removed and analyzed by a TCID50 assay as described in a previous Example, above.
Example 5: Generation of a SuperHuman Library (SHL) 2.0
A superhuman library is generated using the following steps: 1. The best 4 VH and best 4 VK frameworks from a human repertoire of 3500 combinations (IGHV1-46, IGHV1-69, IGHV3-15, IGHV3-23 for heavy and IGKV1-39, IGKV2-28, IGKV3-15, IGKV4-1 forlight) are selected based on a combination of 1) previous demonstrated safety in human mAbs, 2) thermostability, 3) not aggregation prone, 4) a single dominant allele in the frameworks at the amino acid level across all human populations (i.e., not aracist medicine), 5) different canonical topologies of the CDRs, and/or 6) express well in bacteria and display well on phage. 2. Blood is obtained from 140 subjects. 3. Naive (CD27-/IgM+) cells and memory (CD27+/IgG+) cells are sorted from theblood. 4. Pools are checked for quality using next generation sequencing (NGS), and pools with problematic diversity or biochemical liabilities are rejected. 5. VH CDR3 sequences from naive cells are PCR amplified with universal primers. 6. VHCDR1, VH CDR2, VL CDR1, VL CDR2, and VL CDR3 sequences from memory cells are PCR amplified with framework specific primers. 7. Order frameworks as synthetically produced germline segments. 8. Nucleic acid libraries are assembled using PCR-OE. 9. The assemblies from step 8 are checked for quality using NGS sequencing. 10. Light chains are cloned into a vector with a stuffer VH. 11. In-frame material is selected by protein A or protein L after thermal pressure. 12. Heavy chains are clonedinto the vector to replace the stuffer VH. 13. Microbes are transformed with the vectors generated at the end of step 12 using electroporation.
Example 6: Screening for Affinity to SARS CoV-2 Receptor Binding Domain
A primary screen of two 96-well plates of clones randomly selected after round 4 SuperHuman panning of SARS CoV-2.
Samples are immediately assayed on Carterra high-throughput kinetics instrument, bypassing ELISA screening. A majority of the hits are positive and sequenced, unique sequences are obtained.
Clones showing affinity to SARS CoV-2 are confirmed against human and cynomolgus monkey.
Example 7: SARS CoV-2 ELISA and Sanger Screening of 2 Plates of Antibody Clones
An ELISA panning antibody clones from two plates against SARS CoV-2 is carried out.
Sanger sequencing of these clones is also carried out. Extreme diversity of round 3 outputs ensured that hits against any epitope can be recovered by screening a few 96-well plates of clones.
Diversity is found not only in the VH CDR3 sequences, but also in the VH CDR1 and VH CDR2 sequences.
Example 8: Combining Design and Selection Processes to Produce an Antibody Library with Diverse VII and VK Sequences
Functional selection for expression and thermostability during construction is applied to produce a library with over 95% functional diversity across 40 million light chains. The antibody library is created with 7.6.times.10.sup.10transformants.
First, a VK (kappa light chain) library is produced by cloning into a vector the desired light chain and temporary stuffer VH sequence. The VK library is displayed and subjected to a heat stress at over 65.degree. C. In-frame material isselected using protein A/L. The stuffer VH sequence in the library resulting from the protein A/L, selection is replaced with the target VH sequence.
Example 9: Generation of a SuperHuman Library (SHL) 3.0
A superhuman library is generated using the following steps: 1. Six antibody frameworks (IGHV1-46, IGHV3-23, IGKV1-39, IGKV2-28, IGKV3-15, and IGKV4-1) are selected based on a combination of 1) previous demonstrated safety in human mAbs, 2)thermostability, 3) not aggregation prone, 4) a single dominant allele in the frameworks at the amino acid level across all human populations (i.e. not a racist medicine), 5) different canonical topologies of the CDRs, and/or 6) express well in bacteriaand display well on phage. 2. Blood is obtained from 50-100 subjects. 3. Naive (CD27-/IgM+ or CD27-/IgD+) cells and memory cells are sorted from the blood. 4. Pools are checked for quality using next generation sequencing (NGS), and pools withproblematic diversity or biochemical liabilities are rejected. 5. VH CDR3 sequences from naive cells are PCR amplified with universal primers. 6. Favorable VH CDR1, VH CDR2, VL CDR1, VL CDR2, and VL CDR3 sequences without liabilities are selected byDNA synthesis based on (1) being observed present in human natural antibodies, (2) being observed not under-performing under selection of SuperHuman 2.0 against a variety of antigens, (3) being free of biochemical liabilities (C, exposed M, deaminationsites, acid hydrolysis sites, N-linked glycosylation sites, amber stop codons, opal stop codons, highly positively charged), (4) not being more mutated than a threshold (e.g., no more than 3 amino acid mutations per CDR). Stated differently, VH CDR1,VHCDR2, VL CDR1, VL CDR2, and VL CDR3 sequences are synthesized if they meet the following criteria: a. have no more than 4 amino acid mutations away from the respective germline CDR for the respective framework used; and b. are identified as present inat least 2 of the subjects during NGS and are enriched without a fitness disadvantage when evaluating a pool of 55,000 hits against 11 antigens from SuperHuman 2.0, or have not been observed in a person but to have heavily enriched during panning in thesame SuperHuman 2.0 pool; and c. do not contain any biochemical liabilities (N-linked glycosylation, deamination, acid hydrolysis, positive charge endopeptidic cleavage, free cysteines, free methionines, alternative stop codons, cryptic splice sites, tevcleavage sites, or overly positively charged CDRs). 7. Order frameworks as synthetically produced 100% germline segments with no mutations. 8. Nucleic acid libraries are assembled using PCR-OE or another method for DNA assembly. 9. The assembliesfrom step 8 are checked for quality using NGS sequencing. 10. Light chains are cloned into a vector with a stuffer VH 11. In-frame material is selected by protein A or protein L after thermal pressure. 12. Heavy chains are cloned into the vector toreplace the stuffer VH. 13. Microbes are transformed with the vectors generated at the end of step 12 using electroporation.
While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutionswill now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention herein may be employed in practicing the invention. It is intended that the followingclaims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.
SEQUENCE LISTINGS
1
SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 443 <210> SEQ IDNO 1 <211> LENGTH: 208 <212> TYPE: PRT <213> ORGANISM: Middle East respiratory syndrome-related coronavirus <400> SEQUENCE: 1 Val Glu Cys Asp Phe Ser Pro Leu Leu Ser Gly Thr Pro Pro Gln Val 1 5 10 15 Tyr Asn Phe Lys Arg Leu ValPhe Thr Asn Cys Asn Tyr Asn Leu Thr 20 25 30 Lys Leu Leu Ser Leu Phe Ser Val Asn Asp Phe Thr Cys Ser Gln Ile 35 40 45 Ser Pro Ala Ala Ile Ala Ser Asn Cys Tyr Ser Ser Leu Ile Leu Asp 50 55 60 Tyr Phe Ser Tyr Pro Leu Ser Met Lys Ser Asp Leu Ser Val Ser Ser65 70 75 80 Ala Gly Pro Ile Ser Gln Phe Asn Tyr Lys Gln Ser Phe Ser Asn Pro 85 90 95 Thr Cys Leu Ile Leu Ala Thr Val Pro His Asn Leu Thr Thr Ile Thr 100 105 110 Lys Pro Leu Lys Tyr Ser Tyr Ile Asn Lys Cys Ser Arg Leu Leu Ser 115 120 125 Asp Asp Arg ThrGlu Val Pro Gln Leu Val Asn Ala Asn Gln Tyr Ser 130 135 140 Pro Cys Val Ser Ile Val Pro Ser Thr Val Trp Glu Asp Gly Asp Tyr 145 150 155 160 Tyr Arg Lys Gln Leu Ser Pro Leu Glu Gly Gly Gly Trp Leu Val Ala 165 170 175 Ser Gly Ser Thr Val Ala Met Thr GluGln Leu Gln Met Gly Phe Gly 180 185 190 Ile Thr Val Gln Tyr Gly Thr Asp Thr Asn Ser Val Cys Pro Lys Leu 195 200 205 <210> SEQ ID NO 2 <211> LENGTH: 200 <212> TYPE: PRT <213> ORGANISM: Severe acute respiratory syndrome coronavirus2 <400> SEQUENCE: 2 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr PheLys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys ValIle Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro 195 200 <210> SEQ ID NO 3 <211> LENGTH:202 <212> TYPE: PRT <213> ORGANISM: Human SARS coronavirus <400> SEQUENCE: 3 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 1 5 10 15 Lys Phe Pro Ser Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys 20 25 30 Val Ala AspTyr Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe 35 40 45 Lys Cys Tyr Gly Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser 50 55 60 Asn Val Tyr Ala Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln 65 70 75 80 Ile Ala Pro Gly Gln Thr Gly Val Ile Ala AspTyr Asn Tyr Lys Leu 85 90 95 Pro Asp Asp Phe Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile 100 105 110 Asp Ala Thr Ser Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg 115 120 125 His Gly Lys Leu Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe 130 135240 Ser Pro Asp Gly Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp 145 150 155 160 Pro Leu Asn Asp Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln 165 170 175 Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala 180 185 190 Thr Val Cys GlyPro Lys Leu Ser Thr Asp 195 200 <210> SEQ ID NO 4 <211> LENGTH: 202 <212> TYPE: PRT <213> ORGANISM: Human SARS coronavirus <400> SEQUENCE: 4 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 1 5 10 15 Thr PhePro Ser Val Tyr Ala Trp Glu Arg Lys Arg Ile Ser Asn Cys 20 25 30 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Thr Ser Phe Ser Thr Phe 35 40 45 Lys Cys Tyr Gly Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser 50 55 60 Asn Val Tyr Ala Asp Ser Phe Val Val Lys GlyAsp Asp Val Arg Gln 65 70 75 80 Ile Ala Pro Gly Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu 85 90 95 Pro Asp Asp Phe Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile 100 105 110 Asp Ala Thr Ser Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Ser Leu Arg 115 120125 His Gly Lys Leu Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe 130 135 140 Ser Pro Asp Gly Lys Pro Cys Thr Pro Pro Ala Phe Asn Cys Tyr Trp 145 150 155 160 Pro Leu Asn Asp Tyr Gly Phe Phe Thr Thr Asn Gly Ile Gly Tyr Gln 165 170 175 Pro Tyr Arg ValVal Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala 180 185 190 Thr Val Cys Gly Pro Lys Leu Ser Thr Asp 195 200 <210> SEQ ID NO 5 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 5 Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys 20 <210> SEQ ID NO 6 <211> LENGTH: 23<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 6 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser ValGly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 7 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 7 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 8
<211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 8 Asp Ile Gln Met Thr Gln SerPro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 9 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 9 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 10 <211> LENGTH: 23 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 10 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr IleThr Cys 20 <210> SEQ ID NO 11 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 11Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 12 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 12 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 13 <211> LENGTH: 23<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 13 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser ValGly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 14 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 14 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 15 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 15 Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys 20 <210> SEQ IDNO 16 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 16 Asp Ile Gln Met Thr Gln SerPro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 17 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Descriptionof Artificial Sequence: Synthetic peptide <400> SEQUENCE: 17 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 18 <211> LENGTH: 23 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 18 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr IleThr Cys 20 <210> SEQ ID NO 19 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 19Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 20 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 20 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 21 <211> LENGTH: 23<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 21 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser ValGly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20
<210> SEQ ID NO 22 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 22 AspIle Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Glu Arg Ala Thr Ile Asn Cys 20 <210> SEQ ID NO 23 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 23 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 24 <211> LENGTH: 23<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 24 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser ValGly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 25 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 25 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 26 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 26 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ IDNO 27 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 27 Asp Ile Gln Met Thr Gln SerPro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 28 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Descriptionof Artificial Sequence: Synthetic peptide <400> SEQUENCE: 28 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys 20 <210> SEQ ID NO 29 <211> LENGTH: 12 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 29 Arg Ala Ser Glu Ser Val Ser Ser Arg Tyr Leu Ala 1 5 10 <210> SEQ ID NO 30 <211>LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 30 Gln Ala Ser Gln Gly Ile Arg Asn Asp Leu Gly 1 510 <210> SEQ ID NO 31 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 31 Arg AlaSer Gln Ser Ile Gly Tyr Tyr Leu Asn 1 5 10 <210> SEQ ID NO 32 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 32 Arg Ala Ser Gln Gly Ile Ser Asn Asn Leu Asn 1 5 10 <210> SEQ ID NO 33 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 33 Arg Ala Ser Gln Asp Ile Arg Asn Glu Leu Gly 1 5 10 <210> SEQ ID NO 34 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 34 Arg Ala Ser Gln Gly Ile Arg Asn Asp Leu Ala 1 5 10 <210> SEQ ID NO 35 <211> LENGTH: 11 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 35 Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn 1 5 10 <210> SEQ ID NO 36 <211>LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 36 Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn 1 510 <210> SEQ ID NO 37 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:
<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 37 Arg Ala Ser Gln Ser Ile Ser Thr Tyr Leu Asn 1 5 10 <210> SEQ ID NO 38 <211> LENGTH: 11 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 38 Arg Ala Ser Gln Ser Ile Tyr Ser Trp Leu Ala 1 5 10 <210> SEQ ID NO 39 <211>LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 39 Arg Ala Ser Gln Ser Val Ser Ser Asn Tyr Leu Ala1 5 10 <210> SEQ ID NO 40 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 40 ArgAla Ser Gln His Ile Ser Ser Tyr Leu Asn 1 5 10 <210> SEQ ID NO 41 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic peptide <400> SEQUENCE: 41 Arg Ala Ser Gln Ala Ile Thr Asn Tyr Leu Ala 1 5 10 <210> SEQ ID NO 42 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 42 Gln Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn 1 5 10 <210> SEQ ID NO 43 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 43 Gln Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn 1 5 10 <210> SEQ ID NO 44 <211> LENGTH: 11 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 44 Arg Ala Ser Gln Gly Ile Arg Asn Tyr Leu Ala 1 5 10 <210> SEQ ID NO 45<211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 45 Arg Ala Ser Gln Ser Ile Ser Ser TyrLeu Asn 1 5 10 <210> SEQ ID NO 46 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE:46 Lys Ser Ser Gln Ser Val Phe Ser Ser Ser Asn Asn Lys Asn Tyr Leu 1 5 10 15 Ala <210> SEQ ID NO 47 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 47 Arg Ala Ser Glu Asn Ile Asp Ser Trp Leu Ala 1 5 10 <210> SEQ ID NO 48 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 48 Arg Ala Ser Glu Asn Ile Asp Ser Trp Leu Ala 1 5 10 <210> SEQ ID NO 49 <211> LENGTH: 11 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 49 Arg Ala Ser Gln Thr Ile Tyr Ser Tyr Leu Asn 1 5 10 <210> SEQ ID NO 50 <211>LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 50 Gln Ala Ser Gln Ser Ile Tyr Asn Tyr Leu Asn 1 510 <210> SEQ ID NO 51 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 51 Arg ValSer Gln Gly Ile Ser Ser Tyr Leu Asn 1 5 10 <210> SEQ ID NO 52 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 52 Arg Ala Ser Gln Gly Ile Ser Asn Asn Leu Asn 1 5 10 <210> SEQ ID NO 53 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 53 Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 1 5 10 15
<210> SEQ ID NO 54 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 54Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 55 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 55 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 56 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 56 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 57 <211> LENGTH: 15<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 57 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr1 5 10 15 <210> SEQ ID NO 58 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 58Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 59 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 59 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 60 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 60 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 61 <211> LENGTH: 15<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 61 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr1 5 10 15 <210> SEQ ID NO 62 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 62Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 63 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 63 Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 64 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 64 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 65 <211> LENGTH: 15<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 65 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr1 5 10 15 <210> SEQ ID NO 66 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 66Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 67 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 67 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 68 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 68 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 69 <211> LENGTH: 15<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 69 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr1 5 10 15 <210> SEQ ID NO 70 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 70
Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 71 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Descriptionof Artificial Sequence: Synthetic peptide <400> SEQUENCE: 71 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 72 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 72 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 73 <211> LENGTH: 15<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 73 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr1 5 10 15 <210> SEQ ID NO 74 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 74Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 75 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 75 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 76 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 76 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 1 5 10 15 <210> SEQ ID NO 77 <211> LENGTH: 7<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 77 Gly Ala Ser Thr Arg Ala Thr 1 5 <210> SEQ ID NO 78<211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 78 Asp Ala Ser Arg Leu Gln Ser 1 5<210> SEQ ID NO 79 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 79 Ala Ala SerSer Leu Gln Ser 1 5 <210> SEQ ID NO 80 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400>SEQUENCE: 80 Ala Ala Ser Ser Leu Gln Ser 1 5 <210> SEQ ID NO 81 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 81 Ala Ala Ser Ser Leu Gln Ser 1 5 <210> SEQ ID NO 82 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of ArtificialSequence: Synthetic peptide <400> SEQUENCE: 82 Ala Ala Ser Ser Leu Gln Ser 1 5 <210> SEQ ID NO 83 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 83 Ala Ala Ser Asn Leu Gln Ser 1 5 <210> SEQ ID NO 84 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 84 Ala Ala Ser Ser Leu Gln Ser 1 5 <210> SEQ ID NO 85 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 85 Ala Ala Ser Thr Leu Gln Ser 1 5 <210> SEQ ID NO 86 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 86 Asp Ala Ser Ser Leu Glu Ser 1 5 <210> SEQ ID NO 87 <211> LENGTH: 7 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:
Synthetic peptide <400> SEQUENCE: 87 Ala Val Ser Ser Arg Ala Thr 1 5 <210> SEQ ID NO 88 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 88 Ala Ala Ser Ala Leu Gln Ser 1 5 <210> SEQ ID NO 89 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 89 Ala Ala Ser Ser Leu Gln Ser 1 5 <210> SEQ ID NO 90 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 90 Gly Ala Ser Thr Leu Ser Asp 1 5 <210> SEQ ID NO 91 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 91 Gly Ala Ser Thr Leu Ser Asp 1 5 <210> SEQ ID NO 92 <211> LENGTH: 7 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 92 Ala Ala Ser Thr Leu Gln Ser 1 5 <210> SEQ ID NO 93 <211> LENGTH: 7 <212>TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 93 Ala Ala Ser Arg Leu Gln Ser 1 5 <210> SEQ ID NO 94 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 94 Trp Ala Ser Thr Arg Glu Ser 1 5 <210> SEQID NO 95 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 95 Glu Ala Ser Thr Leu Glu Ser1 5 <210> SEQ ID NO 96 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 96 Glu AlaSer Thr Leu Glu Ser 1 5 <210> SEQ ID NO 97 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400>SEQUENCE: 97 Asp Ala Ser Asn Leu Glu Thr 1 5 <210> SEQ ID NO 98 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 98 Asp Ala Ser Asn Leu Glu Thr 1 5 <210> SEQ ID NO 99 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of ArtificialSequence: Synthetic peptide <400> SEQUENCE: 99 Ala Ala Ser Ile Leu Gln Ser 1 5 <210> SEQ ID NO 100 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 100 Ala Ala Ser Ser Leu Glu Ser 1 5 <210> SEQ ID NO 101 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 101 Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr 20 2530 <210> SEQ ID NO 102 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 102Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 103 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 103
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 104 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 104 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro GluAsp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 105 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpolypeptide <400> SEQUENCE: 105 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 106 <211> LENGTH: 31 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 106 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 107 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic polypeptide <400> SEQUENCE: 107 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 108 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 108 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly SerGly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 109 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 109 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210>SEQ ID NO 110 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 110 Gly Val Pro SerArg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 111 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 111 Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val TyrTyr 20 25 30 <210> SEQ ID NO 112 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400>SEQUENCE: 112 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 113 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 113 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser LeuGln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 114 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic polypeptide <400> SEQUENCE: 114 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 115 <211> LENGTH: 31 <212>TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 115 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 15 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 116 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Descriptionof Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 116 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 117 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 117
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 118 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 118 Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser LeuGln Ala Glu Asp Val Ala Val Tyr Tyr 20 25 30 <210> SEQ ID NO 119 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic polypeptide <400> SEQUENCE: 119 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 120 <211> LENGTH: 31 <212>TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 120 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 15 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 121 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Descriptionof Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 121 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 122 <211>LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 122 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly SerGly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 123 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 123 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210>SEQ ID NO 124 <211> LENGTH: 31 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 124 Gly Val Pro SerArg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 1 5 10 15 Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 20 25 30 <210> SEQ ID NO 125 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 125 Cys Gln Gln Gly Tyr Lys Asn Pro Pro Thr Phe 1 5 10 <210> SEQ ID NO 126 <211> LENGTH: 12 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 126 Cys Gln Gln Tyr Tyr Ser Thr Pro Pro Leu Thr Phe 1 5 10 <210> SEQ ID NO 127 <211>LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 127 Cys Gln Gln Ser Tyr Thr Thr Pro Leu Thr Phe 1 510 <210> SEQ ID NO 128 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 128 CysGln Gln Tyr Asp Thr Phe Pro Leu Thr Phe 1 5 10 <210> SEQ ID NO 129 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic peptide <400> SEQUENCE: 129 Cys Gln Gln Ser Tyr Ser Thr Pro Pro Trp Thr Phe 1 5 10 <210> SEQ ID NO 130 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 130 Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe 1 5 10 <210> SEQ ID NO 131 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 131 Cys Gln Gln Ala Asn Ser Phe Pro Ser Thr Phe 1 5 10 <210> SEQ ID NO 132 <211> LENGTH: 11 <212>TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 132 Cys Gln Gln Ser Tyr Ser Thr Pro Leu Thr Phe
1 5 10 <210> SEQ ID NO 133 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400>SEQUENCE: 133 Cys Gln Gln Ser Tyr Ser Met Pro Leu Thr Phe 1 5 10 <210> SEQ ID NO 134 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 134 Cys Gln Gln Leu Asn Ser Tyr Pro Tyr Thr Phe 1 5 10 <210> SEQ ID NO 135 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 135 Cys Gln Gln Tyr Gly Ser Ser Pro Leu Thr Phe 1 5 10 <210> SEQ ID NO 136 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 136 Cys Gln Gln Gly Tyr Gly Thr Pro Tyr Thr Phe 1 5 10 <210> SEQ ID NO 137 <211> LENGTH: 11<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 137 Cys Gln Gln Tyr Tyr Ser Tyr Pro Pro Thr Phe 1 5 10<210> SEQ ID NO 138 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 138 Cys GlnGln Gly Tyr Ser Thr Pro Tyr Ser Phe 1 5 10 <210> SEQ ID NO 139 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 139 Cys Gln Gln Gly Tyr Ser Thr Pro Tyr Ser Phe 1 5 10 <210> SEQ ID NO 140 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 140 Cys Gln Gln Ser Tyr Ser Pro Pro Leu Thr Phe 1 5 10 <210> SEQ ID NO 141 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 141 Cys Gln Gln Ser Tyr Ser Thr Pro Leu Thr Phe 1 5 10 <210> SEQ ID NO 142 <211> LENGTH: 11 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 142 Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe 1 5 10 <210> SEQ ID NO 143<211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 143 Cys His Gln Tyr Leu Ser Ser Pro GluThr Phe 1 5 10 <210> SEQ ID NO 144 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400>SEQUENCE: 144 Cys His Gln Tyr Leu Ser Ser Pro Glu Thr Phe 1 5 10 <210> SEQ ID NO 145 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 145 Cys Gln Gln Ala Ile Ser Phe Pro Leu Thr Phe 1 5 10 <210> SEQ ID NO 146 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 146 Cys Gln Gln Ala Ile Ser Phe Pro Leu Thr Phe 1 5 10 <210> SEQ ID NO 147 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 147 Cys Gln Gln Gly Tyr Ser Thr Pro Phe Thr Phe 1 5 10 <210> SEQ ID NO 148 <211> LENGTH: 11<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 148 Cys Gln Gln Gly Asn Gly Phe Pro Leu Thr Phe 1 5 10<210> SEQ ID NO 149 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide
<400> SEQUENCE: 149 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 150 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 150 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 151 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 151 Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 152 <211> LENGTH: 10 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 152 Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 153 <211> LENGTH:10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 153 Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 1 5 10<210> SEQ ID NO 154 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 154 Gly GlnGly Thr Lys Leu Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 155 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 155 Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 156 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 156 Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 157 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 157 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 158 <211> LENGTH: 10 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 158 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 159 <211> LENGTH:10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 159 Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 1 5 10<210> SEQ ID NO 160 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 160 Gly GlnGly Thr Lys Leu Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 161 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 161 Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 162 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 162 Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 163 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 163 Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 164 <211> LENGTH: 10 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 164 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 165 <211> LENGTH:10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 165 Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 1 5 10<210> SEQ ID NO 166 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence
<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 166 Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 167 <211> LENGTH: 10 <212> TYPE:PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 167 Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 168<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 168 Gly Gln Gly Thr Lys Val Glu Ile LysArg 1 5 10 <210> SEQ ID NO 169 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE:169 Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 170 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic peptide <400> SEQUENCE: 170 Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 171 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 171 Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 1 5 10 <210> SEQ ID NO 172 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 172 Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 1 5 10 <210> SEQ ID NO 173 <211> LENGTH: 26 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 173 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 SerVal Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 174 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 174 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 20 25 <210> SEQ ID NO 175 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 175 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys AlaAla Ser Gly 20 25 <210> SEQ ID NO 176 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400>SEQUENCE: 176 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 177 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 177 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25<210> SEQ ID NO 178 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 178 Gln ValGln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 179 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 179 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO180 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 180 Gln Val Gln Leu Val Gln Ser GlyAla Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 181 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence:
Synthetic peptide <400> SEQUENCE: 181 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 182 <211> LENGTH: 26 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 182 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 SerVal Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 183 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 183 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 184 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 184 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys LysAla Ser Gly 20 25 <210> SEQ ID NO 185 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400>SEQUENCE: 185 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 186 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 186 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25<210> SEQ ID NO 187 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 187 Gln ValGln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 188 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 188 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO189 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 189 Gln Val Gln Leu Val Gln Ser GlyAla Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 190 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 190 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 191 <211> LENGTH: 26<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 191 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys ProGly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 192 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of ArtificialSequence: Synthetic peptide <400> SEQUENCE: 192 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 193 <211> LENGTH: 26 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 193 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 SerVal Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 194 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 194 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 195 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE:
<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 195 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQID NO 196 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 196 Gln Val Gln Leu Val GlnSer Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Tyr Val Ser Cys Lys Ala Ser Gly 20 25 <210> SEQ ID NO 197 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 197 Asp Thr Phe Ser Asn Tyr Gly Ile Ser 1 5 <210> SEQ ID NO 198 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 198 Phe Ser Phe Ser Asn Tyr Asp Met His 1 5 <210> SEQ ID NO 199 <211> LENGTH: 9 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 199 Phe Thr Phe Ser Gly Ser Ala Met His 1 5 <210> SEQ ID NO 200 <211> LENGTH: 9<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 200 Gly Thr Phe Arg Ser Thr Ala Ile Ser 1 5 <210> SEQ IDNO 201 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 201 Gly Thr Phe Ser Ser Tyr AlaIle Ser 1 5 <210> SEQ ID NO 202 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE:202 Gly Thr Phe Thr Ser Tyr His Met His 1 5 <210> SEQ ID NO 203 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 203 Tyr Ile Phe Thr Ser Tyr Pro Ile His 1 5 <210> SEQ ID NO 204 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 204 Tyr Thr Phe Ile Asn Tyr Asp Ile Asn 1 5 <210> SEQ ID NO 205 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 205 Tyr Thr Phe Thr Asp Tyr His Met His 1 5 <210> SEQ ID NO 206 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 206 Tyr Thr Phe Thr Asp Tyr Tyr Ile Gln 1 5 <210> SEQ ID NO 207 <211> LENGTH: 9 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 207 Tyr Thr Phe Thr Asp Tyr Tyr Met Gln 1 5 <210> SEQ ID NO 208 <211> LENGTH: 9<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 208 Tyr Thr Phe Thr Glu Asn Glu Met His 1 5 <210> SEQ IDNO 209 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 209 Tyr Thr Phe Thr Glu Asn GluMet His 1 5 <210> SEQ ID NO 210 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE:210 Tyr Thr Phe Thr Glu Asn Glu Met His 1 5 <210> SEQ ID NO 211 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 211
Tyr Thr Phe Thr Glu Asn Glu Met His 1 5 <210> SEQ ID NO 212 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic peptide <400> SEQUENCE: 212 Tyr Thr Phe Thr Gly Asn Tyr Ile His 1 5 <210> SEQ ID NO 213 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 213 Tyr Thr Phe Thr Gly Ser Tyr Ala Ile Ser 1 5 10 <210> SEQ ID NO 214 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 214 Tyr Thr Phe Thr Asn Tyr Gly Ile Ser 1 5 <210> SEQ ID NO 215 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 215 Tyr Thr Phe Thr Arg Tyr Tyr Ile His 1 5 <210> SEQ ID NO 216 <211> LENGTH: 9 <212>TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 216 Tyr Thr Phe Thr Arg Tyr Tyr Ile His 1 5 <210> SEQ ID NO 217<211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 217 Tyr Thr Phe Thr Ser Tyr Asp Ile Asn1 5 <210> SEQ ID NO 218 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 218 TyrThr Phe Thr Ser Tyr Asp Ile Asn 1 5 <210> SEQ ID NO 219 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide<400> SEQUENCE: 219 Tyr Thr Phe Thr Ser Tyr Glu Ile Asn 1 5 <210> SEQ ID NO 220 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 220 Tyr Thr Phe Thr Ser Tyr Gly Ile Ser 1 5 <210> SEQ ID NO 221 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 221 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 222 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 222 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 1 5 10 <210> SEQ ID NO 223 <211>LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 223 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu TyrVal 1 5 10 <210> SEQ ID NO 224 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE:224 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 225 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of ArtificialSequence: Synthetic peptide <400> SEQUENCE: 225 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 226 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 226 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 227 <211> LENGTH: 13 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 227 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 228<211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:
Synthetic peptide <400> SEQUENCE: 228 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 229 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 229 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 230 <211> LENGTH: 13 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 230 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 231<211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 231 Trp Val Arg Gln Ala Pro Gly Gln GlyLeu Glu Trp Met 1 5 10 <210> SEQ ID NO 232 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400>SEQUENCE: 232 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 233 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 233 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 234 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 234 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 235 <211> LENGTH: 13 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 235 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO236 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 236 Trp Val Arg Gln Ala Pro Gly GlnGly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 237 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide<400> SEQUENCE: 237 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 238 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 238 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 239 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 239 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 240 <211> LENGTH: 13 <212>TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 240 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210>SEQ ID NO 241 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 241 Trp Val Arg Gln AlaPro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 242 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 242 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 243 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 243 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 244 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 244 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 1 5 10 <210> SEQ ID NO 245 <211>LENGTH: 13
<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 245 Gly Trp Met Asn Pro Asn Ser Gly Gly Thr Asn TyrAla 1 5 10 <210> SEQ ID NO 246 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE:246 Ala Val Ile Ser Tyr Asp Gly Gly Phe Lys Leu Tyr Ala 1 5 10 <210> SEQ ID NO 247 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of ArtificialSequence: Synthetic peptide <400> SEQUENCE: 247 Ser Ala Ile Ser Arg Asn Gly Gly Thr Thr Tyr Tyr Ala 1 5 10 <210> SEQ ID NO 248 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 248 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala 1 5 10 <210> SEQ ID NO 249 <211> LENGTH: 13 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 249 Gly Ile Val Asn Pro Ser Ser Gly Ser Thr Thr Tyr Ala 1 5 10 <210> SEQ ID NO 250<211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 250 Gly Trp Met Asn Pro Asn Ser Gly AsnThr Gly Tyr Ala 1 5 10 <210> SEQ ID NO 251 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400>SEQUENCE: 251 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala 1 5 10 <210> SEQ ID NO 252 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 252 Gly Val Ile Asn Pro Ser Ala Gly Ser Thr Ser Tyr Ala 1 5 10 <210> SEQ ID NO 253 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 253 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Ser Tyr Ala 1 5 10 <210> SEQ ID NO 254 <211> LENGTH: 13 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 254 Gly Trp Ile Asn Pro Asn Ser Gly Gly Pro Asn Tyr Ala 1 5 10 <210> SEQ ID NO255 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 255 Gly Trp Ile Asp Pro His Ser GlyAla Thr Asn Tyr Ala 1 5 10 <210> SEQ ID NO 256 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide<400> SEQUENCE: 256 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala 1 5 10 <210> SEQ ID NO 257 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 257 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala 1 5 10 <210> SEQ ID NO 258 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 258 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala 1 5 10 <210> SEQ ID NO 259 <211> LENGTH: 13 <212>TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 259 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala 1 5 10 <210>SEQ ID NO 260 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 260 Gly Trp Met Asn ProAsn Ser Gly Asn Thr Gly Tyr Ala 1 5 10 <210> SEQ ID NO 261 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 261 Gly Trp Ile Asn Pro Lys Thr Gly Asp Thr Asn Tyr Ala 1 5 10
<210> SEQ ID NO 262 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 262Gly Trp Ile Ser Ala Arg Asn Gly Asn Thr Asn Tyr Ala 1 5 10 <210> SEQ ID NO 263 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of ArtificialSequence: Synthetic peptide <400> SEQUENCE: 263 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Thr Tyr Ala 1 5 10 <210> SEQ ID NO 264 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 264 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Thr Tyr Ala 1 5 10 <210> SEQ ID NO 265 <211> LENGTH: 13 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 265 Gly Ile Ile Asp Pro Ser Gly Gly Ser Thr Ser Tyr Ala 1 5 10 <210> SEQ ID NO 266<211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 266 Gly Trp Met Asn Ser Asn Ser Gly SerThr Gly Tyr Ala 1 5 10 <210> SEQ ID NO 267 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400>SEQUENCE: 267 Gly Ile Ile Asn Pro Ser Asp Gly Ser Ser Thr Tyr Ala 1 5 10 <210> SEQ ID NO 268 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 268 Gly Gly Ile Ile Pro Met Phe Gly Thr Thr Asn Tyr Ala 1 5 10 <210> SEQ ID NO 269 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 269 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp ThrAla Val 20 25 30 Tyr Tyr <210> SEQ ID NO 270 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide<400> SEQUENCE: 270 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn 1 5 10 15 Ser Leu Tyr Leu Arg Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 271 <211> LENGTH: 34 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 271 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 1 5 10 15Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 272 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 272 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQID NO 273 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 273 Gln Lys Phe Gln GlyArg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 274 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 274 Leu Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg SerGlu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 275 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpolypeptide <400> SEQUENCE: 275 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 276 <211> LENGTH: 34 <212>TYPE: PRT <213> ORGANISM: Artificial Sequence
<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 276 His Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser LeuArg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 277 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic polypeptide <400> SEQUENCE: 277 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 278 <211> LENGTH: 34<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 278 Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp GluSer Thr Ser 1 5 10 15 Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 279 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 279 His Ser Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr<210> SEQ ID NO 280 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 280 GlnLys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 281 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 281 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser LeuArg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 282 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic polypeptide <400> SEQUENCE: 282 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 283 <211> LENGTH: 34<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 283 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp ThrSer Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 284 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 284 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr<210> SEQ ID NO 285 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 285 GlnGlu Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 286 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 286 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser LeuArg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 287 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic polypeptide <400> SEQUENCE: 287 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 288 <211> LENGTH: 34<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 288 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp ThrSer Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val
20 25 30 Tyr Tyr <210> SEQ ID NO 289 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide<400> SEQUENCE: 289 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 290 <211> LENGTH: 34 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 290 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 291 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 291 Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 1 5 10 15 Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQID NO 292 <211> LENGTH: 34 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 292 Gln Lys Phe Gln GlyArg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser 1 5 10 15 Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 20 25 30 Tyr Tyr <210> SEQ ID NO 293 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 293 Cys Ala Ile Gly Thr Thr Val Val Thr Pro Phe Gly Tyr Trp 1 5 10 <210> SEQ ID NO 294 <211> LENGTH: 19<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 294 Cys Ala Arg Gly Gln Val Arg Gly Ser Gly Pro Gln Val ValVal Met 1 5 10 15 Asp Val Trp <210> SEQ ID NO 295 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide<400> SEQUENCE: 295 Cys Ala Lys Asp Gly Thr Leu Ile Thr Thr Thr Leu Asp Tyr Trp 1 5 10 15 <210> SEQ ID NO 296 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 296 Cys Ala Arg Ala Gly Tyr Ser Ser Ser Ser Gly Tyr Tyr Tyr Tyr Gly 1 5 10 15 Met Asp Val Trp 20 <210> SEQ ID NO 297 <211> LENGTH: 16 <212> TYPE:PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 297 Cys Ala Arg Val Arg Gly Ser Ala Ala Ile Ala Met Met Asp Val Trp 1 5 10 15<210> SEQ ID NO 298 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 298 Cys AlaSer Phe Glu Arg Phe Gly Glu Leu Val Pro Glu Thr Phe Asp 1 5 10 15 Tyr Trp <210> SEQ ID NO 299 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 299 Cys Ala Arg Asp Arg Gly Ser Tyr Asp Thr Asp Ala Phe Asp Ile Trp 1 5 10 15 <210> SEQ ID NO 300 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 300 Cys Ala Ser Ala His Ser Ser Ser Trp Tyr Ser Asp Trp Phe Asp Pro 1 5 10 15 Trp <210> SEQ ID NO 301 <211>LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 301 Cys Ala Gly Met Gly Met Gly Arg Asp Gly Tyr AsnSer Arg Ala Phe 1 5 10 15 Asp Ile Trp <210> SEQ ID NO 302 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 302 Cys Ala Arg Val Asp Tyr Gly Asp Tyr Gly Arg Leu Glu Asp Tyr Trp 1 5 10 15 <210> SEQ ID NO 303 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:
<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 303 Cys Ala Arg Leu Glu Gly Gly Ser Tyr Trp Thr Gly Tyr Phe Asp Leu 1 5 10 15 Trp <210> SEQ ID NO 304 <211> LENGTH: 22<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 304 Cys Ala Lys Thr Arg Tyr Gly Gly Asn Ser Arg Ser Arg TyrTyr Tyr 1 5 10 15 Tyr Gly Met Asp Val Trp 20 <210> SEQ ID NO 305 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic peptide <400> SEQUENCE: 305 Cys Ala Arg Asp Leu Met Asp Ile Val Val Val Pro Trp Leu Gly Gly 1 5 10 15 Met Asp Val Trp 20 <210> SEQ ID NO 306 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 306 Cys Ala Arg Asp Ser Gly Val Asp Thr Ala Thr Leu Arg Tyr Tyr Tyr 1 5 10 15 Tyr Gly Met Asp Val Trp 20 <210> SEQ ID NO307 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 307 Cys Ala Arg Asp Ser Gly Val AspThr Ala Thr Leu Arg Tyr Tyr Tyr 1 5 10 15 Tyr Gly Met Asp Val Trp 20 <210> SEQ ID NO 308 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 308 Cys Ala Lys Asp Val Gln Asn Tyr Tyr Gly Ser Gly Ser Ser Phe Asp 1 5 10 15 Tyr Trp <210> SEQ ID NO 309 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 309 Cys Ala Arg Gly Ser Ser Gly Tyr Tyr Phe Gly Trp 1 5 10 <210> SEQ ID NO 310 <211> LENGTH: 15<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 310 Cys Thr Thr Asp Pro Val Leu Glu Trp Phe Gly Tyr Ser IleTrp 1 5 10 15 <210> SEQ ID NO 311 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE:311 Cys Ala Lys Gly Ala Pro His Asp Tyr Ile Trp Gly Ser Tyr Arg Pro 1 5 10 15 Asp Ala Phe Asp Ile Trp 20 <210> SEQ ID NO 312 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 312 Cys Ala Lys Gly Ala Pro His Asp Tyr Ile Trp Gly Ser Tyr Arg Pro 1 5 10 15 Asp Ala Phe Asp Ile Trp 20 <210> SEQ ID NO 313 <211> LENGTH: 13<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 313 Cys Ala Thr Val Thr Pro Gly Tyr Gly Met Asp Val Trp 1 5 10<210> SEQ ID NO 314 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 314 Cys AlaArg Gly Trp Met Ala Tyr Asp Ala Phe Asp Ile Trp 1 5 10 <210> SEQ ID NO 315 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of ArtificialSequence: Synthetic peptide <400> SEQUENCE: 315 Cys Ala Arg Asp Arg Gly Tyr Ser Tyr Asp His Asp Gln Ile Tyr Tyr 1 5 10 15 Tyr Tyr Gly Met Asp Val Trp 20 <210> SEQ ID NO 316 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 316 Cys Ala Arg Asp Arg Gly Asp Thr Ile Asp Tyr Trp 1 5 10 <210> SEQ ID NO 317 <211> LENGTH:10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 317 Gly Gln Gly Thr Leu Val Asn Val Ser Ser 1 5 10<210> SEQ ID NO 318 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:
Synthetic peptide <400> SEQUENCE: 318 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 319 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 319 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 320 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 320 Gly Lys Gly Thr Thr Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 321 <211> LENGTH: 10 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 321 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 322<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 322 Gly Gln Gly Thr Leu Val Thr Val SerSer 1 5 10 <210> SEQ ID NO 323 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE:323 Gly Gln Gly Thr Met Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 324 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic peptide <400> SEQUENCE: 324 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 325 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 325 Gly Gln Gly Thr Met Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 326 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 326 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 327 <211> LENGTH: 10 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 327 Gly Arg Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 328<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 328 Gly Gln Gly Thr Thr Val Thr Val SerSer 1 5 10 <210> SEQ ID NO 329 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE:329 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 330 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic peptide <400> SEQUENCE: 330 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 331 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 331 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 332 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 332 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 333 <211> LENGTH: 10 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 333 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 334<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 334 Gly Gln Gly Thr Met Val Thr Val SerSer 1 5 10 <210> SEQ ID NO 335 <211> LENGTH: 10
<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 335 Gly Gln Gly Thr Met Val Thr Val Ser Ser 1 5 10<210> SEQ ID NO 336 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 336 Gly GlnGly Thr Met Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 337 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 337 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 338 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 338 Gly Gln Gly Thr Met Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 339 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 339 Gly Gln Gly Thr Thr Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 340 <211> LENGTH: 10 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 340 Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210> SEQ ID NO 341 <211> LENGTH:119 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 341 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val LysLys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Thr Phe Ser Asn Tyr 20 25 30 Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln GlyArg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ile Gly Thr Thr Val Val Thr Pro Phe Gly Tyr Trp Gly Gln Gly 100 105 110 Thr Leu Val Asn Val Ser Ser 115<210> SEQ ID NO 342 <211> LENGTH: 124 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 342 GluVal Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Asn Tyr 20 25 30 Asp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Val Ile Ser Tyr Asp Gly Gly PheLys Leu Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 Leu Arg Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Gln Val Arg Gly Ser Gly Pro Gln Val Val Val Met Asp 100105 110 Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 <210> SEQ ID NO 343 <211> LENGTH: 120 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic polypeptide <400> SEQUENCE: 343 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Gly Ser 20 25 30 Ala Met His Trp Val Arg Gln Ala ProGly Lys Gly Leu Glu Tyr Val 35 40 45 Ser Ala Ile Ser Arg Asn Gly Gly Thr Thr Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 8590 95 Ala Lys Asp Gly Thr Leu Ile Thr Thr Thr Leu Asp Tyr Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> SEQ ID NO 344 <211> LENGTH: 125 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 344 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe ArgSer Thr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu SerSer Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Ala Gly Tyr Ser Ser Ser Ser Gly Tyr Tyr Tyr Tyr Gly Met 100 105 110 Asp Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser 115 120 125 <210> SEQ ID NO 345 <211> LENGTH: 121<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 345 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys LysPro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45
Gly Ile Val Asn Pro Ser Ser Gly Ser Thr Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Val Arg Gly SerAla Ala Ile Ala Met Met Asp Val Trp Gly 100 105 110 Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 <210> SEQ ID NO 346 <211> LENGTH: 123 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 346 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Thr Ser Tyr 20 25 30 His MetHis Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Leu Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu AspThr Ala Val Tyr Tyr Cys 85 90 95 Ala Ser Phe Glu Arg Phe Gly Glu Leu Val Pro Glu Thr Phe Asp Tyr 100 105 110 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> SEQ ID NO 347 <211> LENGTH: 121 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 347 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser CysLys Ala Ser Gly Tyr Ile Phe Thr Ser Tyr 20 25 30 Pro Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr ValTyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Gly Ser Tyr Asp Thr Asp Ala Phe Asp Ile Trp Gly 100 105 110 Gln Gly Thr Met Val Thr Val Ser Ser 115 120 <210> SEQ ID NO 348 <211> LENGTH:122 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 348 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val LysLys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ile Asn Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Val Ile Asn Pro Ser Ala Gly Ser Thr Ser Tyr Ala His Lys Phe 50 55 60 Gln GlyArg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ser Ala His Ser Ser Ser Trp Tyr Ser Asp Trp Phe Asp Pro Trp 100 105 110 Gly Gln Gly Thr Leu Val Thr Val SerSer 115 120 <210> SEQ ID NO 349 <211> LENGTH: 124 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400>SEQUENCE: 349 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 His Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn ProAsn Ser Gly Asn Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Gly Met Gly Met Gly Arg Asp Gly Tyr Asn Ser ArgAla Phe Asp 100 105 110 Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser 115 120 <210> SEQ ID NO 350 <211> LENGTH: 121 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION:Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 350 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30 Tyr Ile Gln Trp Val ArgGln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asn Pro Asn Ser Gly Gly Pro Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val TyrTyr Cys 85 90 95 Ala Arg Val Asp Tyr Gly Asp Tyr Gly Arg Leu Glu Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> SEQ ID NO 351 <211> LENGTH: 122 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 351 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly TyrThr Phe Thr Asp Tyr 20 25 30 Tyr Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Asp Pro His Ser Gly Ala Thr Asn Tyr Ala His Ser Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 MetGlu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Leu Glu Gly Gly Ser Tyr Trp Thr Gly Tyr Phe Asp Leu Trp 100 105 110 Gly Arg Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> SEQ ID NO 352 <211> LENGTH: 127 <212>TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 352 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 15 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Glu Asn 20 25 30 Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys ThrArg Tyr Gly Gly Asn Ser Arg Ser Arg Tyr Tyr Tyr Tyr 100 105 110 Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 125 <210> SEQ ID NO 353 <211> LENGTH: 125 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 353 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly TyrThr Phe Thr Glu Asn 20 25 30 Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 MetGlu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Leu Met Asp Ile Val Val Val Pro Trp Leu Gly Gly Met 100 105 110 Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 125 <210> SEQ ID NO 354 <211> LENGTH:127 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 354 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val LysLys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Glu Asn 20 25 30 Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln GlyArg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Ser Gly Val Asp Thr Ala Thr Leu Arg Tyr Tyr Tyr Tyr 100 105 110 Gly Met Asp Val Trp Gly Gln Gly ThrThr Val Thr Val Ser Ser 115 120 125 <210> SEQ ID NO 355 <211> LENGTH: 127 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpolypeptide <400> SEQUENCE: 355 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Glu Asn 20 25 30 Glu Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Ser Gly Val AspThr Ala Thr Leu Arg Tyr Tyr Tyr Tyr 100 105 110 Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 125 <210> SEQ ID NO 356 <211> LENGTH: 123 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 356 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Asn20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser LeuArg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Asp Val Gln Asn Tyr Tyr Gly Ser Gly Ser Ser Phe Asp Tyr 100 105 110 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> SEQ ID NO 357 <211> LENGTH: 118 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 357 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Ser 20 25 30 Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp 35 40 45 Met Gly Trp Ile Asn Pro Lys Thr Gly Asp Thr Asn Tyr Ala Gln Glu 50 55 60 Phe Gln Gly Arg Val Thr Met Thr ArgAsp Thr Ser Thr Ser Thr Val 65 70 75 80 Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr 85 90 95 Cys Ala Arg Gly Ser Ser Gly Tyr Tyr Phe Gly Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <210> SEQ ID NO 358 <211>LENGTH: 120 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 358 Gln Val Gln Leu Val Gln Ser Gly Ala GluVal Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 20 25 30 Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Ile Ser Ala Arg Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Thr Asp Pro Val Leu Glu Trp Phe Gly Tyr Ser Ile Trp Gly Gln 100 105 110 Gly Thr Met Val Thr Val SerSer 115 120 <210> SEQ ID NO 359 <211> LENGTH: 127 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400>SEQUENCE: 359 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr 20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser LeuArg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Ala Pro His Asp Tyr Ile Trp Gly Ser Tyr Arg Pro Asp 100 105 110 Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser 115 120 125 <210> SEQ ID NO 360 <211> LENGTH: 127<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 360 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys LysPro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly ArgVal Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Ala Pro His Asp Tyr Ile Trp Gly Ser Tyr Arg Pro Asp 100 105 110 Ala Phe Asp Ile Trp Gly Gln Gly Thr MetVal Thr Val Ser Ser 115 120 125 <210> SEQ ID NO 361 <211> LENGTH: 118 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpolypeptide <400> SEQUENCE: 361 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045 Gly Ile Ile Asp Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Thr Val Thr Pro Gly TyrGly Met Asp Val Trp Gly Gln Gly Thr 100 105 110 Thr Val Thr Val Ser Ser 115 <210> SEQ ID NO 362 <211> LENGTH: 119 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Descriptionof Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 362 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Asp Ile Asn Trp Val Arg Gln Ala ProGly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Ser Asn Ser Gly Ser Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 8590 95 Ala Arg Gly Trp Met Ala Tyr Asp Ala Phe Asp Ile Trp Gly Gln Gly 100 105 110 Thr Met Val Thr Val Ser Ser 115 <210> SEQ ID NO 363 <211> LENGTH: 128 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 363 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr20 25 30 Glu Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Asn Pro Ser Asp Gly Ser Ser Thr Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser LeuArg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Gly Tyr Ser Tyr Asp His Asp Gln Ile Tyr Tyr Tyr 100 105 110 Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 115 120 125 <210> SEQ ID NO 364 <211> LENGTH: 117<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 364 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys LysPro Gly Ser 1 5 10 15 Ser Val Tyr Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Ile Ile Pro Met Phe Gly Thr Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly ArgVal Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Gly Asp Thr Ile Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <210> SEQID NO 365 <211> LENGTH: 109 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 365 Glu Ile Val Met ThrGln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Glu Ser Val Ser Ser Arg 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro AlaArg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln 65 70 75 80 Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Tyr Lys Asn Pro 85 90 95 Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210> SEQ ID NO366 <211> LENGTH: 109 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 366 Asp Ile Gln Met Thr GlnSer Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Gly Ile Arg Asn Asp 20 25 30 Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45
Tyr Asp Ala Ser Arg Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Pro 85 90 95 Leu Thr Phe Gly Gln GlyThr Lys Val Glu Ile Lys Arg 100 105 <210> SEQ ID NO 367 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpolypeptide <400> SEQUENCE: 367 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Gly Tyr Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Thr Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr LysVal Glu Ile Lys Arg 100 105 <210> SEQ ID NO 368 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide<400> SEQUENCE: 368 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Asn 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr AlaAla Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Thr Phe Pro Leu 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu IleLys Arg 100 105 <210> SEQ ID NO 369 <211> LENGTH: 109 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400>SEQUENCE: 369 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Arg Asn Glu 20 25 30 Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser SerLeu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro 85 90 95 Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg100 105 <210> SEQ ID NO 370 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE:370 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu GlnSer Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105<210> SEQ ID NO 371 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 371 AspIle Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Asn Leu Gln Ser GlyVal Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Ser 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <210>SEQ ID NO 372 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 372 Asp Ile Gln MetThr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro SerArg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210> SEQ ID NO373 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 373 Asp Ile Gln Met Thr GlnSer Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Thr Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg PheSer Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Met Pro Leu 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210> SEQ ID NO 374<211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:
Synthetic polypeptide <400> SEQUENCE: 374 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Tyr Ser Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala ProLys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Tyr 85 90 95 Thr PheGly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210> SEQ ID NO 375 <211> LENGTH: 109 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic polypeptide <400> SEQUENCE: 375 Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg LeuLeu 35 40 45 Ile Tyr Ala Val Ser Ser Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln 65 70 75 80 Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 85 90 95 Leu Thr Phe Gly GlyGly Thr Lys Val Glu Ile Lys Arg 100 105 <210> SEQ ID NO 376 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpolypeptide <400> SEQUENCE: 376 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln His Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045 Tyr Ala Ala Ser Ala Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Gly Thr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr LysVal Glu Ile Lys Arg 100 105 <210> SEQ ID NO 377 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide<400> SEQUENCE: 377 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ala Ile Thr Asn Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr AlaAla Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Tyr Ser Tyr Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu IleLys Arg 100 105 <210> SEQ ID NO 378 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400>SEQUENCE: 378 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser ThrLeu Ser Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Thr Pro Tyr 85 90 95 Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100105 <210> SEQ ID NO 379 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 379Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Gly Ala Ser Thr Leu Ser AspGly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Thr Pro Tyr 85 90 95 Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105<210> SEQ ID NO 380 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 380 AspIle Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Tyr 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Thr Leu Gln Ser GlyVal Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Pro Pro Leu 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210>SEQ ID NO 381 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 381 Asp Ile Gln MetThr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Arg Leu Gln Ser Gly Val Pro SerArg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210> SEQ ID NO 382 <211> LENGTH: 114 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 382 Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser GlnSer Val Phe Ser Ser 20 25 30 Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 35 40 45 Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 60 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 65 70 75 80 IleSer Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 85 90 95 Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile 100 105 110 Lys Arg <210> SEQ ID NO 383 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 383 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile ThrCys Arg Ala Ser Glu Asn Ile Asp Ser Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Glu Ala Ser Thr Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu GlnPro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys His Gln Tyr Leu Ser Ser Pro Glu 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210> SEQ ID NO 384 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 384 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg AlaSer Glu Asn Ile Asp Ser Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Glu Ala Ser Thr Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 7075 80 Glu Asp Phe Ala Thr Tyr Tyr Cys His Gln Tyr Leu Ser Ser Pro Glu 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210> SEQ ID NO 385 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 385 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser GlnThr Ile Tyr Ser Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 GluAsp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Ile Ser Phe Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <210> SEQ ID NO 386 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 386 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile TyrAsn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe AlaThr Tyr Tyr Cys Gln Gln Ala Ile Ser Phe Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 100 105 <210> SEQ ID NO 387 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 387 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Val Ser Gln Gly Ile Ser Ser Tyr20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ile Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr TyrTyr Cys Gln Gln Gly Tyr Ser Thr Pro Phe 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <210> SEQ ID NO 388 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 388 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Asn 20 25 30 LeuAsn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys GlnGln Gly Asn Gly Phe Pro Leu 85 90 95 Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg 100 105 <210> SEQ ID NO 389 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 389
Gly Thr Phe Ser Ser Tyr Thr Ile Ser 1 5 <210> SEQ ID NO 390 <211> LENGTH: 14 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic peptide <400> SEQUENCE: 390 Met Gly Gly Ile Thr Pro Ile Leu Gly Ile Ala Asn Tyr Ala 1 5 10 <210> SEQ ID NO 391 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 391 Cys Ala Arg Asp Thr Val Met Gly Gly Met Asp Val 1 5 10 <210> SEQ ID NO 392 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 392 Gly Gly Asn Asn Ile Gly Ser Lys Ser Val His 1 5 10 <210> SEQ ID NO 393 <211> LENGTH: 7<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 393 Asp Asp Ser Asp Arg Pro Ser 1 5 <210> SEQ ID NO 394<211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 394 Gln Val Trp Asp Ser Ser Ser Asp TyrVal 1 5 10 <210> SEQ ID NO 395 <211> LENGTH: 118 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400>SEQUENCE: 395 Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 Thr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Ile Thr ProIle Leu Gly Ile Ala Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Thr Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Thr Val Met Gly Gly Met Asp Val Trp GlyGln Gly Thr 100 105 110 Thr Val Thr Val Ser Ser 115 <210> SEQ ID NO 396 <211> LENGTH: 107 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic polypeptide <400> SEQUENCE: 396 Ser Tyr Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Lys 1 5 10 15 Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Ser Val 20 25 30 His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val ValTyr 35 40 45 Asp Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 50 55 60 Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly 65 70 75 80 Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Ser Asp Tyr 85 90 95 Val Phe Gly Thr GlyThr Lys Val Thr Val Leu 100 105 <210> SEQ ID NO 397 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide<400> SEQUENCE: 397 Phe Ala Phe Ser Ser Tyr Ala Met His 1 5 <210> SEQ ID NO 398 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 398 Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala 1 5 10 <210> SEQ ID NO 399 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220>FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 399 Cys Ala Arg Asp Arg Ser Tyr Tyr Leu Asp Tyr 1 5 10 <210> SEQ ID NO 400 <211> LENGTH: 11 <212> TYPE: PRT <213>ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 400 Arg Ala Ser Gln Ser Val Arg Ser Asn Leu Ala 1 5 10 <210> SEQ ID NO 401 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 401 Asp Ala Ser Thr Arg Ala Thr 1 5 <210> SEQID NO 402 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 402 Cys Gln Gln Arg Ser AsnTrp Pro Pro Thr 1 5 10 <210> SEQ ID NO 403 <211> LENGTH: 117 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide<400> SEQUENCE: 403 Glu Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro Gly Lys 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ala Phe Ser Ser Tyr 20 25 30 Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr IleSer Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Tyr Leu Asp Tyr Trp Gly Gln Gly Thr Leu 100 105 110 Val Thr Val Ser Ser 115 <210> SEQ ID NO 404<211> LENGTH: 107 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 404 Glu Thr Thr Leu Thr Gln SerPro Ala Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Asn 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Pro Leu Ile 35 40 45 Tyr Asp Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe SerGly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 65 70 75 80 Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro 85 90 95 Thr Phe Gly Gln Gly Thr Lys Val Glu Val Lys 100 105 <210> SEQ ID NO 405 <211>LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 405 Tyr Thr Phe Thr Thr Tyr Arg Met His 1 5<210> SEQ ID NO 406 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 406 Gly AlaIle Tyr Pro Gly Asn Ser Asp Thr Thr Tyr Asn 1 5 10 <210> SEQ ID NO 407 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence:Synthetic peptide <400> SEQUENCE: 407 Cys Thr Arg Glu Gly Ile Pro Gln Leu Leu Arg Thr Leu Asp Tyr 1 5 10 15 <210> SEQ ID NO 408 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 408 Arg Ala Ser Gln Glu Ile Ser Gly Tyr Leu Ser 1 5 10 <210> SEQ ID NO 409 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 409 Ala Ala Ser Thr Leu Asp Ser 1 5 <210> SEQ ID NO 410 <211> LENGTH: 10 <212> TYPE: PRT<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 410 Cys Leu Gln Tyr Val Ser Tyr Pro Trp Thr 1 5 10 <210> SEQ ID NO 411<211> LENGTH: 121 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 411 Glu Val Gln Leu Glu Glu SerGly Thr Val Leu Ala Arg Pro Gly Ala 1 5 10 15 Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr 20 25 30 Arg Met His Trp Ile Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ala Ile Tyr Pro Gly Asn Ser Asp Thr Thr Tyr Asn Gln LysPhe 50 55 60 Lys Asp Lys Ala Lys Leu Thr Ala Val Thr Ser Thr Ser Ser Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Thr Asn Glu Asp Ser Ala Val Tyr Phe Cys 85 90 95 Thr Arg Glu Gly Ile Pro Gln Leu Leu Arg Thr Leu Asp Tyr Trp Gly 100 105 110 Gln Gly Thr SerVal Thr Val Ser Ser 115 120 <210> SEQ ID NO 412 <211> LENGTH: 107 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide<400> SEQUENCE: 412 Asp Ile Leu Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly 1 5 10 15 Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr 20 25 30 Leu Ser Trp Leu Gln Glu Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile 35 40 45 Tyr AlaAla Ser Thr Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly 50 55 60 Ser Arg Ser Gly Ser Asp Tyr Ser Leu Thr Ile Ser Ser Leu Glu Ser 65 70 75 80 Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Tyr Val Ser Tyr Pro Trp 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu IleLys 100 105 <210> SEQ ID NO 413 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE:413 Phe Thr Phe Arg Asn Tyr Ala Met His 1 5 <210> SEQ ID NO 414 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpeptide <400> SEQUENCE: 414 Ala Val Ile Thr Ser Asp Gly Arg Asn Lys Phe Tyr Ala 1 5 10 <210> SEQ ID NO 415 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence:
Synthetic peptide <400> SEQUENCE: 415 Cys Val Thr Gln Arg Asp Asn Ser Arg Asp Tyr Phe Pro His Tyr Phe 1 5 10 15 His Asp Met Asp Val 20 <210> SEQ ID NO 416 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 416 Arg Ser Ser Gln Ser Leu Val Tyr Ser Asp Gly Asp Thr Tyr Leu Asn 1 5 10 15 <210> SEQ ID NO 417 <211>LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 417 Gln Val Ser Asn Arg Asp Ser 1 5 <210> SEQID NO 418 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 418 Cys Met Gln Gly Ser HisTrp Pro Pro Thr 1 5 10 <210> SEQ ID NO 419 <211> LENGTH: 127 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide<400> SEQUENCE: 419 Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Arg Asn Tyr 20 25 30 Ala Met His Trp Val Arg Gln Ala Pro Ala Thr Gly Leu Gln Trp Leu 35 40 45 Ala ValIle Thr Ser Asp Gly Arg Asn Lys Phe Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Glu Asp Ser Lys Asn Thr Leu Tyr 65 70 75 80 Leu Gln Met Asp Ser Leu Arg Gly Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Thr Gln Arg Asp Asn Ser Arg Asp TyrPhe Pro His Tyr Phe His 100 105 110 Asp Met Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 125 <210> SEQ ID NO 420 <211> LENGTH: 112 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 420 Asp Val Val Leu Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val Tyr Ser 20 25 30 AspGly Asp Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly Gln Ser 35 40 45 Pro Arg Arg Leu Ile Tyr Gln Val Ser Asn Arg Asp Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val GlyVal Tyr Tyr Cys Met Gln Gly 85 90 95 Ser His Trp Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> SEQ ID NO 421 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 421 Tyr Gly Phe Ile Thr Tyr Trp Ile Gly 1 5 <210> SEQ ID NO 422 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: ArtificialSequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 422 Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser 1 5 10 <210> SEQ ID NO 423 <211> LENGTH: 13<212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 423 Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val 1 5 10<210> SEQ ID NO 424 <211> LENGTH: 17 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 424 Lys SerSer Gln Ser Val Leu Tyr Ser Ser Ile Asn Lys Asn Tyr Leu 1 5 10 15 Ala <210> SEQ ID NO 425 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description ofArtificial Sequence: Synthetic peptide <400> SEQUENCE: 425 Trp Ala Ser Thr Arg Glu Ser 1 5 <210> SEQ ID NO 426 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 426 Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Thr 1 5 10 <210> SEQ ID NO 427 <211> LENGTH: 119 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 427 Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu 1 5 10 15 Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly TyrGly Phe Ile Thr Tyr 20 25 30 Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met 35 40 45 Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe 50 55 60 Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr 65 70 75 80 LeuGln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys 85 90 95 Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly 100 105 110 Thr Thr Val Thr Val Ser Ser
115 <210> SEQ ID NO 428 <211> LENGTH: 113 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400>SEQUENCE: 428 Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 1 5 10 15 Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser 20 25 30 Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 35 40 45 Pro Pro Lys Leu LeuIle Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 60 Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 65 70 75 80 Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 85 90 95 Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr LysVal Glu Ile 100 105 110 Lys <210> SEQ ID NO 429 <211> LENGTH: 16 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide<400> SEQUENCE: 429 Cys Ala Arg Asp Arg Gly Ser Tyr Asp Thr Asp Ala Phe Asp Ile Trp 1 5 10 15 <210> SEQ ID NO 430 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 430 Tyr Ile Phe Thr Ser Tyr Pro Ile His 1 5 <210> SEQ ID NO 431 <211> LENGTH: 13 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 431 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala 1 5 10 <210> SEQ ID NO 432 <211> LENGTH: 11 <212>TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 432 Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn 1 5 10 <210> SEQ IDNO 433 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 433 Ala Ala Ser Asn Leu Gln Ser 15 <210> SEQ ID NO 434 <400> SEQUENCE: 434 000 <210> SEQ ID NO 435 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of ArtificialSequence: Synthetic peptide <400> SEQUENCE: 435 Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 1 5 10 <210> SEQ ID NO 436 <211> LENGTH: 121 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHERINFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 436 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Ser Tyr 20 25 30 Pro IleHis Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Trp Met Asn Pro Asn Ser Gly Asn Thr Gly Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu AspThr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Gly Ser Tyr Asp Thr Asp Ala Phe Asp Ile Trp Gly 100 105 110 Gln Gly Thr Met Val Thr Val Ser Ser 115 120 <210> SEQ ID NO 437 <211> LENGTH: 108 <212> TYPE: PRT <213> ORGANISM:Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 437 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile ThrCys Arg Ala Ser Gln Asp Ile Ser Asn Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Ala Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu GlnPro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Ser 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 100 105 <210> SEQ ID NO 438 <400> SEQUENCE: 438 000 <210> SEQ ID NO 439 <400> SEQUENCE: 439000 <210> SEQ ID NO 440 <400> SEQUENCE: 440 000 <210> SEQ ID NO 441 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of ArtificialSequence: Synthetic peptide <400> SEQUENCE: 441 Cys Gln Gln Ala Asn Ser Phe Pro Ser Thr Phe 1 5 10 <210> SEQ ID NO 442 <211> LENGTH: 6 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223>OTHER INFORMATION: Description of Artificial Sequence: Synthetic 6xHis tag <400> SEQUENCE: 442
His His His His His His 1 5 <210> SEQ ID NO 443 <211> LENGTH: 100 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Syntheticpolypeptide <220> FEATURE: <221> NAME/KEY: MISC_FEATURE <222> LOCATION: (1)..(100) <223> OTHER INFORMATION: This sequence may encompass 3-20 "Gly Gly Gly Gly Ser" repeating units <220> FEATURE: <223> OTHER INFORMATION:See specification as filed for detailed description of substitutions and preferred embodiments <400> SEQUENCE: 443 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 1 5 10 15 Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser GlyGly 20 25 30 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 35 40 45 Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 50 55 60 Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 65 70 75 80 Gly Gly Gly Gly SerGly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 85 90 95 Gly Gly Gly Ser 100
* * * * *
Americans are partying again. But elsewhere, the pandemic is getting worse. - The Washington Post
Thu, 03 Jun 2021 11:29
You're reading an excerpt from the Today's WorldView newsletter. Sign up to get the rest, including news from around the globe, interesting ideas and opinions to know, sent to your inbox every weekday.
In the United States, life is returning to normal. Restaurants and bars are filling up again, vacations are being booked and flights are selling out. At sporting events, maskless fans are hugging and cheering. Memorial Day weekend, the country's unofficial start to the summer, was celebrated with much more gusto and many more family barbecues than it was a year ago.
That's all for good reason: A majority of Americans have received at least one dose of a coronavirus vaccine, and daily new infections and deaths are at their lowest levels in almost a year. The pandemic is slowly receding from the daily lives of many Americans as businesses open up and local authorities ease restrictions. Britain, which on Tuesday reported no new coronavirus-related deaths for the first time since March 2020, can also see the sunlit uplands of a post-pandemic future.
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''Covid-19 won't end with a bang or a parade,'' wrote Devi Sridhar, chair of global public health at the University of Edinburgh. ''Throughout history, pandemics have ended when the disease ceases to dominate daily life and retreats into the background like other health challenges.''
But the pandemic is hardly in retreat elsewhere. The emergence of more virulent variants of the virus in countries like Brazil and India and the slowness of vaccination efforts in many places outside the West have contributed to deadly new waves. Coronavirus case counts worldwide are already higher in 2021 than they were in 2020. The death toll almost certainly will be.
Southeast Asia, once a bastion of resistance to the virus as it ravaged Western countries, is in the grip of a harrowing spike in infections. Cases in Thailand and Vietnam rose dramatically over the past month. Malaysia is now registering more new infections per million people than any medium- or large-size country in Asia, surpassing India, which remains a global hot spot. On Tuesday, the Malaysian government implemented a nationwide lockdown that will last for the next two weeks.
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''The economy will certainly suffer. The people will suffer even more, those who live. Many are dying and will die,'' wrote columnist Munir Majid in the New Straits Times. ''We are staring at the abyss.''
In Africa, concerns are growing over the possible arrival of a new wave powered by a more transmissible variant of the virus, with the health systems in many countries at risk of being quickly subsumed by a surge of infections. A recent study found that the continent has the world's highest death rate of patients critically ill with covid-19, thanks to limited intensive care facilities and reserves of vital medical supplies like oxygen.
In parts of Latin America, the virus rages on, largely unabated. Peru, according to its own government-adjusted data, now has the worst covid-19 mortality rate per capita in the world. The country is slated to stage a closely contested presidential runoff election this weekend.
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Even in East Asia, where a handful of nations set the gold standard in preventing community spread, the virus is on the march. Taiwan has seen an explosion of cases over the past month. In Japan, which still intends to host the Summer Olympics, numerous areas including Tokyo remain under a state of emergency. It's a sign, argue some public health experts, that the strict methods that kept places like Taiwan, South Korea and Singapore safer than their counterparts in the West for all of last year may not be sustainable in the long term.
For a number of reasons, the vaccine rollouts in these countries have been slow, hampered by a lack of supply. In an interview earlier this year with Today's WorldView, Koji Tomita, Japan's ambassador in Washington, described his country and other East Asian states that initially managed to clamp down on community spread '-- but built up little herd immunity '-- as ''prisoners of their own success.''
Public health advocates and international organizations recognize the main problem: The global gap in vaccinations. In the United States, there's already discussion of booster shots for the general public, while front-line medical workers in some developing countries have yet to even receive a first dose of a vaccine. In a joint statement, the heads of the International Monetary Fund, the World Bank, the World Trade Organization and the World Health Organization laid out a $50 billion plan for collective action that would accelerate vaccine distribution to poor and middle-income countries and expand and diversify production capacity throughout the world.
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''Inequitable vaccine distribution is leaving millions of people vulnerable to the virus while allowing deadly variants to emerge and ricochet back across the world,'' they wrote in an op-ed published in The Washington Post. ''As variants spread, even countries with advanced vaccination programs have been forced to reimpose stricter public health measures and travel restrictions. The ongoing pandemic is deepening divergence in economic fortunes, with negative consequences for all.''
''It would be a monumental error for any country to think the danger has passed,'' WHO Director General Tedros Adhanom Ghebreyesus said Monday at the close of the World Health Assembly. He warned that insufficient global coordination at present means that ''we will still face the same vulnerabilities that allowed a small outbreak to become a global pandemic.''
Attention now moves to this month's meeting of the Group of Seven nations, where leaders of these traditional world powers are expected to step up and deliver on the global need for vaccines. The Biden administration also opted to support negotiations at the WTO over a possible waiver of international property protections on coronavirus vaccines, which could lead to more countries being able to produce them. But the waiver is still opposed by major European governments, while advocates contend that these discussions should have taken place at a much earlier stage in the pandemic.
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Now, time is of the essence, as more transmissible variants appear to be burning rapidly through societies without much immunological protection. ''It is, of course, understandable that every nation wants to vaccinate its own first, but a country with high levels of vaccination, especially among its more vulnerable populations, can hold things off, especially if they also had big outbreaks before,'' wrote Zeynep Tufekci in the New York Times, arguing that wealthier nations like the United States should be actively prioritizing providing for other countries over its own population. ''In addition, excess stockpiles can go where they are needed without even slowing down existing vaccination programs.''
Anthony S. Fauci, the leading infectious-disease expert in the United States, appeared to recognize the broader threat. ''As long as there is some degree of activity throughout the world, there's always a danger of variants emerging and diminishing somewhat the effectiveness of our vaccines,'' he told the Guardian.
Iranian Navy ships could reach the Atlantic by Thursday
Wed, 02 Jun 2021 22:18
The Makran anchored north of Larak Island in the Persian Gulf. | Satellite image (C)2021 Maxar Technologies
The two Iranian Navy ships steaming south along the east coast of Africa are expected to round the Cape of Good Hope and reach the Atlantic Ocean as early as Thursday, according to two U.S. officials with direct knowledge.
National security officials tracking the ships do not know the ships' final destination, but believe they may be ultimately bound for Venezuela, POLITICO first reported on Saturday. The ships were still moving south on Wednesday, and at their current pace they are on track to turn west around the Cape on Thursday, said the people, who requested anonymity to discuss sensitive operations.
Advertisement''Our belief that it's heading toward Venezuela has not changed,'' one of the people said.
Iranian warships sailing into the Atlantic Ocean would present a major test for the Biden administration, which has been trying to re-engage Tehran in negotiations over its nuclear program. Iran has previously threatened to send warships into the Atlantic, but never followed through, settling for an emergency port call in South Africa in 2016.
Tehran's intent in sending the ships toward the Atlantic is not clear. But a spokesperson for the National Security Council noted that Venezuela purchased weapons from Iran over a year ago, and warned that any new delivery of weapons "would be a provocative act and a threat to our partners in this hemisphere."
"We would reserve the right to take appropriate measures '-- in concert with our partners '-- to deter the delivery or transit of such weapons," the person said, speaking on condition of anonymity to discuss a sensitive topic.
AdvertisementThe Iranian ships include a frigate and the Makran, a former oil tanker that was converted to a floating forward staging base, according to the officials.
Tehran and Caracas have previously worked together to defy the United States and to further both governments' goals. Iran has in the past sent tankers to dock in Venezuela and deliver oil, in defiance of U.S. sanctions.
''Tehran is intent on deepening its footprint in Latin America and in the Western Hemisphere more broadly. Venezuela offers Tehran a forward operating base in the region,'' said Behnam Ben Taleblu, an Iran expert at the hawkish Foundation for Defense of Democracies, whose scholars often advocate for a tough U.S. policy aimed at undermining Iran's Islamist regime. Taleblu noted that the Makran's movement, in particular, has raised eyebrows.
Top officials in Tehran have implicitly confirmed the ships' movement. In response to POLITICO's reporting, the Iranian Foreign Ministry on Monday warned U.S. officials to avoid miscalculations about the country's warships sailing in international waters.
Advertisement''Iran is always present in international waters and has this right under international law and can be present in international waters,'' Foreign Ministry spokesperson Saeed Khatibzadeh told reporters in Tehran.
''No country can violate this right,'' he said. ''Those who have sit in glass houses should be careful.''
Over the past few days, the ships have alternatively stopped and indicated they might turn around, the U.S. officials said. But since Friday they have made significant progress south along the coast.
The Biden administration updated lawmakers on the ships' progress on Tuesday, one of the people said.
After POLITICO first reported on the ships' movements, Sen. Marco Rubio (R-Fla.), the vice chair of the Senate Intelligence Committee, suggested that the U.S. should prevent the ships from reaching Venezuela.
''There are only two reasons why an Iranian warship would travel half a world away to make a port call in Venezuela,'' Rubio wrote on Twitter. ''To deliver military cargo they have sold them; to test the U.S. by conducting joint exercises with them. We should allow neither to happen.''
However, a U.S. defense official said there are currently no plans to send U.S. Navy ships to monitor or deter the Iranian task force. U.S. Southern Command typically operates two littoral combat ships in the South and Central America region.
The ships' cargo is also unknown. However, satellite photos of the Makran taken by Maxar Technologies in April and May and shared with POLITICO show the vessel leaving a port in Iran in April with seven high-speed fast attack craft on its deck. The images were first reported by USNI News. Another picture taken in May shows the Makran north of Larak Island in the Strait of Hormuz with the boats still onboard.
AdvertisementThe boats seen in the images are consistent with the fast attack craft operated by the Islamic Revolutionary Guard Corps Navy, which frequently patrol the Persian Gulf and the Strait of Hormuz. This type of boat has been used in recent months to harass U.S. ships operating in international waters.
Pentagon spokesperson John Kirby declined to comment on the ships' movement during a press briefing on Tuesday.
''I'm not going to speculate about what the Iranian Navy might or might not do,'' Kirby said. However, he noted that Adm. Craig Faller, commander of U.S. Southern Command, ''has at his disposal capabilities to help secure our interest and to meet our commitments in that part of the world.''
Taleblu noted that Iran's ship movements have created geopolitical challenges in the past, and urged the Biden administration to watch the latest development closely.
''Sanctioned Iranian and Venezuelan actors have reportedly [bartered] jet fuel for gasoline in the past and may be using the tanker trade or port calls for other purposes,'' he wrote in an email. ''As the Biden team looks to unwind sanctions on Iran, discerning where the U.S. is on such activity is getting harder, and that's a big problem.''
Also Wednesday, a major Iranian Navy vessel, the Kharg, sank after catching fire, while a huge blaze broke out at an oil refinery that serves the Iranian capital.
While the exact cause of the fires was not yet clear, various Iranian infrastructure and military assets have been damaged by explosions and fires in the past that analysts have suspected is the work of Israel, which views Iran as a major adversary and is trying to damage its nuclear program.
The Kharg went down in the Gulf of Oman near the Strait of Hormuz. Iranian media quoted a Navy spokesperson as saying there was a 20-hour battle to bring the blaze under control, but to no avail.
AdvertisementThe fire began in the vessel's engine room, according to Iran's semi-official Fars News agency, which quoted the unnamed spokesperson. The media outlet reported that the ship had been in service for 40 years and was used for both logistical and training purposes.
The fire at the oil refinery struck the state-owned Tondgooyan Petrochemical Co. to the south of Tehran, The Associated Press reported, sending up huge black plumes of smoke.
Nahal Toosi and Betsy Woodruff Swan contributed to this report.
Inside Citizen: The public safety app pushing surveillance boundaries
Wed, 02 Jun 2021 21:35
The smartphone app Citizen describes itself in simple terms: a safety network that sends alerts about nearby incidents including crime. But in recent months, its business has pushed into potentially dangerous new territory, alarming law enforcement officials and people who worked there.
In Los Angeles, the company's CEO, Andrew Frame, ordered his staff to put a $30,000 reward on the capture of a man he incorrectly thought was responsible for starting a brushfire that was threatening homes. The sheriff's office denounced the move, saying it put the man in danger, and the man was cleared of wrongdoing.
Days later, people started to see what looked like a law enforcement SUV bearing Citizen's logo driving around Los Angeles. It turned out to be a test of a private security force for people willing to pay the company a monthly fee, and it was quickly denounced on social media as a dystopian idea that could interfere with the 911 system. The company then abandoned the test.
These attempts by Citizen to branch out are causing alarm among both experts and people who have worked at Citizen, because they say the company seems to be heading in a new, more aggressive direction that may end up doing more harm than good.
"Why does Andrew Frame get to decide to put a bounty on anyone's head?" said one former Citizen employee, who said he was disgusted by the turn the company has taken, including its use of an online wanted poster not authorized by police. Like other former Citizen employees, he agreed to be interviewed about his experience at the company on the condition of anonymity, saying he feared retaliation from Citizen management for speaking against the company.
"It should make everyone afraid, because it could be anyone," the former employee said. "There's no oversight."
Citizen, which is based in New York City and initially went by the name Vigilante, got to this juncture in a roundabout journey, marked over the past two years by a major shake-up in senior management, the departure of a co-founder, the elimination of the company's growth team and what former employees called a desperate search to find a way to make money from the information it's been collecting in about 30 U.S. cities.
It's not unusual for tech startups to cycle through business ideas and focus on growth as they figure out what they want to be. But because Citizen is focused on public safety, the stakes behind each idea are higher.
"When you're dealing with public safety, it's more difficult to take risks than if you're dealing with restaurant reviews," said a second former Citizen employee.
Ben Jealous, a former president of the NAACP and a former partner at a firm that invested in Citizen, has helped to burnish the company's reputation, comparing it to street lights as a basic safety tool. In a statement Tuesday, he said he still believes in the app's ability to help vulnerable communities find missing people and avoid danger, but he also expressed concern.
"These were serious mistakes that cannot be repeated," Jealous said through a personal spokesperson. "I'm hopeful that the company will both course correct quickly as they've done in the past and put checks in place to prevent future missteps."
Citizen founder and CEO Andrew Frame speaks in San Francisco on Sept. 19, 2017. Steve Jennings / Getty images fileNBC News spoke with eight former employees of Citizen who collectively described a startup that frequently acts without thinking through consequences, and often fails to live up to its marketing themes about putting safety over other priorities such as attracting new users.
Three of the former employees said they believed Citizen was moving closer to the earlier version of the app, Vigilante, which launched in 2016 and was banned from Apple's App Store for encouraging people to rush toward violence. That version was marketed as a way for civilians to take the law into their own hands and respond to crime in progress, rather than avoid it.
Frame did not respond to a request for an interview. A spokesperson for Citizen said he had declined the request and that no one else was available for an interview.
In a statement, the company said it wants to create a network of people protecting one another, despite the fire incident in Los Angeles, which the company called a mistake.
"One of the goals when we founded the company was to create symmetry of information between the community and law enforcement '-- so nobody has to wonder why there's a police car on their corner or helicopters overhead," the company said in response to written questions. "Citizen creates an open, shared safety system where police and citizens can hold each other accountable. This is the only way to rebuild trust between community and law enforcement."
It is also "completely untrue" that there had been turmoil or high turnover within the company since the start of 2020, a spokesperson said.
From Vigilante to Citizen Citizen is one of a handful of apps that have risen in popularity in recent years as a way for people to track, report and share local news and discuss crime close to home.
"It's extending the dragnet of surveillance into residential space, and that I believe is something new," said Lauren Bridges, a doctoral candidate in critical data studies at the Annenberg School for Communication at the University of Pennsylvania. She has written about the impact of another home security tech product, Amazon's Ring cameras.
But unlike the neighborhood-focused social media network Nextdoor and the Neighbors app, which is used to share videos from Ring cameras, Citizen's focus is squarely on local crime. Opening the app brings the user to a map of their nearby area with a line sweeping around the screen reminiscent of a radar tracking system, showing incidents.
Citizen captures information about crime from several sources '-- including law enforcement radio traffic '-- and presents it to people in a localized form. Last year, it added localized information about the spread of Covid-19.
Residents can use the app to broadcast video live from the scene of a fire, car wreck, crime or other incident, and law enforcement officers can, too.
Citizen is available in about 30 cities nationwide and says on its website that it's "working to expand our coverage rapidly to more cities." The company has raised more than $130 million in funding from some of the biggest venture capital firms, including Sequoia Capital and Greycroft, according to Crunchbase, a website that tracks startups.
The app has found some success, though not the kind typically encouraged by startups backed with tens of millions of dollars in venture capital. It has been downloaded about 11.7 million times since its launch, according to Apptopia, a tech research firm. Its growth has been steady over the past two years, according to Apptopia data, though well behind the most popular consumer apps.
Citizen, a smartphone app, is designed to alert you when crimes, emergencies and other dangerous events occur in your area. CitizenAnd users tend to engage with the app consistently. Categorized in app stores as a "news" app, Citizen is in the top 20 percent for seven-day retention among Apple iOS users and the top 10 percent among Google Android users. Downloads peaked in June 2020, during nationwide protests over police violence, Apptopia research says.
Citizen said in response to written questions that it has a clear strategy and business plan, but it did not say what the plan is, other than that it does not involve selling user data or advertisements. It said it had more than doubled its user base in 2020.
But in a possible warning sign, the percentage of negative user reviews has been increasing in recent months, according to Apptopia. In January, about 23 percent of reviews were negative, steadily increasing to 37 percent in May. Some have found the app so off-putting that they decided to delete it. (Citizen noted that it still has a 4.8 rating on Apple's app store.)
At its best, the app serves as something of a neighborhood watch. Its users have been responsible for finding a missing 76-year-old man in New York, alerting a New York apartment dweller to a fire in his own building and helping a person in Atlanta avoid a nearby armed robbery, among other success stories, according to the company.
"We take great care to differentiate incidents and describe them accurately and objectively," Citizen said in a statement. The company says, for example, that it labels incidents as "unconfirmed" unless confirmed by law enforcement.
To some others, though, the information on Citizen isn't so reliable.
A third former employee said he came to doubt the accuracy of most of the information on Citizen because of what he called the lack of in-depth vetting. Citizen staff members often pass along information directly from police scanners, a notoriously unverified source, he said.
"It fuels public insanity and fear," the former employee said. "The effect of Citizen is to make everybody afraid in a community. I'm not a supporter. I tell people that."
Citizen said in a statement that it updates a post if it receives information indicating that a report was a false alarm. It also says its staff members, known as "analysts," often have backgrounds in media or law enforcement that help them filter information. They receive training and follow manuals, according to the company.
Citizen staff members generally spend most of an eight-hour shift monitoring scanner traffic from multiple cities, with different cities each night, often listening to recordings at double-speed to maximize efficiency, a fourth former employee said.
"That sounds like it can get overwhelming, and at times it can be," she said. "I had nightmares every night about either waking up to work late or, worse yet, falling really, really behind on radio clips." She said analysts discussed organizing but didn't form a union while she was there.
She said that one day last year, in the late spring or early summer, Citizen sent a celebratory-but-premature notification that "we had flattened the curve" against Covid-19, but "that was not true at all. There was no proper vetting there," she said.
Atop the company is Frame, 41, the CEO and a co-founder. A teenage prodigy as a hacker who dropped out of high school and avoided jail time as a minor after he breached NASA computer systems, he made tens of millions of dollars from early work at Facebook building network architecture, according to a 2019 profile in Forbes magazine.
Frame started Citizen in 2016 as the Vigilante app, and former employees said they fear he never lost his interest in a swashbuckling, vigilante-style network, despite Apple's veto of that idea and public statements from Citizen afterward disavowing the original ethos.
"The company was spending so much time and effort to try to get away from the Vigilante thing, when it was so clear that Frame loved the Vigilante thing," a fifth former employee said. "He would always show us videos or things related to the Vigilante days." Among the videos he would play for employees was a 2016 marketing video, by then years old, showcasing how civilians might rush toward a violent crime in progress if asked to do so, this person said.
A sixth former employee said that, on one occasion, Frame defended the original Vigilante marketing theme after a staff member in a meeting had offhandedly called it a mistake.
"Andrew was like, 'That wasn't a mistake,'" the former employee said. "He said, 'The worst thing that can befall a company is to be ignored.' He said, 'That's what put this company on the map.'"
A Citizen spokesperson did not answer a written question about whether Frame replays the old Vigilante marketing video for the staff, or whether he's interested in returning to that idea.
A seventh former employee was skeptical that Frame had done anything out of line, saying that while Frame is "definitely a passionate individual," at the same time, there was a "clear red line that he could never cross." That threshold was to not identify specific people in the app, or to start "manhunts."
"I know while I was there that the red line existed, and everyone around Frame was aware of it, and we never had to remind Frame that that line existed either, probably because the platform's entire existence depended on it," this person said.
But by last month, Frame was enthusiastically backing the idea of manhunts, according to screenshots of internal company communications seen by NBC News and first reported by Motherboard.
"We should catch a new bad guy EVERY DAY," Frame told employees via the messaging app Slack, according to the screenshots.
The context was the brushfire in Los Angeles that had forced evacuations. Citizen told people on its app that it was offering a $30,000 reward for information leading to the arrest of what it said was an "arson suspect." It showed a photograph of the person, and during a live broadcast within the app, hosts from Citizen repeatedly asked listeners to "bring this guy to justice," according to Cerise Castle, a journalist who live-tweeted the broadcast.
Frame signed off on and encouraged the reward, according to the Slack screenshots.
"FIND THIS F---," he wrote, using an expletive. "This guy is the devil. Get him," he said.
For Frame, there was a potential personal stake: He lives near the site of the fire, a Citizen spokesperson confirmed.
But it turned out the person was wanted only for questioning, not as a suspect. The company said it received information about a person of interest from a police sergeant '-- including the man's identity and a photo '-- and that its staff members concluded prematurely, on their own, that he was a suspect. The information did not come through the Los Angeles Police Department's designated public information officer, and it's not clear if a Citizen staff member spoke personally with the sergeant or how the company communicated with authorities in the case.
"Typically, we verify information with the appropriate agencies; in this case, we moved too quickly after receiving information about a person of interest, from an LAPD Sergeant, and did not follow our strict protocols for verifying information with the appropriate public safety agencies," Citizen said in a statement.
The reward was potentially "disastrous" because it could have led to someone getting hurt, the Los Angeles sheriff's office said. Sheriff's deputies eventually found the man and released him because they did not have evidence to charge him, according to Spectrum News. They later charged someone else with starting the blaze.
But Citizen isn't ruling out more rewards in the future. The company said it was evaluating the impact and usefulness of offering rewards and would move forward in a way that benefits public safety.
Private securityAnother idea to emerge at the startup recently was Citizen Protect, a $20-a-month service that would give subscribers the ability to call a Citizen staff member at any time as kind of a digital bodyguard. The staff member could video-chat during a walk home at night, for example. Two of the former employees said the idea was panned by some internally as not a product many people would pay for.
Citizen said the Protect product was still being tested, and that as of now, the company has no plans to launch its own private security force. The SUV in Los Angeles was a promotional vehicle and the only one used as part of a pilot project, according to Citizen. "We are constantly testing new ideas," the company said.
The churn of ideas coincided with a nearly wholesale turnover in senior management during 2020, according to interviews with former employees and profiles on LinkedIn.
Luis Samaniego, a Citizen co-founder, left last year to work at a company that makes retail checkout software. He declined an interview request. And others who left last year included the head of design, the head of growth and the head of product '-- accounting for many of Frame's direct reports. The senior staff members who remained included the head of engineering, the head of central operations and Frame himself.
"The upper management kept changing repeatedly, to the point where I just stopped keeping track of who had what title," said one of the former employees.
Citizen has sometimes drawn on high-profile supporters such as Jealous and William Bratton, who has led police departments in Boston, New York and Los Angeles, to enhance its image. Bratton has served on Citizen's board and praised its usefulness for information about Covid-19. He did not respond to a request for an interview about Citizen's latest projects.
Researchers who have studied the rise of crime-monitoring apps said Citizen's expansion is alarming in part because, for some users, it may turn surveillance into a kind of hobby.
"It's turning neighbors into a kind of informant, who is then reporting on happenings in a residential space," said Bridges, the Penn doctoral candidate.
In the case of Amazon's Ring security cameras, the value to law enforcement hasn't always lived up to the hype. NBC News reported last year that, in a sample of 40 law enforcement agencies that had partnered with Ring to share videos, about a third had made zero arrests as a result of the footage.
Lilly Irani, a communication professor at the University of California, San Diego, said there's a danger that the Citizen app plays into people's racial stereotypes of what a crime suspect might look like, especially if there's a repeat of the brushfire reward.
And she said apps like Citizen may encourage people to think they're solving society's problems when, in fact, their online browsing and posting may be a distraction from getting involved in tangible solutions.
"It's harder to call your City Council member than it is to download an app and click a button," Irani said.
Opinion | A frantic warning from 100 leading experts: Our democracy is in grave danger - The Washington Post
Wed, 02 Jun 2021 21:02
Democrats can't say they weren't warned.
With yet another GOP effort to restrict voting underway in Texas, President Biden is now calling on Congress to act in the face of the Republican ''assault on democracy.'' Importantly, Biden cast that attack as aimed at ''Black and Brown Americans,'' meriting federal legislation in response.
That is a welcome escalation. But it remains unclear whether 50 Senate Democrats will ever prove willing to reform or end the filibuster, and more to the point, whether Biden will put real muscle behind that cause. If not, such protections will never, ever pass.
Now, in a striking intervention, more than 100 scholars of democracy have signed a new public statement of principles that seeks to make the stakes unambiguously, jarringly clear: On the line is nothing less than the future of our democracy itself.
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''Our entire democracy is now at risk,'' the scholars write in the statement, which I obtained before its release. ''History will judge what we do at this moment.''
And these scholars underscore the crucial point: Our democracy's long-term viability might depend on whether Democrats reform or kill the filibuster to pass sweeping voting rights protections.
''We urge members of Congress to do whatever is necessary '-- including suspending the filibuster '-- in order to pass national voting and election administration standards,'' the scholars write, in a reference to the voting rights protections enshrined in the For the People Act, which passed the House and is before the Senate.
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What's striking is that the statement is signed by scholars who specialize in democratic breakdown, such as Pippa Norris, Daniel Ziblatt and Steven Levitsky. Other well-known names include Francis Fukuyama and Jacob Hacker.
''We wanted to create a strong statement from a wide range of scholars, including many who have studied democratic backsliding, to make it clear that democracy in America is genuinely under threat,'' Lee Drutman, senior fellow at New America and a leading organizer of the letter, told me.
''The playbook that the Republican Party is executing at the state and national levels is very much consistent with actions taken by illiberal, anti-democratic, anti-pluralist parties in other democracies that have slipped away from free and fair elections,'' Drutman continued.
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Among these, the scholars note, are efforts by GOP-controlled state legislatures everywhere to restrict access to voting in ways reminiscent of tactics employed before the United States became a real multiracial democracy in the mid-1960s:
Republican lawmakers have openly talked about ensuring the ''purity'' and ''quality'' of the vote, echoing arguments widely used across the Jim Crow South as reasons for restricting the Black vote.
The scholars also sound the alarm about GOP efforts to deepen control of electoral machinery in numerous states, casting them as a live threat to overturn future elections, and a redoubling of emphasis on extreme gerrymanders and other anti-majoritarian tactics:
In future elections, these laws politicizing the administration and certification of elections could enable some state legislatures or partisan election officials to do what they failed to do in 2020: reverse the outcome of a free and fair election. Further, these laws could entrench extended minority rule, violating the basic and longstanding democratic principle that parties that get the most votes should win elections.
Democracy rests on certain elemental institutional and normative conditions. Elections must be neutrally and fairly administered. They must be free of manipulation. Every citizen who is qualified must have an equal right to vote, unhindered by obstruction. And when they lose elections, political parties and their candidates and supporters must be willing to accept defeat and acknowledge the legitimacy of the outcome.
After noting that all these Republican efforts are threatening those fundamental principles, the scholars warn: ''These actions call into question whether the United States will remain a democracy.''
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Crucially, the scholars note that the John Lewis Voting Rights Act '-- which would restore some protections gutted by the Supreme Court '-- would be insufficient, and they call for federal protections such as those in the For the People Act, or S.1.
''Just as it ultimately took federal voting rights law to put an end to state-led voter suppression laws throughout the South" in the 1960s, the scholars write, so must federal law step in again:
True electoral integrity demands a comprehensive set of national standards that ensure the sanctity and independence of election administration, guarantee that all voters can freely exercise their right to vote, prevent partisan gerrymandering from giving dominant parties in the states an unfair advantage in the process of drawing congressional districts, and regulate ethics and money in politics.
It is always far better for major democracy reforms to be bipartisan, to give change the broadest possible legitimacy. However, in the current hyper-polarized political context such broad bipartisan support is sadly lacking.
That is the rub. An acceptance that protecting democracy will never, ever, ever be bipartisan, and will happen only on a partisan basis, is fundamental to accepting the reality of the situation that Democrats face.
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We can go back and forth about specific misgivings that some Democrats have about S.1 '-- see this good Andrew Prokop report for an overview '-- but the core question is whether Democrats will cross that Rubicon. So doing would lead inevitably to the need to reform or end the filibuster.
Sen. Joe Manchin III (D-W.Va.) is the most visible obstacle here. But an unknown number of other moderate Democrats are also reluctant to cross that Rubicon, and it's unclear how much effort Biden will put into making that happen.
And so, when these scholars warn that history is watching, those Democrats are the ones who should take heed.
Trailer exhibition Slavery
Wed, 02 Jun 2021 21:00
This exhibition about slavery takes the form of personal and real-life stories rather than abstract concepts. There are stories from Brazil, Suriname, and the Caribbean, and from South Africa and Asia.
NIH's Collins Told Fauci the Wuhan Theory is Gaining Momentum in Email
Wed, 02 Jun 2021 20:45
STEFANI REYNOLDS/POOL/AFP via Getty ImagesDr. Anthony Fauci, in April 2020, received an email from Francis Collins, the National Institutes of Health (NIH) director, with the subject line noting, ''conspiracy gains momentum,'' which includes a link to a report outlining multiple sources believing the Chinese coronavirus started in a lab.
In the newly released email obtained by BuzzFeed News from the Freedom of Information Act (FOIA), Collins and Fauci discussed what appears to be a ''conspiracy.'' Still, the important parts of the email are redacted.
The original email from Collins, which has almost every part redacted besides name, includes a link to a new report from Mediaite, talking about a Fox News segment with Brett Baier and Sean Hannity speaking about the ''alleged'' conspiracy theory of the Chinese coronavirus starting in a Wuhan lab having some merit, according to BuzzFeed.
The email response from Fauci was redacted.
Email from NIH Collins to Fauci Subject: "conspiracy gains momentum" From: April 2020The email includes a link to a Mediate article with Bret Baier detailing a new report that ''multiple sources'' believe the virus originated in a lab(Obtained by BuzzFeed News via FOIA) pic.twitter.com/kGorSwvmsG
'-- Jacob Bliss (@jacobmbliss) June 2, 2021
The Mediaite report showed a video of Baier detailing his alleged ''multiple sources'' who believed at the time the Chinese coronavirus had originated in a Chinese lab before the virus ''accidentally'' escaped and started to infect the population.
The Mediaite report shows the back and forth conversation:
''This is from multiple sources who have been briefed at the beginning part of the origins of China and the beginning of the virus. They've also seen documents, open source and classified,'' Baier said of his reporting on Hannity Wednesday night. ''We've asked to see those documents directly, but they are saying that it is increasingly likely, that there is increasing confidence that the virus '-- Covid-19 '-- started in a Wuhan lab.''
''Not as a bio-weapon, let's just be clear about that, there is no one who's saying this was a bio-weapon,'' he clarified, prompting host Sean Hannity to ask, ''How would we know that?''
''Well, we wouldn't, but these sources are not saying that. They're saying it occurred naturally because China was trying to show that they could be as good or better than the U.S. in handling viruses, discovering viruses, and that this was a botched effort to contain this and it got out to the population,'' Baier explained. ''So there's increasing confidence that's how it starts.''
''They are 100 percent confident that China altered the data, the statistics, they did a lot of things to contain the information,'' he concluded. ''Meanwhile, they cut down, as you mentioned, travel from Wuhan internally, but left the international flights going, and there obviously is how you have a spread like this.''
BuzzFeed reported, Fauci declined to comment on the story that encompasses this email.
Fauci has been the director of the National Institute of Allergy and Infectious Diseases since 1984.
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NAVY SEALs STORM Gates' Wyoming Ranch - Real Raw News
Wed, 02 Jun 2021 20:25
Less than two weeks after Bill and Melinda Gates called it quits, U.S. Navy SEALs stormed a Gates' owned property in northwest Wyoming and clashed with security forces Gates had hired to protect the 492-acre ranch.
The U.S. military approved the raid after Gates' estranged wife, Melinda, contacted Donald J. Trump with news that Bill, whom she called a psychopathic, evil genius, had visited Epstein Island 24 times between 1997-2017 and, on Epstein's advice, had spent $36,000,000 to excavate his own subterranean ''child dungeon'' beneath Irma Lake Lodge.
A confidential source involved in Trump's Deep State War told Real Raw News that Gates' friendship with the convicted pedophile was the catalyst for Bill and Melinda's divorce. Melinda had long been aware of Bill's philandering with both adult and underage women, but had remained silent to protect her financial interests in the marriage. She reportedly told Trump that Bill and Epstein made frequent weekend getaways to Irma Lake Lodge. Although she admitted she had not personally seen the subterranean complex, she had paperwork and receipts proving its existence.
''He told me to pretend I was an underage frightened schoolgirl and to pretend he was a maniacal genius who liked to play with young girls,'' Melinda said. ''For him it was roleplay, but it really wasn't, because he is exactly what he pretended to be.''
On May 14, Trump spoke to the Joint Chiefs of Staff and asked that the U.S. military confirm the existence of the alleged underground complex. To carry out this task, the military employed two techniques. First, a synthetic aperture radar satellite scanned Irma Lake Lodge. Second, a UAV fitted with ground penetrating radar made several high-altitude passes over the property. While neither technique was able to concretely gauge the size and depth of the underground dungeon, both proved massive excavation had taken place where Melinda Gates said it had.
''It was enough for the military to act on. They didn't want to just bomb the place because they didn't know if kids were still down there. So they opted to send a SEAL team, the same ones who raided Biden's compound and got those kids off the boat,'' our source said.
In the predawn hours on May 17, Navy SEALs launched a tactical assault on Irma Lake Lodge, meeting resistance shortly after they breached the property and crept toward the underground lair. Gates' security personnel, dressed in paramilitary gear and armed with automatic weapons, detected the intrusion and opened fire on the SEALs. The SEALs returned fire in what turned out to be a 15-minute firefight in which one SEAL and 8 enemy combatants lost their lives.
Having suppressed Gates' security, the SEALS found a trap door hidden beneath piles of hay in a horse stable. The door concealed a steel platform'--an elevator of sorts'--that descended 300' below ground and opened into a hewn chamber 150' in diameter and with tunnels branching off in several directions. The SEALs, our source said, spent hours scouring the tunnels for signs of life, but no children were found. However, the operation was not in vain, as they did uncover a facsimile of a young girl's bedroom, with a pink-frame platform bed, stuffed animals, and racks of child-sized clothing. Moreover, three DSLRs on tripods had been aimed to video whoever had lain on the bed. At least one camera still had an SD card.
The SEALs, our source added, seized the cameras before exfiltrating the compound.
In closing, our source said he believes'--but cannot confirm'--the military has infiltrated other properties owned by Gates.
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Frequently Asked Questions '' International Tribunal for Natural Justice
Wed, 02 Jun 2021 19:44
We continue to receive many excellent questions. If you don't find the answer you're looking for in the FAQs on this page, please ask your question here.
I have a question about the wording of the foundational documents of the ITNJ, including the Proclamation, Mission, Treaty, and Constitution.The ITNJ has no built-in leanings towards any group, belief system, religion, government, or culture and therefore, cannot speak to what one group vs. another might believe, nor does it assume to know how any living being might interpret its words. The wording on its founding documents has been carefully crafted with the intent that all will know clearly its mission and goal when all material on the ITNJ.org website is taken into consideration as a whole. It is a fact that not all people agree on all things and this is acknowledged and respected by the ITNJ.
Is there 'legalese' in the foundational documents of the ITNJ, including the Proclamation, Mission, Treaty, and Constitution?No. The common sense meanings of the words give the accurate interpretation of the intrinsic meaning of the Treaty mandating establishment of the ITNJ. We are not here to further obfuscate the true nature of law but rather to make it accessible to The People it purports to serve.
Am I giving up my personal sovereignty by signing the ITNJ Treaty?No. The ITNJ exists to serve as protector of all sovereign beings, everywhere, and to empower you in exercising personal sovereignty.
Where are you storing my e-signature?Your e-signature is stored on our secure servers. We have one of the top IT security experts on our team, doing our best to protect your data.
After signing the ITNJ Treaty, what is the process for rescinding my ratification should I ever decide to do so?Send us an email conveying your choice to rescind your signature ratifying the ITNJ Treaty and we will honor the request as soon as possible by deleting your name from our list of signatories.
How may I view the full text of the ITNJ Constitution?The ITNJ Constitution has been published since 14 February 2015, when the ITNJ was established by Proclamation. Following the Inauguration Events and Ceremonial Seating of 15 June 2015, when the ITNJ Treaty and ITNJ Constitution were signed and sealed into law, the ''Witnesses by'' pages were also published. The full text of the ITNJ Constitution is published as a pdf document. You may need to adjust browser settings or script blockers to allow pdf documents to display properly on your computer in order to download and read the ITNJ Constitution.
What is the symbolism of the ITNJ logo?''The pine cone motif in the ITNJ's logo denotes the pineal gland in homo sapiens. It is the organ within the human brain which connects our mechanical intelligence to our meta~intelligence, ie: our capacity to see outside the box, ergo to step outside the proverbial matrix. It is therefore the anchor point of our consciousness to the heavenly realms.
''The language of law (legalese) has been, and continues to be, a veiled language, by its very design. The (mis)use of words and meanings equates to spellbinding. The ritualised majick that law has been subverted toward has not served humankind, but has contrarily conspired to delude us from our higher expression.
The ITNJ is breaking these invisible bonds and re-purposing the language of law. It is reclaiming jurisprudence and restoring the foundational axis of Trust and Equity.
The 'figure of eight' symbol on the lateral plane in the ITNJ logo alludes to the cycle of infinity. This denotes an absolutist approach by the ITNJ to pure-truth. Pure-truth is not by degrees, and where it is enshrined will ever serve to anchor the heavens to the causal realm.''
~ Sacha Stone, Founder
When was the International Tribunal for Natural Justice established?The International Tribunal for Natural Justice was established by Proclamation on 14 February 2015. That date was chosen in memory of St. Valentine, who died on that day defending the natural rights of the people.
When did the ITNJ begin hearing cases?As projected, the ITNJ began hearing cases in late 4th quarter 2015. The first official hearing took place on December 1, 2015, and the second official hearing took place on December 16, 2015.
When can I file a case to be heard by the Tribunal?The application process to the ITNJ has been temporarily suspended. The Board of Trustees of the ITNJ released a statement on 14 March 2017 in which they clarified why the ITNJ and supporting organizations will for the remainder of 2018 be focusing all resources on the ITNJ Judicial Commission of Inquiry into Human Trafficking and Child Sex Abuse. On the completion of the Commission with its published Judicial Commission Report (in 2019), the Board of Trustees will consider how to best proceed, and may choose to hold a different Commission of Inquiry, or may choose to re-open the application process to the ITNJ.
Are hearings and trials live-streamed?It is the intention for all proceedings (as possible) to be live-streamed unless there are unusual circumstances at a particular venue preventing this action. A founding premise of the ITNJ is truth and transparency, and to that end, we have committed to uphold this by including the filming of proceedings so that they are not conducted in secret (unless witness safety is of concern and/or minor children are involved). The vision is to hold an open court of both virtual and in-situ proceedings, and then publish videos and reports as soon as possible.
What is the purpose of live-streaming hearings and trials?The purpose of live-streaming is to restore trust of the people in the delivery of justice in the world. Live-streaming prevents the subtle doctoring of transcripts which has been known to regularly take place in certain court environments; it gives the public confidence in the court; and most importantly it ensures a high degree of integrity from judges and court officers who know that the eyes of the world are on them.
What makes this Tribunal International?Anyone regardless of location is equally afforded the recognition and protection of the ITNJ and is equally invited to align with the ITNJ.
How does the ITNJ have the authority to claim Universal Jurisdiction?The ITNJ exists outside and above the jurisdiction of any one nation or country by the authority of the People of the World.
The sovereign People of the World are the source of authority. If the People weren't sovereign, they would not be able to authorize a sovereign government, because you cannot delegate authorities you do not have. The People of any nation or country or territory have the right to delegate their authority to representatives they choose to run their government. Case in point: the government of the United States of America is allegedly founded and maintained by the consent of the governed.
Just as the People can authorize their governments to act on their behalf, the People can authorize their Tribunal, the ITNJ, to act on their behalf, and delegate their sovereign authority to administer Natural Law. By their signatures ratifying the Treaty of the International Tribunal for Natural Justice, the People of the World mandate the establishment of the ITNJ and delegate to the officers of the ITNJ their authority to administer Natural Law for all the People of the World, in all the territory of the World.
Who will enforce decisions of the ITNJ?Enforcement is the first question many people ask, and the answer is: The People. Just as The People of the World are the authority behind this Tribunal, The People of the World are the authority behind enforcing the decisions of this Tribunal. The signatures on the ITNJ Treaty constitute the authority and jurisdiction for enforcement under International Law. The more people that sign the treaty, the more force it will have in law. From there, enforcement is an effort of momentum'...building a body of willing individuals unified for the benefit of all.
How does Truth and Reconciliation relate to the mission of the ITNJ?Truth and Reconciliation is a function of the Tribunal that seeks to create a peaceful environment for those who have caused harm to another to meet with those they have harmed in order to reach a mutual agreement. Just as we envision the ITNJ operating its court globally, we also envision Truth and Reconciliation worldwide. For centuries, the violence to People and Planet has been so great that it would take thousands of courts decades to prosecute all the atrocities. Atrocities must end, therefore we focus not on revenge, but on remedy and restitution. Truth and Reconciliation Programs allow those who were swept up into working for corrupt systems to come forward and ask for amnesty. We offer a blueprint for The People of the World to stop all harm perpetrated in their communities and consciously act to restore peace and justice. This is the concept of Justice with Mercy. Some who have been accessory to violations of human rights were either deceived or coerced into the actions they took, and thus should not be treated the same way as those who consciously chose to commit harm of their own volition.
Why are BAR attorneys involved with the ITNJ?''Lawyers around the world are often members of local bars which are professional associations (no different from other professions such as medicine and so on). In most countries there are requirements to take an oath to act fairly for the client, and some countries require an oath to the sovereign (from which one can be exempted as Americans were in Australia as swearing allegiance to The Queen could prejudice their American citizenship). In my case I took an oath of allegiance to The Queen in Australia and in England and also on Norfolk Island (in fact two oaths, one as a barrister, then later as a magistrate). Then I took a similar oath in Ireland (although no queen as Ireland is a republic). Then in the United States I undertook to obey the laws of the United States and its various states. Not one of these oaths prevented me from acting at all times in the interest of justice for all people nor did it stop me from acting against the Crown or the Government. You may recall the classic case in England where it was determined the Crown could and would be sued (''Let Right be Done''). Apart from being a member of the Norfolk Island Bar, I am also a member of The Victorian Bar, and the International Bar Association as well as the South Pacific Lawyers Association and the European Association of Lawyers. I have been admitted to the Inner Temple (England) and Kings' Inns (Ireland where there is no king). Not one of these memberships in any way affects my independence and my ability to act fairly and in the interests of justice whether as a barrister-at-law or a judge. The ITNJ is and will be independent in the interests of natural justice for all peoples. We have already had discussions regarding representation before the ITNJ as clearly spelled out in the Constitution. To those who say ''they do not trust lawyers and judges'' I would ask what remedy they would seek. There are only three ways to change things: politically, you need influence and money and lots of it; revolutionary, you need even more money and lots of people united in the one cause who will act together; legally, you need competent lawyers and honest judges, which is what you will get with the ITNJ.''
Kind regards,John W.B. (ITNJ Chief Justice)
Is the ITNJ affiliated with what is sometimes called the banking cabal housed in the City of London?The headquarters of the ITNJ is located in London, but well outside of the ''City of London''. The city commonly known as London has a population of 8 million plus people and covers a total area of 1,572 sq km (607 sq m). In contrast, the area known as the ''City of London'' is a one-mile square territory which is a sovereign city-state, completely separate from London, UK (similar to Washington DC, which is a ten-mile square sovereign city-state completely separate from the USA). Rest assured, no ITNJ offices are geographically located within the one-mile-square territory called the ''City of London'' and the ITNJ has no affiliation with any corporations housed there.
Does the ITNJ endorse any political groups?Quote from Chief Justice John Walsh of Brannagh following inaccurate claims by certain political groups that they are endorsed by the International Tribunal for Natural Justice:
''The International Tribunal for Natural Justice is a completely independent court and tribunal. The ITNJ will determine issues and administer justice in a fair and impartial manner following the Rule of Law and the principles of Natural Justice. We do not have predetermined views or have any political agenda. We are here for all and not any particular group. We do not have to agree with what you say, but we will fight to the death your right to say it (to misquote Voltaire). No group, political or otherwise, has the right to claim endorsement by the ITNJ nor claim any determination prior to a full and proper hearing before the Tribunal.''
Where is the Committee to Support the ITNJ located?We are international. Members of a core administrative team of the Committee to Support the ITNJ reside in North America, South America, Europe, Australia, Indonesia, etc.
I want to volunteer but there is no Committee to Support the ITNJ in my country.No matter where you live, you are welcome to volunteer. Meetings are held via video conference '' we do our best to accommodate everyone's time zone and availability. Apply to Volunteer Here
Where is the financial reporting published?The initial spring 2015 crowdfunding campaign reached its goal of raising funds for the June 14th and June 15th Inauguration Events, including the Ceremonial Seating during which the ITNJ Treaty and Constitution were signed and sealed into law. We are deeply grateful to all those who donated then and who continue to donate every month. More financials are posted here.
Helpful Resources - New Paradigm Astrology
Wed, 02 Jun 2021 19:32
Helpful Resources wbits-dRay 2021-05-28T07:05:59+00:00 Coronavirus / Covid TreatmentsIn this interview with The New American magazine Senior Editor Alex Newman, the internationally renowned Dr. Peter McCullough''the doctor with the most citations in the National Library of Medicine on these topics''warned that the COVID shot was already causing thousands of deaths and tens of thousands of hospitalizations that have been recorded. And that's just the tip of the iceberg, he warned. In normal circumstances, 50 deaths reported to VAERS would result in a drug being taken off market immediately.
In the case of the COVID shots, thousands have already been reported, and yet the mass vaccination programs continue to be pushed. Dr. McCullough, a professor of medicine who developed a globally acclaimed and highly successful COVID treatment protocol, also emphasized that there have been many unnecessary deaths as a result of policy decisions made at various levels of government.
The Website Peter McCullough mentions in this video is AAPSOnline.org
Posted April 27, 2021
A Guide to Home-Based COVID Treatment '' A Step-By-Step Doctors' PlanJane Orient, MDElizabeth Lee Vliet, MDPeter A. McCullough, MD
Free eBook Download from the Association of American Physicians and Surgeons (aapsonline.org)
How Do I Get COVID-19 Medication?Click for Resource Guide from AmericasFrontlineDoctors.org
Prevent and Fight VirusesThis article is packed with information to fight Covid including, foods, supplements, dosages, and instructions to both prevent yourself from getting it and to cure yourself if you do.
Posted March 5, 2021Open Article in New Tab: Prevent and Fight Viruses
How to Improve Oxygen Level Naturally | Dr. Hansaji Yogendra
Dr. Hansaji Yogendra, Director of The Yoga Institute and President of The International Board of Yoga, gives breath exercises and yogic teachings to assist you in expanding your lung capacity (and more).
Posted May 2, 2021
Immune System
There has never been a more important time to understand how your innate immune system functions. With a healthy immune system, we're able to live in balance with the virome and array of flora that's in every niche of our bodies.
Dr. Zach Bush: The Innate Immune SystemDr. Zach Bush: What Happened Last Year: A Macro Look Ecological & Public Health CrisisDr. Zach Bush's WebsiteAdditional Coronavirus Links
Additional Vaccine InformationEl documental ''The Universal Antidote'' (El Ant­doto Universal)Dr. Thomas Cowan, M.D. discusses the CoronavirusFuture Social DevelopmentThis is the most comprehensive, well written explanation of what the ''Great Reset'' is all about. It explains the relationship of big business, big Pharma, Big Tech, Big government, MSM, the UN, WHO, the CDC and Covid-19, 5G, IoT (Internet of Things), and the plans that have been in existence for some time that are now being played. It is a lengthy article and I cannot stress enough the importance of reading it in its entirety for a full understanding of what we'll all be dealing with for the rest of our lives (and need to resist)! It finally gives a name and face to one of the masterminds of earth's demise as well as mentioning some others.
Read the Article Here >
Additional Links
Summit on Narcissism (especially Caroline Myss)Recession, robots, and rockets: another roaring 20s for world markets?Save Our Sexuality Pornography StatisticsRudolf Steiner's AnthroposophySearch over 100,000 documents from the entire Rudolf Steiner archive.View the Rudolf Steiner Archive Here >
Peter Selg gives his overview of the current global situation from the perspective of Ahriman's agenda.
He also addresses why we don't have the solution for what is happening because we don't have the full, long-term perspective. However, the more people become aware of what is happening as Ahriman working, the better chance of mitigating his complete domination.
He will proceed, and we are not here to stop him, but some of the worst impacts can be softened. Not only that but when we work the scenario, the stumbling block becomes the stepping stone '' huge block = huge stepping stone! Therein lies the gemstone in the center of the whole morass.
For further information on ''Ahriman,'' search for him on the Rudolf Steiner Archive Here >
Technological AdvancesGreg Braden shares mind-blowing science with regard to who/what we are and the dangers of AI and Transhumanism. Absolutely profound sharing that may change your outlook on many fronts! His presentation begins at 20 min. and lasts 20 minutes.
Posted on March 28, 2021
Additional Links
Elon Musk on AIDavid Ickes on AIMoratorium on Gene EditingCoping Mechanisms & Resources for Surviving the 21st CenturyPhysicalGotta keep that physical body, our instrument to navigate, perceive, receive, and give in shape! If you can manage it, a good kundalini yoga kriya first thing in the morning followed by a cold shower is a great way to start the day. I've got a few videos here on the site. If that's not enough for ya' check out the 3HO site. Not enough time? Try the 5 Tibetan Rites of Rejuvenation (about 15 minutes) . Still not enough time? Then try the ''7-minute Workout'' with Rick (that's what I call the guy, LOL)! Got something bothering you physically? Get to the bottom of it with Jacques Martel's ''Complete Dictionary of Ailments & Diseases.'' Last but not least, the ultimate book for healing: Andreas Moritz's ''Timeless Secrets of Health and Rejuvenation.'' Lastly, especially for women, there's nobody like Dr. Northrop, an astrologer herself! EmotionalAnytime we experience loss, it is natural to feel grief. Rather than suppress it or ignore it, there is a treasure to be found in it. Check out the ''5 Stages of Grief.'' When we feel wronged, betrayed, neglected, or abandoned, it's also natural to get stuck in anger and blame. Try Ho'oponopono. My take is that we are all addicted to something. Born into a world of separation, we have an inner void or longing that we seek to fill. More often than not, this can lead to some unhealthy habits. Nobody like Dr. Gabor Mate! SexualityFor healthy sex, there's nobody like Alexandra and her Center for Healthy Sexuality. Besides her great Youtube Channel, you could check out her site and books. I'm on her email list to receive regular ''Mirror of Intimacy'' short daily meditations. Fantastic! To me, this is a must-see video for everyone! Troy Love Talks about way more than ''Finding Peace from Sexual Addiction.'' RelationshipsThe old grandmaster himself, Harville Hendriks wrote, ''How to Get the Love you Want,'' where he explains his ''Intentional Dialogue.'' He does workshops using his ''Imago'' approach to understanding and working with relationships. John Wineland does both ''Men's Work'' and relationship workshops, videos, and more. He's awesome! Bryan Reeves is another excellent resource for couple's work Both John and Bryan studied under David Deida, the author of ''The Superior Man'' (which I'm still working on LOL!). Check him out. From a women's perspective, my wife appreciates Sabrina. Regarding relationship, honesty, empowerment, and more, Brene Brown can't be beaten! SpiritualityFor relationship work, my wife and I have also taken Jai Dev and Simrit's ''Sweetest Love'' course that includes kundalini yoga and more. In addition to that, they offer workshops and online courses to assist in the awakening process. It's a fine line between sexuality and spirituality, but that line disappears with tantra. Here's the best book for tantra that I've found. Sri Chinmoy could also go up top under ''physical'' as I first came into contact with his teachings in a running marathon inspired by them. However, he offers much more! This resource list wouldn't be complete with Spirit Voyage Music, where you can download all the chants and kundalini yoga music you could imagine. When you're looking to receive some insight on anything, there is nothing like a good oracle. My favorite is The Sacred Rebel deck. Bobby Klein's weekly I Ching readings are invaluable. Peter Harper offers tools to build ''presence.''
Dalton parents enraged over 'masturbation' videos for first graders | Fox News
Wed, 02 Jun 2021 19:20
Last fall, parents at the posh $55,000-per-year Dalton School got wind of their first-graders being taught sex-education lessons that included masturbation.
They complained to school administrators, but were told they had simply "misinterpreted" what Dalton's now-notorious "health and wellness" educator Justine Ang Fonte '-- who last month led a controversial and explicit "porn literacy" workshop at another elite prep school '-- was teaching.
But after The Post's expos(C) last week on the porn class, Dalton parents "bombarded" the school with more complaints about Fonte's curriculum, sources told The Post.
The Post viewed video of a cartoon Fonte used in one of her sex-ed classes for 6-year-olds showing little kids talking about "touching themselves" for pleasure.
"Hey, how come sometimes my penis gets big sometimes and points in the air?" asks the little boy in the cartoon, leading to an explanation of what an "erection" is.
The boy nods and says, "Sometimes I touch my penis because it feels good."
Then the little girl character chimes in: "Sometimes, when I'm in my bath or when Mom puts me to bed, I like to touch my vulva too."
Fonte has reassured parents that she does not use the word "masturbation" in class, and that her lessons teach kids not to touch themselves in public.
They are also taught lessons about "consent." While one mother conceded that teaching the concept of consent can be valuable in protecting children from abuse, another said telling kids that that their own parents or grandparents should not touch them without first asking for permission is extreme.
"Literally parents are supposed to say to their kids, May I hug you?" one parent said.
One mother said that another parent told her, "I'm paying $50,000 to these a''holes to tell my kid not to let her grandfather hug her when he sees her?"
Fonte's lessons for first-graders also include subjects such as gender assigned at birth, gender identity and gender expression.
"Kids have no less than five classes on gender identity '' this is pure indoctrination," a Dalton mother said. "This person should absolutely not be teaching children. Ironically, she teaches kids about 'consent' yet she has never gotten consent from parents about the sexually explicit, and age inappropriate material about transgender to first graders."
"We are furious," a third Dalton mother told The Post. "We were horrified to learn this was shown to our first-grade 6- and 7-year old kids without our knowledge or consent. But it's so hard to fight back because you'll get cancelled and your child will suffer."
The second Dalton mother said, "I'm not against all sex education but it's not cool to keep parents in the dark about it."
The parents spoke on the condition of anonymity because they are afraid of retaliation.
The second mom hit back at Dalton administrators who she said are playing mind games with parents and not fessing up to what's really going on in classrooms. The school has said that only a "small group" of parents complained about Fonte's class last fall and that they "misinterpreted" the content. At the same time, however, the school quietly removed the video about kids touching themselves from the curriculum.
"We are not 'confused.' We are in fact just seeing very clearly for the first time what a 'progressive' education really means at Dalton," the mother said. "The fact that the school then gaslit parents into thinking we are confused is abysmal."
Fonte's work at the school is reportedly funded by a $450,000 grant given to Dalton in 2012 by hedge fund billionaire Bill Ackman's Pershing Square Foundation. Ackman's ex-wife Karen is on the Dalton board of trustees.
REPUBLICAN SENATORS INVESTIGATING 'CLOSE COORDINATION' BETWEEN BIDEN ADMINISTRATION, TEACHERS UNIONS ON SCHOOL REOPENINGS
"What we are seeing across the country is that many schools have lost sight of the purpose of education, and are hiding curriculum and teaching materials from parents," a spokesman for FAIR, the Foundation Against Intolerance and Racism, told the Post.
Last week the Post reported on Fonte's workshop, "Porn Literacy: An intersectional focus on mainstream porn," at Columbia Grammar & Preparatory School. The often-explicit slide presentation and lecture to the 120 co-ed juniors included how porn takes care of "three big male vulnerabilities"; statistics on the "orgasm gap" showing straight women have far fewer orgasms with their partners than gay men or women; and photos of partially-nude women, some in bondage, to analyze "what is porn and what is art."
IAN PRIOR: CRITICAL RACE THEORY IN VIRGINIA SCHOOLS NEEDS TO END, I'M A PARENT WATCHING THIS UNFOLD
Fonte's presentation included a list of the most-searched pornographic terms of 2019, including "creampie," "anal," "gangbang," "stepmom" and more.
Shortly after the Post published the Columbia Prep story last week, its head of school Dr. William M. Donohue sent a conciliatory email to school parents saying that the "content and tone of the presentation did not represent our philosophy, which is to educate our students in ways that promote their personal development and overall health, as well as to express respect for them as individuals. '... It was unfortunate that we did not better inform ourselves of the speaker's specific content in advance. I apologize '... Going forward we will certainly learn from this experience."
Fonte has not responded to repeated requests from the Post for comment.
CLICK HERE TO GET THE FOX NEWS APP
A Dalton spokesman said, "As part of Dalton's comprehensive Health curriculum for students, a lesson on Gender & Bodies included two evidence-based and age-appropriate videos approved for students 4 years and older. These videos align with nationally recognized methodologies and standards. We consistently review our Health curriculum, making sure that the content is developmentally appropriate and, if necessary, we adapt our curriculum accordingly. We will continue to listen carefully to parent feedback, respond thoughtfully to community concerns, and develop lessons that are in the best interest of our students, respect our community's values, and correspond with best practices."
To read more of the New York Post, click here.
China Used Russian Strategy To Spread Lies That US Created COVID-19: Report
Wed, 02 Jun 2021 19:08
KEY POINTSChina claims the U.S. engineered the novel coronavirusThe Chinese government is reportedly using a Russian strategy of spreading false allegationsA Chinese man was arrested and detained for claiming the U.S. created the coronavirusThe Chinese government has used a strategy employed by Russians to spread false rumors that the United States created COVID-19, a new investigation revealed.
A nine-month probe conducted by the Associated Press and the Atlantic Council's Digital Forensic Research Lab found that China had weaponized false allegations that the U.S. created the novel coronavirus, spreading it across various social media platforms, including Twitter, Facebook, VK and Weibo.
On Jan. 26, 2020 '-- a few days after U.S. health officials detected the first case of coronavirus in the country '-- a man from China's Inner Mongolia autonomous region uploaded a video to a Chinese social media platform, Kuaishou, claiming that the virus was engineered by Americans.
The video was viewed approximately 14,000 times before it was taken down. The man who posted the video was later arrested and detained for 10 days and fined for spreading false claims.
People's Daily, an official publication of the Central Committee of the Chinese Communist Party, broadcast news of the man's arrest in early February as a reminder that circulating false information was punishable by arrest.
However, China's foreign ministry and at least 30 Chinese diplomats across the world later advanced the same conspiracy and amplified it through the country's state media outlets.
On March 9, an essay claiming that the U.S. military released the virus at an athletic competition held in Wuhan, China in October 2019 circulated on WeChat. This led to an anonymous online petition that demanded the White House to respond to the allegations.
"As China embraced overt disinformation, it leaned on Russian disinformation strategy and infrastructure, turning to a long-established network of Kremlin proxies in the West to seed and spread messaging," the AP reporte noted.
China's disinformation campaign began months after Russian state media announced that the novel coronavirus was linked to a bioweapons test conducted by the U.S. to test Beijing's biological weapons defenses. Zvezda, the Russian Army's media outlet, cited Igor Nikulin as the source of the theory.
Nikulin is a four-time failed political candidate who claimed to have worked with the United Nations on disarmament in Iraq from 1998 to 2003.
The U.N. did not have a record of his service. Richard Butler, the lead U.N. weapons inspector at the time, also said he had never heard of Nikulin.
Nikulin had previously suggested that the U.S. created HIV as a way to weaken the American economy from within.
''If you prove and declare '... that the virus was bred in American laboratories, the American economy will collapse under the onslaught of billions of lawsuits by millions of AIDS carriers around the world,'' he wrote on his website.
The four-week World Health Organization mission to China to uncover the origins of the coronavirus wrapped up with no conclusive findings Photo: National Institutes of Health / Handout
China Says US Lab Fort Detrick Could Be COVID-19 Origin; Claims Explode On Chinese Twitter
Wed, 02 Jun 2021 19:06
KEY POINTSA hypothesis alleges that COVID-19 emerged from Fort DetrickA Chinese official called on the U.S. to be 'transparent' Chinese state-backed media and influencers have picked up the theoryA theory about the origin of the novel coronavirus is exploding on Chinese Twitter after investigators from the World Health Organization wrapped up their work on determining the origins of the virus this month.
Chinese officials have repeatedly advanced their hypothesis that claims COVID-19 emerged from Fort Detrick, a U.S. Army biomedical research laboratory in Maryland. Zeng Guang, chief epidemiologist at the Chinese Center for Disease Control and Prevention, also urged WHO investigators to ''focus'' on the U.S.
''The U.S. has biological laboratories all over the world," Zeng told a Shanghai-based website. ''Why does the U.S. have so many laboratories? What is the purpose of this?''
''In many things, the U.S. requires others to be open and transparent. In the end, it turns out that the U.S. itself is often the most opaque,'' he added.
At a press conference on May 6, China's Foreign Ministry spokeswoman Hua Chunyin said there have been reports about Fort Detrick and called on the U.S. government to ''accept investigation.''
Her statement led numerous outlets to publish reports accusing the U.S. government of a ''cover-up.'' The theory faded in the latter half of 2020 but received renewed attention after WHO refocused on Wuhan and the lab headed by a virologist, Shi Zhengli, who became known as "bat woman" for her bat-cave explorations.
Hua also renewed her calls for transparency and urged the U.S. to allow experts from WHO to conduct ''origin tracing.''
''The U.S. should open the biological lab at Fort Detrick, give more transparency to issues such as its 200+ overseas bio-labs, and invite WHO experts to conduct origin tracing," Hua said on January 18.
Beijing News, a state-backed media, uploaded a video of Hua on Weibo '-- China's Twitter-like social media platform. The clip continues to get traction online and has since been viewed at least 74 million times, with hundreds of thousands of comments. It was also picked up by numerous Chinese influencers.
Many of these influencers appear to be managed by the same company, a CNN examination of user-profiles found.
A further analysis of Weibo data showed that the hashtag ''Foreign Ministry'' attracted 790 million views across 210,000 posts between Jan. 18 and 25. Meanwhile, over 229,000 posts used the hashtag ''Fort Detrick'' and were viewed over 1.48 billion times. Most of the popular posts were made by state-run media and private publications with ties to the Chinese government.
According to the Associated Press's investigation, conspiracies about Fort Detrick started from the Chinese websites and later spread worldwide via other mainstream social media platforms like Facebook.
The four-week World Health Organization mission to China to uncover the origins of the coronavirus wrapped up with no conclusive findings Photo: National Institutes of Health / Handout
Bitcoin 2021 | FAQ
Wed, 02 Jun 2021 18:56
Miami, FLJune 4''5Mana Wynwood
Frequently Asked Questions / How To PrepareHave a question not addressed here? Contact us
How can I connect with other attendees online?
Join the Official Bitcoin 2021 Telegram group for the latest updates, for special announcements, and to connect with other attendees.
What cryptocurrencies will be covered at the event?
Bitcoin Only! This is a Bitcoin only conference. Please stay focused and on topic at the event. Save conversations about other protocols and cryptocurrencies for outside the conference.
Can I cut off my wristband after Day 1?
No. On day one, you'll receive your admission wristband. Keep this wristband on for the entirety of the conference! If you lose your wristband, you'll be required to purchase another ticket in order to enter. If you wish to cut your wristband off (or it falls off), we will provide you with another wristband as long as you physically have the old wristband to turn in for replacement.
What will be provided at the conference?
Bitcoin 2021 will be providing you with sunglasses, sunscreen, privacy mask, hand sanitizer, water, warm weather and incredible content from the best in Bitcoin. Food and beer will be available for purchase throughout the conference, which you can buy with bitcoin, cash or credit card.
Should I bring my laptop or backpack?
We don't recommend bringing large bags or backpacks to the event, as all bags will be checked by security before entering the venue. All attendees will be receiving a fanny pack at registration.
Can I bring a weapon or firearm onsite?
We have a no firearms policy inside the venue. Miami PD will be the only personnel with firearms onsite.
How much BTC should I bring with me?
While this is a Bitcoin conference, we don't recommend bringing large amounts of bitcoin along for the ride. Unfortunately, there will probably be bad actors at this event (they're everywhere), whose sole purpose is to steal your hard-earned BTC. Everything will be Bitcoin enabled, so download your favorite lighting wallet and top if off with what you plan to use at the conference.
Yes, but please know How To HODL Your Alcohol. If you get drunk and act a fool, security will kindly ask you to leave the premises. We will also be checking IDs at the bar.
What are your COVID-19 protocols?
Coming out of the pandemic, we still have to adhere to local, state and federal mandates on large gatherings. All attendees will be provided with a mask and hand sanitizer upon entering the conference. Per the CDC, fully vaccinated attendees "can resume activities without wearing a mask or physical distancing." We will not be checking your vaccination status.
What should I wear to the conference?
Dress casual: Shorts, t-shirts, swim suits, tanks... all acceptable. This isn't your snobby, highbrow, business professional crypto event. For Whale Day and Whale Night, we recommend business professional attire.
Where do I pick up my After Party wristband?
All after party wristbands can be picked up on Friday or Saturday at the Bitcoin 2021 info desk (you can't miss it). The after party wristband will grant you access to BOTH The FTX Official Bitcoin 2021 After Party at The Oasis and the nearby eToro Tap Room at 1-800-LUCKY. Due to capacity limitations, one or the other may be full.
How is privacy being handled?
Bitcoin 2021 will have attendees of all ages. Please be mindful of those around you! Additionally, please be thoughtful of photography and use of cellphone cameras, as not everyone will want to be included in photos. If you're extremely interested in privacy, wear the privacy mask that we'll be providing to each attendee at registration.
Should I rideshare or drive myself?
The drop off and pick up address is 318 NW 23rd street. This address should automatically be in Uber and Lyft systems for the conference days. Paid parking is available in the parking lots adjacent to registration for $20 per day.
Will transportation be provided to the conference and back to the hotels?
We are providing a complimentary shuttle service to Bitcoin 2021 from select hotels. These shuttles will be running from 7:45 a.m. to 9:05 a.m. from the following hotels: Kimpton EPIC, JW Marriott Marquis Miami, The InterContinental Miami, Hyatt Regency Miami and JW Marriott Miami. We are also providing a complimentary shuttle service from Bitcoin 2021 to the Bayfront Park (walkable to most hotels). These are first come first serve
Where can I find the agenda?
The agenda can be found here (and it's subject to change).
Unless you have a Media Pass AND have been approved by our events team, no cameras or video cameras with a lens over 6" are permitted on site. Please be mindful of those around you! Additionally, please be thoughtful of photography and use of cellphone cameras, as not everyone will want to be included in photos.
Due to this being an indoor/outdoor event, as well as capacity limitations, only service dogs are permitted during the event days.
What about my after party ticket?
There will still be an after party at Bitcoin 2021, so if you had previously purchased an after party ticket, you will still have it. If you choose to refund your Bitcoin 2021 ticket, you will receive a refund for your after party ticket as well.
What about my Whale Pass?
There will still be a Whale Day/Whale Night/The Deep at Bitcoin 2021, so if you had previously purchased a Whale Pass, you will still have it. If you choose to refund your Bitcoin 2021 ticket, you will receive a refund for your Whale Pass as well.
What about items I bought in the store?
If you purchased an item from the Bitcoin 2020 store, that item will be available for pickup at Bitcoin 2021. You should also have received an email from a team member with options for shipping. If you ordered items and have not received an email from our team, please email store@b.tc to sort out logistics for the item.
Can't Make It To Miami, How Soon Will I Get My Refund?
All ticket refunds must be requested by February 22, 2021, and will be processed on March 1, 2021. If you indicate that you would like a refund, you will receive confirmation of that refund by February 22.
How do I request a refund?
Refunds are unavailable as our refund period has ended. You are able to transfer your ticket to another attendee via the Eventbrite app. If you require assistance with transferring please complete our Contact Form and a member of our team will reach out.
Will the dates change again?
The conference has confirmed the dates of June 4 and 5, 2021. We have partnered with the Mayor and the City of Miami on making this happen in Miami, and there are no plans to postpone at this time.
Can I travel to the conference from outside of the U.S.?
We are hopeful that we will see the opening up of international travel as the COVID-19 vaccine rollout continues worldwide. But as of now, international travel is a developing situation and the logistics may be vastly different based on attendees' places of origin. For this reason, please write in using our contact form and the Bitcoin 2021 team will do its best to provide any invitation/documentation needed to assist you with International travel.
Can I transfer my ticket to someone else?
Yes, however, you must edit your order information to put your ticket under someone else's name and email address. This does not remove the ticket from your Eventbrite account, but the new attendee will receive an email prompting them to claim tickets when you save the change.
ACCEPTED
Was there a Wuhan lab leak? An inquiry won't dig out the truth. It will deepen the deception
Wed, 02 Jun 2021 18:45
A year ago, the idea that Covid-19 leaked from a lab in Wuhan '' a short distance from the wet market that is usually claimed to be the source of the virus '' was dismissed as a crackpot theory, supported only by Donald Trump, QAnon and hawks on the right looking to escalate tensions dangerously with China.
Now, after what has been effectively a year-long blackout of the lab-leak theory by the corporate media and the scientific establishment, President Joe Biden has announced an investigation to assess its credibility. And as a consequence, what was treated until a few weeks ago as an unhinged, rightwing conspiracy is suddenly being widely aired and seriously considered by liberals.
Every media outlet is running prominent stories wondering whether a pandemic that has killed so many people and destroyed the lives of so many more can be blamed on human hubris and meddling rather than on a natural cause.
For many years, scientists at labs like Wuhan's have conducted Frankenstein-type experiments on viruses. They have modified naturally occurring infective agents '' often found in animals such as bats '' to try to predict the worst-case scenarios for how viruses, especially coronaviruses, might evolve. The claimed purpose has been to ensure humankind gets a head start on any new pandemic, preparing strategies and vaccines in advance to cope.
Viruses are known to have escaped from labs like Wuhan's many times before. And there are now reports, rejected by China, that several staff at Wuhan got sick in late 2019, shortly before Covid-19 exploded on to the world stage. Did a human-manipulated novel coronavirus escape from the lab and spread around the world?
>>
No interest in truthHere we get to the tricky bit. Because nobody in a position to answer that question appears to have any interest in finding out the truth '' or at least, they have no interest in the rest of us learning the truth. Not China. Not US policy-makers. Not the World Health Organisation. And not the corporate media.
The only thing we can state with certainty is this: our understanding of the origins of Covid has been narratively managed over the past 15 months and is still being narratively managed. We are being told only what suits powerful political, scientific and commercial interests.
We now know that we were misdirected a year ago into believing that a lab leak was either fanciful nonsense or evidence of Sinophobia '' when it was very obviously neither. And we should understand now, even though the story has switched 180 degrees, that we are still being misdirected. Nothing that the US administration or the corporate media have told us, or are now telling us, about the origins of the virus can be trusted.
No one in power truly wants to get to the bottom of this story. In fact, quite the reverse. Were we to truly understand its implications, this story might have the potential not only to hugely discredit western political, media and scientific elites but even to challenge the whole ideological basis on which their power rests.
Which is why what we are seeing is not an effort to grapple with the truth of the past year, but a desperate bid by those same elites to continue controlling our understanding of it. Western publics are being subjected to a continuous psy-op by their own officials.
Virus experimentsLast year, the safest story for the western political and scientific establishments to promote was the idea that a wild animal like a bat introduced Covid-19 to the human population. In other words, no one was to blame. The alternative was to hold China responsible for a lab leak, as Trump tried to do.
But there was a very good reason why most US policy-makers did not want to go down that latter path. And it had little to do with a concern either to refrain from conspiracy theories or to avoid provoking unnecessary tension with a nuclear-armed China.
Nicholas Wade, a former New York Times science writer, set out in May, in an in-depth investigation, why the case for a lab leak was scientifically strong, citing some of the world's leading virologists.
But Wade also highlighted a much deeper problem for US elites: just before the first outbreak of Covid, the Wuhan lab was, it seems, cooperating with the US scientific establishment and WHO officials on its virus experiments '' what is known, in scientific parlance, as ''gain-of-function'' research.
Gain-of-function experiments had been paused during the second Obama administration, precisely because of concerns about the danger of a human-engineered virus mutation escaping and creating a pandemic. But under Trump, US officials restarted the programme and were reportedly funding work at the Wuhan lab through a US-based medical organisation called the EcoHealth Alliance.
The US official who pushed this agenda hardest is reported to have been Dr Anthony Fauci '' yes, the US President's chief medical adviser and the official widely credited with curbing Trump's reckless approach to the pandemic. If the lab leak theory is right, the pandemic's saviour in the US might actually have been one of its chief instigators.
And to top it off, senior officials at the WHO have been implicated too, for being closely involved with gain-of-function research through groups like EcoHealth.
Colluding in deceitThis seems to be the real reason why the lab-leak theory was quashed so aggressively last year by western political, medical and media establishments without any effort to seriously assess the claims or investigate them. Not out of any sense of obligation towards the truth or concern about racist incitement against the Chinese. It was done out of naked self-interest.
If anyone doubts that, consider this: the WHO appointed Peter Daszak, the president of the EcoHealth Alliance, the very group that reportedly funded gain-of-function research at Wuhan on behalf of the US, to investigate the lab-leak theory and effectively become the WHO's spokesman on the matter. To say that Daszak had a conflict of interest is to massively understate the problem.
He, of course, has loudly discounted any possibility of a leak and, perhaps not surprisingly, continues to direct the media's attention to Wuhan's wet market.
The extent to which major media are not only negligently failing to cover the story with any seriousness but are also actively continuing to collude in deceiving their audiences '' and sweeping these egregious conflicts of interest under the carpet '' is illustrated by this article published by the BBC at the weekend.
The BBC ostensibly weighs the two possible narratives about Covid's origins. But it mentions none of Wade's explosive findings, including the potential US role in funding gain-of-function research at Wuhan. Both Fauci and Daszak are cited as trusted and dispassionate commentators rather than as figures who have the most to lose from a serious investigation into what happened at the Wuhan lab.
Given this context, the events of the past 15 months look much more like a pre-emptive cover-up: a desire to stop the truth from ever emerging because, if a lab leak did occur, it would threaten the credibility of the very structures of authority on which the power of western elites rests.
Media blackoutSo why, after the strenuously enforced blackout of the past year, are Biden, the corporate media and the scientific establishment suddenly going public with the possibility of a China lab leak?
The answer to that seems clear: because Nicholas Wade's article, in particular, blew open the doors that had been kept tightly shut on the lab-leak hypothesis. Scientists who had formerly feared being associated with Trump or a ''conspiracy theory'' have belatedly spoken up. The cat is out of the bag.
Or as the Financial Times reported of the new official narrative, ''the driving factor was a shift among scientists who had been wary of helping Trump before the election or angering influential scientists who had dismissed the theory''.
The journal Science recently upped the stakes by publishing a letter from 18 prominent scientists stating that the lab-leak and animal-origin theories were equally ''viable'' and that the WHO's earlier investigation had not given ''balanced consideration'' to both '' a polite way of suggesting that the WHO investigation was a fix.
And so we are now being subjected by the Biden administration to Plan B: damage limitation. The US President, the medical establishment and the corporate media are raising the possibility of a Wuhan lab leak, but are excluding all the evidence unearthed by Wade and others that would implicate Fauci and the US policy elite in such a leak, if it occurred. (Meanwhile, Fauci and his supporters have been preemptively muddying the waters by trying to redefine what constitutes gain-of-function.)
The growing clamour on social media, much of it provoked by Wade's research, is one of the main reasons Biden and the media are being forced to address the lab-leak theory, having previously discounted it. And yet Wade's revelations of US and WHO involvement in gain-of-function research, and of potential complicity in a lab leak and a subsequent cover-up are missing from almost all corporate media reporting.
Evasion tacticBiden's so-called investigation is intended to be cynically evasive. It makes the administration look serious about getting to the truth when it is nothing of the sort. It eases pressure on the corporate media that might otherwise be expected to dig out the truth themselves. The narrow focus on the lab leak theory displaces the wider story of potential US and WHO complicity in such a leak and overshadows efforts by outside critics to highlight that very point. And the inevitable delay while the investigation is carried out readily exploits Covid news fatigue as western publics start to emerge from under the pandemic's shadow.
The Biden administration will hope the public's interest rapidly wanes on this story so that the corporate media can let it drop off their radar. In any case, the investigation's findings will most likely be inconclusive, to avoid a war of duelling narratives with China.
But even if the investigation is forced to point the finger at the Chinese, the Biden administration knows that the western corporate media will loyally report its accusations against China as fact '' just as they loyally blacked out any consideration of a lab leak until they were forced to do so over the past few days.
Illusion of truthThe Wuhan story provides a chance to understand more deeply how elites wield their narrative power over us '' to control what we think, or are even capable of thinking. They can twist any narrative to their advantage.
In the calculations of western elites, the truth is largely irrelevant. What is of utmost importance is maintaining the illusion of truth. It is vital to keep us believing that our leaders rule in our best interests; that the western system '' despite all its flaws '' is the best possible one for arranging our political and economic lives; and that we are on a steady, if sometimes rocky, path towards progress.
The job of sustaining the illusion of truth falls to the corporate media. It will be their role now to expose us to a potentially lengthy, certainly lively '' but carefully ring-fenced and ultimately inconclusive '' debate about whether Covid emerged naturally or leaked from the Wuhan lab.
The media's task is to manage smoothly the transition from last year's unquestionable certainty '' that the pandemic had an animal origin '' to a more hesitant, confusing picture that includes the possibility of a human, but very much Chinese, role in the virus' emergence. It is to ensure we do not feel any cognitive dissonance as a theory we were assured was impossible by the experts only weeks ago suddenly becomes only too possible, even though nothing has materially changed in the meantime.
What is essential for the political, media and scientific establishments is that we do not ponder deeper questions:
How is it that the supposedly sceptical, disputatious, raucous media once again spoke mostly with a single and uncritical voice on such a vitally important matter '' in this case, for more than a year on the origins of Covid?Why was that media consensus broken not by a large, well-resourced media organisation, but by a lone, former science writer working independently and publishing in a relatively obscure science magazine?Why did the many leading scientists who are now ready to question the imposed narrative of Covid's animal origin remain silent for so long about the apparently equally credible hypothesis of a lab leak?And most importantly, why should we believe that the political, media and scientific establishments have on this occasion any interest in telling us the truth, or in ensuring our welfare, after they have been shown to have repeatedly lied or stayed silent on even graver matters and over much longer periods, such as about the various ecological catastrophes that have been looming since the 1950s?Class interestsThose questions, let alone the answers, will be avoided by anyone who needs to believe that our rulers are competent and moral and that they pursue the public good rather than their own individual, narrow, selfish interests '' or those of their class or professional group.
Scientists defer slavishly to the scientific establishment because that same establishment oversees a system in which scientists are rewarded with research funding, employment opportunities and promotions. And because scientists have little incentive to question or expose their own professional community's failings, or increase public scepticism towards science and scientists.
Similarly, journalists work for a handful of billionaire-owned media corporations that want to maintain the public's faith in the ''benevolence'' of the power structures that reward billionaires for their supposed genius and ability to improve the lives of the rest of us. The corporate media has no interest in encouraging the public to question whether it can really operate as a neutral conduit that channels information to ordinary people rather than preserves a status quo that benefits a tiny wealth-elite.
And politicians have every reason to continue to persuade us that they represent our interests rather than the billionaire donors whose corporations and media outlets can so easily destroy their careers.
What we are dealing with here is a set of professional classes doing everything in their power to preserve their own interests and the interests of the system that rewards them. And that requires strenuous efforts on their part to make sure we do not understand that policy is driven chiefly by greed and a craving for status, not by the common good or by a concern for truth and transparency.
Which is why no meaningful lessons will be learnt about what really happened in Wuhan. Maintaining the illusion of truth will continue to take precedence over uncovering the truth. And for that reason we are doomed to keep making the same screw-ups. As the next pandemic will doubtless attest.
Fact Sheet: Activity at the Wuhan Institute of Virology - United States Department of State
Wed, 02 Jun 2021 18:44
For more than a year, the Chinese Communist Party (CCP) has systematically prevented a transparent and thorough investigation of the COVID-19 pandemic's origin, choosing instead to devote enormous resources to deceit and disinformation. Nearly two million people have died. Their families deserve to know the truth. Only through transparency can we learn what caused this pandemic and how to prevent the next one.
The U.S. government does not know exactly where, when, or how the COVID-19 virus'--known as SARS-CoV-2'--was transmitted initially to humans. We have not determined whether the outbreak began through contact with infected animals or was the result of an accident at a laboratory in Wuhan, China.
The virus could have emerged naturally from human contact with infected animals, spreading in a pattern consistent with a natural epidemic. Alternatively, a laboratory accident could resemble a natural outbreak if the initial exposure included only a few individuals and was compounded by asymptomatic infection. Scientists in China have researched animal-derived coronaviruses under conditions that increased the risk for accidental and potentially unwitting exposure.
The CCP's deadly obsession with secrecy and control comes at the expense of public health in China and around the world. The previously undisclosed information in this fact sheet, combined with open-source reporting, highlights three elements about COVID-19's origin that deserve greater scrutiny:
1. Illnesses inside the Wuhan Institute of Virology (WIV):
The U.S. government has reason to believe that several researchers inside the WIV became sick in autumn 2019, before the first identified case of the outbreak, with symptoms consistent with both COVID-19 and common seasonal illnesses. This raises questions about the credibility of WIV senior researcher Shi Zhengli's public claim that there was ''zero infection'' among the WIV's staff and students of SARS-CoV-2 or SARS-related viruses.Accidental infections in labs have caused several previous virus outbreaks in China and elsewhere, including a 2004 SARS outbreak in Beijing that infected nine people, killing one.The CCP has prevented independent journalists, investigators, and global health authorities from interviewing researchers at the WIV, including those who were ill in the fall of 2019. Any credible inquiry into the origin of the virus must include interviews with these researchers and a full accounting of their previously unreported illness.2. Research at the WIV:
Starting in at least 2016 '' and with no indication of a stop prior to the COVID-19 outbreak '' WIV researchers conducted experiments involving RaTG13, the bat coronavirus identified by the WIV in January 2020 as its closest sample to SARS-CoV-2 (96.2% similar). The WIV became a focal point for international coronavirus research after the 2003 SARS outbreak and has since studied animals including mice, bats, and pangolins.The WIV has a published record of conducting ''gain-of-function'' research to engineer chimeric viruses. But the WIV has not been transparent or consistent about its record of studying viruses most similar to the COVID-19 virus, including ''RaTG13,'' which it sampled from a cave in Yunnan Province in 2013 after several miners died of SARS-like illness.WHO investigators must have access to the records of the WIV's work on bat and other coronaviruses before the COVID-19 outbreak. As part of a thorough inquiry, they must have a full accounting of why the WIV altered and then removed online records of its work with RaTG13 and other viruses.3. Secret military activity at the WIV:
Secrecy and non-disclosure are standard practice for Beijing. For many years the United States has publicly raised concerns about China's past biological weapons work, which Beijing has neither documented nor demonstrably eliminated, despite its clear obligations under the Biological Weapons Convention.Despite the WIV presenting itself as a civilian institution, the United States has determined that the WIV has collaborated on publications and secret projects with China's military. The WIV has engaged in classified research, including laboratory animal experiments, on behalf of the Chinese military since at least 2017.The United States and other donors who funded or collaborated on civilian research at the WIV have a right and obligation to determine whether any of our research funding was diverted to secret Chinese military projects at the WIV.Today's revelations just scratch the surface of what is still hidden about COVID-19's origin in China. Any credible investigation into the origin of COVID-19 demands complete, transparent access to the research labs in Wuhan, including their facilities, samples, personnel, and records.
As the world continues to battle this pandemic '' and as WHO investigators begin their work, after more than a year of delays '' the virus's origin remains uncertain. The United States will continue to do everything it can to support a credible and thorough investigation, including by continuing to demand transparency on the part of Chinese authorities.
The origin of COVID: Did people or nature open Pandora's box at Wuhan? - Bulletin of the Atomic Scientists
Wed, 02 Jun 2021 18:40
Members of the World Health Organization (WHO) team investigating the origins of the COVID-19 coronavirus arrive by car at the Wuhan Institute of Virology on February 3. (Photo by HECTOR RETAMAL/AFP via Getty Images)
The COVID-19 pandemic has disrupted lives the world over for more than a year. Its death toll will soon reach three million people. Yet the origin of pandemic remains uncertain: The political agendas of governments and scientists have generated thick clouds of obfuscation, which the mainstream press seems helpless to dispel.
In what follows I will sort through the available scientific facts, which hold many clues as to what happened, and provide readers with the evidence to make their own judgments. I will then try to assess the complex issue of blame, which starts with, but extends far beyond, the government of China.
By the end of this article, you may have learned a lot about the molecular biology of viruses. I will try to keep this process as painless as possible. But the science cannot be avoided because for now, and probably for a long time hence, it offers the only sure thread through the maze.
The virus that caused the pandemic is known officially as SARS-CoV-2, but can be called SARS2 for short. As many people know, there are two main theories about its origin. One is that it jumped naturally from wildlife to people. The other is that the virus was under study in a lab, from which it escaped. It matters a great deal which is the case if we hope to prevent a second such occurrence.
I'll describe the two theories, explain why each is plausible, and then ask which provides the better explanation of the available facts. It's important to note that so far there is no direct evidence for either theory. Each depends on a set of reasonable conjectures but so far lacks proof. So I have only clues, not conclusions, to offer. But those clues point in a specific direction. And having inferred that direction, I'm going to delineate some of the strands in this tangled skein of disaster.
A tale of two theories. After the pandemic first broke out in December 2019, Chinese authorities reported that many cases had occurred in the wet market'Š'--'Ša place selling wild animals for meat'Š'--'Šin Wuhan. This reminded experts of the SARS1 epidemic of 2002, in which a bat virus had spread first to civets, an animal sold in wet markets, and from civets to people. A similar bat virus caused a second epidemic, known as MERS, in 2012. This time the intermediary host animal was camels.
The decoding of the virus's genome showed it belonged a viral family known as beta-coronaviruses, to which the SARS1 and MERS viruses also belong. The relationship supported the idea that, like them, it was a natural virus that had managed to jump from bats, via another animal host, to people. The wet market connection, the major point of similarity with the SARS1 and MERS epidemics, was soon broken: Chinese researchers found earlier cases in Wuhan with no link to the wet market. But that seemed not to matter when so much further evidence in support of natural emergence was expected shortly.
Wuhan, however, is home of the Wuhan Institute of Virology, a leading world center for research on coronaviruses. So the possibility that the SARS2 virus had escaped from the lab could not be ruled out. Two reasonable scenarios of origin were on the table.
From early on, public and media perceptions were shaped in favor of the natural emergence scenario by strong statements from two scientific groups. These statements were not at first examined as critically as they should have been.
''We stand together to strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin,'' a group of virologists and others wrote in the Lancet on February 19, 2020, when it was really far too soon for anyone to be sure what had happened. Scientists ''overwhelmingly conclude that this coronavirus originated in wildlife,'' they said, with a stirring rallying call for readers to stand with Chinese colleagues on the frontline of fighting the disease.
Contrary to the letter writers' assertion, the idea that the virus might have escaped from a lab invoked accident, not conspiracy. It surely needed to be explored, not rejected out of hand. A defining mark of good scientists is that they go to great pains to distinguish between what they know and what they don't know. By this criterion, the signatories of the Lancet letter were behaving as poor scientists: They were assuring the public of facts they could not know for sure were true.
It later turned out that the Lancet letter had been organized and drafted by Peter Daszak, president of the EcoHealth Alliance of New York. Daszak's organization funded coronavirus research at the Wuhan Institute of Virology. If the SARS2 virus had indeed escaped from research he funded, Daszak would be potentially culpable. This acute conflict of interest was not declared to the Lancet's readers. To the contrary, the letter concluded, ''We declare no competing interests.''
Peter Daszak, a member of the World Health Organization (WHO) team investigating the origins of the COVID-19 coronavirus, talks on his cellphone at the Hilton Wuhan Optics Valley in Wuhan. (Photo by HECTOR RETAMAL/AFP via Getty Images)Virologists like Daszak had much at stake in the assigning of blame for the pandemic. For 20 years, mostly beneath the public's attention, they had been playing a dangerous game. In their laboratories they routinely created viruses more dangerous than those that exist in nature. They argued that they could do so safely, and that by getting ahead of nature they could predict and prevent natural ''spillovers,'' the cross-over of viruses from an animal host to people. If SARS2 had indeed escaped from such a laboratory experiment, a savage blowback could be expected, and the storm of public indignation would affect virologists everywhere, not just in China. ''It would shatter the scientific edifice top to bottom,'' an MIT Technology Review editor, Antonio Regalado, said in March 2020.
A second statement that had enormous influence in shaping public attitudes was a letter (in other words an opinion piece, not a scientific article) published on 17 March 2020 in the journal Nature Medicine. Its authors were a group of virologists led by Kristian G. Andersen of the Scripps Research Institute. ''Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus,'' the five virologists declared in the second paragraph of their letter.
Unfortunately, this was another case of poor science, in the sense defined above. True, some older methods of cutting and pasting viral genomes retain tell-tale signs of manipulation. But newer methods, called ''no-see-um'' or ''seamless'' approaches, leave no defining marks. Nor do other methods for manipulating viruses such as serial passage, the repeated transfer of viruses from one culture of cells to another. If a virus has been manipulated, whether with a seamless method or by serial passage, there is no way of knowing that this is the case. Andersen and his colleagues were assuring their readers of something they could not know.
The discussion part of their letter begins, ''It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus.'' But wait, didn't the lead say the virus had clearly not been manipulated? The authors' degree of certainty seemed to slip several notches when it came to laying out their reasoning.
The reason for the slippage is clear once the technical language has been penetrated. The two reasons the authors give for supposing manipulation to be improbable are decidedly inconclusive.
First, they say that the spike protein of SARS2 binds very well to its target, the human ACE2 receptor, but does so in a different way from that which physical calculations suggest would be the best fit. Therefore the virus must have arisen by natural selection, not manipulation.
If this argument seems hard to grasp, it's because it's so strained. The authors' basic assumption, not spelt out, is that anyone trying to make a bat virus bind to human cells could do so in only one way. First they would calculate the strongest possible fit between the human ACE2 receptor and the spike protein with which the virus latches onto it. They would then design the spike protein accordingly (by selecting the right string of amino acid units that compose it). Since the SARS2 spike protein is not of this calculated best design, the Andersen paper says, therefore it can't have been manipulated.
But this ignores the way that virologists do in fact get spike proteins to bind to chosen targets, which is not by calculation but by splicing in spike protein genes from other viruses or by serial passage. With serial passage, each time the virus's progeny are transferred to new cell cultures or animals, the more successful are selected until one emerges that makes a really tight bind to human cells. Natural selection has done all the heavy lifting. The Andersen paper's speculation about designing a viral spike protein through calculation has no bearing on whether or not the virus was manipulated by one of the other two methods.
The authors' second argument against manipulation is even more contrived. Although most living things use DNA as their hereditary material, a number of viruses use RNA, DNA's close chemical cousin. But RNA is difficult to manipulate, so researchers working on coronaviruses, which are RNA-based, will first convert the RNA genome to DNA. They manipulate the DNA version, whether by adding or altering genes, and then arrange for the manipulated DNA genome to be converted back into infectious RNA.
Only a certain number of these DNA backbones have been described in the scientific literature. Anyone manipulating the SARS2 virus ''would probably'' have used one of these known backbones, the Andersen group writes, and since SARS2 is not derived from any of them, therefore it was not manipulated. But the argument is conspicuously inconclusive. DNA backbones are quite easy to make, so it's obviously possible that SARS2 was manipulated using an unpublished DNA backbone.
And that's it. These are the two arguments made by the Andersen group in support of their declaration that the SARS2 virus was clearly not manipulated. And this conclusion, grounded in nothing but two inconclusive speculations, convinced the world's press that SARS2 could not have escaped from a lab. A technical critique of the Andersen letter takes it down in harsher words.
Science is supposedly a self-correcting community of experts who constantly check each other's work. So why didn't other virologists point out that the Andersen group's argument was full of absurdly large holes? Perhaps because in today's universities speech can be very costly. Careers can be destroyed for stepping out of line. Any virologist who challenges the community's declared view risks having his next grant application turned down by the panel of fellow virologists that advises the government grant distribution agency.
The Daszak and Andersen letters were really political, not scientific, statements, yet were amazingly effective. Articles in the mainstream press repeatedly stated that a consensus of experts had ruled lab escape out of the question or extremely unlikely. Their authors relied for the most part on the Daszak and Andersen letters, failing to understand the yawning gaps in their arguments. Mainstream newspapers all have science journalists on their staff, as do the major networks, and these specialist reporters are supposed to be able to question scientists and check their assertions. But the Daszak and Andersen assertions went largely unchallenged.
Doubts about natural emergence. Natural emergence was the media's preferred theory until around February 2021 and the visit by a World Health Organization (WHO) commission to China. The commission's composition and access were heavily controlled by the Chinese authorities. Its members, who included the ubiquitous Daszak, kept asserting before, during, and after their visit that lab escape was extremely unlikely. But this was not quite the propaganda victory the Chinese authorities may have been hoping for. What became clear was that the Chinese had no evidence to offer the commission in support of the natural emergence theory.
This was surprising because both the SARS1 and MERS viruses had left copious traces in the environment. The intermediary host species of SARS1 was identified within four months of the epidemic's outbreak, and the host of MERS within nine months. Yet some 15 months after the SARS2 pandemic began, and after a presumably intensive search, Chinese researchers had failed to find either the original bat population, or the intermediate species to which SARS2 might have jumped, or any serological evidence that any Chinese population, including that of Wuhan, had ever been exposed to the virus prior to December 2019. Natural emergence remained a conjecture which, however plausible to begin with, had gained not a shred of supporting evidence in over a year.
And as long as that remains the case, it's logical to pay serious attention to the alternative conjecture, that SARS2 escaped from a lab.
Why would anyone want to create a novel virus capable of causing a pandemic? Ever since virologists gained the tools for manipulating a virus's genes, they have argued they could get ahead of a potential pandemic by exploring how close a given animal virus might be to making the jump to humans. And that justified lab experiments in enhancing the ability of dangerous animal viruses to infect people, virologists asserted.
With this rationale, they have recreated the 1918 flu virus, shown how the almost extinct polio virus can be synthesized from its published DNA sequence, and introduced a smallpox gene into a related virus.
These enhancements of viral capabilities are known blandly as gain-of-function experiments. With coronaviruses, there was particular interest in the spike proteins, which jut out all around the spherical surface of the virus and pretty much determine which species of animal it will target. In 2000 Dutch researchers, for instance, earned the gratitude of rodents everywhere by genetically engineering the spike protein of a mouse coronavirus so that it would attack only cats.
The spike proteins on the coronavirus's surface determine which animal it can infect. Image credit: CDC.govVirologists started studying bat coronaviruses in earnest after these turned out to be the source of both the SARS1 and MERS epidemics. In particular, researchers wanted to understand what changes needed to occur in a bat virus's spike proteins before it could infect people.
Researchers at the Wuhan Institute of Virology, led by China's leading expert on bat viruses, Shi Zheng-li or ''Bat Lady,'' mounted frequent expeditions to the bat-infested caves of Yunnan in southern China and collected around a hundred different bat coronaviruses.
Shi then teamed up with Ralph S. Baric, an eminent coronavirus researcher at the University of North Carolina. Their work focused on enhancing the ability of bat viruses to attack humans so as to ''examine the emergence potential (that is, the potential to infect humans) of circulating bat CoVs [coronaviruses].'' In pursuit of this aim, in November 2015 they created a novel virus by taking the backbone of the SARS1 virus and replacing its spike protein with one from a bat virus (known as SHC014-CoV). This manufactured virus was able to infect the cells of the human airway, at least when tested against a lab culture of such cells.
The SHC014-CoV/SARS1 virus is known as a chimera because its genome contains genetic material from two strains of virus. If the SARS2 virus were to have been cooked up in Shi's lab, then its direct prototype would have been the SHC014-CoV/SARS1 chimera, the potential danger of which concerned many observers and prompted intense discussion.
''If the virus escaped, nobody could predict the trajectory,'' said Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris.
Baric and Shi referred to the obvious risks in their paper but argued they should be weighed against the benefit of foreshadowing future spillovers. Scientific review panels, they wrote, ''may deem similar studies building chimeric viruses based on circulating strains too risky to pursue.'' Given various restrictions being placed on gain-of function (GOF) research, matters had arrived in their view at ''a crossroads of GOF research concerns; the potential to prepare for and mitigate future outbreaks must be weighed against the risk of creating more dangerous pathogens. In developing policies moving forward, it is important to consider the value of the data generated by these studies and whether these types of chimeric virus studies warrant further investigation versus the inherent risks involved.''
That statement was made in 2015. From the hindsight of 2021, one can say that the value of gain-of-function studies in preventing the SARS2 epidemic was zero. The risk was catastrophic, if indeed the SARS2 virus was generated in a gain-of-function experiment.
Inside the Wuhan Institute of Virology. Baric had developed, and taught Shi, a general method for engineering bat coronaviruses to attack other species. The specific targets were human cells grown in cultures and humanized mice. These laboratory mice, a cheap and ethical stand-in for human subjects, are genetically engineered to carry the human version of a protein called ACE2 that studs the surface of cells that line the airways.
Shi returned to her lab at the Wuhan Institute of Virology and resumed the work she had started on genetically engineering coronaviruses to attack human cells. How can we be so sure?
A May 20, 2020, photo of the Wuhan Institute of Virology in Wuhan, where research on bat coronaviruses was conducted. (Photo by Kyodo News via Getty Images)Because, by a strange twist in the story, her work was funded by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the US National Institutes of Health (NIH). And grant proposals that funded her work, which are a matter of public record, specify exactly what she planned to do with the money.
The grants were assigned to the prime contractor, Daszak of the EcoHealth Alliance, who subcontracted them to Shi. Here are extracts from the grants for fiscal years 2018 and 2019. (''CoV'' stands for coronavirus and ''S protein'' refers to the virus's spike protein.)
''Test predictions of CoV inter-species transmission. Predictive models of host range (i.e. emergence potential) will be tested experimentally using reverse genetics, pseudovirus and receptor binding assays, and virus infection experiments across a range of cell cultures from different species and humanized mice.''
''We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential.''
What this means, in non-technical language, is that Shi set out to create novel coronaviruses with the highest possible infectivity for human cells. Her plan was to take genes that coded for spike proteins possessing a variety of measured affinities for human cells, ranging from high to low. She would insert these spike genes one by one into the backbone of a number of viral genomes (''reverse genetics'' and ''infectious clone technology''), creating a series of chimeric viruses. These chimeric viruses would then be tested for their ability to attack human cell cultures (''in vitro'') and humanized mice (''in vivo''). And this information would help predict the likelihood of ''spillover,'' the jump of a coronavirus from bats to people.
The methodical approach was designed to find the best combination of coronavirus backbone and spike protein for infecting human cells. The approach could have generated SARS2-like viruses, and indeed may have created the SARS2 virus itself with the right combination of virus backbone and spike protein.
It cannot yet be stated that Shi did or did not generate SARS2 in her lab because her records have been sealed, but it seems she was certainly on the right track to have done so. ''It is clear that the Wuhan Institute of Virology was systematically constructing novel chimeric coronaviruses and was assessing their ability to infect human cells and human-ACE2-expressing mice,'' says Richard H. Ebright, a molecular biologist at Rutgers University and leading expert on biosafety.
''It is also clear,'' Ebright said, ''that, depending on the constant genomic contexts chosen for analysis, this work could have produced SARS-CoV-2 or a proximal progenitor of SARS-CoV-2.'' ''Genomic context'' refers to the particular viral backbone used as the testbed for the spike protein.
The lab escape scenario for the origin of the SARS2 virus, as should by now be evident, is not mere hand-waving in the direction of the Wuhan Institute of Virology. It is a detailed proposal, based on the specific project being funded there by the NIAID.
Even if the grant required the work plan described above, how can we be sure that the plan was in fact carried out? For that we can rely on the word of Daszak, who has been much protesting for the last 15 months that lab escape was a ludicrous conspiracy theory invented by China-bashers.
On December 9, 2019, before the outbreak of the pandemic became generally known, Daszak gave an interview in which he talked in glowing terms of how researchers at the Wuhan Institute of Virology had been reprogramming the spike protein and generating chimeric coronaviruses capable of infecting humanized mice.
''And we have now found, you know, after 6 or 7 years of doing this, over 100 new SARS-related coronaviruses, very close to SARS,'' Daszak says around minute 28 of the interview. ''Some of them get into human cells in the lab, some of them can cause SARS disease in humanized mice models and are untreatable with therapeutic monoclonals and you can't vaccinate against them with a vaccine. So, these are a clear and present danger'....
''Interviewer: You say these are diverse coronaviruses and you can't vaccinate against them, and no anti-virals'Š'--'Šso what do we do?
''Daszak: Well I think'...coronaviruses'Š'--'Šyou can manipulate them in the lab pretty easily. Spike protein drives a lot of what happen with coronavirus, in zoonotic risk. So you can get the sequence, you can build the protein, and we work a lot with Ralph Baric at UNC to do this. Insert into the backbone of another virus and do some work in the lab. So you can get more predictive when you find a sequence. You've got this diversity. Now the logical progression for vaccines is, if you are going to develop a vaccine for SARS, people are going to use pandemic SARS, but let's insert some of these other things and get a better vaccine.'' The insertions he referred to perhaps included an element called the furin cleavage site, discussed below, which greatly increases viral infectivity for human cells.
In disjointed style, Daszak is referring to the fact that once you have generated a novel coronavirus that can attack human cells, you can take the spike protein and make it the basis for a vaccine.
One can only imagine Daszak's reaction when he heard of the outbreak of the epidemic in Wuhan a few days later. He would have known better than anyone the Wuhan Institute's goal of making bat coronaviruses infectious to humans, as well as the weaknesses in the institute's defense against their own researchers becoming infected.
But instead of providing public health authorities with the plentiful information at his disposal, he immediately launched a public relations campaign to persuade the world that the epidemic couldn't possibly have been caused by one of the institute's souped-up viruses. ''The idea that this virus escaped from a lab is just pure baloney. It's simply not true,'' he declared in an April 2020 interview.
The safety arrangements at the Wuhan Institute of Virology. Daszak was possibly unaware of, or perhaps he knew all too well, the long history of viruses escaping from even the best run laboratories. The smallpox virus escaped three times from labs in England in the 1960's and 1970's, causing 80 cases and 3 deaths. Dangerous viruses have leaked out of labs almost every year since. Coming to more recent times, the SARS1 virus has proved a true escape artist, leaking from laboratories in Singapore, Taiwan, and no less than four times from the Chinese National Institute of Virology in Beijing.
One reason for SARS1 being so hard to handle is that there were no vaccines available to protect laboratory workers. As Daszak mentioned in the December 19 interview quoted above, the Wuhan researchers too had been unable to develop vaccines against the coronaviruses they had designed to infect human cells. They would have been as defenseless against the SARS2 virus, if it were generated in their lab, as their Beijing colleagues were against SARS1.
A second reason for the severe danger of novel coronaviruses has to do with the required levels of lab safety. There are four degrees of safety, designated BSL1 to BSL4, with BSL4 being the most restrictive and designed for deadly pathogens like the Ebola virus.
The Wuhan Institute of Virology had a new BSL4 lab, but its state of readiness considerably alarmed the State Department inspectors who visited it from the Beijing embassy in 2018. ''The new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory,'' the inspectors wrote in a cable of January 19, 2018.
The real problem, however, was not the unsafe state of the Wuhan BSL4 lab but the fact that virologists worldwide don't like working in BSL4 conditions. You have to wear a space suit, do operations in closed cabinets, and accept that everything will take twice as long. So the rules assigning each kind of virus to a given safety level were laxer than some might think was prudent.
Before 2020, the rules followed by virologists in China and elsewhere required that experiments with the SARS1 and MERS viruses be conducted in BSL3 conditions. But all other bat coronaviruses could be studied in BSL2, the next level down. BSL2 requires taking fairly minimal safety precautions, such as wearing lab coats and gloves, not sucking up liquids in a pipette, and putting up biohazard warning signs. Yet a gain-of-function experiment conducted in BSL2 might produce an agent more infectious than either SARS1 or MERS. And if it did, then lab workers would stand a high chance of infection, especially if unvaccinated.
Much of Shi's work on gain-of-function in coronaviruses was performed at the BSL2 safety level, as is stated in her publications and other documents. She has said in an interview with Science magazine that ''[t]he coronavirus research in our laboratory is conducted in BSL-2 or BSL-3 laboratories.''
''It is clear that some or all of this work was being performed using a biosafety standard'Š'--'Šbiosafety level 2, the biosafety level of a standard US dentist's office'Š'--'Šthat would pose an unacceptably high risk of infection of laboratory staff upon contact with a virus having the transmission properties of SARS-CoV-2,'' Ebright says.
''It also is clear,'' he adds, ''that this work never should have been funded and never should have been performed.''
This is a view he holds regardless of whether or not the SARS2 virus ever saw the inside of a lab.
Concern about safety conditions at the Wuhan lab was not, it seems, misplaced. According to a fact sheet issued by the State Department on January 15, 2021, ''The U.S. government has reason to believe that several researchers inside the WIV became sick in autumn 2019, before the first identified case of the outbreak, with symptoms consistent with both COVID-19 and common seasonal illnesses.''
David Asher, a fellow of the Hudson Institute and former consultant to the State Department, provided more detail about the incident at a seminar. Knowledge of the incident came from a mix of public information and ''some high end information collected by our intelligence community,'' he said. Three people working at a BSL3 lab at the institute fell sick within a week of each other with severe symptoms that required hospitalization. This was ''the first known cluster that we're aware of, of victims of what we believe to be COVID-19.'' Influenza could not completely be ruled out but seemed unlikely in the circumstances, he said.
Comparing the rival scenarios of SARS2 origin. The evidence above adds up to a serious case that the SARS2 virus could have been created in a lab, from which it then escaped. But the case, however substantial, falls short of proof. Proof would consist of evidence from the Wuhan Institute of Virology, or related labs in Wuhan, that SARS2 or a predecessor virus was under development there. For lack of access to such records, another approach is to take certain salient facts about the SARS2 virus and ask how well each is explained by the two rival scenarios of origin, those of natural emergence and lab escape. Here are four tests of the two hypotheses. A couple have some technical detail, but these are among the most persuasive for those who may care to follow the argument.
1) The place of origin. Start with geography. The two closest known relatives of the SARS2 virus were collected from bats living in caves in Yunnan, a province of southern China. If the SARS2 virus had first infected people living around the Yunnan caves, that would strongly support the idea that the virus had spilled over to people naturally. But this isn't what happened. The pandemic broke out 1,500 kilometers away, in Wuhan.
Beta-coronaviruses, the family of bat viruses to which SARS2 belongs, infect the horseshoe bat Rhinolophus affinis, which ranges across southern China. The bats' range is 50 kilometers, so it's unlikely that any made it to Wuhan. In any case, the first cases of the COVID-19 pandemic probably occurred in September, when temperatures in Hubei province are already cold enough to send bats into hibernation.
What if the bat viruses infected some intermediate host first? You would need a longstanding population of bats in frequent proximity with an intermediate host, which in turn must often cross paths with people. All these exchanges of virus must take place somewhere outside Wuhan, a busy metropolis which so far as is known is not a natural habitat of Rhinolophus bat colonies. The infected person (or animal) carrying this highly transmissible virus must have traveled to Wuhan without infecting anyone else. No one in his or her family got sick. If the person jumped on a train to Wuhan, no fellow passengers fell ill.
It's a stretch, in other words, to get the pandemic to break out naturally outside Wuhan and then, without leaving any trace, to make its first appearance there.
For the lab escape scenario, a Wuhan origin for the virus is a no-brainer. Wuhan is home to China's leading center of coronavirus research where, as noted above, researchers were genetically engineering bat coronaviruses to attack human cells. They were doing so under the minimal safety conditions of a BSL2 lab. If a virus with the unexpected infectiousness of SARS2 had been generated there, its escape would be no surprise.
2) Natural history and evolution. The initial location of the pandemic is a small part of a larger problem, that of its natural history. Viruses don't just make one time jumps from one species to another. The coronavirus spike protein, adapted to attack bat cells, needs repeated jumps to another species, most of which fail, before it gains a lucky mutation. Mutation'Š'--'Ša change in one of its RNA units'Š'--'Šcauses a different amino acid unit to be incorporated into its spike protein and makes the spike protein better able to attack the cells of some other species.
Through several more such mutation-driven adjustments, the virus adapts to its new host, say some animal with which bats are in frequent contact. The whole process then resumes as the virus moves from this intermediate host to people.
In the case of SARS1, researchers have documented the successive changes in its spike protein as the virus evolved step by step into a dangerous pathogen. After it had gotten from bats into civets, there were six further changes in its spike protein before it became a mild pathogen in people. After a further 14 changes, the virus was much better adapted to humans, and with a further four, the epidemic took off.
But when you look for the fingerprints of a similar transition in SARS2, a strange surprise awaits. The virus has changed hardly at all, at least until recently. From its very first appearance, it was well adapted to human cells. Researchers led by Alina Chan of the Broad Institute compared SARS2 with late stage SARS1, which by then was well adapted to human cells, and found that the two viruses were similarly well adapted. ''By the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV,'' they wrote.
Even those who think lab origin unlikely agree that SARS2 genomes are remarkably uniform. Baric writes that ''early strains identified in Wuhan, China, showed limited genetic diversity, which suggests that the virus may have been introduced from a single source.''
A single source would of course be compatible with lab escape, less so with the massive variation and selection which is evolution's hallmark way of doing business.
The uniform structure of SARS2 genomes gives no hint of any passage through an intermediate animal host, and no such host has been identified in nature.
Proponents of natural emergence suggest that SARS2 incubated in a yet-to-be found human population before gaining its special properties. Or that it jumped to a host animal outside China.
All these conjectures are possible, but strained. Proponents of a lab leak have a simpler explanation. SARS2 was adapted to human cells from the start because it was grown in humanized mice or in lab cultures of human cells, just as described in Daszak's grant proposal. Its genome shows little diversity because the hallmark of lab cultures is uniformity.
Proponents of laboratory escape joke that of course the SARS2 virus infected an intermediary host species before spreading to people, and that they have identified it'Š'--'Ša humanized mouse from the Wuhan Institute of Virology.
3) The furin cleavage site. The furin cleavage site is a minute part of the virus's anatomy but one that exerts great influence on its infectivity. It sits in the middle of the SARS2 spike protein. It also lies at the heart of the puzzle of where the virus came from.
The spike protein has two sub-units with different roles. The first, called S1, recognizes the virus's target, a protein called angiotensin converting enzyme-2 (or ACE2) which studs the surface of cells lining the human airways. The second, S2, helps the virus, once anchored to the cell, to fuse with the cell's membrane. After the virus's outer membrane has coalesced with that of the stricken cell, the viral genome is injected into the cell, hijacks its protein-making machinery and forces it to generate new viruses.
But this invasion cannot begin until the S1 and S2 subunits have been cut apart. And there, right at the S1/S2 junction, is the furin cleavage site that ensures the spike protein will be cleaved in exactly the right place.
The virus, a model of economic design, does not carry its own cleaver. It relies on the cell to do the cleaving for it. Human cells have a protein cutting tool on their surface known as furin. Furin will cut any protein chain that carries its signature target cutting site. This is the sequence of amino acid units proline-arginine-arginine-alanine, or PRRA in the code that refers to each amino acid by a letter of the alphabet. PRRA is the amino acid sequence at the core of SARS2's furin cleavage site.
Viruses have all kinds of clever tricks, so why does the furin cleavage site stand out? Because of all known SARS-related beta-coronaviruses, only SARS2 possesses a furin cleavage site. All the other viruses have their S2 unit cleaved at a different site and by a different mechanism.
How then did SARS2 acquire its furin cleavage site? Either the site evolved naturally, or it was inserted by researchers at the S1/S2 junction in a gain-of-function experiment.
Consider natural origin first. Two ways viruses evolve are by mutation and by recombination. Mutation is the process of random change in DNA (or RNA for coronaviruses) that usually results in one amino acid in a protein chain being switched for another. Many of these changes harm the virus but natural selection retains the few that do something useful. Mutation is the process by which the SARS1 spike protein gradually switched its preferred target cells from those of bats to civets, and then to humans.
Mutation seems a less likely way for SARS2's furin cleavage site to be generated, even though it can't completely be ruled out. The site's four amino acid units are all together, and all at just the right place in the S1/S2 junction. Mutation is a random process triggered by copying errors (when new viral genomes are being generated) or by chemical decay of genomic units. So it typically affects single amino acids at different spots in a protein chain. A string of amino acids like that of the furin cleavage site is much more likely to be acquired all together through a quite different process known as recombination.
Recombination is an inadvertent swapping of genomic material that occurs when two viruses happen to invade the same cell, and their progeny are assembled with bits and pieces of RNA belonging to the other. Beta-coronaviruses will only combine with other beta-coronaviruses but can acquire, by recombination, almost any genetic element present in the collective genomic pool. What they cannot acquire is an element the pool does not possess. And no known SARS-related beta-coronavirus, the class to which SARS2 belongs, possesses a furin cleavage site.
Proponents of natural emergence say SARS2 could have picked up the site from some as yet unknown beta-coronavirus. But bat SARS-related beta-coronaviruses evidently don't need a furin cleavage site to infect bat cells, so there's no great likelihood that any in fact possesses one, and indeed none has been found so far.
The proponents' next argument is that SARS2 acquired its furin cleavage site from people. A predecessor of SARS2 could have been circulating in the human population for months or years until at some point it acquired a furin cleavage site from human cells. It would then have been ready to break out as a pandemic.
If this is what happened, there should be traces in hospital surveillance records of the people infected by the slowly evolving virus. But none has so far come to light. According to the WHO report on the origins of the virus, the sentinel hospitals in Hubei province, home of Wuhan, routinely monitor influenza-like illnesses and ''no evidence to suggest substantial SARSCoV-2 transmission in the months preceding the outbreak in December was observed.''
So it's hard to explain how the SARS2 virus picked up its furin cleavage site naturally, whether by mutation or recombination.
That leaves a gain-of-function experiment. For those who think SARS2 may have escaped from a lab, explaining the furin cleavage site is no problem at all. ''Since 1992 the virology community has known that the one sure way to make a virus deadlier is to give it a furin cleavage site at the S1/S2 junction in the laboratory,'' writes Steven Quay, a biotech entrepreneur interested in the origins of SARS2. ''At least 11 gain-of-function experiments, adding a furin site to make a virus more infective, are published in the open literature, including [by] Dr. Zhengli Shi, head of coronavirus research at the Wuhan Institute of Virology.''
4) A question of codons. There's another aspect of the furin cleavage site that narrows the path for a natural emergence origin even further.
As everyone knows (or may at least recall from high school), the genetic code uses three units of DNA to specify each amino acid unit of a protein chain. When read in groups of 3, the 4 different kinds of DNA unit can specify 4 x 4 x 4 or 64 different triplets, or codons as they are called. Since there are only 20 kinds of amino acid, there are more than enough codons to go around, allowing some amino acids to be specified by more than one codon. The amino acid arginine, for instance, can be designated by any of the six codons CGU, CGC, CGA, CGG, AGA or AGG, where A, U, G and C stand for the four different kinds of unit in RNA.
Here's where it gets interesting. Different organisms have different codon preferences. Human cells like to designate arginine with the codons CGT, CGC or CGG. But CGG is coronavirus's least popular codon for arginine. Keep that in mind when looking at how the amino acids in the furin cleavage site are encoded in the SARS2 genome.
Now the functional reason why SARS2 has a furin cleavage site, and its cousin viruses don't, can be seen by lining up (in a computer) the string of nearly 30,000 nucleotides in its genome with those of its cousin coronaviruses, of which the closest so far known is one called RaTG13. Compared with RaTG13, SARS2 has a 12-nucleotide insert right at the S1/S2 junction. The insert is the sequence T-CCT-CGG-CGG-GC. The CCT codes for proline, the two CGG's for two arginines, and the GC is the beginning of a GCA codon that codes for alanine.
There are several curious features about this insert but the oddest is that of the two side-by-side CGG codons. Only 5 percent of SARS2's arginine codons are CGG, and the double codon CGG-CGG has not been found in any other beta-coronavirus. So how did SARS2 acquire a pair of arginine codons that are favored by human cells but not by coronaviruses?
Proponents of natural emergence have an up-hill task to explain all the features of SARS2's furin cleavage site. They have to postulate a recombination event at a site on the virus's genome where recombinations are rare, and the insertion of a 12-nucleotide sequence with a double arginine codon unknown in the beta-coronavirus repertoire, at the only site in the genome that would significantly expand the virus's infectivity.
''Yes, but your wording makes this sound unlikely'Š'--'Šviruses are specialists at unusual events,'' is the riposte of David L. Robertson, a virologist at the University of Glasgow who regards lab escape as a conspiracy theory. ''Recombination is naturally very, very frequent in these viruses, there are recombination breakpoints in the spike protein and these codons appear unusual exactly because we've not sampled enough.''
Robertson is correct that evolution is always producing results that may seem unlikely but in fact are not. Viruses can generate untold numbers of variants but we see only the one-in-a-billion that natural selection picks for survival. But this argument could be pushed too far. For instance, any result of a gain-of-function experiment could be explained as one that evolution would have arrived at in time. And the numbers game can be played the other way. For the furin cleavage site to arise naturally in SARS2, a chain of events has to happen, each of which is quite unlikely for the reasons given above. A long chain with several improbable steps is unlikely to ever be completed.
For the lab escape scenario, the double CGG codon is no surprise. The human-preferred codon is routinely used in labs. So anyone who wanted to insert a furin cleavage site into the virus's genome would synthesize the PRRA-making sequence in the lab and would be likely to use CGG codons to do so.
''When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus,'' said David Baltimore, an eminent virologist and former president of CalTech. ''These features make a powerful challenge to the idea of a natural origin for SARS2,'' he said. [1]
A third scenario of origin. There's a variation on the natural emergence scenario that's worth considering. This is the idea that SARS2 jumped directly from bats to humans, without going through an intermediate host as SARS1 and MERS did. A leading advocate is the virologist David Robertson who notes that SARS2 can attack several other species besides humans. He believes the virus evolved a generalist capability while still in bats . Because the bats it infects are widely distributed in southern and central China, the virus had ample opportunity to jump to people, even though it seems to have done so on only one known occasion. Robertson's thesis explains why no one has so far found a trace of SARS2 in any intermediate host or in human populations surveilled before December 2019. It would also explain the puzzling fact that SARS2 has not changed since it first appeared in humans'Š'--'Šit didn't need to because it could already attack human cells efficiently.One problem with this idea, though, is that if SARS2 jumped from bats to people in a single leap and hasn't changed much since, it should still be good at infecting bats. And it seems it isn't.
''Tested bat species are poorly infected by SARS-CoV-2 and they are therefore unlikely to be the direct source for human infection,'' write a scientific group skeptical of natural emergence.
Still, Robertson may be onto something. The bat coronaviruses of the Yunnan caves can infect people directly. In April 2012 six miners clearing bat guano from the Mojiang mine contracted severe pneumonia with COVID-19-like symptoms and three eventually died. A virus isolated from the Mojiang mine, called RaTG13, is still the closest known relative of SARS2. Much mystery surrounds the origin, reporting and strangely low affinity of RaTG13 for bat cells, as well as the nature of 8 similar viruses that Shi reports she collected at the same time but has not yet published despite their great relevance to the ancestry of SARS2. But all that is a story for another time. The point here is that bat viruses can infect people directly, though only in special conditions.
So who else, besides miners excavating bat guano, comes into particularly close contact with bat coronaviruses? Well, coronavirus researchers do. Shi says she and her group collected more than 1,300 bat samples during some eight visits to the Mojiang cave between 2012 and 2015, and there were doubtless many expeditions to other Yunnan caves.
Imagine the researchers making frequent trips from Wuhan to Yunnan and back, stirring up bat guano in dark caves and mines, and now you begin to see a possible missing link between the two places. Researchers could have gotten infected during their collecting trips, or while working with the new viruses at the Wuhan Institute of Virology. The virus that escaped from the lab would have been a natural virus, not one cooked up by gain of function.
The direct-from-bats thesis is a chimera between the natural emergence and lab escape scenarios. It's a possibility that can't be dismissed. But against it are the facts that 1) both SARS2 and RaTG13 seem to have only feeble affinity for bat cells, so one can't be fully confident that either ever saw the inside of a bat; and 2) the theory is no better than the natural emergence scenario at explaining how SARS2 gained its furin cleavage site, or why the furin cleavage site is determined by human-preferred arginine codons instead of by the bat-preferred codons.
Where we are so far. Neither the natural emergence nor the lab escape hypothesis can yet be ruled out. There is still no direct evidence for either. So no definitive conclusion can be reached.
That said, the available evidence leans more strongly in one direction than the other. Readers will form their own opinion. But it seems to me that proponents of lab escape can explain all the available facts about SARS2 considerably more easily than can those who favor natural emergence.
It's documented that researchers at the Wuhan Institute of Virology were doing gain-of-function experiments designed to make coronaviruses infect human cells and humanized mice. This is exactly the kind of experiment from which a SARS2-like virus could have emerged. The researchers were not vaccinated against the viruses under study, and they were working in the minimal safety conditions of a BSL2 laboratory. So escape of a virus would not be at all surprising. In all of China, the pandemic broke out on the doorstep of the Wuhan institute. The virus was already well adapted to humans, as expected for a virus grown in humanized mice. It possessed an unusual enhancement, a furin cleavage site, which is not possessed by any other known SARS-related beta-coronavirus, and this site included a double arginine codon also unknown among beta-coronaviruses. What more evidence could you want, aside from the presently unobtainable lab records documenting SARS2's creation?
Proponents of natural emergence have a rather harder story to tell. The plausibility of their case rests on a single surmise, the expected parallel between the emergence of SARS2 and that of SARS1 and MERS. But none of the evidence expected in support of such a parallel history has yet emerged. No one has found the bat population that was the source of SARS2, if indeed it ever infected bats. No intermediate host has presented itself, despite an intensive search by Chinese authorities that included the testing of 80,000 animals. There is no evidence of the virus making multiple independent jumps from its intermediate host to people, as both the SARS1 and MERS viruses did. There is no evidence from hospital surveillance records of the epidemic gathering strength in the population as the virus evolved. There is no explanation of why a natural epidemic should break out in Wuhan and nowhere else. There is no good explanation of how the virus acquired its furin cleavage site, which no other SARS-related beta-coronavirus possesses, nor why the site is composed of human-preferred codons. The natural emergence theory battles a bristling array of implausibilities.
The records of the Wuhan Institute of Virology certainly hold much relevant information. But Chinese authorities seem unlikely to release them given the substantial chance that they incriminate the regime in the creation of the pandemic. Absent the efforts of some courageous Chinese whistle-blower, we may already have at hand just about all of the relevant information we are likely to get for a while.
So it's worth trying to assess responsibility for the pandemic, at least in a provisional way, because the paramount goal remains to prevent another one. Even those who aren't persuaded that lab escape is the more likely origin of the SARS2 virus may see reason for concern about the present state of regulation governing gain-of-function research. There are two obvious levels of responsibility: the first, for allowing virologists to perform gain-of-function experiments, offering minimal gain and vast risk; the second, if indeed SARS2 was generated in a lab, for allowing the virus to escape and unleash a world-wide pandemic. Here are the players who seem most likely to deserve blame.
Chinese virologists. First and foremost, Chinese virologists are to blame for performing gain-of-function experiments in mostly BSL2-level safety conditions which were far too lax to contain a virus of unexpected infectiousness like SARS2. If the virus did indeed escape from their lab, they deserve the world's censure for a foreseeable accident that has already caused the deaths of three million people. True, Shi was trained by French virologists, worked closely with American virologists and was following international rules for the containment of coronaviruses. But she could and should have made her own assessment of the risks she was running. She and her colleagues bear the responsibility for their actions.I have been using the Wuhan Institute of Virology as a shorthand for all virological activities in Wuhan. It's possible that SARS2 was generated in some other Wuhan lab, perhaps in an attempt to make a vaccine that worked against all coronaviruses. But until the role of other Chinese virologists is clarified, Shi is the public face of Chinese work on coronaviruses, and provisionally she and her colleagues will stand first in line for opprobrium.
2. Chinese authorities. China's central authorities did not generate SARS2, but they sure did their utmost to conceal the nature of the tragedy and China's responsibility for it. They suppressed all records at the Wuhan Institute of Virology and closed down its virus databases. They released a trickle of information, much of which may have been outright false or designed to misdirect and mislead. They did their best to manipulate the WHO's inquiry into the virus's origins, and led the commission's members on a fruitless run-around. So far they have proved far more interested in deflecting blame than in taking the steps necessary to prevent a second pandemic.
3. The worldwide community of virologists. Virologists around the world are a loose-knit professional community. They write articles in the same journals. They attend the same conferences. They have common interests in seeking funds from governments and in not being overburdened with safety regulations.
Virologists knew better than anyone the dangers of gain-of-function research. But the power to create new viruses, and the research funding obtainable by doing so, was too tempting. They pushed ahead with gain-of-function experiments. They lobbied against the moratorium imposed on Federal funding for gain-of-function research in 2014, and it was raised in 2017.
The benefits of the research in preventing future epidemics have so far been nil, the risks vast. If research on the SARS1 and MERS viruses could only be done at the BSL3 safety level, it was surely illogical to allow any work with novel coronaviruses at the lesser level of BSL2. Whether or not SARS2 escaped from a lab, virologists around the world have been playing with fire.
Their behavior has long alarmed other biologists. In 2014 scientists calling themselves the Cambridge Working Group urged caution on creating new viruses. In prescient words, they specified the risk of creating a SARS2-like virus. ''Accident risks with newly created 'potential pandemic pathogens' raise grave new concerns,'' they wrote. ''Laboratory creation of highly transmissible, novel strains of dangerous viruses, especially but not limited to influenza, poses substantially increased risks. An accidental infection in such a setting could trigger outbreaks that would be difficult or impossible to control.''
When molecular biologists discovered a technique for moving genes from one organism to another, they held a public conference at Asilomar in 1975 to discuss the possible risks. Despite much internal opposition, they drew up a list of stringent safety measures that could be relaxed in future'Š'--'Šand duly were'Š'--'Šwhen the possible hazards had been better assessed.
When the CRISPR technique for editing genes was invented, biologists convened a joint report by the US, UK and Chinese national academies of science to urge restraint on making heritable changes to the human genome. Biologists who invented gene drives have also been open about the dangers of their work and have sought to involve the public.
You might think the SARS2 pandemic would spur virologists to re-evaluate the benefits of gain-of-function research, even to engage the public in their deliberations. But no. Many virologists deride lab escape as a conspiracy theory, and others say nothing. They have barricaded themselves behind a Chinese wall of silence which so far is working well to allay, or at least postpone, journalists' curiosity and the public's wrath. Professions that cannot regulate themselves deserve to get regulated by others, and this would seem to be the future that virologists are choosing for themselves.
4. The US role in funding the Wuhan Institute of Virology.[2] From June 2014 to May 2019, Daszak's EcoHealth Alliance had a grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to do gain-of-function research with coronaviruses at the Wuhan Institute of Virology. Whether or not SARS2 is the product of that research, it seems a questionable policy to farm out high-risk research to foreign labs using minimal safety precautions. And if the SARS2 virus did indeed escape from the Wuhan institute, then the NIH will find itself in the terrible position of having funded a disastrous experiment that led to the death of more than 3 million worldwide, including more than half a million of its own citizens.
The responsibility of the NIAID and NIH is even more acute because for the first three years of the grant to EcoHealth Alliance there was a moratorium on funding gain-of-function research. When the moratorium expired in 2017, it didn't just vanish but was replaced by a reporting system, the Potential Pandemic Pathogens Control and Oversight (P3CO) Framework, which required agencies to report for review any dangerous gain-of-function work they wished to fund.
The moratorium, referred to officially as a ''pause,'' specifically barred funding any gain-of-function research that increased the pathogenicity of the flu, MERS or SARS viruses. It defined gain-of-function very simply and broadly as ''research that improves the ability of a pathogen to cause disease.''
But then a footnote on p.2 of the moratorium document states that ''[a]n exception from the research pause may be obtained if the head of the USG funding agency determines that the research is urgently necessary to protect the public health or national security.''
This seemed to mean that either the director of the NIAID, Anthony Fauci, or the director of the NIH, Francis Collins, or maybe both, would have invoked the exemption in order to keep the money flowing to Shi's gain-of-function research, and later to avoid notifying the federal reporting system of her research.
''Unfortunately, the NIAID Director and the NIH Director exploited this loophole to issue exemptions to projects subject to the Pause ''preposterously asserting the exempted research was 'urgently necessary to protect public health or national security''--thereby nullifying the Pause,'' Dr. Richard Ebright said in an interview with Independent Science News.
But it's not so clear that the NIH thought it necessary to invoke any loopholes. Fauci told a Senate hearing on May 11 that ''the NIH and NIAID categorically has not funded gain-of-function research to be conducted in the Wuhan Institute of Virology.''
This was a surprising statement in view of all the evidence about Shi's experiments with enhancing coronaviruses and the language of the moratorium statute defining gain-of-function as ''any research that improves the ability of a pathogen to cause disease.''
The explanation may be one of definition. Daszak's EcoHealth Alliance, for one, believes that the term gain-of-function applies only to enhancements of viruses that infect humans, not to animal viruses. ''So gain-of-function research refers specifically to the manipulation of human viruses so as to be either more easily transmissible or to cause worse infection or be easier to spread,'' an Alliance official told The Dispatch Fact Check.
If the NIH shares the EcoHealth Alliance view that ''gain of function'' applies only to human viruses, that would explain why Fauci could assure the Senate it had never funded such research at the Wuhan Institute of Virology. But the legal basis of such a definition is unclear, and it differs from that of the moratorium language which was presumably applicable.
Definitions aside, the bottom line is that the National Institutes of Health was supporting research of a kind that could have generated the SARS2 virus, in an unsupervised foreign lab that was doing work in BSL2 biosafety conditions.In conclusion. If the case that SARS2 originated in a lab is so substantial, why isn't this more widely known? As may now be obvious, there are many people who have reason not to talk about it. The list is led, of course, by the Chinese authorities. But virologists in the United States and Europe have no great interest in igniting a public debate about the gain-of-function experiments that their community has been pursuing for years.
Nor have other scientists stepped forward to raise the issue. Government research funds are distributed on the advice of committees of scientific experts drawn from universities. Anyone who rocks the boat by raising awkward political issues runs the risk that their grant will not be renewed and their research career will be ended. Maybe good behavior is rewarded with the many perks that slosh around the distribution system. And if you thought that Andersen and Daszak might have blotted their reputation for scientific objectivity after their partisan attacks on the lab escape scenario, look at the second and third names on this list of recipients of an $82 million grant announced by the National Institute of Allergy and Infectious Diseases in August 2020.
The US government shares a strange common interest with the Chinese authorities: Neither is keen on drawing attention to the fact that Shi's coronavirus work was funded by the US National Institutes of Health. One can imagine the behind-the-scenes conversation in which the Chinese government says, ''If this research was so dangerous, why did you fund it, and on our territory too?'' To which the US side might reply, ''Looks like it was you who let it escape. But do we really need to have this discussion in public?''
Fauci is a longtime public servant who served with integrity under President Trump and has resumed leadership in the Biden Administration in handling the COVID-19 epidemic. Congress, no doubt understandably, may have little appetite for hauling him over the coals for the apparent lapse of judgment in funding gain-of-function research in Wuhan.
To these serried walls of silence must be added that of the mainstream media. To my knowledge, no major newspaper or television network has yet provided readers with an in-depth news story of the lab escape scenario, such as the one you have just read, although some have run brief editorials or opinion pieces. One might think that any plausible origin of a virus that has killed three million people would merit a serious investigation. Or that the wisdom of continuing gain-of-function research, regardless of the virus's origin, would be worth some probing. Or that the funding of gain-of-function research by the NIH and NIAID during a moratorium on such funding would bear investigation. What accounts for the media's apparent lack of curiosity?
The virologists' omert is one reason. Science reporters, unlike political reporters, have little innate skepticism of their sources' motives; most see their role largely as purveying the wisdom of scientists to the unwashed masses. So when their sources won't help, these journalists are at a loss.
Another reason, perhaps, is the migration of much of the media toward the left of the political spectrum. Because President Trump said the virus had escaped from a Wuhan lab, editors gave the idea little credence. They joined the virologists in regarding lab escape as a dismissible conspiracy theory. During the Trump administration, they had no trouble in rejecting the position of the intelligence services that lab escape could not be ruled out. But when Avril Haines, President Biden's director of national intelligence, said the same thing, she too was largely ignored. This is not to argue that editors should have endorsed the lab escape scenario, merely that they should have explored the possibility fully and fairly.
People round the world who have been pretty much confined to their homes for the last year might like a better answer than their media are giving them. Perhaps one will emerge in time. After all, the more months pass without the natural emergence theory gaining a shred of supporting evidence, the less plausible it may seem. Perhaps the international community of virologists will come to be seen as a false and self-interested guide. The common sense perception that a pandemic breaking out in Wuhan might have something to do with a Wuhan lab cooking up novel viruses of maximal danger in unsafe conditions could eventually displace the ideological insistence that whatever Trump said can't be true.
And then let the reckoning begin.
Notes
[1] This quotation was added to the article after initial publication.
[2] Section revised May 18, 2021
Acknowledgements
The first person to take a serious look at the origins of the SARS2 virus was Yuri Deigin, a biotech entrepreneur in Russia and Canada. In a long and brilliant essay, he dissected the molecular biology of the SARS2 virus and raised, without endorsing, the possibility that it had been manipulated. The essay, published on April 22, 2020, provided a roadmap for anyone seeking to understand the virus's origins. Deigin packed so much information and analysis into his essay that some have doubted it could be the work of a single individual and suggested some intelligence agency must have authored it. But the essay is written with greater lightness and humor than I suspect are ever found in CIA or KGB reports, and I see no reason to doubt that Deigin is its very capable sole author.
In Deigin's wake have followed several other skeptics of the virologists' orthodoxy. Nikolai Petrovsky calculated how tightly the SARS2 virus binds to the ACE2 receptors of various species and found to his surprise that it seemed optimized for the human receptor, leading him to infer the virus might have been generated in a laboratory. Alina Chan published a paper showing that SARS2 from its first appearance was very well adapted to human cells.
One of the very few establishment scientists to have questioned the virologists' absolute rejection of lab escape is Richard Ebright, who has long warned against the dangers of gain-of-function research. Another is David A. Relman of Stanford University. ''Even though strong opinions abound, none of these scenarios can be confidently ruled in or ruled out with currently available facts,'' he wrote. Kudos too to Robert Redfield, former director of the Centers for Disease Control and Prevention, who told CNN on March 26, 2021 that the ''most likely'' cause of the epidemic was ''from a laboratory,'' because he doubted that a bat virus could become an extreme human pathogen overnight, without taking time to evolve, as seemed to be the case with SARS2.
Steven Quay, a physician-researcher, has applied statistical and bioinformatic tools to ingenious explorations of the virus's origin, showing for instance how the hospitals receiving the early patients are clustered along the Wuhan '–2 subway line which connects the Institute of Virology at one end with the international airport at the other, the perfect conveyor belt for distributing the virus from lab to globe.
In June 2020 Milton Leitenberg published an early survey of the evidence favoring lab escape from gain-of-function research at the Wuhan Institute of Virology.
Many others have contributed significant pieces of the puzzle. ''Truth is the daughter,'' said Francis Bacon, ''not of authority but time.'' The efforts of people such as those named above are what makes it so.
Everyone vaccinated for covid will DIE, warns French virologist
Wed, 02 Jun 2021 18:21
There is
no chance of long-term survival for anyone who received a Wuhan coronavirus (Covid-19) injection, according to leading French virologist Luc Montagnier.
Everyone who is getting jabbed for the Chinese Virus will die,
he reportedly stated during a recent interview, which you can watch below
at Brighteon.com."There is no hope and no possible treatment for those who have already been vaccinated," Montagnier stated plainly during the segment. "We must be prepared to cremate the bodies."
After studying at length the ingredients contained in the injections and what they do, Montagnier came to the conclusion that every single person who gets the shot will eventually die from antibody-dependent enhancement, or ADE."That is all that can be said," he added.Montagnier
is credited with being the first to discover HIV, by the way, having warned last spring that the Wuhan Flu contains artificially spliced DNA from the autoimmune-provoking virus. It now appears as though these same alterations can be found in Chinese Virus "vaccines," which are priming people's bodies for eventual sudden death.Montagnier also stated last year that the "presence of elements of HIV and germs of malaria in the genome of coronavirus is highly suspect and the characteristics of the virus could not have arisen naturally." It turns out he was right.
Wuhan Flu shots were designed to "slow kill" the masses through time-delayed deathIt is one thing for the genetically modified (GMO) virus to be intentionally released, but a whole different thing for the medical establishment to then introduce an injection for it right in the middle of an alleged "pandemic."In Montagnier's view, this approach is an "unacceptable mistake," at best, because all it will do is spread even more "variants" of the Chinese Virus and kill more people '' which appears to have been the plan all along.We have Donald Trump and his "Operation Warp Speed" scheme to thank for this nightmare, by the way. While some of his diehard supporters still insist that Trump should not be blamed because he was simply "misled" by his cabinet concerning the nature of the injections, Trump himself is
aggressively pushing them even to this day, despite the tens of thousands of known cases of injury and death.Evidence continues to mount that Chinese Virus injections were designed to be a "slow" kill for many, meaning their detrimental impact takes a bit of time to manifest. For some, however, injury and death will come immediately, as we have seen in the headlines as of late.All of this would explain the mad rush to vaccinate people at "warp speed," using any ploy or coercion tactic necessary to reach the desired target. Once enough vaccinated people start dropping dead, the remaining unvaccinated will more than likely resist, which is why the Biden regime is moving quickly to get as many people injected as possibly, preferably before July 4."The powers that be have your DNA from the swab tests in a database link with an artificial intelligence that will determine the best time for one to die, and it will be by a 'natural' cause like stroke or heart attack," one commenter at
Disclose.tv wrote about people who are not necessarily vaccinated but who have undergone a covid "test.""A certain frequency will resonate with the target only by the mobility tower closest to your home. Skynet is not sending droids, but frequencies."More of the latest news about the death and destruction being brought to bear by Wuhan coronavirus (Covid-19) injections can be found at
ChemicalViolence.com.
Sources for this article include:coe-llc.comDisclose.tvBrighteon.comNaturalNews.comNaturalNews.comNaturalNews.com
China reports first human case of H10N3 bird flu | Reuters
Wed, 02 Jun 2021 18:16
Workers vaccinate chicks with the H9 bird flu vaccine at a farm in Changfeng county, Anhui province, April 14, 2013. REUTERS/Stringer/File Photo
A 41-year-old man in China's eastern province of Jiangsu has been confirmed as the first human case of infection with a rare strain of bird flu known as H10N3, Beijing's National Health Commission (NHC) said on Tuesday.
Many different strains of bird flu are present in China and some sporadically infect people, usually those working with poultry. There is no indication that H10N3 can spread easily in humans.
The man, a resident of the city of Zhenjiang, was hospitalized on April 28 and diagnosed with H10N3 on May 28, the health commission said. It did not give details on how the man was infected.
His condition is now stable and he is ready to be discharged. Investigation of his close contacts found no other cases, the NHC said. No other cases of human infection with H10N3 have been reported globally, it added.
H10N3 is low pathogenic, which means it causes relatively less severe disease in poultry and is unlikely to cause a large-scale outbreak, the NHC added.
The World Health Organization (WHO), in a reply to Reuters in Geneva, said: "The source of the patient's exposure to the H10N3 virus is not known at this time, and no other cases were found in emergency surveillance among the local population. At this time, there is no indication of human-to-human transmission.
"As long as avian influenza viruses circulate in poultry, sporadic infection of avian influenza in humans is not surprising, which is a vivid reminder that the threat of an influenza pandemic is persistent," the WHO added.
The strain is "not a very common virus", said Filip Claes, regional laboratory coordinator of the Food and Agriculture Organization's Emergency Centre for Transboundary Animal Diseases at the regional office for Asia and the Pacific.
Only around 160 isolates of the virus were reported in the 40 years to 2018, mostly in wild birds or waterfowl in Asia and some limited parts of North America, and none had been detected in chickens so far, he added.
Analysing the genetic data of the virus will be necessary to determine whether it resembles older viruses or if it is a novel mix of different viruses, Claes said.
There have been no significant numbers of human infections with bird flu since the H7N9 strain killed around 300 people during 2016-2017.
(Refiles to make para 7 quote read 'humans' instead of 'human')
Our Standards: The Thomson Reuters Trust Principles.
Why Dr. Michael Osterholm Delayed His Second Vaccine Shot
Wed, 02 Jun 2021 18:03
Dr. Michael Osterholm. Photo: Stuart Isett for Fortune Brainstorm Health
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Michael Osterholm has spent the past year as afraid of getting Covid as anyone else. ''You know how many times I've woken up in the morning and said, I wonder if today's the day I could get infected?'' One of the world's leading epidemiologists, he is reassured by the fact that he doesn't go anywhere'--''I'm the guy who has the same tank of gas in his car that he had three months ago'''--but he, too, is desperate to be done with the pandemic.
''I miss my grandkids,'' he told Intelligencer from his Minneapolis-area home, his assured voice turning wistful. ''My God, I miss my grandkids.''
Osterholm, 67, is the director of the Center for Infectious Disease Research and Policy at the University of Minnesota and has spent the past four decades studying epidemics, but he became nationally famous a year ago for his stark predictions during the first shocking wave of the pandemic in the U.S.
''In April, I said, 'These are just the foothills. We haven't even gotten to the mountains yet'--and there are big ones coming,''' he recalls. ''People, of course, dismissed that as just hyperbole and just scary. Well, you saw what happened.''
His hair-raising, accurate prediction made him something of a Dr. Doom whose expertise was sought after by everyone from CNN to Joe Rogan. Last fall he earned a spot as an adviser for the Biden transition team, where he controversially floated the potential need for a nationwide lockdown.
Now, Osterholm has a new prediction: More virulent variants, particularly B.1.1.7 first identified in the UK, will likely kick off a surge in cases and deaths in the U.S. in a matter of weeks'--just as most states lift restrictions. He's staking his credibility on being right, and potentially his health, by delaying his own second vaccine shot, which he says should be done across the country in order to make more first shots available to as many people as possible, offering some protection before the wave crests yet again.
This question of delaying second doses has sharply divided the health and science community. But on Monday, the CDC's vaccination advisory board, ACIP, agreed that the data on changing doses is too limited to make new recommendations'--and one dose might not be enough to protect against variants, the advisers pointed out.
Cases, hospitalizations, and deaths dropped dramatically after the U.S. reached its highest peak in January, while vaccinations are climbing steadily past 2 million per day. People are beginning to talk about having a normal summer. But before then, Osterholm believes, another surge will pummel the country.
''This big spike that went up and came down, it gives us this false sense of security that somehow, we're in control. And we're not,'' he said. First of all, viruses are complicated and often tend to come in waves, he said'--and we're at a terrible starting point for another spike.
''Last summer, in July, 70,000 cases a day was a house-on-fire event in this country. Today, we kind of feel like we've won, and we're at 70,000 cases a day,'' he said. ''We are right now more open to virus transmission than any time since March. Everybody is enjoying this new Covid-19 holiday. Governors have opened up virtually everything.'' Yet in the past two weeks, new daily cases have stopped falling.
One major difference since last March are variants of concern. B.1.1.7, for instance, is about 40 to 70 percent more infectious and causes much more severe illness. It likely arrived in the U.S. in November, and now it's in every state'--and it is more than doubling every week. But there's another big difference this March: extremely safe, effective vaccines that work against these variants. ''The challenge we have right now is we have variants versus the vaccine,'' Osterholm said'--and the battle is also a race against time.
More than 54 million Americans are above the age of 65'--the age group where 80 percent of the deaths occur, and the group most likely to develop severe illness that results in hospitalization, straining health care systems. About 41 percent of those 65 and up have been vaccinated so far, but they need to be prioritized even more, Osterholm said: ''What we're trying to do is protect as many lives as possible.''
Osterholm has a gift for making these statistics deeply personal. ''Imagine I'm sitting on one side of the table, and I have two doses of vaccine, one in each hand,'' he said. ''On the other side of the table is my mom and my dad, or my grandpa and my grandma. And they both are over 65, they both have an underlying health condition. And I'm gonna look them in the eye and say, okay, I can give both doses to one of you, or I can give one dose to each of you. What would you like me to do? Wouldn't you want, particularly with evidence of the protection we have, to protect both of them, and not leave one totally vulnerable?''
There are a couple of different scenarios Osterholm and his colleagues have outlined to maximize vaccinations. For starters, he asked, ''why are we giving two doses to people who have already had Covid? We already have compelling data that you get a very good response after the first dose.'' Second, he says, the Moderna vaccine trial looked at the effectiveness of two full doses and two half-doses'--and the results were the same for both. Why not switch to two half-doses, and get twice as many people vaccinated?
Finally, Osterholm wants to delay second doses of the two-shot Pfizer/BioNTech and Moderna vaccines for everyone else'--but only until after the surge, which he expects to happen over the next two or three months. By then, the U.S. is expected to have enough doses to vaccinate all adults fully.
A single dose of the mRNA vaccines seems to offer at least the same response as the single-dose vaccine from Johnson & Johnson, Osterholm pointed out. ''Why would you say it's okay to approve one and say the other two are problems if you don't get both doses?'' And data from the single Johnson & Johnson shot showed increased protection the more time went on. It's possible with just one dose of Moderna or Pfizer, ''you would likely see the very same increases over time,'' he said.
The catch, though, is that the Moderna and Pfizer trials didn't study what happened when you only get one dose. Although the first dose seemed to offer some protection on its own, that protection was extended and strengthened by the second follow-up dose'--a point critics of Osterholm's school of thought are quick to make. But that is why advocates such as Osterholm argue for delaying, not abolishing, the second dose.
The experts who favor sticking to the vaccination plan that has been proven to work'--two doses, spaced three or four weeks apart'--say we need to follow the science. But, Osterholm said, that's exactly what he's trying to do. ''All of that data was collected before anything had to do with the variants. The variants are a brand-new set of data.''
And new research on the effectiveness of the first dose is emerging. ''There is sufficient data to support that, at least for the short term, you clearly have enough protection against serious illness, hospitalizations, and death,'' he said. ''So, it's a bit disingenuous for people to say we have all the science based on the submission of the vaccines for approval. There's much, much more that's come out.''
Ongoing scientific trials could even show that waiting a few more weeks might allow your immune system to respond better, which is the case with certain other vaccines, Osterholm said. ''These studies were never set up to measure, ultimately, your immune response or dosing. They were set up so that you could get a product approved quickly with authorization.''
But even before new research was made public, Osterholm decided to delay his own second shot. ''You have to walk the talk and talk the walk. I would be a hypocrite if I didn't believe that vaccine wouldn't provide me adequate protection through this surge,'' he said. He believes what he says about being protected from severe illness or death by a single dose.
''I just know that there are thousands of grandpas and grandmas, moms and dads, brothers and sisters that could be protected with a single dose,'' he said. ''If we keep up doing what we're doing, they're not going to have that chance before this surge comes.''
And that surge is a major factor in why he advocates for this plan. When he first began talking about delaying doses at the beginning of the year, he said, ''a lot of people just missed the surge piece completely. 'There he goes again,' you know. People will say I scare people, but whatever. It's never to scare people out of their wits, it's to scare them into their wits.''
He likens his prediction about another surge to meteorologists watching a hurricane swirl across the Doppler. If it looks like a category-five storm is headed toward the coast, they need to warn people of the potential danger'--even if it downgrades or takes a turn back out to the ocean. ''You had a responsibility to let the public know,'' he said. ''I'd much rather be sorry for something I did than something I didn't do.''
In emergency situations, he said, you can't wait until you have complete information, or it will be too late.
''I'm sitting here saying this surge is coming,'' he said. ''Do I know how big it's going to be? I don't. But I can tell you, in Europe, they've all been in lockdown since Christmas in many countries, and they still have a problem.''
Recently, on his podcast, Osterholm spoke about the professional risks of vocally backing a plan like this. ''This could be the end of my career. But I could not sleep with myself at night if I didn't do this,'' he said.
In our interview, he took a lighter approach. ''I mean, some people thought I ended my career 40 years ago,'' he said, laughing, before sobering again. ''I've been doing this since the beginning of time. I never for a moment forget the responsibility I have to the public, to tell the truth, no matter how hard it is, no matter who else doesn't agree with you, and to always say what I know and don't know.''
''I've tried to wrap my arms around what it means to have 500,000 people die from Covid,'' Osterholm said. In their work, epidemiologists deal with numbers'--with population-wide statistics and calculations. ''But I know some of these numbers,'' he said, his voice quiet. ''They were people loved by people.''
He believes warning about a coming surge'--and rallying to protect more people quickly'--could be his greatest contribution to combating the pandemic. ''To me, that is what's very personal,'' he said. ''My job right now is just to save as many lives as possible in the next six to 12 weeks. Whatever it takes.''
Even so, decisions like these never get easier. ''You always ask yourself, is this the right thing to do?'' he said. ''I'm not afraid of being wrong. I own it, if I am. I'm more afraid of knowing what I know and not speaking out. Because that could make the difference between whether somebody's grandma and grandpa are going to be there to give one of their grandkids a hug and a kiss goodnight,'' he said. ''That's what I worry about. I'm dispensable. Grandpa and grandma are not.''
''I want to be so wrong on this one,'' he said. ''I will publicly celebrate me being wrong if this [surge] doesn't happen, because I just wish we didn't have to go through this.''
One Great Story: A Nightly Newsletter for the Best of New YorkThe one story you shouldn't miss today, selected by New York's editors.
By submitting your email, you agree to our Terms and Privacy Notice and to receive email correspondence from us. Deaths of Despair Have Surged Among People of Color What It Cost to Survive How the West Lost COVID See All The Pandemic's Dr. Doom Bets It All politics
Trump Wasn't Cut Out for a Blogger's Life
By Sarah Jones
After just a month, the ex-president is tired of blogging.
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The GOP Can Win Without Waging War on Democracy
By Eric Levitz
But they want to never lose.
11:51 a.m.2021 special elections
2021 special elections
Democrat Wins Big in New Mexico Special Congressional Election
By Ed Kilgore
Republicans may still flip the House in 2022, but this year's special elections don't indicate that a GOP wave is building.
covid-19
Is the Second Shot Giving Young Men a Dangerous Heart Condition?
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New data from Israel suggests a link between myocarditis and Pfizer's vaccine, but the CDC isn't there yet.
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The Vaccine Hesitant on Why They Finally Got the Shot
By Sarah Jones
It's not about science, it's about trust.
6/1/2021trump organization
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The Trump Organization Wants to Sell Its D.C. Hotel Again
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The ex-president's business reportedly found a new real-estate broker to help ditch its lease in D.C., after the old broker dropped out following 1/6.
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Biden Vows to Renew Voting Rights Push in Speech Commemorating Tulsa Massacre
By Matt Stieb
At the 100th anniversary of the Tulsa massacre, Biden announced that Kamala Harris would lead the effort to secure a new Voting Rights Act.
games
Let's Have a Good-Faith Discussion About Naomi Osaka
By Will Leitch
Her abrupt exit from the French Open over anxiety around press conferences does not lend itself to a simple narrative.
cyberattacks
Beef Shortages Are Probably on the Way, Thanks to Latest Hack
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Close to a fifth of U.S. beef production has been shut down following a ransomware attack on the firm JBS.
student debt
Has Biden Abandoned Student-Loan Forgiveness?
By Eric Levitz
Canceling student debt wasn't included in Biden's budget. While it remains possible, he appears more inclined to expand existing debt-relief programs.
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What We Know About the Dangerous COVID B.1.617.2 Delta Variant
By Chas Danner
The strain, originally discovered in India, has now spread to more than 60 countries, and it may be the most transmissible one yet.
6/1/2021
DeSantis marks the start of Pride Month by signing an anti-transgender bill into law
Florida Gov. Ron DeSantis (R) on Tuesday signed a bill into law that would bar female transgender students from women's sports.
Why it matters: Florida is the eighth state so far this year to block trans student athletes from playing on sports teams that match their gender identity, per ACLU data. A record number of bills targeting trans youth have been introduced by Republican lawmakers.
Between the lines: ''Supporters of the effort to restrict transgender athlete participation have cited no examples of competitive issues in Florida,'' the Miami Herald reports.
covid-19
WHO Renames COVID Variants, Calling National Labels 'Stigmatizing'
By Nia Prater
The Greek alphabet will be used instead of Britain, Brazil, India, and so on.
6/1/2021the national interest
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Texas Republicans Want to Make Trump's Coup Nice and Legal
By Jonathan Chait
Michael Flynn said a Myanmar-style military coup ''should happen''; Republicans prefer to use the legislature.
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Fans' Bad Behavior Isn't New. The Outrage Over It Is.
By Will Leitch
Players have been complaining about how they're treated by fans for years, and now they're finally being heard.
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The GOP Has Discovered Joe Biden's Political Superpower
By Gabriel Debenedetti
There's a reason he isn't showing up much in Republican talking points.
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How Far Along Is New York City in Its Reopening This Spring?
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Bars can now stay open until 4 a.m.
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The Global Vaccination Effort Is Still Undercut by Deep Inequalities
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The disparities that were clear from the outset of the vaccine drive are still profound several months later.
5/31/2021international affairs
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China Will Allow Married Couples to Have 3 Children
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The country is facing a significant demographic crisis, but most experts are skeptical that boosting the child limit again will reverse the trend.
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The Problem With the Lee Greenwood Bible
By Ed Kilgore
On this Memorial Day, we should honor the distinctly American tradition of church-state separation and avoid conflating God and country.
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Texas Democrats Block Voting Restrictions Bill, For Now
By Chas Danner
The GOP-led bill bans drive-thru voting, caps poll hours, and adds new rules for mail-in ballots, among other measures to limit voting access.
5/31/2021foreign interests
foreign interests
The End of the Netanyahu Era?
By Jonah Shepp
A coalition deal is likely to end the career of Israel's longest-serving prime minister, but the damage he has done will have a long tail.
5/31/2021
This may not come as a surprise
Avowed QAnon disciple and confessed felon retired Lt. Gen. Michael Flynn has called for a Myanmar-like military coup in America. ''It should happen,'' Donald Trump's former national security adviser said in an astonishing declaration at a QAnon conference Sunday. '...
Flynn presented his dark vision of a military coup and dictatorship in the U.S. in response to a question from the audience at the conference. '"I wanna know why what happened in Myanmar can't happen here?'' an unidentified member of the audience asked Flynn, though he pronounced the nation as ''Minnimar.''
''No reason,'' Flynn responded to wild screams of approval. ''It should happen.''
5/31/2021the truth is in here
the truth is in here
What Can We Expect From the Pentagon's UFO Report?
By Matt Stieb
A guide to the government's forthcoming unclassified report on UFOs for those who want to believe '-- and the merely curious.
5/30/2021
Looks like Netanyahu is finally finished
JERUSALEM (AP) '-- Hard-line party joins PM Netanyahu's opponents in coalition talks, in key step toward ousting longtime Israeli leader.
'--@JonLemire voting rights
Democrats Need a New Plan to Defend Voting Rights
By Ed Kilgore
The outlook is dim for voting-rights legislation. DOJ enforcement and voter mobilization may be Democrats' best shot for defending democracy.
5/29/2021
CDC updates its summer camp mask guidelines
The federal government relaxed its guidance Friday for summer camps, saying that vaccinated adolescents do not need to wear masks at camp and that even younger campers who have not been inoculated can generally shed face coverings when outdoors. The updated guidelines from the Centers for Disease Control and Prevention remove some glaring inconsistencies between earlier camp recommendations that all staffers and campers wear masks and more recent general announcements that face coverings are rarely needed outdoors and that vaccinated people can often forgo masks entirely. Still, even the updated guidance comes with a complex set of considerations that may prompt camps to change policies just days before they open. '...
At camps where not everyone is vaccinated, the guidance says, vaccinated people do not need masks. But unvaccinated people are ''strongly encouraged'' to wear masks indoors, and they should wear masks outdoors in crowds or when close to others for prolonged periods. But because it may not be possible for camp organizers to know who is vaccinated and who is not, the CDC notes that camps may simply choose to apply the agency's previous guidance: masks for all.
covid-19
What It Feels Like to Be an 'Adverse Event'
By Chris Stanton
Is my heart problem because of the vaccine? Am I crazy for thinking that?
maga
Greene's Logic: Democrats Are Nazis, So Their Agenda Is Like the Holocaust
By Ed Kilgore
In the MAGA world, where all Democrats are socialists, and Adolf Hitler was a socialist, all Democratic initiatives are like the Holocaust.
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0),utils_1.addExceptionMechanism(t,e.mechanism)),t.extra=tslib_1.__assign(tslib_1.__assign({},t.extra),{arguments:n}),t}),core_1.captureException(r)}),r}};try{for(var o in r)Object.prototype.hasOwnProperty.call(r,o)&&(n[o]=r[o])}catch(r){}r.prototype=r.prototype||{},n.prototype=r.prototype,Object.defineProperty(r,"__sentry_wrapped__",{enumerable:!1,value:n}),Object.defineProperties(n,{__sentry__:{enumerable:!1,value:!0},__sentry_original__:{enumerable:!1,value:r}});try{Object.getOwnPropertyDescriptor(n,"name").configurable&&Object.defineProperty(n,"name",{get:function(){return r.name}})}catch(r){}return n}function injectReportDialog(r){if(void 0===r&&(r={}),r.eventId)if(r.dsn){var e=document.createElement("script");e.async=!0,e.src=new core_1.API(r.dsn).getReportDialogEndpoint(r),r.onLoad&&(e.onload=r.onLoad),(document.head||document.body).appendChild(e)}else utils_1.logger.error("Missing dsn option in showReportDialog call");else utils_1.logger.error("Missing eventId option in showReportDialog call")}exports.shouldIgnoreOnError=shouldIgnoreOnError,exports.ignoreNextOnError=ignoreNextOnError,exports.wrap=wrap,exports.injectReportDialog=injectReportDialog;}, {"355":355,"356":356,"358":358}];window.modules["362"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var globalhandlers_1=require(370);exports.GlobalHandlers=globalhandlers_1.GlobalHandlers;var trycatch_1=require(371);exports.TryCatch=trycatch_1.TryCatch;var breadcrumbs_1=require(369);exports.Breadcrumbs=breadcrumbs_1.Breadcrumbs;var linkederrors_1=require(372);exports.LinkedErrors=linkederrors_1.LinkedErrors;var useragent_1=require(373);exports.UserAgent=useragent_1.UserAgent;}, {"369":369,"370":370,"371":371,"372":372,"373":373}];window.modules["363"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355),UNKNOWN_FUNCTION="?",chrome=/^\s*at (?:(.*?) ?\()?((?:file|https?|blob|chrome-extension|address|native|eval|webpack||[-a-z]+:|.*bundle|\/).*?)(?::(\d+))?(?::(\d+))?\)?\s*$/i,gecko=/^\s*(.*?)(?:\((.*?)\))?(?:^|@)?((?:file|https?|blob|chrome|webpack|resource|moz-extension|capacitor).*?:\/.*?|\[native code\]|[^@]*(?:bundle|\d+\.js)|\/[\w\-. /=]+)(?::(\d+))?(?::(\d+))?\s*$/i,winjs=/^\s*at (?:((?:\[object object\])?.+) )?\(?((?:file|ms-appx|https?|webpack|blob):.*?):(\d+)(?::(\d+))?\)?\s*$/i,geckoEval=/(\S+) line (\d+)(?: > eval line \d+)* > eval/i,chromeEval=/\((\S*)(?::(\d+))(?::(\d+))\)/,reactMinifiedRegexp=/Minified React error #\d+;/i;function computeStackTrace(e){var n=null,a=0;e&&("number"==typeof e.framesToPop?a=e.framesToPop:reactMinifiedRegexp.test(e.message)&&(a=1));try{if(n=computeStackTraceFromStacktraceProp(e))return popFrames(n,a)}catch(e){}try{if(n=computeStackTraceFromStackProp(e))return popFrames(n,a)}catch(e){}return{message:extractMessage(e),name:e&&e.name,stack:[],failed:!0}}function computeStackTraceFromStackProp(e){if(!e||!e.stack)return null;for(var n,a,r,t=[],c=e.stack.split("\n"),s=0;s eval")>-1&&(n=geckoEval.exec(a[3]))?(a[1]=a[1]||"eval",a[3]=n[1],a[4]=n[2],a[5]=""):0!==s||a[5]||void 0===e.columnNumber||(t[0].column=e.columnNumber+1),r={url:a[3],func:a[1]||UNKNOWN_FUNCTION,args:a[2]?a[2].split(","):[],line:a[4]?+a[4]:null,column:a[5]?+a[5]:null}}!r.func&&r.line&&(r.func=UNKNOWN_FUNCTION),t.push(r)}return t.length?{message:extractMessage(e),name:e.name,stack:t}:null}function computeStackTraceFromStacktraceProp(e){if(!e||!e.stacktrace)return null;for(var n,a=/ line (\d+).*script (?:in )?(\S+)(?:: in function (\S+))?$/i,r=/ line (\d+), column (\d+)\s*(?:in (?:]+)>|([^)]+))\((.*)\))? in (.*):\s*$/i,t=e.stacktrace.split("\n"),c=[],s=0;s"}0!==t.length&&core_1.getCurrentHub().addBreadcrumb({category:"ui."+e.name,message:t},{event:e.event,name:e.name,global:e.global})},e.prototype._xhrBreadcrumb=function(e){if(e.endTimestamp){if(e.xhr.__sentry_own_request__)return;var t=e.xhr.__sentry_xhr__||{},r=t.method,a=t.url,s=t.status_code,o=t.body;core_1.getCurrentHub().addBreadcrumb({category:"xhr",data:{method:r,url:a,status_code:s},type:"http"},{xhr:e.xhr,input:o})}else;},e.prototype._fetchBreadcrumb=function(e){e.endTimestamp&&(e.fetchData.url.match(/sentry_key/)&&"POST"===e.fetchData.method||(e.error?core_1.getCurrentHub().addBreadcrumb({category:"fetch",data:e.fetchData,level:types_1.Severity.Error,type:"http"},{data:e.error,input:e.args}):core_1.getCurrentHub().addBreadcrumb({category:"fetch",data:tslib_1.__assign(tslib_1.__assign({},e.fetchData),{status_code:e.response.status}),type:"http"},{input:e.args,response:e.response})))},e.prototype._historyBreadcrumb=function(e){var t=utils_1.getGlobalObject(),r=e.from,a=e.to,s=utils_1.parseUrl(t.location.href),o=utils_1.parseUrl(r),n=utils_1.parseUrl(a);o.path||(o=s),s.protocol===n.protocol&&s.host===n.host&&(a=n.relative),s.protocol===o.protocol&&s.host===o.host&&(r=o.relative),core_1.getCurrentHub().addBreadcrumb({category:"navigation",data:{from:r,to:a}})},e.id="Breadcrumbs",e}();exports.Breadcrumbs=Breadcrumbs;}, {"355":355,"356":356,"357":357,"358":358}];window.modules["370"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355),core_1=require(356),types_1=require(357),utils_1=require(358),eventbuilder_1=require(354),helpers_1=require(361),GlobalHandlers=function(){function e(t){this.name=e.id,this._onErrorHandlerInstalled=!1,this._onUnhandledRejectionHandlerInstalled=!1,this._options=tslib_1.__assign({onerror:!0,onunhandledrejection:!0},t)}return e.prototype.setupOnce=function(){Error.stackTraceLimit=50,this._options.onerror&&(utils_1.logger.log("Global Handler attached: onerror"),this._installGlobalOnErrorHandler()),this._options.onunhandledrejection&&(utils_1.logger.log("Global Handler attached: onunhandledrejection"),this._installGlobalOnUnhandledRejectionHandler())},e.prototype._installGlobalOnErrorHandler=function(){var t=this;this._onErrorHandlerInstalled||(utils_1.addInstrumentationHandler({callback:function(n){var r=n.error,i=core_1.getCurrentHub(),a=i.getIntegration(e),o=r&&!0===r.__sentry_own_request__;if(a&&!helpers_1.shouldIgnoreOnError()&&!o){var l=i.getClient(),s=utils_1.isPrimitive(r)?t._eventFromIncompleteOnError(n.msg,n.url,n.line,n.column):t._enhanceEventWithInitialFrame(eventbuilder_1.eventFromUnknownInput(r,void 0,{attachStacktrace:l&&l.getOptions().attachStacktrace,rejection:!1}),n.url,n.line,n.column);utils_1.addExceptionMechanism(s,{handled:!1,type:"onerror"}),i.captureEvent(s,{originalException:r})}},type:"error"}),this._onErrorHandlerInstalled=!0)},e.prototype._installGlobalOnUnhandledRejectionHandler=function(){var t=this;this._onUnhandledRejectionHandlerInstalled||(utils_1.addInstrumentationHandler({callback:function(n){var r=n;try{"reason"in n?r=n.reason:"detail"in n&&"reason"in n.detail&&(r=n.detail.reason)}catch(e){}var i=core_1.getCurrentHub(),a=i.getIntegration(e),o=r&&!0===r.__sentry_own_request__;if(!a||helpers_1.shouldIgnoreOnError()||o)return!0;var l=i.getClient(),s=utils_1.isPrimitive(r)?t._eventFromRejectionWithPrimitive(r):eventbuilder_1.eventFromUnknownInput(r,void 0,{attachStacktrace:l&&l.getOptions().attachStacktrace,rejection:!0});s.level=types_1.Severity.Error,utils_1.addExceptionMechanism(s,{handled:!1,type:"onunhandledrejection"}),i.captureEvent(s,{originalException:r})},type:"unhandledrejection"}),this._onUnhandledRejectionHandlerInstalled=!0)},e.prototype._eventFromIncompleteOnError=function(e,t,n,r){var i,a=utils_1.isErrorEvent(e)?e.message:e;if(utils_1.isString(a)){var o=a.match(/^(?:[Uu]ncaught (?:exception: )?)?(?:((?:Eval|Internal|Range|Reference|Syntax|Type|URI|)Error): )?(.*)$/i);o&&(i=o[1],a=o[2])}var l={exception:{values:[{type:i||"Error",value:a}]}};return this._enhanceEventWithInitialFrame(l,t,n,r)},e.prototype._eventFromRejectionWithPrimitive=function(e){return{exception:{values:[{type:"UnhandledRejection",value:"Non-Error promise rejection captured with value: "+String(e)}]}}},e.prototype._enhanceEventWithInitialFrame=function(e,t,n,r){e.exception=e.exception||{},e.exception.values=e.exception.values||[],e.exception.values[0]=e.exception.values[0]||{},e.exception.values[0].stacktrace=e.exception.values[0].stacktrace||{},e.exception.values[0].stacktrace.frames=e.exception.values[0].stacktrace.frames||[];var i=isNaN(parseInt(r,10))?void 0:r,a=isNaN(parseInt(n,10))?void 0:n,o=utils_1.isString(t)&&t.length>0?t:utils_1.getLocationHref();return 0===e.exception.values[0].stacktrace.frames.length&&e.exception.values[0].stacktrace.frames.push({colno:i,filename:o,function:"?",in_app:!0,lineno:a}),e},e.id="GlobalHandlers",e}();exports.GlobalHandlers=GlobalHandlers;}, {"354":354,"355":355,"356":356,"357":357,"358":358,"361":361}];window.modules["371"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355),utils_1=require(358),helpers_1=require(361),DEFAULT_EVENT_TARGET=["EventTarget","Window","Node","ApplicationCache","AudioTrackList","ChannelMergerNode","CryptoOperation","EventSource","FileReader","HTMLUnknownElement","IDBDatabase","IDBRequest","IDBTransaction","KeyOperation","MediaController","MessagePort","ModalWindow","Notification","SVGElementInstance","Screen","TextTrack","TextTrackCue","TextTrackList","WebSocket","WebSocketWorker","Worker","XMLHttpRequest","XMLHttpRequestEventTarget","XMLHttpRequestUpload"],TryCatch=function(){function t(e){this.name=t.id,this._options=tslib_1.__assign({XMLHttpRequest:!0,eventTarget:!0,requestAnimationFrame:!0,setInterval:!0,setTimeout:!0},e)}return t.prototype.setupOnce=function(){var t=utils_1.getGlobalObject();(this._options.setTimeout&&utils_1.fill(t,"setTimeout",this._wrapTimeFunction.bind(this)),this._options.setInterval&&utils_1.fill(t,"setInterval",this._wrapTimeFunction.bind(this)),this._options.requestAnimationFrame&&utils_1.fill(t,"requestAnimationFrame",this._wrapRAF.bind(this)),this._options.XMLHttpRequest&&"XMLHttpRequest"in t&&utils_1.fill(XMLHttpRequest.prototype,"send",this._wrapXHR.bind(this)),this._options.eventTarget)&&(Array.isArray(this._options.eventTarget)?this._options.eventTarget:DEFAULT_EVENT_TARGET).forEach(this._wrapEventTarget.bind(this))},t.prototype._wrapTimeFunction=function(t){return function(){for(var e=[],n=0;n=this._limit)return t;var i=tracekit_1.computeStackTrace(r[e]),n=parsers_1.exceptionFromStacktrace(i);return this._walkErrorTree(r[e],e,tslib_1.__spread([n],t))},r.id="LinkedErrors",r}();exports.LinkedErrors=LinkedErrors;}, {"355":355,"356":356,"358":358,"363":363,"364":364}];window.modules["373"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355),core_1=require(356),utils_1=require(358),global=utils_1.getGlobalObject(),UserAgent=function(){function e(){this.name=e.id}return e.prototype.setupOnce=function(){core_1.addGlobalEventProcessor(function(r){var t,s,i;if(core_1.getCurrentHub().getIntegration(e)){if(!global.navigator&&!global.location&&!global.document)return r;var n=(null===(t=r.request)||void 0===t?void 0:t.url)||(null===(s=global.location)||void 0===s?void 0:s.href),l=(global.document||{}).referrer,o=(global.navigator||{}).userAgent,a=tslib_1.__assign(tslib_1.__assign(tslib_1.__assign({},null===(i=r.request)||void 0===i?void 0:i.headers),l&&{Referer:l}),o&&{"User-Agent":o}),u=tslib_1.__assign(tslib_1.__assign({},n&&{url:n}),{headers:a});return tslib_1.__assign(tslib_1.__assign({},r),{request:u})}return r})},e.id="UserAgent",e}();exports.UserAgent=UserAgent;}, {"355":355,"356":356,"358":358}];window.modules["374"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355),core_1=require(356),types_1=require(357),utils_1=require(358),CATEGORY_MAPPING={event:"error",transaction:"transaction",session:"session"},BaseTransport=function(){function t(t){this.options=t,this._buffer=new utils_1.PromiseBuffer(30),this._rateLimits={},this._api=new core_1.API(t.dsn,t._metadata),this.url=this._api.getStoreEndpointWithUrlEncodedAuth()}return t.prototype.sendEvent=function(t){throw new utils_1.SentryError("Transport Class has to implement `sendEvent` method")},t.prototype.close=function(t){return this._buffer.drain(t)},t.prototype._handleResponse=function(t){var e=t.requestType,r=t.response,s=t.headers,i=t.resolve,n=t.reject,a=types_1.Status.fromHttpCode(r.status);this._handleRateLimit(s)&&utils_1.logger.warn("Too many requests, backing off until: "+this._disabledUntil(e)),a!==types_1.Status.Success?n(r):i({status:a})},t.prototype._disabledUntil=function(t){var e=CATEGORY_MAPPING[t];return this._rateLimits[e]||this._rateLimits.all},t.prototype._isRateLimited=function(t){return this._disabledUntil(t)>new Date(Date.now())},t.prototype._handleRateLimit=function(t){var e,r,s,i,n=Date.now(),a=t["x-sentry-rate-limits"],o=t["retry-after"];if(a){try{for(var l=tslib_1.__values(a.trim().split(",")),u=l.next();!u.done;u=l.next()){var _=u.value.split(":",2),p=parseInt(_[0],10),d=1e3*(isNaN(p)?60:p);try{for(var f=(s=void 0,tslib_1.__values(_[1].split(";"))),y=f.next();!y.done;y=f.next()){var h=y.value;this._rateLimits[h||"all"]=new Date(n+d)}}catch(t){s={error:t}}finally{try{y&&!y.done&&(i=f.return)&&i.call(f)}finally{if(s)throw s.error}}}}catch(t){e={error:t}}finally{try{u&&!u.done&&(r=l.return)&&r.call(l)}finally{if(e)throw e.error}}return!0}return!!o&&(this._rateLimits.all=new Date(n+utils_1.parseRetryAfterHeader(n,o)),!0)},t}();exports.BaseTransport=BaseTransport;}, {"355":355,"356":356,"357":357,"358":358}];window.modules["375"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355),core_1=require(356),utils_1=require(358),base_1=require(374);function getNativeFetchImplementation(){var e,t,r=utils_1.getGlobalObject();if(utils_1.isNativeFetch(r.fetch))return r.fetch.bind(r);var i=r.document,s=r.fetch;if("function"==typeof(null===(e=i)||void 0===e?void 0:e.createElement))try{var n=i.createElement("iframe");n.hidden=!0,i.head.appendChild(n),(null===(t=n.contentWindow)||void 0===t?void 0:t.fetch)&&(s=n.contentWindow.fetch),i.head.removeChild(n)}catch(e){utils_1.logger.warn("Could not create sandbox iframe for pure fetch check, bailing to window.fetch: ",e)}return s.bind(r)}var FetchTransport=function(e){function t(t,r){void 0===r&&(r=getNativeFetchImplementation());var i=e.call(this,t)||this;return i._fetch=r,i}return tslib_1.__extends(t,e),t.prototype.sendEvent=function(e){return this._sendRequest(core_1.eventToSentryRequest(e,this._api),e)},t.prototype.sendSession=function(e){return this._sendRequest(core_1.sessionToSentryRequest(e,this._api),e)},t.prototype._sendRequest=function(e,t){var r=this;if(this._isRateLimited(e.type))return Promise.reject({event:t,type:e.type,reason:"Transport locked till "+this._disabledUntil(e.type)+" due to too many requests.",status:429});var i={body:e.body,method:"POST",referrerPolicy:utils_1.supportsReferrerPolicy()?"origin":""};return void 0!==this.options.fetchParameters&&Object.assign(i,this.options.fetchParameters),void 0!==this.options.headers&&(i.headers=this.options.headers),this._buffer.add(new utils_1.SyncPromise(function(t,s){r._fetch(e.url,i).then(function(i){var n={"x-sentry-rate-limits":i.headers.get("X-Sentry-Rate-Limits"),"retry-after":i.headers.get("Retry-After")};r._handleResponse({requestType:e.type,response:i,headers:n,resolve:t,reject:s})}).catch(s)}))},t}(base_1.BaseTransport);exports.FetchTransport=FetchTransport;}, {"355":355,"356":356,"358":358,"374":374}];window.modules["376"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355),core_1=require(356),utils_1=require(358),base_1=require(374),XHRTransport=function(e){function t(){return null!==e&&e.apply(this,arguments)||this}return tslib_1.__extends(t,e),t.prototype.sendEvent=function(e){return this._sendRequest(core_1.eventToSentryRequest(e,this._api),e)},t.prototype.sendSession=function(e){return this._sendRequest(core_1.sessionToSentryRequest(e,this._api),e)},t.prototype._sendRequest=function(e,t){var s=this;return this._isRateLimited(e.type)?Promise.reject({event:t,type:e.type,reason:"Transport locked till "+this._disabledUntil(e.type)+" due to too many requests.",status:429}):this._buffer.add(new utils_1.SyncPromise(function(t,r){var n=new XMLHttpRequest;for(var o in n.onreadystatechange=function(){if(4===n.readyState){var o={"x-sentry-rate-limits":n.getResponseHeader("X-Sentry-Rate-Limits"),"retry-after":n.getResponseHeader("Retry-After")};s._handleResponse({requestType:e.type,response:n,headers:o,resolve:t,reject:r})}},n.open("POST",e.url),s.options.headers)s.options.headers.hasOwnProperty(o)&&n.setRequestHeader(o,s.options.headers[o]);n.send(e.body)}))},t}(base_1.BaseTransport);exports.XHRTransport=XHRTransport;}, {"355":355,"356":356,"358":358,"374":374}];window.modules["377"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var utils_1=require(358),SENTRY_API_VERSION="7",API=function(){function t(t,e){void 0===e&&(e={}),this.dsn=t,this._dsnObject=new utils_1.Dsn(t),this.metadata=e}return t.prototype.getDsn=function(){return this._dsnObject},t.prototype.getBaseApiEndpoint=function(){var t=this._dsnObject,e=t.protocol?t.protocol+":":"",n=t.port?":"+t.port:"";return e+"//"+t.host+n+(t.path?"/"+t.path:"")+"/api/"},t.prototype.getStoreEndpoint=function(){return this._getIngestEndpoint("store")},t.prototype.getStoreEndpointWithUrlEncodedAuth=function(){return this.getStoreEndpoint()+"?"+this._encodedAuth()},t.prototype.getEnvelopeEndpointWithUrlEncodedAuth=function(){return this._getEnvelopeEndpoint()+"?"+this._encodedAuth()},t.prototype.getStoreEndpointPath=function(){var t=this._dsnObject;return(t.path?"/"+t.path:"")+"/api/"+t.projectId+"/store/"},t.prototype.getRequestHeaders=function(t,e){var n=this._dsnObject,o=["Sentry sentry_version="+SENTRY_API_VERSION];return o.push("sentry_client="+t+"/"+e),o.push("sentry_key="+n.publicKey),n.pass&&o.push("sentry_secret="+n.pass),{"Content-Type":"application/json","X-Sentry-Auth":o.join(", ")}},t.prototype.getReportDialogEndpoint=function(t){void 0===t&&(t={});var e=this._dsnObject,n=this.getBaseApiEndpoint()+"embed/error-page/",o=[];for(var r in o.push("dsn="+e.toString()),t)if("dsn"!==r)if("user"===r){if(!t.user)continue;t.user.name&&o.push("name="+encodeURIComponent(t.user.name)),t.user.email&&o.push("email="+encodeURIComponent(t.user.email))}else o.push(encodeURIComponent(r)+"="+encodeURIComponent(t[r]));return o.length?n+"?"+o.join("&"):n},t.prototype._getEnvelopeEndpoint=function(){return this._getIngestEndpoint("envelope")},t.prototype._getIngestEndpoint=function(t){return""+this.getBaseApiEndpoint()+this._dsnObject.projectId+"/"+t+"/"},t.prototype._encodedAuth=function(){var t={sentry_key:this._dsnObject.publicKey,sentry_version:SENTRY_API_VERSION};return utils_1.urlEncode(t)},t}();exports.API=API;}, {"358":358}];window.modules["378"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var utils_1=require(358),noop_1=require(379),BaseBackend=function(){function t(t){this._options=t,this._options.dsn||utils_1.logger.warn("No DSN provided, backend will not do anything."),this._transport=this._setupTransport()}return t.prototype.eventFromException=function(t,e){throw new utils_1.SentryError("Backend has to implement `eventFromException` method")},t.prototype.eventFromMessage=function(t,e,n){throw new utils_1.SentryError("Backend has to implement `eventFromMessage` method")},t.prototype.sendEvent=function(t){this._transport.sendEvent(t).then(null,function(t){utils_1.logger.error("Error while sending event: "+t)})},t.prototype.sendSession=function(t){this._transport.sendSession?this._transport.sendSession(t).then(null,function(t){utils_1.logger.error("Error while sending session: "+t)}):utils_1.logger.warn("Dropping session because custom transport doesn't implement sendSession")},t.prototype.getTransport=function(){return this._transport},t.prototype._setupTransport=function(){return new noop_1.NoopTransport},t}();exports.BaseBackend=BaseBackend;}, {"358":358,"379":379}];window.modules["379"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var types_1=require(357),utils_1=require(358),NoopTransport=function(){function e(){}return e.prototype.sendEvent=function(e){return utils_1.SyncPromise.resolve({reason:"NoopTransport: Event has been skipped because no Dsn is configured.",status:types_1.Status.Skipped})},e.prototype.close=function(e){return utils_1.SyncPromise.resolve(!0)},e}();exports.NoopTransport=NoopTransport;}, {"357":357,"358":358}];window.modules["380"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355),hub_1=require(381),types_1=require(357),utils_1=require(358),integration_1=require(382),BaseClient=function(){function t(t,e){this._integrations={},this._processing=0,this._backend=new t(e),this._options=e,e.dsn&&(this._dsn=new utils_1.Dsn(e.dsn))}return t.prototype.captureException=function(t,e,n){var r=this,i=e&&e.event_id;return this._process(this._getBackend().eventFromException(t,e).then(function(t){return r._captureEvent(t,e,n)}).then(function(t){i=t})),i},t.prototype.captureMessage=function(t,e,n,r){var i=this,s=n&&n.event_id,o=utils_1.isPrimitive(t)?this._getBackend().eventFromMessage(String(t),e,n):this._getBackend().eventFromException(t,n);return this._process(o.then(function(t){return i._captureEvent(t,n,r)}).then(function(t){s=t})),s},t.prototype.captureEvent=function(t,e,n){var r=e&&e.event_id;return this._process(this._captureEvent(t,e,n).then(function(t){r=t})),r},t.prototype.captureSession=function(t){"string"!=typeof t.release?utils_1.logger.warn("Discarded session because of missing or non-string release"):(this._sendSession(t),t.update({init:!1}))},t.prototype.getDsn=function(){return this._dsn},t.prototype.getOptions=function(){return this._options},t.prototype.flush=function(t){var e=this;return this._isClientProcessing(t).then(function(n){return e._getBackend().getTransport().close(t).then(function(t){return n&&t})})},t.prototype.close=function(t){var e=this;return this.flush(t).then(function(t){return e.getOptions().enabled=!1,t})},t.prototype.setupIntegrations=function(){this._isEnabled()&&(this._integrations=integration_1.setupIntegrations(this._options))},t.prototype.getIntegration=function(t){try{return this._integrations[t.id]||null}catch(e){return utils_1.logger.warn("Cannot retrieve integration "+t.id+" from the current Client"),null}},t.prototype._updateSessionFromEvent=function(t,e){var n,r,i,s=!1,o=!1,a=e.exception&&e.exception.values;if(a){o=!0;try{for(var u=tslib_1.__values(a),l=u.next();!l.done;l=u.next()){var _=l.value.mechanism;if(_&&!1===_.handled){s=!0;break}}}catch(t){n={error:t}}finally{try{l&&!l.done&&(r=u.return)&&r.call(u)}finally{if(n)throw n.error}}}var c=e.user;if(!t.userAgent){var p=e.request?e.request.headers:{};for(var d in p)if("user-agent"===d.toLowerCase()){i=p[d];break}}t.update(tslib_1.__assign(tslib_1.__assign({},s&&{status:types_1.SessionStatus.Crashed}),{user:c,userAgent:i,errors:t.errors+Number(o||s)})),this.captureSession(t)},t.prototype._sendSession=function(t){this._getBackend().sendSession(t)},t.prototype._isClientProcessing=function(t){var e=this;return new utils_1.SyncPromise(function(n){var r=0,i=setInterval(function(){0==e._processing?(clearInterval(i),n(!0)):(r+=1,t&&r>=t&&(clearInterval(i),n(!1)))},1)})},t.prototype._getBackend=function(){return this._backend},t.prototype._isEnabled=function(){return!1!==this.getOptions().enabled&&void 0!==this._dsn},t.prototype._prepareEvent=function(t,e,n){var r=this,i=this.getOptions().normalizeDepth,s=void 0===i?3:i,o=tslib_1.__assign(tslib_1.__assign({},t),{event_id:t.event_id||(n&&n.event_id?n.event_id:utils_1.uuid4()),timestamp:t.timestamp||utils_1.dateTimestampInSeconds()});this._applyClientOptions(o),this._applyIntegrationsMetadata(o);var a=e;n&&n.captureContext&&(a=hub_1.Scope.clone(a).update(n.captureContext));var u=utils_1.SyncPromise.resolve(o);return a&&(u=a.applyToEvent(o,n)),u.then(function(t){return"number"==typeof s&&s>0?r._normalizeEvent(t,s):t})},t.prototype._normalizeEvent=function(t,e){if(!t)return null;var n=tslib_1.__assign(tslib_1.__assign(tslib_1.__assign(tslib_1.__assign(tslib_1.__assign({},t),t.breadcrumbs&&{breadcrumbs:t.breadcrumbs.map(function(t){return tslib_1.__assign(tslib_1.__assign({},t),t.data&&{data:utils_1.normalize(t.data,e)})})}),t.user&&{user:utils_1.normalize(t.user,e)}),t.contexts&&{contexts:utils_1.normalize(t.contexts,e)}),t.extra&&{extra:utils_1.normalize(t.extra,e)});return t.contexts&&t.contexts.trace&&(n.contexts.trace=t.contexts.trace),n},t.prototype._applyClientOptions=function(t){var e=this.getOptions(),n=e.environment,r=e.release,i=e.dist,s=e.maxValueLength,o=void 0===s?250:s;"environment"in t||(t.environment="environment"in e?n:"production"),void 0===t.release&&void 0!==r&&(t.release=r),void 0===t.dist&&void 0!==i&&(t.dist=i),t.message&&(t.message=utils_1.truncate(t.message,o));var a=t.exception&&t.exception.values&&t.exception.values[0];a&&a.value&&(a.value=utils_1.truncate(a.value,o));var u=t.request;u&&u.url&&(u.url=utils_1.truncate(u.url,o))},t.prototype._applyIntegrationsMetadata=function(t){var e=Object.keys(this._integrations);e.length>0&&(t.sdk=t.sdk||{},t.sdk.integrations=tslib_1.__spread(t.sdk.integrations||[],e))},t.prototype._sendEvent=function(t){this._getBackend().sendEvent(t)},t.prototype._captureEvent=function(t,e,n){return this._processEvent(t,e,n).then(function(t){return t.event_id},function(t){utils_1.logger.error(t)})},t.prototype._processEvent=function(t,e,n){var r=this,i=this.getOptions(),s=i.beforeSend,o=i.sampleRate;if(!this._isEnabled())return utils_1.SyncPromise.reject(new utils_1.SentryError("SDK not enabled, will not send event."));var a="transaction"===t.type;return!a&&"number"==typeof o&&Math.random()>o?utils_1.SyncPromise.reject(new utils_1.SentryError("Discarding event because it's not included in the random sample (sampling rate = "+o+")")):this._prepareEvent(t,n,e).then(function(t){if(null===t)throw new utils_1.SentryError("An event processor returned null, will not send event.");if(e&&e.data&&!0===e.data.__sentry__||a||!s)return t;var n=s(t,e);if(void 0===n)throw new utils_1.SentryError("`beforeSend` method has to return `null` or a valid event.");return utils_1.isThenable(n)?n.then(function(t){return t},function(t){throw new utils_1.SentryError("beforeSend rejected with "+t)}):n}).then(function(t){if(null===t)throw new utils_1.SentryError("`beforeSend` returned `null`, will not send event.");var e=n&&n.getSession&&n.getSession();return!a&&e&&r._updateSessionFromEvent(e,t),r._sendEvent(t),t}).then(null,function(t){if(t instanceof utils_1.SentryError)throw t;throw r.captureException(t,{data:{__sentry__:!0},originalException:t}),new utils_1.SentryError("Event processing pipeline threw an error, original event will not be sent. Details have been sent as a new event.\nReason: "+t)})},t.prototype._process=function(t){var e=this;this._processing+=1,t.then(function(t){return e._processing-=1,t},function(t){return e._processing-=1,t})},t}();exports.BaseClient=BaseClient;}, {"355":355,"357":357,"358":358,"381":381,"382":382}];window.modules["381"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var scope_1=require(392);exports.addGlobalEventProcessor=scope_1.addGlobalEventProcessor,exports.Scope=scope_1.Scope;var session_1=require(391);exports.Session=session_1.Session;var hub_1=require(390);exports.getActiveDomain=hub_1.getActiveDomain,exports.getCurrentHub=hub_1.getCurrentHub,exports.getHubFromCarrier=hub_1.getHubFromCarrier,exports.getMainCarrier=hub_1.getMainCarrier,exports.Hub=hub_1.Hub,exports.makeMain=hub_1.makeMain,exports.setHubOnCarrier=hub_1.setHubOnCarrier;}, {"390":390,"391":391,"392":392}];window.modules["382"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355),hub_1=require(381),utils_1=require(358);function getIntegrationsToSetup(e){var t=e.defaultIntegrations&&tslib_1.__spread(e.defaultIntegrations)||[],n=e.integrations,r=[];if(Array.isArray(n)){var s=n.map(function(e){return e.name}),a=[];t.forEach(function(e){-1===s.indexOf(e.name)&&-1===a.indexOf(e.name)&&(r.push(e),a.push(e.name))}),n.forEach(function(e){-1===a.indexOf(e.name)&&(r.push(e),a.push(e.name))})}else"function"==typeof n?(r=n(t),r=Array.isArray(r)?r:[r]):r=tslib_1.__spread(t);var i=r.map(function(e){return e.name});return-1!==i.indexOf("Debug")&&r.push.apply(r,tslib_1.__spread(r.splice(i.indexOf("Debug"),1))),r}function setupIntegration(e){-1===exports.installedIntegrations.indexOf(e.name)&&(e.setupOnce(hub_1.addGlobalEventProcessor,hub_1.getCurrentHub),exports.installedIntegrations.push(e.name),utils_1.logger.log("Integration installed: "+e.name))}function setupIntegrations(e){var t={};return getIntegrationsToSetup(e).forEach(function(e){t[e.name]=e,setupIntegration(e)}),t}exports.installedIntegrations=[],exports.getIntegrationsToSetup=getIntegrationsToSetup,exports.setupIntegration=setupIntegration,exports.setupIntegrations=setupIntegrations;}, {"355":355,"358":358,"381":381}];window.modules["383"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0}),exports.SDK_VERSION="6.3.5";}, {}];window.modules["384"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355);function getSdkMetadataForEnvelopeHeader(e){if(e.metadata&&e.metadata.sdk){var t=e.metadata.sdk;return{name:t.name,version:t.version}}}function enhanceEventWithSdkInfo(e,t){return t?(e.sdk=e.sdk||{},e.sdk.name=e.sdk.name||t.name,e.sdk.version=e.sdk.version||t.version,e.sdk.integrations=tslib_1.__spread(e.sdk.integrations||[],t.integrations||[]),e.sdk.packages=tslib_1.__spread(e.sdk.packages||[],t.packages||[]),e):e}function sessionToSentryRequest(e,t){var n=getSdkMetadataForEnvelopeHeader(t);return{body:JSON.stringify(tslib_1.__assign({sent_at:(new Date).toISOString()},n&&{sdk:n}))+"\n"+JSON.stringify({type:"session"})+"\n"+JSON.stringify(e),type:"session",url:t.getEnvelopeEndpointWithUrlEncodedAuth()}}function eventToSentryRequest(e,t){var n=getSdkMetadataForEnvelopeHeader(t),s=e.type||"event",a="transaction"===s,r=e.debug_meta||{},i=r.transactionSampling,d=tslib_1.__rest(r,["transactionSampling"]),o=i||{},g=o.method,p=o.rate;0===Object.keys(d).length?delete e.debug_meta:e.debug_meta=d;var _={body:JSON.stringify(n?enhanceEventWithSdkInfo(e,t.metadata.sdk):e),type:s,url:a?t.getEnvelopeEndpointWithUrlEncodedAuth():t.getStoreEndpointWithUrlEncodedAuth()};if(a){var u=JSON.stringify(tslib_1.__assign({event_id:e.event_id,sent_at:(new Date).toISOString()},n&&{sdk:n}))+"\n"+JSON.stringify({type:e.type,sample_rates:[{id:g,rate:p}]})+"\n"+_.body;_.body=u}return _}exports.sessionToSentryRequest=sessionToSentryRequest,exports.eventToSentryRequest=eventToSentryRequest;}, {"355":355}];window.modules["385"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var hub_1=require(381),utils_1=require(358);function initAndBind(e,n){!0===n.debug&&utils_1.logger.enable();var i=hub_1.getCurrentHub(),t=new e(n);i.bindClient(t)}exports.initAndBind=initAndBind;}, {"358":358,"381":381}];window.modules["386"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var tslib_1=require(355),hub_1=require(381);function callOnHub(t){for(var e=[],r=1;r=0?tslib_1.__spread(this._breadcrumbs,[e]).slice(-s):tslib_1.__spread(this._breadcrumbs,[e]),this._notifyScopeListeners(),this},t.prototype.clearBreadcrumbs=function(){return this._breadcrumbs=[],this._notifyScopeListeners(),this},t.prototype.applyToEvent=function(t,s){var e;if(this._extra&&Object.keys(this._extra).length&&(t.extra=tslib_1.__assign(tslib_1.__assign({},this._extra),t.extra)),this._tags&&Object.keys(this._tags).length&&(t.tags=tslib_1.__assign(tslib_1.__assign({},this._tags),t.tags)),this._user&&Object.keys(this._user).length&&(t.user=tslib_1.__assign(tslib_1.__assign({},this._user),t.user)),this._contexts&&Object.keys(this._contexts).length&&(t.contexts=tslib_1.__assign(tslib_1.__assign({},this._contexts),t.contexts)),this._level&&(t.level=this._level),this._transactionName&&(t.transaction=this._transactionName),this._span){t.contexts=tslib_1.__assign({trace:this._span.getTraceContext()},t.contexts);var i=null===(e=this._span.transaction)||void 0===e?void 0:e.name;i&&(t.tags=tslib_1.__assign({transaction:i},t.tags))}return this._applyFingerprint(t),t.breadcrumbs=tslib_1.__spread(t.breadcrumbs||[],this._breadcrumbs),t.breadcrumbs=t.breadcrumbs.length>0?t.breadcrumbs:void 0,this._notifyEventProcessors(tslib_1.__spread(getGlobalEventProcessors(),this._eventProcessors),t,s)},t.prototype._notifyEventProcessors=function(t,s,e,i){var n=this;return void 0===i&&(i=0),new utils_1.SyncPromise(function(r,_){var o=t[i];if(null===s||"function"!=typeof o)r(s);else{var a=o(tslib_1.__assign({},s),e);utils_1.isThenable(a)?a.then(function(s){return n._notifyEventProcessors(t,s,e,i+1).then(r)}).then(null,_):n._notifyEventProcessors(t,a,e,i+1).then(r).then(null,_)}})},t.prototype._notifyScopeListeners=function(){var t=this;this._notifyingListeners||(this._notifyingListeners=!0,this._scopeListeners.forEach(function(s){s(t)}),this._notifyingListeners=!1)},t.prototype._applyFingerprint=function(t){t.fingerprint=t.fingerprint?Array.isArray(t.fingerprint)?t.fingerprint:[t.fingerprint]:[],this._fingerprint&&(t.fingerprint=t.fingerprint.concat(this._fingerprint)),t.fingerprint&&!t.fingerprint.length&&delete t.fingerprint},t}();function getGlobalEventProcessors(){var t=utils_1.getGlobalObject();return t.__SENTRY__=t.__SENTRY__||{},t.__SENTRY__.globalEventProcessors=t.__SENTRY__.globalEventProcessors||[],t.__SENTRY__.globalEventProcessors}function addGlobalEventProcessor(t){getGlobalEventProcessors().push(t)}exports.Scope=Scope,exports.addGlobalEventProcessor=addGlobalEventProcessor;}, {"355":355,"358":358}];window.modules["393"] = [function(require,module,exports){var LogLevel;Object.defineProperty(exports,"__esModule",{value:!0}),function(e){e[e.None=0]="None",e[e.Error=1]="Error",e[e.Debug=2]="Debug",e[e.Verbose=3]="Verbose"}(LogLevel=exports.LogLevel||(exports.LogLevel={}));}, {}];window.modules["394"] = [function(require,module,exports){var SessionStatus;Object.defineProperty(exports,"__esModule",{value:!0}),function(e){e.Ok="ok",e.Exited="exited",e.Crashed="crashed",e.Abnormal="abnormal"}(SessionStatus=exports.SessionStatus||(exports.SessionStatus={}));}, {}];window.modules["395"] = [function(require,module,exports){var Severity;Object.defineProperty(exports,"__esModule",{value:!0}),function(r){r.Fatal="fatal",r.Error="error",r.Warning="warning",r.Log="log",r.Info="info",r.Debug="debug",r.Critical="critical"}(Severity=exports.Severity||(exports.Severity={})),function(r){r.fromString=function(e){switch(e){case"debug":return r.Debug;case"info":return r.Info;case"warn":case"warning":return r.Warning;case"error":return r.Error;case"fatal":return 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t)&&(t.publicKey=t.user),this.user=t.publicKey||"",this.protocol=t.protocol,this.publicKey=t.publicKey||"",this.pass=t.pass||"",this.host=t.host,this.port=t.port||"",this.path=t.path||"",this.projectId=t.projectId},t.prototype._validate=function(){var t=this;if(["protocol","publicKey","host","projectId"].forEach(function(r){if(!t[r])throw new error_1.SentryError(ERROR_MESSAGE+": "+r+" missing")}),!this.projectId.match(/^\d+$/))throw new error_1.SentryError(ERROR_MESSAGE+": Invalid projectId "+this.projectId);if("http"!==this.protocol&&"https"!==this.protocol)throw new error_1.SentryError(ERROR_MESSAGE+": Invalid protocol "+this.protocol);if(this.port&&isNaN(parseInt(this.port,10)))throw new error_1.SentryError(ERROR_MESSAGE+": Invalid port "+this.port)},t}();exports.Dsn=Dsn;}, {"355":355,"402":402}];window.modules["402"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var 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document.location.href}catch(e){return""}}exports.getGlobalObject=getGlobalObject,exports.uuid4=uuid4,exports.parseUrl=parseUrl,exports.getEventDescription=getEventDescription,exports.consoleSandbox=consoleSandbox,exports.addExceptionTypeValue=addExceptionTypeValue,exports.addExceptionMechanism=addExceptionMechanism,exports.getLocationHref=getLocationHref;var SEMVER_REGEXP=/^(0|[1-9]\d*)\.(0|[1-9]\d*)\.(0|[1-9]\d*)(?:-((?:0|[1-9]\d*|\d*[a-zA-Z-][0-9a-zA-Z-]*)(?:\.(?:0|[1-9]\d*|\d*[a-zA-Z-][0-9a-zA-Z-]*))*))?(?:\+([0-9a-zA-Z-]+(?:\.[0-9a-zA-Z-]+)*))?$/;function parseSemver(e){var t=e.match(SEMVER_REGEXP)||[],n=parseInt(t[1],10),r=parseInt(t[2],10),a=parseInt(t[3],10);return{buildmetadata:t[5],major:isNaN(n)?void 0:n,minor:isNaN(r)?void 0:r,patch:isNaN(a)?void 0:a,prerelease:t[4]}}exports.parseSemver=parseSemver;var defaultRetryAfter=6e4;function parseRetryAfterHeader(e,t){if(!t)return defaultRetryAfter;var n=parseInt(""+t,10);if(!isNaN(n))return 1e3*n;var r=Date.parse(""+t);return isNaN(r)?defaultRetryAfter:r-e}function addContextToFrame(e,t,n){void 0===n&&(n=5);var r=t.lineno||0,a=e.length,o=Math.max(Math.min(a,r-1),0);t.pre_context=e.slice(Math.max(0,o-n),o).map(function(e){return string_1.snipLine(e,0)}),t.context_line=string_1.snipLine(e[Math.min(a-1,o)],t.colno||0),t.post_context=e.slice(Math.min(o+1,a),o+1+n).map(function(e){return string_1.snipLine(e,0)})}function stripUrlQueryAndFragment(e){return e.split(/[\?#]/,1)[0]}exports.parseRetryAfterHeader=parseRetryAfterHeader,exports.addContextToFrame=addContextToFrame,exports.stripUrlQueryAndFragment=stripUrlQueryAndFragment;}).call(this)}).call(this,typeof global !== "undefined" ? global : typeof self !== "undefined" ? self : typeof window !== "undefined" ? window : {})}, {"407":407,"411":411}];window.modules["410"] = [function(require,module,exports){Object.defineProperty(exports,"__esModule",{value:!0});var error_1=require(402),syncpromise_1=require(412),PromiseBuffer=function(){function 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e=triggerHandlers.bind(null,"dom"),t=makeDOMEventHandler(e,!0);global.document.addEventListener("click",t,!1),global.document.addEventListener("keypress",t,!1),["EventTarget","Node"].forEach(function(t){var r=global[t]&&global[t].prototype;r&&r.hasOwnProperty&&r.hasOwnProperty("addEventListener")&&(object_1.fill(r,"addEventListener",function(t){return function(r,n,o){if("click"===r||"keypress"==r)try{var a=this.__sentry_instrumentation_handlers__=this.__sentry_instrumentation_handlers__||{},i=a[r]=a[r]||{refCount:0};if(!i.handler){var l=makeDOMEventHandler(e);i.handler=l,t.call(this,r,l,o)}i.refCount+=1}catch(e){}return t.call(this,r,n,o)}}),object_1.fill(r,"removeEventListener",function(e){return function(t,r,n){if("click"===t||"keypress"==t)try{var 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this.client.passwordless.verify(mt.blacklist(t,["popupHandler"]),function(n){if(n)return e(n);t.username=t.phoneNumber||t.email,t.password=t.verificationCode,delete t.email,delete t.phoneNumber,delete t.verificationCode,delete t.type,r.client.loginWithResourceOwner(t,e)})},Te.prototype.signupAndLogin=function(t,e){var r=this;return this.client.dbConnection.signup(t,function(n){if(n)return e(n);r.loginWithCredentials(t,e)})},Oe.create=function(t){return new Oe(t)},Oe.prototype.login=function(t,e){this.handler=new de({auth0:this.auth0,url:this.authenticationUrl,eventListenerType:t?"message":"load",callback:this.getCallbackHandler(e,t),timeout:this.timeout,eventValidator:this.getEventValidator(),timeoutCallback:function(){e(null,"#error=timeout&error_description=Timeout+during+authentication+renew.")},usePostMessage:t||!1}),this.handler.init()},Oe.prototype.getEventValidator=function(){var t=this;return{isValid:function(e){switch(e.event.type){case"message":return e.event.origin===t.postMessageOrigin&&e.event.source===t.handler.iframe.contentWindow&&(!1===t.postMessageDataType||e.event.data.type&&e.event.data.type===t.postMessageDataType);case"load":if("about:"===e.sourceObject.contentWindow.location.protocol)return!1;default:return!0}}}},Oe.prototype.getCallbackHandler=function(t,e){return function(r){var n;n=e?"object"==typeof r.event.data&&r.event.data.hash?r.event.data.hash:r.event.data:r.sourceObject.contentWindow.location.hash,t(null,n)}},ke.prototype.login=function(t,e){var r,i;return r=n(this.baseOptions.rootUrl,"usernamepassword","login"),t.username=t.username||t.email,t=mt.blacklist(t,["email","onRedirecting"]),i=mt.merge(this.baseOptions,["clientID","redirectUri","tenant","responseType","responseMode","scope","audience"]).with(t),i=this.transactionManager.process(i),i=mt.toSnakeCase(i,["auth0Client"]),this.request.post(r).send(i).end(Et(e))},ke.prototype.callback=function(t){var e,r=_t.getDocument();(e=r.createElement("div")).innerHTML=t,r.body.appendChild(e).children[0].submit()},Se.prototype.login=function(t,e){if(_t.getWindow().location.host!==this.baseOptions.domain)throw new Error("This method is meant to be used only inside the Universal Login Page.");var r,n=mt.merge(this.baseOptions,["clientID","redirectUri","tenant","responseType","responseMode","scope","audience","_csrf","state","_intstate","nonce"]).with(t);return ct.check(n,{type:"object",message:"options parameter is not valid"},{responseType:{type:"string",message:"responseType option is required"}}),(r=new ke(this.baseOptions)).login(n,function(n,i){if(n)return e(n);function o(){r.callback(i)}if("function"==typeof t.onRedirecting)return t.onRedirecting(function(){o()});o()})},Se.prototype.signupAndLogin=function(t,e){var r=this;return r.client.client.dbConnection.signup(t,function(n){return n?e(n):r.login(t,e)})},Se.prototype.getSSOData=function(t,e){var r,i="";return"function"==typeof t&&(e=t,t=!1),ct.check(t,{type:"boolean",message:"withActiveDirectories parameter is not valid"}),ct.check(e,{type:"function",message:"cb parameter is not valid"}),t&&(i="?"+D({ldaps:1,client_id:this.baseOptions.clientID})),r=n(this.baseOptions.rootUrl,"user","ssodata",i),this.request.get(r,{noHeaders:!0}).withCredentials().end(Et(e))};var Ae=function(){},Ce={lang:"en",templates:{auth0:function(t){var e="code"===t.type?"Enter the code shown above":"Solve the formula shown above";return'\n
\n
\n
\n'},recaptcha_v2:function(){return''},error:function(){return'Error getting the bot detection challenge. Please contact the system administrator.
'}}};var De=function(t,e,r,n){function i(n){n=n||Ae,t.getChallenge(function(t,o){return t?(e.innerHTML=r.templates.error(t),n(t)):o.required?(e.style.display="","auth0"===o.provider?function(t,e,r,n){t.innerHTML=e.templates[r.provider](r),t.querySelector(".captcha-reload").addEventListener("click",function(t){t.preventDefault(),n()})}(e,r,o,i):"recaptcha_v2"===o.provider&&function(t,e,r){var n=t.hasAttribute("data-wid")&&t.getAttribute("data-wid");function i(e){t.querySelector('input[name="captcha"]').value=e||""}if(n)return i(),void window.grecaptcha.reset(n);t.innerHTML=e.templates[r.provider](r);var o=t.querySelector(".recaptcha");!function(t,e,r){var n="recaptchaCallback_"+Math.floor(1000001*Math.random());window[n]=function(){delete window[n],r()};var i=window.document.createElement("script");i.src="https://www.google.com/recaptcha/api.js?hl="+e+"&onload="+n,i.async=!0,window.document.body.appendChild(i)}(0,e.lang,function(){n=window.grecaptcha.render(o,{callback:i,"expired-callback":function(){i()},"error-callback":function(){i()},sitekey:r.siteKey}),t.setAttribute("data-wid",n)})}(e,r,o),void n()):(e.style.display="none",void(e.innerHTML=""))})}return r=mt.merge(Ce).with(r||{}),i(n),{reload:i,getValue:function(){var t=e.querySelector('input[name="captcha"]');if(t)return t.value}}};function xe(){return new Date}function je(t){ct.check(t,{type:"object",message:"options parameter is not valid"},{domain:{type:"string",message:"domain option is required"},clientID:{type:"string",message:"clientID option is required"},responseType:{optional:!0,type:"string",message:"responseType is not valid"},responseMode:{optional:!0,type:"string",message:"responseMode is not valid"},redirectUri:{optional:!0,type:"string",message:"redirectUri is not valid"},scope:{optional:!0,type:"string",message:"scope is not valid"},audience:{optional:!0,type:"string",message:"audience is not valid"},popupOrigin:{optional:!0,type:"string",message:"popupOrigin is not valid"},leeway:{optional:!0,type:"number",message:"leeway is not valid"},plugins:{optional:!0,type:"array",message:"plugins is not valid"},maxAge:{optional:!0,type:"number",message:"maxAge is not valid"},_disableDeprecationWarnings:{optional:!0,type:"boolean",message:"_disableDeprecationWarnings option is not valid"},_sendTelemetry:{optional:!0,type:"boolean",message:"_sendTelemetry option is not valid"},_telemetryInfo:{optional:!0,type:"object",message:"_telemetryInfo option is not valid"},_timesToRetryFailedRequests:{optional:!0,type:"number",message:"_timesToRetryFailedRequests option is not valid"}}),t.overrides&&ct.check(t.overrides,{type:"object",message:"overrides option is not valid"},{__tenant:{optional:!0,type:"string",message:"__tenant option is required"},__token_issuer:{optional:!0,type:"string",message:"__token_issuer option is required"},__jwks_uri:{optional:!0,type:"string",message:"__jwks_uri is required"}}),this.baseOptions=t,this.baseOptions.plugins=new he(this,this.baseOptions.plugins||[]),this.baseOptions._sendTelemetry=!1!==this.baseOptions._sendTelemetry||this.baseOptions._sendTelemetry,this.baseOptions._timesToRetryFailedRequests=t._timesToRetryFailedRequests?parseInt(t._timesToRetryFailedRequests,0):0,this.baseOptions.tenant=this.baseOptions.overrides&&this.baseOptions.overrides.__tenant||this.baseOptions.domain.split(".")[0],this.baseOptions.token_issuer=this.baseOptions.overrides&&this.baseOptions.overrides.__token_issuer||"https://"+this.baseOptions.domain+"/",this.baseOptions.jwksURI=this.baseOptions.overrides&&this.baseOptions.overrides.__jwks_uri,this.transactionManager=new fe(this.baseOptions),this.client=new qe(this.baseOptions),this.redirect=new ve(this,this.baseOptions),this.popup=new Te(this,this.baseOptions),this.crossOriginAuthentication=new me(this,this.baseOptions),this.webMessageHandler=new ye(this),this._universalLogin=new Se(this,this.baseOptions),this.ssodataStorage=new Dt(this.baseOptions)}function Ee(t,e){this.baseOptions=e,this.request=t}function Ie(t,e){this.baseOptions=e,this.request=t}function qe(t,e){2===arguments.length?this.auth0=t:e=t,ct.check(e,{type:"object",message:"options parameter is not valid"},{domain:{type:"string",message:"domain option is required"},clientID:{type:"string",message:"clientID option is required"},responseType:{optional:!0,type:"string",message:"responseType is not valid"},responseMode:{optional:!0,type:"string",message:"responseMode is not valid"},redirectUri:{optional:!0,type:"string",message:"redirectUri is not valid"},scope:{optional:!0,type:"string",message:"scope is not valid"},audience:{optional:!0,type:"string",message:"audience is not valid"},_disableDeprecationWarnings:{optional:!0,type:"boolean",message:"_disableDeprecationWarnings option is not valid"},_sendTelemetry:{optional:!0,type:"boolean",message:"_sendTelemetry option is not valid"},_telemetryInfo:{optional:!0,type:"object",message:"_telemetryInfo option is not valid"}}),this.baseOptions=e,this.baseOptions._sendTelemetry=!1!==this.baseOptions._sendTelemetry||this.baseOptions._sendTelemetry,this.baseOptions.rootUrl=this.baseOptions.domain&&0===this.baseOptions.domain.toLowerCase().indexOf("http")?this.baseOptions.domain:"https://"+this.baseOptions.domain,this.request=new bt(this.baseOptions),this.passwordless=new Ee(this.request,this.baseOptions),this.dbConnection=new Ie(this.request,this.baseOptions),this.warn=new St({disableWarnings:!!e._disableDeprecationWarnings}),this.ssodataStorage=new Dt(this.baseOptions)}function Re(t){ct.check(t,{type:"object",message:"options parameter is not valid"},{domain:{type:"string",message:"domain option is required"},token:{type:"string",message:"token option is required"},_sendTelemetry:{optional:!0,type:"boolean",message:"_sendTelemetry option is not valid"},_telemetryInfo:{optional:!0,type:"object",message:"_telemetryInfo option is not valid"}}),this.baseOptions=t,this.baseOptions.headers={Authorization:"Bearer "+this.baseOptions.token},this.request=new bt(this.baseOptions),this.baseOptions.rootUrl=n("https://"+this.baseOptions.domain,"api","v2")}je.prototype.parseHash=function(t,e){var r,n;e||"function"!=typeof t?t=t||{}:(e=t,t={});var i=_t.getWindow(),o=void 0===t.hash?i.location.hash:t.hash;if((r=function(t,e){var r=function(t){if(!t)return k;if(null!==t.decoder&&void 0!==t.decoder&&"function"!=typeof t.decoder)throw new TypeError("Decoder has to be a function.");if(void 0!==t.charset&&"utf-8"!==t.charset&&"iso-8859-1"!==t.charset)throw new TypeError("The charset option must be either utf-8, iso-8859-1, or undefined");var e=void 0===t.charset?k.charset:t.charset;return{allowDots:void 0===t.allowDots?k.allowDots:!!t.allowDots,allowPrototypes:"boolean"==typeof t.allowPrototypes?t.allowPrototypes:k.allowPrototypes,arrayLimit:"number"==typeof t.arrayLimit?t.arrayLimit:k.arrayLimit,charset:e,charsetSentinel:"boolean"==typeof t.charsetSentinel?t.charsetSentinel:k.charsetSentinel,comma:"boolean"==typeof t.comma?t.comma:k.comma,decoder:"function"==typeof t.decoder?t.decoder:k.decoder,delimiter:"string"==typeof t.delimiter||u.isRegExp(t.delimiter)?t.delimiter:k.delimiter,depth:"number"==typeof t.depth||!1===t.depth?+t.depth:k.depth,ignoreQueryPrefix:!0===t.ignoreQueryPrefix,interpretNumericEntities:"boolean"==typeof t.interpretNumericEntities?t.interpretNumericEntities:k.interpretNumericEntities,parameterLimit:"number"==typeof t.parameterLimit?t.parameterLimit:k.parameterLimit,parseArrays:!1!==t.parseArrays,plainObjects:"boolean"==typeof t.plainObjects?t.plainObjects:k.plainObjects,strictNullHandling:"boolean"==typeof t.strictNullHandling?t.strictNullHandling:k.strictNullHandling}}(e);if(""===t||null==t)return r.plainObjects?Object.create(null):{};for(var n="string"==typeof t?function(t,e){var r,n={},i=e.ignoreQueryPrefix?t.replace(/^\?/,""):t,o=e.parameterLimit===1/0?void 0:e.parameterLimit,s=i.split(e.delimiter,o),a=-1,c=e.charset;if(e.charsetSentinel)for(r=0;r-1&&(h=O(h)?[h]:h),T.call(n,p)?n[p]=u.combine(n[p],h):n[p]=h}return n}(t,r):t,i=r.plainObjects?Object.create(null):{},o=Object.keys(n),s=0;s0&&-1!==s.indexOf("token")&&!r.hasOwnProperty("access_token")?e(jt.buildResponse("invalid_hash","response_type contains `token`, but the parsed hash does not contain an `access_token` property")):s.length>0&&-1!==s.indexOf("id_token")&&!r.hasOwnProperty("id_token")?e(jt.buildResponse("invalid_hash","response_type contains `id_token`, but the parsed hash does not contain an `id_token` property")):this.validateAuthenticationResponse(t,r,e)},je.prototype.validateAuthenticationResponse=function(t,e,r){var n=this;t.__enableIdPInitiatedLogin=t.__enableIdPInitiatedLogin||t.__enableImpersonation;var i=e.state,o=this.transactionManager.getStoredTransaction(i),s=t.state||o&&o.state||null,a=s===i;if((i||s||!t.__enableIdPInitiatedLogin)&&!a)return r({error:"invalid_token",errorDescription:"`state` does not match."});var u=t.nonce||o&&o.nonce||null,c=o&&o.organization,p=t.state||o&&o.appState||null,h=function(t,i){return t?r(t):(o&&o.lastUsedConnection&&(i&&(s=i.sub),n.ssodataStorage.set(o.lastUsedConnection,s)),r(null,function(t,e,r){return{accessToken:t.access_token||null,idToken:t.id_token||null,idTokenPayload:r||null,appState:e||null,refreshToken:t.refresh_token||null,state:t.state||null,expiresIn:t.expires_in?parseInt(t.expires_in,10):null,tokenType:t.token_type||null,scope:t.scope||null}}(e,p,i)));var s};return e.id_token?this.validateToken(e.id_token,u,function(t,r){if(!t){if(c){if(!r.org_id)return h(jt.invalidToken("Organization Id (org_id) claim must be a string present in the ID token"));if(r.org_id!==c)return h(jt.invalidToken('Organization Id (org_id) claim value mismatch in the ID token; expected "'+c+'", found "'+r.org_id+'"'))}return e.access_token&&r.at_hash?(new pe).validateAccessToken(e.access_token,"RS256",r.at_hash,function(t){return t?h(jt.invalidToken(t.message)):h(null,r)}):h(null,r)}if("invalid_token"!==t.error||t.errorDescription&&t.errorDescription.indexOf("Nonce (nonce) claim value mismatch in the ID token")>-1)return h(t);var i=(new pe).decode(e.id_token);return"HS256"!==i.header.alg?h(t):(i.payload.nonce||null)!==u?h({error:"invalid_token",errorDescription:'Nonce (nonce) claim value mismatch in the ID token; expected "'+u+'", found "'+i.payload.nonce+'"'}):e.access_token?n.client.userInfo(e.access_token,function(t,e){return t?h(t):h(null,e)}):h({error:"invalid_token",description:"The id_token cannot be validated because it was signed with the HS256 algorithm and public clients (like a browser) can't store secrets. Please read the associated doc for possible ways to fix this. Read more: https://auth0.com/docs/errors/libraries/auth0-js/invalid-token#parsing-an-hs256-signed-id-token-without-an-access-token"})}):h(null,null)},je.prototype.validateToken=function(t,e,r){new pe({issuer:this.baseOptions.token_issuer,jwksURI:this.baseOptions.jwksURI,audience:this.baseOptions.clientID,leeway:this.baseOptions.leeway||60,maxAge:this.baseOptions.maxAge,__clock:this.baseOptions.__clock||xe}).verify(t,e,function(t,e){if(t)return r(jt.invalidToken(t.message));r(null,e)})},je.prototype.renewAuth=function(t,e){var r=!!t.usePostMessage,n=t.postMessageDataType||!1,i=t.postMessageOrigin||_t.getWindow().origin,o=t.timeout,s=this,a=mt.merge(this.baseOptions,["clientID","redirectUri","responseType","scope","audience","_csrf","state","_intstate","nonce"]).with(t);a.responseType=a.responseType||"token",a.responseMode=a.responseMode||"fragment",a=this.transactionManager.process(a),ct.check(a,{type:"object",message:"options parameter is not valid"}),ct.check(e,{type:"function",message:"cb parameter is not valid"}),a.prompt="none",a=mt.blacklist(a,["usePostMessage","tenant","postMessageDataType","postMessageOrigin"]),Oe.create({authenticationUrl:this.client.buildAuthorizeUrl(a),postMessageDataType:n,postMessageOrigin:i,timeout:o}).login(r,function(t,r){if("object"==typeof r)return e(t,r);s.parseHash({hash:r},e)})},je.prototype.checkSession=function(t,e){var r=mt.merge(this.baseOptions,["clientID","responseType","redirectUri","scope","audience","_csrf","state","_intstate","nonce"]).with(t);return"code"===r.responseType?e({error:"error",error_description:"responseType can't be `code`"}):(t.nonce||(r=this.transactionManager.process(r)),r.redirectUri?(ct.check(r,{type:"object",message:"options parameter is not valid"}),ct.check(e,{type:"function",message:"cb parameter is not valid"}),r=mt.blacklist(r,["usePostMessage","tenant","postMessageDataType"]),void this.webMessageHandler.run(r,Et(e,{forceLegacyError:!0,ignoreCasing:!0}))):e({error:"error",error_description:"redirectUri can't be empty"}))},je.prototype.changePassword=function(t,e){return this.client.dbConnection.changePassword(t,e)},je.prototype.passwordlessStart=function(t,e){var r=mt.merge(this.baseOptions,["responseType","responseMode","redirectUri","scope","audience","_csrf","state","_intstate","nonce"]).with(t.authParams);return t.authParams=this.transactionManager.process(r),this.client.passwordless.start(t,e)},je.prototype.signup=function(t,e){return this.client.dbConnection.signup(t,e)},je.prototype.authorize=function(t){var e=mt.merge(this.baseOptions,["clientID","responseType","responseMode","redirectUri","scope","audience","_csrf","state","_intstate","nonce","organization","invitation"]).with(t);ct.check(e,{type:"object",message:"options parameter is not valid"},{responseType:{type:"string",message:"responseType option is required"}}),(e=this.transactionManager.process(e)).scope=e.scope||"openid profile email",_t.redirect(this.client.buildAuthorizeUrl(e))},je.prototype.signupAndAuthorize=function(t,e){var r=this;return this.client.dbConnection.signup(mt.blacklist(t,["popupHandler"]),function(n){if(n)return e(n);t.realm=t.connection,t.username||(t.username=t.email),r.client.login(t,e)})},je.prototype.login=function(t,e){var r=mt.merge(this.baseOptions,["clientID","responseType","redirectUri","scope","audience","_csrf","state","_intstate","nonce","onRedirecting","organization","invitation"]).with(t);r=this.transactionManager.process(r),_t.getWindow().location.host===this.baseOptions.domain?(r.connection=r.realm,delete r.realm,this._universalLogin.login(r,e)):this.crossOriginAuthentication.login(r,e)},je.prototype.passwordlessLogin=function(t,e){var r=mt.merge(this.baseOptions,["clientID","responseType","redirectUri","scope","audience","_csrf","state","_intstate","nonce","onRedirecting"]).with(t);if(r=this.transactionManager.process(r),_t.getWindow().location.host===this.baseOptions.domain)this.passwordlessVerify(r,e);else{var n=mt.extend({credentialType:"http://auth0.com/oauth/grant-type/passwordless/otp",realm:r.connection,username:r.email||r.phoneNumber,otp:r.verificationCode},mt.blacklist(r,["connection","email","phoneNumber","verificationCode"]));this.crossOriginAuthentication.login(n,e)}},je.prototype.crossOriginAuthenticationCallback=function(){this.crossOriginVerification()},je.prototype.crossOriginVerification=function(){this.crossOriginAuthentication.callback()},je.prototype.logout=function(t){_t.redirect(this.client.buildLogoutUrl(t))},je.prototype.passwordlessVerify=function(t,e){var r=this,n=mt.merge(this.baseOptions,["clientID","responseType","responseMode","redirectUri","scope","audience","_csrf","state","_intstate","nonce","onRedirecting"]).with(t);return ct.check(n,{type:"object",message:"options parameter is not valid"},{responseType:{type:"string",message:"responseType option is required"}}),n=this.transactionManager.process(n),this.client.passwordless.verify(n,function(i){if(i)return e(i);function o(){_t.redirect(r.client.passwordless.buildVerifyUrl(n))}if("function"==typeof t.onRedirecting)return t.onRedirecting(function(){o()});o()})},je.prototype.renderCaptcha=function(t,e,r){return De(this.client,t,e,r)},Ee.prototype.buildVerifyUrl=function(t){var e,r;return ct.check(t,{type:"object",message:"options parameter is not valid"},{connection:{type:"string",message:"connection option is required"},verificationCode:{type:"string",message:"verificationCode option is required"},phoneNumber:{optional:!1,type:"string",message:"phoneNumber option is required",condition:function(t){return!t.email}},email:{optional:!1,type:"string",message:"email option is required",condition:function(t){return!t.phoneNumber}}}),e=mt.merge(this.baseOptions,["clientID","responseType","responseMode","redirectUri","scope","audience","_csrf","state","_intstate","protocol","nonce"]).with(t),this.baseOptions._sendTelemetry&&(e.auth0Client=this.request.getTelemetryData()),e=mt.toSnakeCase(e,["auth0Client"]),r=D(e),n(this.baseOptions.rootUrl,"passwordless","verify_redirect","?"+r)},Ee.prototype.start=function(t,e){var r,i;return ct.check(t,{type:"object",message:"options parameter is not valid"},{connection:{type:"string",message:"connection option is required"},send:{type:"string",message:"send option is required",values:["link","code"],value_message:"send is not valid ([link, code])"},phoneNumber:{optional:!0,type:"string",message:"phoneNumber option is required",condition:function(t){return"code"===t.send||!t.email}},email:{optional:!0,type:"string",message:"email option is required",condition:function(t){return"link"===t.send||!t.phoneNumber}},authParams:{optional:!0,type:"object",message:"authParams option is required"}}),ct.check(e,{type:"function",message:"cb parameter is not valid"}),r=n(this.baseOptions.rootUrl,"passwordless","start"),(i=mt.merge(this.baseOptions,["clientID","responseType","redirectUri","scope"]).with(t)).scope&&(i.authParams=i.authParams||{},i.authParams.scope=i.authParams.scope||i.scope),i.redirectUri&&(i.authParams=i.authParams||{},i.authParams.redirect_uri=i.authParams.redirectUri||i.redirectUri),i.responseType&&(i.authParams=i.authParams||{},i.authParams.response_type=i.authParams.responseType||i.responseType),delete i.redirectUri,delete i.responseType,delete i.scope,i=mt.toSnakeCase(i,["auth0Client","authParams"]),this.request.post(r).send(i).end(Et(e))},Ee.prototype.verify=function(t,e){var r,i;return ct.check(t,{type:"object",message:"options parameter is not valid"},{connection:{type:"string",message:"connection option is required"},verificationCode:{type:"string",message:"verificationCode option is required"},phoneNumber:{optional:!1,type:"string",message:"phoneNumber option is required",condition:function(t){return!t.email}},email:{optional:!1,type:"string",message:"email option is required",condition:function(t){return!t.phoneNumber}}}),ct.check(e,{type:"function",message:"cb parameter is not valid"}),i=mt.pick(t,["connection","verificationCode","phoneNumber","email","auth0Client"]),i=mt.toSnakeCase(i,["auth0Client"]),r=n(this.baseOptions.rootUrl,"passwordless","verify"),this.request.post(r).send(i).end(Et(e))},Ie.prototype.signup=function(t,e){var r,i,o;return ct.check(t,{type:"object",message:"options parameter is not valid"},{connection:{type:"string",message:"connection option is required"},email:{type:"string",message:"email option is required"},password:{type:"string",message:"password option is required"}}),ct.check(e,{type:"function",message:"cb parameter is not valid"}),r=n(this.baseOptions.rootUrl,"dbconnections","signup"),o=(i=mt.merge(this.baseOptions,["clientID","state"]).with(t)).user_metadata||i.userMetadata,i=mt.blacklist(i,["scope","userMetadata","user_metadata"]),i=mt.toSnakeCase(i,["auth0Client"]),o&&(i.user_metadata=o),this.request.post(r).send(i).end(Et(e))},Ie.prototype.changePassword=function(t,e){var r,i;return ct.check(t,{type:"object",message:"options parameter is not valid"},{connection:{type:"string",message:"connection option is required"},email:{type:"string",message:"email option is required"}}),ct.check(e,{type:"function",message:"cb parameter is not valid"}),r=n(this.baseOptions.rootUrl,"dbconnections","change_password"),i=mt.merge(this.baseOptions,["clientID"]).with(t,["email","connection"]),i=mt.toSnakeCase(i,["auth0Client"]),this.request.post(r).send(i).end(Et(e))},qe.prototype.buildAuthorizeUrl=function(t){var e,r;return ct.check(t,{type:"object",message:"options parameter is not valid"}),e=mt.merge(this.baseOptions,["clientID","responseType","responseMode","redirectUri","scope","audience"]).with(t),ct.check(e,{type:"object",message:"options parameter is not valid"},{clientID:{type:"string",message:"clientID option is required"},redirectUri:{optional:!0,type:"string",message:"redirectUri option is required"},responseType:{type:"string",message:"responseType option is required"},nonce:{type:"string",message:"nonce option is required",condition:function(t){return-1===t.responseType.indexOf("code")&&-1!==t.responseType.indexOf("id_token")}},scope:{optional:!0,type:"string",message:"scope option is 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universalRest.post(t,e,!0)}function getProducts(e,r,t){return searchByQueryWithRawResults(universalAgora.buildProductsQuery(e),r).then(e=>{const r=universalQuery.formatSearchResult(e);return{total:e.hits.total,products:t?universalAgora.filterByLocale(r):r}})}function getMerchantsList(e){return searchByQueryWithRawResults(universalAgora.buildMerchantsAggregation(1e6,_get(e,"site.agoraLocale")),e).then(universalQuery.formatAggregationResults({aggregationName:"merchants",field:"key",subfield:"name"}))}module.exports.getProduct=universalAgora.getProduct,module.exports.getProducts=getProducts,module.exports.getMerchantsList=getMerchantsList,module.exports.searchByQueryWithRawResults=searchByQueryWithRawResults,module.exports.buildMerchantsByUrlQuery=universalAgora.buildMerchantsByUrlQuery;}, {"9":9,"19":19,"1340":1340,"1341":1341}];window.modules["1340"] = [function(require,module,exports){"use strict";const _map=require(72),_get=require(9),_isArray=require(171),_set=require(129),_isObject=require(108),_cloneDeep=require(90),_uniq=require(113);function formatSearchResult(e){return _map(e.hits.hits,"_source")}function newQuery(e){if(!e)throw new Error("An `index` is required to construct a query");return{index:e,type:"_doc",body:{query:{}}}}function addShould(e,o){var t=_get(e,"body.query.bool.should",void 0),r=_isArray(o);return t?r?_set(e,"body.query.bool.should",t.concat(o)):(t.push(o),_set(e,"body.query.bool.should",t)):_set(e,"body.query.bool.should",r?o:[o]),e}function addMust(e,o){var t=_get(e,"body.query.bool.must",void 0),r=_isArray(o);return t?r?_set(e,"body.query.bool.must",t.concat(o)):(t.push(o),_set(e,"body.query.bool.must",t)):_set(e,"body.query.bool.must",r?o:[o]),e}function addMustNot(e,o){var t=_get(e,"body.query.bool.must_not",void 0),r=_isArray(o);return t?r?_set(e,"body.query.bool.must_not",t.concat(o)):(t.push(o),_set(e,"body.query.bool.must_not",t)):_set(e,"body.query.bool.must_not",r?o:[o]),e}function addFilter(e,o){var t=_get(e,"body.query.bool.filter",void 0);if(!_isObject(o))throw new Error("Filter query required to be an object");return t?_isArray(t)?(t.push(o),_set(e,"body.query.bool.filter",t)):_set(e,"body.query.bool.filter",[_cloneDeep(t),o]):_set(e,"body.query.bool.filter",o),e}function addMinimumShould(e,o){if("number"!=typeof o)throw new Error("A number is required as the second argument");return _set(e,"body.query.bool.minimum_should_match",o),e}function addSort(e,o){var t=_get(e,"body.sort");return _isArray(t)||_set(e,"body.sort",t=[]),t.push(o),e}function addSize(e,o){if(!o&&0!==o)return e;if(o=parseInt(o),isNaN(o))throw new Error(`Second argument must be a number: ${o}`);return _set(e,"body.size",o)}function addFrom(e,o){if(!o&&0!==o)return e;if(o=parseInt(o),isNaN(o))throw new Error(`Second argument must be a number: ${o}`);return _set(e,"body.from",o)}function onlyWithTheseFields(e,o){if(!_isArray(o))throw new Error("Second argument is required to be an Array");return _set(e,"body._source.include",_uniq(o)),e}function onlyWithinThisSite(e,o){return o.subsiteSlug?addFilter(e,{term:{subsite:o.subsiteSlug}}):(addFilter(e,{term:{site:o.slug}}),addMustNot(e,{exists:{field:"subsite"}})),e}function onlyWithinThisDomain(e,o){return addFilter(e,{prefix:{canonicalUrl:`http://${o.host}`}}),e}function withinThisSiteAndCrossposts(e,o){var t={term:{}},r={bool:{should:[],minimum_should_match:1}};return t.term["crosspost."+(o.subsiteSlug||o.slug)]=!0,r.bool.should.push(t),o.subsiteSlug?r.bool.should.push({term:{subsite:o.subsiteSlug}}):(r.bool.should.push({term:{site:o.slug}}),addMustNot(e,{exists:{field:"subsite"}})),addFilter(e,r),e}function withinThisDomainOrCrossposts(e,o){return addShould(e,{term:{[`crosspost.${o.subsiteSlug||o.slug}`]:!0}}),addShould(e,{prefix:{canonicalUrl:`http://${o.host}`}}),addMinimumShould(e,1),e}function moreLikeThis(e,o,t){let r={fields:["tags"],like:{_index:e.index,_type:"_doc",_id:o},include:!1,min_term_freq:1,max_query_terms:12,min_doc_freq:1};return{more_like_this:Object.assign(r,t)}}function addAggregation(e={},o){const{body:t={}}=e;return o?(t.aggs?_set(e,"body.aggs",Object.assign(t.aggs,o)):_set(e,"body.aggs",o),e):e}function formatAggregationResults({aggregationName:e="",field:o="",subfield:t="",skipEmpty:r=!0}){return function(s={}){let u=_get(s,`aggregations.${e}${t?"."+t+".":"."}buckets`,[]);return r&&(u=u.filter(e=>0!==_get(e,"doc_count",0))),u.map(e=>e[o]||"")}}function addGeo(e,o){if(!_isArray(o))throw new Error("Second argument is required to be an Array");if(2!==o.length)throw new Error("Array must be length 2");if(o.some(isNaN))throw new Error("Array must only contain numbers");return _set(e,"body.query.geo_shape.location.shape.type","point"),_set(e,"body.query.geo_shape.location.shape.coordinates",o),e}function combineFunctionScoreQueries(e,o){let t=_cloneDeep(_get(e,"body.query",{})),r=_cloneDeep(_get(o,"body.query",{})),s=_get(e,"body.sort");return _set(e,"body.query",{}),_set(e,"body.query.function_score.functions",[]),e.body.query.function_score.functions.push({filter:t,weight:20}),e.body.query.function_score.functions.push({filter:r,weight:10}),e.body.query.function_score.score_mode="max",e.body.query.function_score.min_score=10,_isArray(s)||_set(e,"body.sort",s=[]),s.unshift({_score:"desc"}),e}function addNestedObjQuery(e,o,t){if(!e)throw new Error("There is no base query to perform the addNestedObjQuery operation");if(!o)throw new Error("There is no nested object path to perform the nested query against");if(!t)throw new Error("There is no nested query path to perform the nested query against");return _set(e,"nested",{path:o,query:t}),e}function addMatchAll(e){return _set(e,"body.query",{match_all:{}}),e}function addMultiMatch(e,o){const t=_get(e,"body.query.bool.must",void 0),{fields:r,type:s,string:u}=o,i={multi_match:{query:u,fields:r,type:s}};return t?(t.push(i),_set(e,"body.query.bool.must",t)):_set(e,"body.query.bool.must",[i]),e}module.exports=newQuery,module.exports.addGeo=addGeo,module.exports.addAggregation=addAggregation,module.exports.addShould=addShould,module.exports.addFilter=addFilter,module.exports.addMust=addMust,module.exports.addMustNot=addMustNot,module.exports.addMinimumShould=addMinimumShould,module.exports.addSort=addSort,module.exports.addSize=addSize,module.exports.addFrom=addFrom,module.exports.onlyWithTheseFields=onlyWithTheseFields,module.exports.onlyWithinThisSite=onlyWithinThisSite,module.exports.onlyWithinThisDomain=onlyWithinThisDomain,module.exports.withinThisSiteAndCrossposts=withinThisSiteAndCrossposts,module.exports.withinThisDomainOrCrossposts=withinThisDomainOrCrossposts,module.exports.formatAggregationResults=formatAggregationResults,module.exports.formatSearchResult=formatSearchResult,module.exports.moreLikeThis=moreLikeThis,module.exports.combineFunctionScoreQueries=combineFunctionScoreQueries,module.exports.addNestedObjQuery=addNestedObjQuery,module.exports.addMatchAll=addMatchAll,module.exports.addMultiMatch=addMultiMatch;}, {"9":9,"72":72,"90":90,"108":108,"113":113,"129":129,"171":171}];window.modules["1341"] = [function(require,module,exports){(function (process,__filename){(function (){"use strict";const _forEach=require(62),_get=require(9),_filter=require(155),_map=require(72),_isEmpty=require(109),urlParse=require(73),log=require(32).setup({file:__filename}),queryService=require(1340),universalRest=require(19),AGORA_HOST=window.process.env.AGORA_HOST,AGORA_ELASTIC_PREFIX=window.process.env.AGORA_ELASTIC_PREFIX,AGORA_ENDPOINT=AGORA_HOST?`${AGORA_HOST}/api/v1`:null,requestHeader={"Content-Type":"application/json"},PRODUCTS_INDEX="agora-products",AFFILIATES_INDEX="affiliates",RETAILERS_INDEX="retailers",FILTER_KEY={merchants:"name",affiliates:"affiliate"},URL_RE=/^https?:\/\/.*$/;function getProducts(e,t){const{limit:r=100,start:a=0,search:s="",sortDate:i="desc"}=e,n=`${AGORA_ENDPOINT}/products?limit=${r}&start=${a}&search=${encodeURIComponent(s)}&sortDate=${i}`;return fetch(n).then(handleResponse).then(e=>t?filterByLocale(e,t):e).then(e=>({total:e.length,products:e})).catch(handleError(n))}function getProduct(e,t){const r=`${AGORA_ENDPOINT}/products/${e}`;if(!AGORA_ENDPOINT)throw new Error("No Agora endpoint has been set");if("string"!=typeof e)throw new Error("request must provide a product id");return fetch(r).then(handleResponse).then(e=>t?filterByLocale(e,t):e).catch(handleError(r))}function postProduct(e){const t=`${AGORA_ENDPOINT}/products`,r={method:"POST",headers:requestHeader,body:JSON.stringify(e)};return fetch(t,r).then(handleResponse).catch(handleError(t))}function putProduct(e,t){const r=`${AGORA_ENDPOINT}/products/${e}`,a={method:"PUT",headers:requestHeader,body:JSON.stringify(t)};return fetch(r,a).then(handleResponse).catch(handleError(r))}function patchProduct(e,t){const r=`${AGORA_ENDPOINT}/products/${e}`,a={method:"PATCH",headers:requestHeader,body:JSON.stringify(t)};return fetch(r,a).then(handleResponse).catch(handleError(r))}function deleteProduct(e){const t=`${AGORA_ENDPOINT}/products/${e}`;return fetch(t,{method:"DELETE",headers:requestHeader}).then(handleResponse).catch(handleError(t))}function getMerchantList(e){const{limit:t=100,fields:r=""}=e;return Promise.resolve([{name:"Amazon"}]).catch(handleError(""))}function getMerchant(e){const t=`${AGORA_ENDPOINT}/merchants/${e}`;if("string"!=typeof e)throw new Error("request must provide a merchant id");return fetch(t).then(handleResponse).catch(handleError(t))}function patchMerchant(e,t){const r=`${AGORA_ENDPOINT}/merchants/${e}`,a={method:"PATCH",headers:requestHeader,body:JSON.stringify(t)};return fetch(r,a).then(handleResponse).catch(handleError(r))}function postMerchant(e){const t=`${AGORA_ENDPOINT}/merchants`,r={method:"POST",headers:requestHeader,body:JSON.stringify(e)};return fetch(t,r).then(handleResponse).catch(handleError(t))}function putMerchant(e,t){const r=`${AGORA_ENDPOINT}/merchants/${e}`,a={method:"PUT",headers:requestHeader,body:JSON.stringify(t)};return fetch(r,a).then(handleResponse).catch(handleError(r))}function deleteMerchant(e){const t=`${AGORA_ENDPOINT}/merchants/${e}`;return fetch(t,{method:"DELETE",headers:requestHeader}).then(handleResponse).catch(handleError(t))}function migrateMerchants(e){const t=`${AGORA_ENDPOINT}/merchants/migrate-affiliate`,r={method:"POST",headers:requestHeader,body:JSON.stringify(e)};return fetch(t,r).then(handleResponse).catch(handleError(t))}function getRetailers(e){const{limit:t=100,start:r=0}=e,a=`${AGORA_ENDPOINT}/retailers?limit=${t}&start=${r}`;return fetch(a).then(handleResponse).then(e=>({total:e.length,retailers:e})).catch(handleError(a))}function getRetailer(e){const t=`${AGORA_ENDPOINT}/retailers/${e}`;return fetch(t).then(handleResponse).catch(handleError(t))}function postRetailer(e){const t=`${AGORA_ENDPOINT}/retailers`,r={method:"POST",headers:requestHeader,body:JSON.stringify(e)};return fetch(t,r).then(handleResponse).catch(handleError(t))}function putRetailer(e,t){const r=`${AGORA_ENDPOINT}/retailers/${e}`,a={method:"PUT",headers:requestHeader,body:JSON.stringify(t)};return fetch(r,a).then(handleResponse).catch(handleError(r))}function deleteRetailer(e){const t=`${AGORA_ENDPOINT}/retailers/${e}`;return fetch(t,{method:"DELETE",headers:requestHeader}).then(handleResponse).catch(handleError(t))}function getAffiliates(e){const{limit:t=100,start:r=0}=e,a=`${AGORA_ENDPOINT}/affiliates?limit=${t}&start=${r}`;return fetch(a).then(handleResponse).then(e=>({total:e.length,affiliates:e})).catch(handleError(a))}function getAffiliateRetailers(e){const t=`${AGORA_ENDPOINT}/retailers/${e}/affiliates`;return fetch(t).then(handleResponse).catch(handleError(t))}function getAffiliateRetailer(e,t){const r=`${AGORA_ENDPOINT}/retailers/${e}/affiliates/${t}`;return fetch(r).then(handleResponse).catch(handleError(r))}function postAffiliateRetailer(e,t){const r=`${AGORA_ENDPOINT}/retailers/${e}/affiliates`,a={method:"POST",headers:requestHeader,body:JSON.stringify(t)};return fetch(r,a).then(handleResponse).catch(handleError(r))}function putAffiliateRetailer(e,t,r){const a=`${AGORA_ENDPOINT}/retailers/${e}/affiliates/${t}`,s={method:"PUT",headers:requestHeader,body:JSON.stringify(r)};return fetch(a,s).then(handleResponse).catch(handleError(a))}function deleteAffiliateRetailer(e,t){const r=`${AGORA_ENDPOINT}/retailers/${e}/affiliates/${t}`;return fetch(r,{method:"DELETE",headers:requestHeader}).catch(handleError(r))}function postLocale(e){const t=`${AGORA_ENDPOINT}/locales/`,r={method:"POST",headers:requestHeader,body:JSON.stringify(e)};return fetch(t,r).then(handleResponse).catch(handleError(t))}function patchLocale(e,t){const r=`${AGORA_ENDPOINT}/locales/${e}`,a={method:"PATCH",headers:requestHeader,body:JSON.stringify(t)};return fetch(r,a).then(handleResponse).catch(handleError(r))}function handleResponse(e){try{return e.json().then(t=>{if(e.status>=400){const e=_get(t,"message.details[0].message");throw new Error(e)}return t})}catch(e){throw new Error(e.message)}}function handleError(e){return t=>{throw log("warn",`Failed request to ${e}`,t),new Error(`request to ${e} failed`)}}function buildProductsQuery({search:e="",limit:t=100,start:r=0,sortDate:a="",filters:s,locale:i}){const n=queryService(PRODUCTS_INDEX),c=s&&Object.keys(s).length?Object.keys(s).filter(e=>Array.isArray(s[e])&&s[e].length):[],o={},l={};if(prependElasticPrefix(n),e||c.length||i||queryService.addMatchAll(n),i&&(queryService.addMust(o,{match:{"locales.locale":i}}),queryService.addMust(l,{match:{"merchants.locale":i}})),e)if(isURL(e))queryService.addMust(n,[queryService.addNestedObjQuery({},"merchants",{match:{"merchants.buyUrl":e}})]);else{const t={};queryService.addShould(t,[{match:{"locales.productId":e}},{match:{"locales.name":{query:e,boost:2}}}]),queryService.addMinimumShould(t,1),queryService.addMust(o,_get(t,"body.query"))}if(c.length){const e={};c.forEach(t=>{const r=s[t],a=FILTER_KEY[t],i={};a&&(i[`merchants.${a}`]=r,queryService.addMust(e,{terms:i}))}),queryService.addMust(l,_get(e,"body.query"))}return _isEmpty(o)||queryService.addMust(n,[queryService.addNestedObjQuery({},"locales",_get(o,"body.query"))]),_isEmpty(l)||queryService.addMust(n,[queryService.addNestedObjQuery({},"merchants",_get(l,"body.query"))]),queryService.addSize(n,t),r>=0&&queryService.addFrom(n,r),"desc"===a||"asc"===a?queryService.addSort(n,{updatedAt:{order:a}}):e&&queryService.addSort(n,{_score:{order:"desc"}}),n}function prependElasticPrefix(e){return e.index=AGORA_ELASTIC_PREFIX?`${AGORA_ELASTIC_PREFIX}_${e.index}`:e.index,e}function buildMerchantsAggregation(e=1e6,t){const r=queryService(PRODUCTS_INDEX);return prependElasticPrefix(r),queryService.addMust(r,{match:{active:!0}}),t&&queryService.addMust(r,queryService.addNestedObjQuery({},"merchants",_get(queryService.addMust({},{match:{"merchants.locale":t}}),"body.query"))),queryService.addAggregation(r,{merchants:{nested:{path:"merchants"},aggs:{name:{terms:{field:"merchants.name",size:e}}}}}),queryService.addSize(r,0),r}function isURL(e){return URL_RE.test(e)}function filterByLocale(e,t,r={locales:"US"}){const a=Array.isArray(e);if(_isEmpty(e))return a?[]:{};const s=["locales","merchants"],i=a?e:[e],n=Object.keys(r),c=_map(i,e=>{const a=Object.assign({},e);return _forEach(s,s=>{if(Object.keys(a).includes(s)){const i=t?_filter(e[s],["locale",t]):e[s];a[s]=i,!i.length&&n.includes(s)&&(a[s]=(_filter(e[s],["locale",r[s]])||[]).map(e=>(e.id=null,e.locale=t,e)))}}),a.name=_get(a,"locales[0].name",""),a});return a&&c.length?c:_get(c,"[0]",{})}function searchByQueryWithRawResults(e,t){const r=`//${t.site.host}${80!==t.site.port?`:${t.site.port}`:""}${t.site.path}/_agora/_search`;return universalRest.post(r,e,!0)}function buildMerchantsByUrlQuery(e){const t=queryService(PRODUCTS_INDEX);return prependElasticPrefix(t),queryService.addNestedObjQuery(t.body.query,"merchants",{match:{"merchants.buyUrl":e}}),t}function getAffiliatesByLocale(e,t){const r=queryService(AFFILIATES_INDEX);return prependElasticPrefix(r),queryService.addMust(r,{match:{locale:e}}),queryService.addSize(r,1e3),queryService.addSort(r,{name:"asc"}),searchByQueryWithRawResults(r,t).then(e=>_get(e,"hits.hits",[]).map(e=>_get(e,"_source",{})))}function buildRetailersQuery({search:e="",limit:t=50,start:r=0,direction:a="asc",locale:s="US"}){const i=queryService(RETAILERS_INDEX);return prependElasticPrefix(i),queryService.addMust(i,{match:{locale:s}}),e?queryService.addMultiMatch(i,{fields:["name","domains^2"],string:e,type:"phrase_prefix"}):(queryService.addSort(i,{"name.keyword":a}),queryService.addSize(i,t),r>=0&&queryService.addFrom(i,r)),i}function getRetailersList(e,t){return searchByQueryWithRawResults(buildRetailersQuery(e),t).then(e=>({total:_get(e,"hits.total",0),retailers:_get(e,"hits.hits",[]).map(e=>_get(e,"_source",{}))}))}function getRetailersByAffiliateId(e,t,r){const a=queryService(RETAILERS_INDEX);return e?(prependElasticPrefix(a),queryService.addMust(a,{match:{locale:r}}),queryService.addMust(a,[queryService.addNestedObjQuery({},"affiliateRetailers",{match:{"affiliateRetailers.affiliateId":e}})]),queryService.addSize(a,1e4),queryService.addSort(a,{"name.keyword":"asc"}),searchByQueryWithRawResults(a,t).then(e=>_get(e,"hits.hits",[]).map(e=>_get(e,"_source",{})))):Promise.reject()}function getMerchantsList(e){return searchByQueryWithRawResults(buildMerchantsAggregation(1e6,_get(e,"site.agoraLocale")),e).then(queryService.formatAggregationResults({aggregationName:"merchants",field:"key",subfield:"name"}))}function queryRetailersByUrl(e,t,r){const a=urlParse(e).host.split("www.").join(""),s=queryService(RETAILERS_INDEX);return queryService.addMust(s,{match:{locale:r}}),queryService.addMust(s,{match:{domains:a}}),prependElasticPrefix(s),queryService.addSize(s,10),searchByQueryWithRawResults(s,t).then(e=>_get(e,"hits.hits",[]).map(e=>_get(e,"_source",{})))}function queryRetailersByName(e,t,r){const a=queryService(RETAILERS_INDEX);return queryService.addMust(a,{match:{locale:r}}),queryService.addMust(a,{match:{"name.keyword":e}}),prependElasticPrefix(a),queryService.addSize(a,10),searchByQueryWithRawResults(a,t).then(e=>_get(e,"hits.hits",[]).map(e=>_get(e,"_source",{})))}require(229),module.exports={buildProductsQuery:buildProductsQuery,buildMerchantsAggregation:buildMerchantsAggregation,getProducts:getProducts,getProduct:getProduct,postProduct:postProduct,putProduct:putProduct,patchProduct:patchProduct,deleteProduct:deleteProduct,getMerchantList:getMerchantList,getMerchant:getMerchant,postMerchant:postMerchant,patchMerchant:patchMerchant,putMerchant:putMerchant,deleteMerchant:deleteMerchant,migrateMerchants:migrateMerchants,getRetailers:getRetailers,getRetailersList:getRetailersList,getRetailer:getRetailer,postRetailer:postRetailer,putRetailer:putRetailer,deleteRetailer:deleteRetailer,getRetailersByAffiliateId:getRetailersByAffiliateId,getAffiliates:getAffiliates,getAffiliateRetailers:getAffiliateRetailers,getAffiliateRetailer:getAffiliateRetailer,postAffiliateRetailer:postAffiliateRetailer,putAffiliateRetailer:putAffiliateRetailer,deleteAffiliateRetailer:deleteAffiliateRetailer,isURL:isURL,filterByLocale:filterByLocale,patchLocale:patchLocale,postLocale:postLocale,buildMerchantsByUrlQuery:buildMerchantsByUrlQuery,getAffiliatesByLocale:getAffiliatesByLocale,searchByQueryWithRawResults:searchByQueryWithRawResults,getMerchantsList:getMerchantsList,queryRetailersByUrl:queryRetailersByUrl,queryRetailersByName:queryRetailersByName};}).call(this)}).call(this,require(25),"/services/universal/agora.js")}, 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")),n=n.slice(n.lastIndexOf("/")+1);const l={kw:getKeywords(),network:r,page_type:a,entry_group:i,keywords:t,pn:n};return"Homepage"===a?o="homepage":"Section Page"===a&&(o=(o=window.location.pathname).replace(/\//g,"")),i&&-1===i.indexOf(" ")&&(o=i),customMappings[i]&&(o=customMappings[i]),window.location.hostname.match(/\.aws\./i)&&(l.clay_sandbox_env=r),new window.ConcertAds({cmd:[],slots:[],dfpVariables:l,slugPath:"/"+o.replace(/'--|''/g,"-"),loggedIn:"unauthenticated"!==e,paywallActive:getPaywallStatus(e)})}function getKeywords(){try{const e=window._nymPermutive.article.keywords;return e&&e.length>0&&e.some(Boolean)?e:(document.querySelector('meta[name="keywords"]')||document.querySelector('meta[property="article:tag"]')).getAttribute("content").split(",").map(function(e){return e.trim()})}catch(e){return}}function getData(e){if(window._nymPermutive){if(e in window._nymPermutive)return window._nymPermutive[e];if(window._nymPermutive.article&&e in window._nymPermutive.article)return window._nymPermutive.article[e];if(window._nymPermutive.user&&e in window._nymPermutive.user)return window._nymPermutive.user[e]}}function htmlDecode(e){var t=document.createElement("div");return t.innerHTML=e,0===t.childNodes.length?"":t.childNodes[0].nodeValue}function getAuthStatus(){const e=JSON.parse(localStorage.getItem("auth0:profile")),t=e?e["http://nymag.com/app_metadata"]:null;return t?t.has_subscription?"entitled":"unentitled":"unauthenticated"}function getPaywallStatus(e){const t=getData("totalCount")||0;return Boolean(t>=3&&"entitled"!==e)}window.ConcertAds?installConcertAds():window.addEventListener("concertAdsReady",installConcertAds);}, {"76":76}];window.modules["curated-feed.client"] = [function(require,module,exports){"use strict";const dom=require(4),lazyLoad=require(117);function lazyLoadImage(e){const o=dom.find(e,"img[data-src]"),t=dom.findAll(e,"source[data-srcset]"),a=dom.closest(e,".feed-item");if(o&&a){new lazyLoad.LazyLoader(a,o,t).init()}}function handleLazyLoad(e){(dom.findAll(e,".feed-item")||[]).forEach(lazyLoadImage)}module.exports=(e=>{const o=e.querySelectorAll("button.show-more");function t(e){const{currentTarget:o}=e;if(o){const e=o.parentElement.parentElement;e&&e.querySelector(".content").classList.toggle("collapsed")}}o&&o.forEach(function(e){e.addEventListener("click",t)}),handleLazyLoad(e)});}, {"4":4,"117":117}];window.modules["coral-talk.client"] = [function(require,module,exports){"use strict";const dom=require(4),store=require(137),visibility=require(5),auth0=require(7),TALK_AUTH="talk:auth_token";let coralEmbed,hasEmbedScriptLoaded=!1,hasCoralTalkRendered=!1;function renderComments(e){if(hasEmbedScriptLoaded&&!hasCoralTalkRendered){const t={talk:`${e.CORAL_TALK_HOST}`,auth_token:getAuthToken(),asset_url:e.TALK_ASSET_URL};hasCoralTalkRendered=!0,coralEmbed=window.Coral.Talk.render(e.commentStreamContainer,t)}}function getAuthToken(e){var t=e&&e["http://nymag.com/coral_talk"]||auth0.getTalkJwt(),i=store.get(TALK_AUTH);return t?i&&t==i?i:(store.set(TALK_AUTH,t),t):(i&&store.remove(TALK_AUTH),null)}function coralLogin(){coralEmbed.login(getAuthToken())}function embedScript(e,t){let i=document.createElement("script");i.type="text/javascript",i.async=!0,i.src=e,i.addEventListener("load",()=>{hasEmbedScriptLoaded=!0,renderComments(t)}),document.getElementsByTagName("head")[0].appendChild(i)}function initVerificationMessage(){auth0.isAuthenticated()&&auth0.refresh();let e=document.querySelector(".coral-talk-container");auth0.isAuthenticated()&&!auth0.isEmailVerified()&&(e.insertAdjacentHTML("beforebegin",'\n\n Please verify your account to enable commenting. 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'),document.querySelector(".activation-link").addEventListener("click",sendVerificationEmail))}function sendVerificationEmail(){let e=document.querySelector(".coral-talk-verify-address");return fetch(`https://${window.location.host}/_user/verification-email?user_id=${auth0.getUserID()}`,{method:"GET",headers:{"Content-Type":"application/json"}}).then(e=>e).then(t=>{t&&200==t.status?e.innerHTML="Verification email was sent successfully":e.innerHTML=`${t.statusText}`}).catch(e=>console.log(e))}function attemptScriptEmbedding(e,t){initVerificationMessage(),hasEmbedScriptLoaded?renderComments(t):embedScript(t.EMBED_URL,t)}function addVisibilityListener(e,t){new visibility.Visible(e,{preloadThreshold:750}).on("preload",()=>attemptScriptEmbedding(e,t))}function removeSignInButton(e){e&&e.parentNode&&dom.removeElement(e)}function init(e){const t=e.getAttribute("data-coral-talk-host"),i=`${t}/static/embed.js`,n=`http://${document.documentElement.getAttribute("data-uri")}.html`,a="true"===e.getAttribute("data-maintenance"),o=-1!==n.indexOf("@published"),r=e.querySelector(".coral-talk-container"),s=e.querySelector(".coral-talk-btn-signin"),c={CORAL_TALK_HOST:t,EMBED_URL:i,commentStreamContainer:r,signInButton:s,TALK_ASSET_URL:n};!a&&o&&(auth0.on("init",()=>{addVisibilityListener(e,c),s.addEventListener("click",()=>auth0.showLogin()),auth0.isAuthenticated()&&removeSignInButton(s)}),auth0.on("login",t=>{removeSignInButton(s),getAuthToken(t),visibility.isElementInViewport(e)&&attemptScriptEmbedding(c),hasCoralTalkRendered&&coralLogin()}),auth0.on("logout",()=>{store.remove(TALK_AUTH)}))}module.exports=init;}, {"4":4,"5":5,"7":7,"137":137}];window.modules["choreographer.client"] = [function(require,module,exports){"use strict";const cookie=require(63),_get=require(9),_omit=require(95),{insertSpeedBumpComponents:insertSpeedBumpComponents}=require(99),{insertNewsletterSpeedBumpComponents:insertNewsletterSpeedBumpComponents}=require(100),{generateGrowl:generateGrowl}=require(98),gtm=require(3),{getLocalStorage:getLocalStorage,setLocalStorage:setLocalStorage}=require(45),{reportPaywall:reportPaywall}=require(75),moment=require(50),{getClientHistory:getClientHistory,updateClientHistoryWithPageData:updateClientHistoryWithPageData}=require(101),auth0=require(7),{Scenario:Scenario}=require(96),cidReadyEvent="nymcid-set",cidKey="nymcid",isProduction=require(8)(),logger=require(94).Logger(()=>getLocalStorage("show_choreographer_logs")),{Verdon:Verdon}=require(97),TEST_COHORT_FLAG="optimizeCohort";function displayDebug(e=""){if("entitlement"!==e.split("#").pop())return;const t=_get(window,"dataLayer[0].userDetails",{}),o=_get(window,"dataLayer[0].pageDetails.featureTypes",""),n=o.includes("magazine")?"magazine":"",r=o.includes("feature")?"featured":"",i="Value of Article: "+(n||r||"article"),a=_get(JSON.parse(localStorage.getItem("auth0:profile")),"http://nymag.com/app_metadata"),l="Authentication Status: "+(a?"authenticated":"unauthenticated"),s="Entitlement Status: "+(!!a&&a.has_subscription?"entitled":"unentitled"),c=Object.keys(_omit(t,"newYorkMediaUserID")).map(e=>`${e}: ${t[e]}`),d=document.body,g=document.createElement("div"),u=document.createElement("ul");[i,l,s,...c].map(e=>{const t=document.createElement("li");return t.classList.add("debug-item"),t.appendChild(document.createTextNode(e)),t}).forEach(e=>{u.appendChild(e)}),u.classList.add("data-bullets"),g.classList.add("debug-choreographer"),g.classList.add("display-debug-data"),g.appendChild(u),d.appendChild(g)}function initializeChoreographer(e){const t=e.getAttribute("data-site-slug"),o=pageShouldCountAsView(t),n=auth0.isSubscriber();return t?getClientId(cidKey,8e3).then(e=>(logger.h1("Choreographer initialized"),logger.log(`clientId: ${e}`),logger.log(`page counts as a view: ${o}`),window.nymViewsResponse||(o?updateClientHistoryWithPageData(e,t):getClientHistory(e)))).then(r=>{if(logger.group(),logger.h2("Client history"),logger.table(r),logger.groupEnd(),isNCR())return;const{scenarios:i,touts:a,testCohort:l=""}=readJSONFromScript(e.querySelector("script"));if(!(l===(document.body.dataset[TEST_COHORT_FLAG]||"")))return;const s=i.map(e=>Scenario(Object.assign({},e,{history:r,siteSlug:t,isSubscriber:n}))).filter(e=>(logger.group(),logger.h2("Evaluating scenarios"),logger.log(e),logger.groupEnd(),e.shouldShow)).reduce((e,{action:t,min:o,count:n})=>{const r=a.find(({value:e})=>e===t);return r?(e[r.type]=r,e[r.type].viewCount=n-o,e):e},{});logger.group(),logger.h2("Active Touts"),logger.log(s),logger.groupEnd(),executeTouts(e,o,s,r)}).catch(console.error):console.error("siteSlug not found.")}function documentIncludesComponent(e){return document.querySelector(`[data-uri*="/${e}/"]`)}function pageShouldCountAsView(e){const t="strategist"===e,o=["product","product-grid"].find(e=>documentIncludesComponent(e));return t||!o}function executeTouts(e,t,o={},n){const{global:r}=n,i={featureArticleCount:r.Feature||0,magazineArticleCount:r.Magazine||0,standardArticleCount:r.Article||0,totalArticleCount:r.total||0},a=window.concertAds,l=window.ConcertAds;if(o["speed-bump"]&&(_get(a,"adsBlocked",!0)?insertSpeedBumpComponents(findTemplate(e,"speed-bump"),o["speed-bump"],i):a.lifecycle.listenAndPlayback(l.events.slotsInserted,()=>{insertSpeedBumpComponents(findTemplate(e,"speed-bump"),o["speed-bump"],i)})),o["newsletter-speed-bump"]&&(_get(a,"adsBlocked",!0)?insertNewsletterSpeedBumpComponents(findTemplate(e,"newsletter-speed-bump"),o["newsletter-speed-bump"],i):a.lifecycle.listenAndPlayback(l.events.slotsInserted,()=>{insertNewsletterSpeedBumpComponents(findTemplate(e,"newsletter-speed-bump"),o["newsletter-speed-bump"],i)})),o["branded-growl"]&&brandedTakeoverTime(o["branded-growl"])&&t)return logger.log("should show branded growl"),void growlManager(findTemplate(e,"branded-growl"),{baseTrackingData:i,body:o["branded-growl"].brandedGrowlBody,contentClass:"branded-content",cta:o["branded-growl"].brandedGrowlCTA,imageUrl:o["branded-growl"].imageUrl,link:o["branded-growl"].brandedGrowlLink,name:o["branded-growl"].name,scrollDepth:o["branded-growl"].brandedGrowlScrollDepth,title:o["branded-growl"].brandedGrowlTitle,toutType:"branded growl"},"#branded-growl");if(t&&o["content-cliff"])contentCliff(findTemplate(e,"content-cliff"),o["content-cliff"],o["content-cliff"].viewsLeft,n);else{if(t&&o["cliff-takeover"])return/coronavirus news|pivot|paywall exclude/i.test(window._nymGtmPage.tags)?void(isProduction&&logger.log("Content cliff no-op due to excluded tag match: ",window._nymGtmPage.tags)):void cliffTakeover(findTemplate(e,"paywall-reader-interface"),i,o["cliff-takeover"]);if(o["growl-newletter"]||!o["promo-growl"])if(o["baby-growl"])babyGrowl(findTemplate(e,"paywall-reader-interface"),i,o["baby-growl"]);else{if(!o["warning-growl-2"])return o["warning-growl"]&&shouldWarn()?(setContentCliffWarningDisplayed(),logger.log("should show warning"),void growlManager(findTemplate(e,"warning-growl"),{contentClass:"warning-content",title:o["warning-growl"].warningGrowlTitle,name:o["warning-growl"].name,scrollDepth:o["warning-growl"].warningGrowlScrollDepth,cta:o["warning-growl"].warningGrowlCTA,body:o["warning-growl"].warningGrowlBody,link:o["warning-growl"].warningGrowlLink,baseTrackingData:i,toutType:"warning growl"},"#warning-growl")):void 0;warningGrowl(findTemplate(e,"paywall-reader-interface"),i,o["warning-growl-2"])}else growlManager(findTemplate(e,"growl-message"),{contentClass:"promo-content",title:void 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document.createRange().createContextualFragment(e)}(),p={creative:i,id:c,name:n,position:"growl"};u.querySelector("a").addEventListener("click",()=>promotionReport("Click",s,p)),generateGrowl(e,g,{content:u,scrollDepth:o,onShow:()=>promotionReport("View",s,p)})}function contentCliff(e,t,o,n){const{first_visit:r,global:i}=n,a={totalArticleCount:i.total||0,standardArticleCount:i.Article||0,featureArticleCount:i.Feature||0,magazineArticleCount:i.Magazine||0},{contentCliffBody:l}=t,s=document.importNode(e,!0).querySelector(".content-cliff"),c=document.querySelector(".article-content > .clay-paragraph"),d={creative:l,id:"content cliff",name:"Content Cliff",position:"in-article"};s&&(c.insertAdjacentHTML("afterend",s.outerHTML),require("content-cliff.client")(document.querySelector(".content-cliff"),{contentCliffOptions:t,viewsLeft:o,firstVisit:Number(r),onShow:()=>promotionReport("View",a,d),onClickCliff:()=>promotionReport("Click",a,d)}))}function verdonFosseToutSetter(e,t,o,n,r){const i=new Verdon({container:".paywall-reader-interface",url:"https://fosse.nymag.com/fosse/v1.6.1/index.html"}),a=e.type,l={email:auth0.getEmail(),isAuthenticated:auth0.isAuthenticated(),isSubscriber:auth0.isSubscriber()};n.classList.add(a),i.once("frame:ready",()=>{i.sendMessage("tout:show",{readerState:l,toutType:a,toutData:e}),r&&i.sendMessage("frame:height")}),i.on("tout:visible",()=>{promotionReport("View",t,o)}),i.on("tout:sign-in",()=>{auth0.showLogin(window.location.href)}),i.on("tout:log-out",()=>{auth0.logout()}),i.on("tout:dismiss",()=>{n.classList.add("dismiss"),i.sendMessage("tout:hide",{toutType:a,toutData:e})}),i.on("tout:subscribe",()=>{e.ctaLink=replaceQueryParams(e.ctaLink),promotionReport("Click",t,o),window.open(e.ctaLink,"_blank")}),i.on("frame:height",e=>{n.style.height=`${e.payload.currentHeight+10}px`}),i.on("tout:view-account",()=>{window.location.href="https://subs.nymag.com/account"})}function promotionReport(e,t,o){const{creative:n,id:r,name:i,position:a}=o;t.event=`eec.promotion${e}`,t.ecommerce={promoView:{promotions:[{creative:n.trim(),id:r,name:i,position:a}]}},gtm.reportNow(t),reportPaywall({creative:n.trim(),eventType:e,id:r,name:i,position:a})}function babyGrowl(e,t,o){const n=document.importNode(e,!0).querySelector(".paywall-reader-interface"),r={creative:o.babygrowlDescription,id:"baby growl",name:"baby growl",position:"growl"};document.body.appendChild(n),o.ctaLink=o.babygrowlCtaLink,o.ctaText=o.babygrowlMessage,o.headline=o.babygrowlDescription,verdonFosseToutSetter(o,t,r,n)}function cliffTakeover(e,t,o){const{cliffTakeoverCTA:n,cliffTakeoverCtaLink:r,cliffTakeoverDescription:i,cliffTakeoverImage:a,cliffTakeoverPromo:l,cliffTakeoverStatus:s,type:c}=o,d=document.importNode(e,!0).querySelector(".paywall-reader-interface"),g=document.querySelectorAll(".clay-paragraph"),u={creative:l,id:"content cliff",name:"Content Cliff",position:"growl"},p={cta:n,ctaLink:r,description:i,image:a,promo:l,status:s,type:c};document.body.appendChild(d),g.forEach((e,t)=>{0!==t&&e.remove()}),verdonFosseToutSetter(p,t,u,d,!0),document.querySelector("html").style.overflowY="hidden",document.body.style.position="fixed"}function warningGrowl(e,t,o){const{type:n,warningGrowl2CTA:r,warningGrowl2CtaLink:i,warningGrowl2Description:a,warningGrowl2Image:l,warningGrowl2Promo:s,warningGrowl2Status:c}=o,d=document.importNode(e,!0).querySelector(".paywall-reader-interface"),g={creative:s,id:"warning growl",name:"Warning Growl",position:"growl"},u={cta:r,ctaLink:i,description:a,image:l,promo:s,status:c,type:n};document.body.appendChild(d),verdonFosseToutSetter(u,t,g,d,!0)}function getClientId(e="",t=8e3){let o=cookie.get(e);return o?Promise.resolve(o):new Promise((o,n)=>{const r=setTimeout(()=>{n(`could not find key: ${e} on cookie after ${t}ms`)},t);window.addEventListener(cidReadyEvent,()=>{clearTimeout(r),o(cookie.get(e))})})}function readJSONFromScript(e){try{return JSON.parse(e.innerHTML)}catch(e){return{touts:[],scenarios:[]}}}function findTemplate(e,t=""){const o=e&&e.querySelector(`[data-template-id="${t}"]`);return o&&o.content}function isNCR(){return/[?&]source=ncr/.test(location.search)}function brandedTakeoverTime(e){const{startTime:t,endTime:o,startDate:n,endDate:r}=e,i=n.concat(" ",t),a=r.concat(" ",o),l=moment(i),s=moment(a);return moment().isBetween(l,s)}function optimizeDebugger(){return new Promise(e=>{const t=window.location.search||"";if(t){const o=new URLSearchParams(t),n=o.get("optimize-attribute-name")||"",r=o.get("optimize-attribute-value")||"",i=o.get("optimize-delay")||0,a=o.get("optimize-cookie")||!1;setTimeout(()=>{a&&(document.cookie=randomNymcid()),document.body.setAttribute(`data-${n}`,r),e()},i)}else e()})}function 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{"4":4,"45":45,"84":84,"161":161}];window.modules["speed-bump.client"] = [function(require,module,exports){"use strict";const gtm=require(3),visibility=require(5);module.exports=((e,i)=>{if(!i||!e)return;const{name:o,speedbumpDescription:r,speedbumpMessage:t,speedbumpLink:n,baseTrackingData:s}=i,c=new visibility.Visible(e,{shownThreshold:.5});e.querySelector(".description").innerHTML=r,e.querySelector(".promo-link").innerHTML=t,e.querySelector(".promo-link").href=n,e.classList.remove("collapsed"),c.on("shown",function(){if(visibility.isElementNotHidden(e)){let e=s;e.event="eec.promotionView",e.ecommerce={promoView:{promotions:[{name:o,creative:r,id:"speed bump",position:"in-article"}]}},gtm.reportNow(e),c.destroy()}}),e.querySelector(".promo-link").addEventListener("click",function(){let e=s;e.event="eec.promotionClick",e.ecommerce={promoClick:{promotions:[{name:o,creative:r,id:"speed bump",position:"in-article"}]}},gtm.reportNow(e)})});}, 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Haberman: Trump pressing conservative media to write election was 'stolen' | TheHill
Wed, 02 Jun 2021 17:46
Former President Trump Donald TrumpRNC warns it will advise presidential candidates against future debates if panel doesn't make changes Washington Post issues correction on 2020 report on Tom Cotton, lab-leak theory National Enquirer publisher fined for breaking law with McDougal payment: WSJ MORE wants conservative media to legitimize his conspiracy theories about the 2020 presidential election being stolen and that he'll soon be reinstated, New York Times reporter Maggie Haberman Maggie Lindsy HabermanThe Hill's 12:30 Report: Biden faces pressure amid infrastructure negotiations The Hill's 12:30 Report - Biden's next social safety net push The Hill's 12:30 Report - Presented by ExxonMobil - Pence sets the stage for 2024 MORE said Wednesday.
''He has been trying to get conservative writers to publish, you know, in a more mainstream way that this election was, quote unquote, stolen from him,'' Haberman told CNN ''New Day'' co-host John Berman, without naming any writers.
She said Trump has been ''laser focused'' on the Arizona election audit and reaching out to other conservative politicians and commentators for support, hoping they'll help promote the idea that the elections will be overturned.
''And none of that is possible. But this is the kind of thing that he is trying to flush into the conservative media ecosystem,'' Haberman said. ''And I expect it to get more intense the more he is under investigation by the Manhattan district attorney and the state attorney general in New York and the threat of indictment over the coming months.''
A spokesperson for Trump did not immediately provide a comment on Haberman's remarks.
Haberman's CNN appearance came a day after she tweeted that Trump has been privately asserting that he would be ''reinstated'' as president.
''Trump has been telling a number of people he's in contact with that he expects he will get reinstated by August (No, that isn't how it works but simply sharing the information),'' she tweeted.
Trump has been telling a number of people he's in contact with that he expects he will get reinstated by August (no that isn't how it works but simply sharing the information). https://t.co/kaXSXKnpF0
'-- Maggie Haberman (@maggieNYT) June 1, 2021 Her post reignited a debate on Twitter about reporting on discredited conspiracy theories of the former president and his supporters.
Her reporting did not give his ravings any appearance of legitimacy at all.
'-- James Surowiecki (@JamesSurowiecki) June 1, 2021 Haberman addressed the criticism on ''New Day,'' telling Berman and co-host Brianna Keilar that ignoring Trump and his theories won't make them go away.
''You know, why people are attacking me for reporting the news ... this has always been a bit of a mystery,'' Haberman said.
''As I said before, I think people are in their own media ecosystems. And I think that there are a lot of people around [President] Biden and a lot of people who support Biden who want to pretend that if they call Trump the former guy, and if you don't say his name, that the only thing that would matter is if you give him attention. He's the former president. He is in control of the Republican Party to a big extent.''
Facing Indictments in New York, Donald Trump Removes Blog Section of His Website | Showbiz411
Wed, 02 Jun 2021 17:41
Home Politics Facing Indictments in New York, Donald Trump Removes Blog Section of His... No more bloviating for Donald Trump.
The former and unloved president has excised the blog section of his website at www.donaldjtrump.com. It's gone but for a few short platitudes.
Trump boasted to his base that the website was going to be a incredible new platform to communicate with them on since Twitter, Facebook, and YouTube had removed him.
But now as his possible indictments in New York are heating up and a grand jury is considering his fate, Trump has backed off his idiotic proclamations.
Only yesterday he claimed that he'd be ''reinstated'' as president come August. This seemed to me like the result of onset dementia. It must have appeared that way to his lawyers as well.
So goodbye again, Donnie. Start working on your prison diaries.
Fauci Emails Give Insight To Early Days Of COVID Response
Wed, 02 Jun 2021 13:59
Pool / Getty ImagesAnthony Fauci waits to testify on Capitol Hill in June 2020
The woman's email arrived in Anthony Fauci's inbox on Feb. 28, 2020, with a one-word subject line: ''URGENT.''
The coronavirus crisis was still in its early stages, and Fauci, the US government's top infectious disease scientist, was already under tremendous pressure, both because of the health threat facing the country and the political climate fostered by the Trump administration.
''I understand Vice President Pence has ordered you to not inform the public about Coronavirus without approval. This is quite terrifying, especially since Trump has already shown his desire to spread false or incomplete information about this public health crisis,'' the woman wrote.
She had tracked down Fauci's email, which is not easily accessible on government websites, because she had a pressing question: ''I'm planning to fly domestically TOMORROW [REDACTED]. Is it safe??''
Of course, Fauci had urgent matters of his own to attend to, but he replied to the stranger anyway the next day. ''There is much misinformation,'' he wrote back. ''I actually have not been muzzled at all by the Vice President. And BTW, it is safe to fly domestically [REDACTED].''
More than 3,200 pages of emails obtained through a Freedom of Information Act lawsuit filed by BuzzFeed News '-- covering the period from January to June 2020 '-- provide a rare glimpse into how Fauci approached his job during the biggest health crisis of the last century, showing him dealing directly with the public, health officials, reporters, and even celebrities. (The Washington Post also received more than 800 pages of emails and published a story about them on Monday.)
The emails reviewed by BuzzFeed News reveal him sparring over an antiviral drug with Ezekiel Emanuel, a former Obama administration health adviser, fielding questions about vaccines, and receiving an update from Mark Zuckerberg on Facebook's plans for a coronavirus ''information hub.'' Zuckerberg also asked whether the social media company could provide resources to accelerate vaccine testing. And Fauci even responded to an offer from actor Morgan Fairchild to use her Twitter account on his behalf.
Obtained by BuzzFeed News via FOIA Obtained by BuzzFeed News via FOIA''It would be great if you could tweet to your many Twitter followers,'' he responded to Fairchild. ''The American public should not be frightened, but should be prepared to mitigate an outbreak in this country by measures including social distancing, teleworking, temporary closure of schools, etc.''
Obtained by BuzzFeed News via FOIAThe emails show Fauci received a flurry of correspondence about the theory that coronavirus leaked from a lab in Wuhan. One such email sent to Fauci on April 16, 2020 by Francis Collins, the director of the National Institute of Health, under the subject line "conspiracy gains momentum" contained a link to a news story highlighting a Fox News report that said the allegation had merit. Fauci's response to Collins is entirely blacked out.
The records also lay bare Fauci's ambivalence toward his newfound celebrity status but also his embrace of a documentary crew who would tell his story. Additionally, the emails hint at the personal toll this past year has taken on him. In one email sent on Feb. 18, weeks before COVID-19 was declared a global pandemic, he wrote that he had only been able to see his wife for 45 minutes in the previous 10 days.
Fauci, who has been director of the National Institute of Allergy and Infectious Diseases since 1984, declined to comment for this story.
Some of the emails were reviewed by the Trump White House before being turned over to BuzzFeed News. They represent just a portion of what was requested, and they are filled with redactions, making them an incomplete record of the time period and Fauci's correspondence. Additional tranches are expected to be released in the coming months.
However, the emails do give a sense of the type of communicator Fauci is: courteous, low-key, and empathetic. He politely interacts with the office assistants who help him with his correspondence, and he sweats over the proper way to let people down.
When a White House fellow and physician emails Fauci and offers to team up to write an opinion piece on the coronavirus and ''unite the nation,'' the NIAID director asks a colleague, ''How do we nicely say no to this person?''
And when health professionals write him with harsh criticism of Trump's handling of the pandemic, he doesn't take the bait. Instead, he replies with a "thank you."
Obtained by BuzzFeed News via FOIAHis tone is a mix of friendly and formal, employing phrases like ''let us discuss,'' ''many thanks,'' and '-- in rare displays of displeasure '-- a delicate ''yikes!'' He signs off as ''Tony.''
Even though he tends to sidestep controversy, Fauci does defend his decisions and push back.
In March 2020, Fauci and a few other colleagues received an email from Gregg Gonsalves, a prominent Yale School of Public Health epidemiologist, urging the NIAID director and his team to act promptly on the virus. The subject line was ''We Are Desperate for Advice.''
''For those I know, I don't doubt your commitment to public service,'' Gonsalves wrote. ''But time is running out. We need vocally, unequivocal leadership now, that offers real guidance to communities about what to do, what might happen next.''
Obtained by BuzzFeed News via FOIAFauci clearly resented any implication that his health team's response was being shaped by the political values of the Trump administration, and he responded curtly three hours later.
''Gregg: I am surprised you included me in your note," he wrote. "I genuflect to no one but science and always, always speak my mind when it comes to public health. I have consistently corrected misstatements by others and will continue to do so.''
Obtained by BuzzFeed News via FOIA Obtained by BuzzFeed News via FOIAFauci, 80, has tackled the world's most difficult health crises and infectious diseases, such as HIV/AIDS, Ebola, and Zika, earning respect in his field and the trust of many Americans. As the COVID-19 crisis deepened, his inbox filled with queries from people seeking guidance, solace, or morsels of medical advice.
On March 4, under the subject line ''A humble request for your wisdom,'' a woman wrote to Fauci and asked whether a person inoculated against pneumonia would be protected against COVID-19.
One hour later, at 9:45 p.m. on a Wednesday, Fauci replied that complications from COVID-19 are ''heavily skewed'' toward people who are older or have underlying conditions. He went into a lengthy explanation:
''Most of the pneumonias are pure viral pneumonia and so this vaccination will not help that,'' he wrote. ''However, on the chance that you have a pure viral pneumonia that gets secondarily complicated by a bacterial pneumonia (pneumococcal) the vaccine would be beneficial.
''If you are 65 years of age or older, you should get pneumonvax23 anyway regardless of the risk of coronavirus infection. Thanks, Tony.''
Five minutes later, the woman wrote back, ''Oh my god. '... I honestly never expected you to reply and I thank you from the bottom of my heart for being so generous!''
Some writers emailed mainly to vent. Among them: a Florida infectious disease specialist who was upset that some Americans were not taking proper precautions.
''I am putting my life on the line so folks can go pump iron, drink beer, have a burger and get a tan,'' Doug Brust emailed Fauci on March 18.
"The band is playing on. Again,'' Brust wrote, a reference to one of the most famous books of the AIDS epidemic, And the Band Played On, which exposed the hapless efforts of the government and the public medical establishment to address the health crisis.
Obtained by BuzzFeed News via FOIAAnd reporters, of course, reached out with questions for the doctor considered the country's foremost expert. One email exchange, however, shows how even Fauci couldn't see all that was coming.
Just a day after the first reported COVID-19 death in the United States, the managing editor of ABC News' medical unit emailed Fauci and asked him if he agreed with what a source at the Department of Homeland Security told him: that epidemiology models showed that 98 million people could be infected with COVID-19 and deaths from the virus could reach 500,000.
''That seems exceptionally high,'' Fauci responded.
His guidance was not always welcomed by his own bosses at the White House. He faced a wide range of harassment, including angry tweets from Trump that questioned his expertise.
Those conflicts also get referenced in the emails. In April, a top Chinese health official emailed Fauci about vaccines. As part of that thread, the official expressed concern about him ''being attacked by some people.''
''Thank you for your kind note. All is well despite some crazy people in this world,'' Fauci replied.
Even as he gained enemies and roused critics, many of the emails also reflect his growing stature around the world.
''Dear '-- highly respected '-- Dr. Fauci,'' a doctor from Austria writes in bolded text. ''Why do I try to childishly support a respected expert and personally highly honored Gentleman like you '-- Dr. Fauxi? Because for me '-- it is heartbreaking and unbelievably disturbing, what was and is going on of the last 4 months in the USA.''
He goes on to lay out a strategy for nations to cope with the devastating effects of the pandemic.
''Not a crazy note. Please respond on my behalf,'' Fauci writes to a staff member.
On May 5, 2020, Mary Harris, an NIAID employee, wrote: ''I am grateful to say my Director is Dr. Anthony Fauci and share with my family, friends, and church that if you said it, it's gospel.''
Along the way, the scientist was becoming a celebrity. Just a couple of months into the pandemic, T-shirts, bobbleheads, socks, and even prayer candles with his face plastered on them were being sold. Fauci's emails show he was clearly uncomfortable with the attention.
''Click on the 'Cuomo Crush' and 'Fauci Fever' link below. It will blow your mind. Our society is really totally nuts,'' Fauci wrote in an April 8, 2020, email he forwarded to undisclosed recipients after he received a Google alert about news stories mentioning his name.
The previous month, a colleague had emailed Fauci a Washington Post article headlined ''Fauci Socks, Fauci Doughnuts, Fauci Fan Art: The Coronavirus Experts Attract a Cult Following.'' The top of the article tells the story of a Rochester, New York, shop that had sold out of donuts with Fauci's face on them.
''Truly surrealistic,'' Fauci wrote. ''Hopefully this all stops soon.'' Later, he added: ''It is not at all pleasant, that is for sure.''
But it didn't stop, and, at times, Fauci actually couldn't help but get a kick out of it, including when Brad Pitt played him on Saturday Night Live.
''One reviewer of the SNL show said that Pitt looked 'exactly like me.' That statement made my year, '' Fauci wrote to a colleague.
The emails also reveal behind-the-scenes negotiations over a documentary about Fauci's work. He first sent a note to his team about the project on April 12, a month after the World Health Organization had declared the coronavirus a pandemic.
''Let us discuss this tomorrow before we do anything. No one has any 'exclusives' on anything about me,'' he wrote to his team.
Still, there is little in his correspondence that strays from the central issues: the pandemic and how best to save lives. His exchanges with Ezekiel Emanuel, the former Obama health adviser, reflect the high stakes.
Emanuel, an oncologist, bioethicist, and vice provost of the University of Pennsylvania, sent Fauci an email on Feb. 25, 2020, asking for an updated assessment of the virus and noting that he was having a ''hard time seeing this as serious as everyone else.''
''Am I blind? Yes very transmissible but low mortality like flu in many ways - the elderly, those with comorbidities, and total impact is likely to be less than flu," Emanuel wrote.
Later, in April, Emanuel sent Fauci an email saying he was ''perplexed'' by his ''seeming strong endorsement'' of the antiviral drug remdesivir to treat COVID-19.
''Was it just a bit forced?'' Emanuel asked. ''My reading was the data was weak and in normal times for normal disease it is not enough to approve. And very unlikely to really impact COVID-19 disease pattern--regardless of supply issues.''
Fauci countered: ''I did not 'strongly' endorse it. I specifically said it was not a knockout drug and was only a baby step in the direction of developing more and better drugs. I said that it was important because it proved in a well-powered, randomized, placebo-controlled clinical trial that one can suppress the virus enough to see a clinical effect, as modest as the effect was. I do not think I forced anything.''
The next day, Emanuel sent another email, apologizing for misinterpreting Fauci's comments about the drug and inviting him over for dinner ''on the porch.''
''You are a national '-- international '-- treasure. And we are depending on your sanity and smarts.'' '—
'Fort Detrick base is full of suspicions': China asks US for explanation of 2019 respiratory disease after Biden's new Covid probe '-- RT World News
Wed, 02 Jun 2021 13:47
Beijing has called on the US to provide an explanation for a respiratory disease in northern Virginia and a large-scale outbreak of e-cigarette disease in Wisconsin after Washington launched a new probe into Covid-19's origins.
Speaking on Thursday, Chinese Foreign Ministry spokesman Zhao Lijian asked the US to reflect on its own role in the pandemic and not ''dump'' responsibility on China alone. Citing the 33 million Covid-19 cases in the US and 600,000 deaths, Zhao asked ''How safe is your conscience?''
I also want to emphasize that the Fort Detrick base is full of suspicions. There are more than 200 biological laboratories in the United States spreading around the world. How many secrets are there?
The spokesman said that there was an unexplained respiratory disease in northern Virginia in July 2019 and a large-scale outbreak of e-cigarette disease in Wisconsin. ''When will the US release detailed data and information on relevant cases to the international community? The United States owes an explanation to the international community.''
Also on rt.com Biden gives intel agencies 90 days to pinpoint Covid origins '' after report he torpedoed Trump-era probe of Wuhan lab leak theory The Maryland-based US Fort Detrick center hosts a biolab which has become a hot topic on China's Twitter-like Weibo. In 2019, the Centers for Disease Control and Prevention decided to issue a ''cease and desist order'' to halt operations at the germ lab over safety concerns.
Zhao's comment comes after US President Joe Biden said on Wednesday that he was giving intelligence agencies 90 days to pinpoint the origins of Covid-19. Biden said his administration would continue to push China to ''participate in a full, transparent, evidence-based international investigation and to provide access to all relevant data and evidence.''
Reinforcing a statement from the Chinese Embassy in Washington, DC on Wednesday evening, Zhao called on the US to stop ''ignoring facts and science'' and refrain from ''repeatedly clamoring to reinvestigate China.''
An earlier report from the World Health Organization after a mission in January suggested that early cases in Wuhan were believed to have been acquired from ''a zoonotic source as many reported visiting or working in the Huanan Wholesale Seafood Market.'' However, pinpointing the source was not possible.
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Is Dr. Fauci the Mastermind Behind the Creation of SARS-CoV-2? - Part II '' RedState
Wed, 02 Jun 2021 13:45
This is part two of an article series detailing Dr. Fauci's funding of Dual-Use Research of Concern (DURC) and Gain-of-function research through the NIH and NIAID. Part I can be found here.
In the early part of 2003, doctors around the world became baffled by thousands of cases of people with flu-like symptoms and pneumonia. Originally beginning in the Hong Kong region and then spreading around the world, this mystery illness was killing people faster than they could be diagnosed. When American businessman Johnny Chen became ill on a flight to Singapore, the plane diverted to Hanoi in Vietnam to rush Chen to the hospital. There, doctors were unable to stop the progression of Chen's symptoms, and within hours of his arrival, Chen was dead. Over the course of the next several days, nearly 40 people would become ill at that hospital with 7 of those people dying from this new mysterious disease. That disease went on to infect people all over the world. China was among the worst hit, with over 5,000 cases and 318 deaths, followed by Canada and the US, with over 300 cases and 30 deaths.
It wasn't until the SARS virus genome was identified by Canadian scientists in April 2003 that the world began to understand the cause of all the sickness and death that was spreading across the globe. Then in May 2003, researchers out of Erasmus University in the Netherlands were able to determine that this new virus, the definitive culprit in the sickness that had spread to nearly every continent. The doctor that led that research? Dr. Ron Fouchier. (Remember that name.)
In the years that followed this new outbreak, virologists and epidemiologists around the world raised concerns about the return of SARS or worse yet, the rise of a more severe form of SARS through another zoonotic spillover event, like the one that led to the outbreak of SARS-CoV. A relatively new type of research called ''gain-of-function'' was promoted as the means to defeat SARS and prevent the next outbreak. That form of research was already being used to experiment with various influenza strains, so it only made sense to apply the research to other viral strains as a means of developing treatments for potential mutations. As covered yesterday, this type of research requires the use of genetic science to mutate viruses to make them more deadly and transmissible. Despite the list of threats that comes with performing those types of experiments, scientists pressed forward in their studies.
At the forefront of US research into the SARS virus was Dr. Ralph Baric of the University of North Carolina. Beginning as early as 2004, Dr. Baric was given grants from the National Institutes of Health and Dr. Anthony Fauci's National Institute of Allergy and Infectious Diseases to perform genomic research on the SARS virus in the hopes of giving us a bit of insight into a means of understanding the initial outbreak of the deadly disease.
Baric 2004 StudyBaric 2004 StudyOver the course of five years, Baric was awarded more than $1.4 million to study the SARS virus. The goal of the research was to find ways to prevent new strains, but only produced a means of treating and preventing the original SARS virus. It was late in that study that Dr. Baric used the research to create what is called a recombinant virus or a mutation or new strain of certain viruses. These mutations can be natural but that also doesn't mean that those viral mutations would have occurred naturally. Baric's work was used as a means of additional study into SARS and was referenced by other doctors conducting NIH and NIAID funded research into the SARS virus:
''However, few zoonotic strains of SARS-CoV have been isolated and maintained in cell culture and this presents a challenge in assessing the efficacy of candidate SARS vaccines against zoonotic strains. Ralph Baric (UNC) has applied synthetic biology and reverse genetics techniques to generate recombinant isogenic viruses bearing variant spike glycoproteins derived from animal sources.''
If this could be considered the birth of gain-of-function studies of the SARS virus, Dr. Ralph Baric could be considered the ''father'' of it. It was hardly a ''side project'' of Dr. Baric's research. It was the focal point. From 2007-2012, Dr. Baric received at least $18,500,000 in grants from the NIH and NIAID to study the SARS virus, including more than $5.6 million in the development of a SARS vaccine.
The MERS outbreak in 2012 renewed fears of the potential of a viral outbreak and ignited an urgency to double efforts on gain-of-function research. MERS, or the Middle East Respiratory Syndrome, is also a coronavirus and was found to have infected humans through bats and camels, with the latter likely providing a zoonotic link between the bat virus and human infection. According to the ECDC (European Centre for Disease Prevention and Control), MERS infected 2,586 people globally and was responsible for killing 939 of those people, primarily in Saudi Arabia. Again, Dr. Ron Fouchier of Erasmus University in Rotterdam, Netherlands was instrumental in sequencing and identifying the new viral strain. It seems no matter where you look in this story, the same five names keep coming up.
As a direct result of the MERS outbreak, Dr. Baric's gain-of-function research was kicked into overdrive, with the awarding of a 10-million-dollar grant by the NIH. This new grant, which focused primarily on the SARS and MERS viruses, was awarded in September 2013, less than four months Dr. Fouchier identified the new strain of coronavirus responsible for the MERS outbreak. Baric's lab at the University of North Carolina at Chapel Hill was quick to announce his newly landed funding.
From the release: (emphasis added)
''This new research promises to identify novel genes and genetic functions that promote virus pathogenesis in the host, leading to new targets for antiviral development and vaccine design,'' Baric said. ''Our group will focus on genes that contribute to highly pathogenic coronavirus infections, using SARS-CoV and MERS-CoV as a model.''
Other team leaders on the grant include Blossom Damania, Ph.D., professor of microbiology and immunology at UNC, whose research will focus on the human herpesviruses, and Yoshihiro Kawaoka, PhD, DVM, professor of virology at the University of Wisconsin, who will study Ebola and the highly pathogenic influenza virus gene that regulate disease severity following infection.''
As discussed yesterday, gain-of-function research done by Dr. Fouchier and Dr. Kawaoka led to concerns raised by scientists and government officials about the potential of accidentally creating or releasing a new, deadlier, and more transmissible strain of influenza. This discovery led to a pause in US government funding of gain-of-function research in 2014. NIH director (and co-author of the WaPo Op-Ed defending gain-of-function experiments), Dr. Francis Collins explained:
''During this pause, NIH will not provide new funding for any projects involving these experiments and encourages those currently conducting this type of work '-- whether federally funded or not '-- to voluntarily pause their research while the government determines how to proceed.''
On October 21, 2014, the United States Department of Health and Human Services sent a letter to UNC and Dr. Baric identifying gain-of-function research Baric was then performing under an NIH grant and requesting they pause that research until which time guidelines could be developed. Despite that request, Baric's research continued.
In November 2015, Baric addressed this (emphasis added):
''The latest study was already underway before the US moratorium began, and the US National Institutes of Health (NIH) allowed it to proceed while it was under review by the agency, says Ralph Baric, an infectious-disease researcher at the University of North Carolina at Chapel Hill, a co-author of the study. The NIH eventually concluded that the work was not so risky as to fall under the moratorium, he says.''
Here we have conflicting statements. The director of the NIH requested that all studies pause, the HHS requested the pause, the White House requested the pause, yet Baric is telling us the NIH told him he could continue his clearly gain-of-function research because it ''was not so risky,'' without producing any letter saying so. And, records show that NIAID continued funding Baric's grant for three more years in violation of policy:
''In effect, the NIAID will not support GoF (gain-of-function) research identified in the pause after the end of the current budget period. Neither competing nor non-competing renewal applications will be funded to support applicable GoF research.''
What is happening here?
Baric wasn't the only one ordered to cease that type of research; in fact, at least 14 other institutions received letters to pause research, including Dr. Yoshihiro Kawaoka at the University of Wisconsin, who complied with the request. In fact, Kawaoka did not resume his experiments on the H5N1 influenza virus until after the 2017 lifting of the gain-of-function ban and the release of gain-of-function guidelines by the HHS. Baric, however, presumably taking his direction from Dr. Fauci and the NIAID, continued his research.
During that pause, Dr. Baric (along with Dr. Shi Zhengli of WIV) was able to synthesize a new SARS virus, called SHC014, which took a viral strain of SARS that was previously unable to infect human cells and engineered it so that the viral strain was now able to infect humans, specifically ''human airway cells'' and which ''resisted all vaccines and immunotherapy.'' This again ignited a debate about the safety of this research and raised questions about how it was conducted against the recommendation of the HHS.
Clearly, it cannot be denied that, despite all of Dr. Fauci's protestations to the contrary, NIH-funded gain-of-function research, which was conducted against the guidance of the White House and HHS, was shared with the Director at the Wuhan Institute of Virology. And if Dr. Fauci didn't authorize those subsequent grant payments, who did?
Come back tomorrow for Part III, which will dive into the funding mechanisms which were used by the NIH to use US taxpayer dollars to fund research at the Wuhan Institute of Virology.
Having shut down Trump's Covid-19 origin probe, Biden now entrusts it to same spies who gave us 'Russiagate' '-- RT Op-ed
Wed, 02 Jun 2021 13:42
Nebojsa Malic
is a Serbian-American journalist, blogger and translator, who wrote a regular column for Antiwar.com from 2000 to 2015, and is now senior writer at RT. Follow him on Telegram @TheNebulator and on Twitter @NebojsaMalic
is a Serbian-American journalist, blogger and translator, who wrote a regular column for Antiwar.com from 2000 to 2015, and is now senior writer at RT. Follow him on Telegram @TheNebulator and on Twitter @NebojsaMalic
Just as it emerged that the Joe Biden administration shut down a State Department probe into the coronavirus origins, the White House ordered the US intelligence community to ''redouble'' its efforts on the matter. How convenient.
In a statement released on Wednesday, President Biden said he had ordered the US spies in March to give him a report on the origins of the virus, and gave them 90 days to provide a ''definitive conclusion.''
Also on rt.com Biden gives intel agencies 90 days to pinpoint Covid origins '' after report he torpedoed Trump-era probe of Wuhan lab leak theory Within minutes, the compliant corporate media acknowledged their marching orders, putting ''redouble their efforts'' into every headline. In a sense, the statement wasn't so much an order to the spies, but a set of instructions to the Narrative managers.
That's because the development of the Narrative on the coronavirus over the past several weeks has been, how shall we say, problematic for the current administration. For over a year, the corporate media and Big Tech have insisted that the virus evolved naturally, declaring anything else a ''debunked conspiracy theory'' and banning everyone who dared mention it.
That's until former New York Times reporter Nicholas Wade penned an article questioning this, and it escaped the Memory Hole. Within weeks, the press had executed a dizzying U-turn, quietly retracted or stealth-edited both their stories and ''fact checks,'' and tried pretending they'd always believed the Wuhan Institute of Virology lab escape theory was at least possible. Nice try, but no.
You may remember that much of the really bad coverage was focused on @SenTomCotton's suggestion that we better understand the potential for a lab leak from Wuhan.The difference in framing here from @nytimes between May 2020 and May 2021 is...stark. pic.twitter.com/dr5kPPbq3a
'-- Drew Holden (@DrewHolden360) May 25, 2021Some US researchers, British tabloids, and even former President Donald Trump noticed this and pointed it out. Then, on Tuesday, CNN '' that stalwart bastion of Our Democracy '' lobbed another hand grenade into Biden's back yard: his administration had actually shut down a State Department-led probe into the origins of the virus, right around the time he claimed to have asked the spies to get on the case.
The old inquiry was run out of the State Department's Arms Control and Verification Bureau, and the decision to terminate it was made ''after Biden officials were briefed on the team's draft findings in February and March of this year,'' CNN reported citing a State Department spokesperson.
So Biden had shut down a State Department probe as either too politicized or a waste of resources '' CNN's sources allege both '' but then turned it over to the same spies that had generated the infamous ''Intelligence Community Assessment'' about the ''Russian meddling'' in 2016 that fed the Democrats' ''Russiagate'' frenzy for the next four years. Let's just say their methodology leaves something to be desired.
Also on rt.com We want to believe: 'Russian hacking' memo REVEALS how US intel pinned leaks to Kremlin Another part of Biden's statement that jumps out is his insistence that the spy agencies ''include work by our National Labs and other agencies of our government to augment'' their efforts. Did he mean the Department of Energy's 17 facilities around the US '' and if so, why? Or was this a reference to the National Institutes of Health and its division for infectious diseases, headed by Biden's Covid Czar Dr. Anthony 'Infallible' Fauci? We can only guess.
Thing is, having Fauci anywhere near the probe into Covid-19's origins would be entirely disqualifying, due to a conflict of interest. His National Institute of Allergy and Infectious Diseases '' through the NIH '' has funded research into ''understanding the risk of bat coronavirus emergence.'' The recipient of their grant has been EcoHealth Alliance, a New York nonprofit run by Peter Daszak. This is the same group that ''partners with the Wuhan Institute of Virology (WIV) in China,'' for its research, as Nature magazine reported in August 2020, citing Daszak himself fulminating about the NIH cutting off his funding.
There's been a lot of controversy over research into bat coronavirus at Wuhan Institute led by "Bat Woman" Shi Zhengli. A major funder was Fauci's NIAID award R01AI110964 "Understanding the risk of Bat Coronavirus Emergence". See award searchhttps://t.co/4Q4il5wE0Lpic.twitter.com/kddGqf6Q3W
'-- Stephen McIntyre (@ClimateAudit) April 17, 2020When confronted with this by Senator Rand Paul (R-Kentucky) earlier this month, Fauci denied such research was involved, or that NIH ever funded the Wuhan lab. Later, speaking with friendly fact-checkers, Fauci argued it would ''almost be irresponsible'' to not collaborate with China given the 2003 SARS outbreak there, and called the EcoHealth funding ''a very minor collaboration as part of a subcontract of a grant.''
So he never funded the research except he did and it was very minor and it would have been irresponsible not to but ''a ridiculous leap'' (in Fauci's own words) to suggest this had anything to do with the very family of viruses they were supposed to be studying? Enough to make your head spin.
including the NC lab that collaborated with the Wuhan Virology Institute. Strange, that the NIH stopped funding that Dr. Fauci claims never existed . . . . https://t.co/lpd0qrvD98
'-- Senator Rand Paul (@RandPaul) May 18, 2021Given the previous record of everyone involved, it's safe to conclude that Biden's probe is going to be a politicized effort to craft a Narrative absolving Fauci '' as well as Biden himself, for shutting down the State Department probe. It's possible the White House could also use it as ammunition against China '' giving the Republicans something to buy into.
Meanwhile, the axis of corporate media and Big Tech will declare the ''science is settled'' and proceed to deal with far more important issues '' such as whether the fur color of the future First Cat will promote equity.
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The statements, views and opinions expressed in this column are solely those of the author and do not necessarily represent those of RT.
Chinese Foreign Ministry: U.S. Army Caused Vaping Deaths
Wed, 02 Jun 2021 13:37
Chinese Foreign Ministry spokeswoman Hua Chunying floated the idea Friday that deaths related to the use of e-cigarettes, or vaping, in America in 2019 may have been secret Chinese coronavirus cases caused by a U.S. Army laboratory leak.
The Chinese coronavirus pandemic began in Wuhan, China, late last year. While the Chinese government initially accepted that the origin of the new virus was a wild animal and seafood market in Wuhan, it has since refuted that assertion, instead suggesting that the virus originated in America.
The earliest known case of Chinese coronavirus was documented, according to leaked Communist Party data, on November 17, 2019. No cases of infection are known to have occurred before then.
More recently, Secretary of State Mike Pompeo has stated that ''enormous evidence'' exists linking the pandemic to the Wuhan Institute of Virology, a biological laboratory located near the meat market. While no evidence has surfaced, nor has any American official suggested, that the virus could have been engineered in the laboratory, some have suggested an accident or the illegal sale of laboratory animals may have resulted in the initial human exposure to the pathogen.
A reporter asked Hua to comment on Pompeo's repeated comments linking the pandemic to the Wuhan Institute of Virology on Friday and she responded with suspicions that American laboratories on the other side of the world from the origin of the virus could be responsible for it. She noted, in particular, a U.S. Army research base at Fort Detrick, Maryland, shut down last year, which the Communist Party has insisted is the source of the virus.
''The safety of biolabs in the US now poses the biggest risk to the US regulatory authority,'' Hua claimed.
''There are also reports that soon after the closure [of the Fort Detrick laboratory], 'E-cigarette disease' broke out in the surroundings,'' Hua claimed. ''According to data released by the US CDC in late February, the flu season that begins in the winter of 2019 has infected at least 32 million people in the United States, including 18,000 deaths from flu-related illnesses. CDC Director Michael Redfield has publicly acknowledged that some of the deaths from influenza were actually caused by COVID-19. These are all public records in US media reports available online.''
Hua concluded with a demand to allow an ''international inspection'' of the Maryland location.
Hua's claim of an outbreak of ''e-cigarette disease'' is a reference to what the U.S. Centers for Disease Control (CDC) have dubbed ''newly identified lung disease linked to vaping,'' or EVALI. Doctors have traced the disease, which impairs lung function, back to the use of vapes. As of February, the latest statistics on the CDC website, the United States has documented 2,807 cases of EVALI and 68 deaths associated with it.
The CDC describes the symptoms of EVALI as ''respiratory symptoms, including cough, shortness of breath, or chest pain'' as well as fever and, sometimes, gastrointestinal issues. These symptoms are similar to some Chinese coronavirus symptoms, but the CDC noted that studies have found no lung infection in patients with EVALI, meaning no pathogen appears present in their bodies.
American medical authorities also found no incidents of EVALI patients infecting anyone else or of anyone not using e-cigarettes with the disease, suggesting it is not caused by a contagious pathogen. There is no evidence that more recent EVALI patients, those diagnosed after the announcement of a discovery of a new coronavirus, have tested positive for it. The Chinese coronavirus is highly contagious and believed to spread through water droplets in the air.
The distribution of cases of EVALI throughout the United States does not corroborate Hua's contention that the shutdown of the Fort Detrick laboratory occurred prior to a massive outbreak of EVALI in the region. According to the CDC, Illinois, Texas, New York, and California have documented the highest numbers of cases.
Hua's remarks on Friday were not the first time that the Chinese government attempted to link vaping illnesses to the Chinese coronavirus. In March, the Global Times, a state propaganda outlet, claimed that ''some have connected the cases with novel coronavirus,'' without specifying who, exactly, had done so.
One thing the EVALI cases and the pandemic have in common is that both may have originated in China. Prior to the sweeping ban by the Food and Drug Administration (FDA) on many vaping products in January, China produced about 90 percent of the world's e-cigarettes, according to the Global Times. Over 80 percent of those available for purchase in the United States and European Union originated in China. As the Global Times explained in 2018:
Its invention is also deeply connected with China. Chinese pharmacist Hon Lik reportedly invented the device in the early 2000s, hoping that it could help him quit smoking. But it soon gave rise to a multi-billion-dollar industry. He is now employed as a consultant by Fontem Ventures, a subsidiary of British multinational tobacco company Imperial Brands, which specializes in vaping technology.
The Times admitted that the industry in China was ''highly'' unregulated.
Shenzhen, a southern Chinese city considered one of its largest industrial centers, is home to a booming counterfeit vaping product industry. Juul, the largest U.S. vaping company, traced all counterfeit Juul products on the market back to China in a 2019 study. Raids triggered by this research revealed that many factories making these products in China did so under unsafe, unsanitary conditions that may have resulted in contaminated e-cigarette liquids. Many of these products contained THC, the active ingredient in cannabis, which is not considered safe to consume through e-cigarettes.
The state-run Global Times admitted in October that counterfeit products were behind many EVALI cases.
''While Juul Labs Inc dominates the North American market for pod e-cigarettes, many reports of deaths and injuries in the US have been tied to makeshift brands with no identifiable owner,'' the newspaper reported. ''The most prominent, Dank Vapes, was linked to 24 patients with lung illness, according to a study from the New England Journal of Medicine. The products contained THC, the psychoactive ingredient in marijuana.''
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Lukashenko Lashes Out After BBC & Others Admit Detained Activist's Ukrainian Azov Battalion Ties | ZeroHedge
Wed, 02 Jun 2021 13:31
Belarus' long time leader Alexander Lukashenko has spoken out on Wednesday over the Ryanair diverted flight saga, pushing back against widespread accusations coming from the former Soviet satellite country's opposition but especially Western leaders that his security services engaged in "state hijacking" of the airliner carrying activist and blogger Roman Protasevich. Promises of EU and US additional sanctions were swift after Protasevich and his girlfriend were detained on charges of inciting riots and publishing the personal information of police and officers of the state online. State airline Belavia is also facing an airspace ban over Europe and carriers out of the EU are avoiding flying over Belarus.
Instead of concealing the ordeal or downplaying the detention which has attracted international media scrutiny and outrage, Lukashenko has gone on the offense, lashing out at his critics while justifying the detention of Protasevich, calling him an "extremist" who was ultimately taking cues from a foreign entity in his activism and journalism, or even "inciting riots" - as he's being charged with. "One extremist with his female accomplice. So let his numerous Western patrons answer this question: Which intelligence services did this individual work for?" Lukashenko said as quoted by the Belarus Segodnya newspaper.
Via EPA"Not only him but his accomplice as well. These Western advocates should answer one more question: who paid him for taking part in the war in Donbass?" Belarus' president added, "Perhaps, they fear this the most. So they're making a fuss. His experience as a mercenary is huge."
It's long been reported and a subject of controversy in Belarusian and Eastern European media that Pratasevich was indeed in war-torn Donbas in Ukraine at the height of fighting there in 2015. And BBC among others is now acknowledging:
"Mr Protasevich confirmed in an interview last year that he had spent a year in the conflict-hit Donbas region and was wounded, but said he was covering the conflict as a journalist and photographer."
He was "embedded" with the far-right and neo-Nazi linked Azov Battalion while they fought fierce battles against pro-Russia separatists. However, BBC notes that Protasevich has insisted he was only there as a journalist: "A former commander of the Azov unit has backed Mr Protasevich's version of events, confirming that he spent time with them as a journalist and was wounded," the report says.
Anglo-American journalists working the Russia beat doing a bang-up job maintaining disciplined silence over Protasevich's Nazi ties. You only need state censorship if journalists won't self-censor, which ours do as a motor reflex. https://t.co/7eeKhYTSTx
'-- Mark Ames (@MarkAmesExiled) May 26, 2021Minsk is now accusing the young detained activist of essentially being a mercenary and "terrorist" who's long plotted the overthrow of the legitimate government. Lukashenko added in his Wednesday comments:
"These facts are well-known not only here, but in brotherly Russia, and also throughout the world. And he did not hide this. Well, here, in Belarus, he and his accomplices also plotted a massacre and a bloody coup," Lukashenko said further.
Photographs of Protasevich's time in Eastern Ukraine increasingly point to him having been more than a mere journalist in the conflict...
A much clearer picture of #Protasevich at the Azov parade in Mariupol in 2015. The account is a bot but here's the original from Azov Vkontaktehttps://t.co/6Y1w5lXqoW
'-- Volodymyr Ishchenko (@Volod_Ishchenko) May 26, 2021The Belarusian president stressed and claimed further that "there was a terrorist on that plane."
Via Sky NewsInstead of skirting the issue, Lukashenko owned up directly to authorizing Protasevich being removed from the plane along with his girlfriend:
"According to the law, this person had been put on a terrorist list, and his organization is recognized as an extremist one. Who does not know this? And that we detained him, a Belarusian national, and his partner who holds our residence permit at the airport, this is our sovereign right to do so," he said.
However, the president stated the Ryanair flight was not initially diverted because of efforts to apprehend Protasevich, but because there was a bomb threat. The West has accused the bomb threat of being a ruse orchestrated to force the plane's emergency diversion and landing.
Via TASS"As we predicted, ill-wishers from outside and inside the country have changed their ways of attacking our country," Lukashenko said, according to state media. "They crossed many red lines, crossed the boundaries of common sense and human morality."
Russia Examines Pandemic Evidence Leading To Pentagon After Assassination of Two US Army Doctors
Wed, 02 Jun 2021 13:24
World's Largest English Language News Service with Over 500Articles Updated Daily
"The News You Need Today'...For The World You'll Live In Tomorrow."
What You Aren'tBeing Told About The World You Live In
How The ''Conspiracy Theory'' Label Was Conceived To Derail TheTruth Movement
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May 27, 2021
Russia Examines Pandemic Evidence Leading To Pentagon After Assassination ofTwo USArmy Doctors
By: Sorcha Faal, and asreported to her Western Subscribers
A sobering new Security Council (SC) reportcirculating in the Kremlin todayfirst noting President Putin will meet with Belarus President Alexander Lukashenkotomorrow in Sochi, says theannouncement of these talks was quickly followed by Belarusian Defense Minister Viktor Khrenin noting the highintensity of NATO reconnaissance activity, as well as operational and combatpreparations near the Belarusian border '--NATO combat preparations preceded by a Ryanair flight from Athens-Greece to Vilnius-Lithuania being diverted because of a bomb threat and landing in Belarus '--afterwhich Belarus police authoritiesremoved from this flight and placed into custody Belarus citizen RomanProtasevich and his female companion'--saw Protasevich having been previously charged with organizing riots and instigatingsocial hatred in Belarus , while in Ukraine he was a Nazi fighter for the terrorist group AzovBattalion '--facts leading to troubling questions beingasked as to who is supporting this Nazi terroristand allowing him protected travel across Europe,which President Lukashenko posed tothe West during a BBC interview asking: '' So let his numerous Western patrons answer this question:Which intelligence services did this individual work for? '''--factsabout this Nazi terrorist well knownto the Western media'--but insuppressing the truth sees them being called out by social media postings like:'' Anglo-American journalists working the Russia beat doing abang-up job maintaining disciplined silence over Protasevich's Nazi ties'...You only need state censorship if journalists won't self-censor,which ours do as a motor reflex ''.
With Russia defending Belarus in its capture of this Nazi terrorist, predictably new leftist media calls for sanctions are being made '--callsquickly met by French President EmmanuelMacron telling reporters yesterday: '' With Russia, the policy of progressive sanctions on frozensituations is no longer an effective policy...What would you like us todo?...Do we start an armed conflict?...Do we completely cut off relations?...Dowe go further with sanctions '' but where to?"...We are at a moment oftruth in our relationship with Russia, which should lead us to rethink theterms of the tension that we decide to put in place '''--astance consistent with PresidentMacron's past statements, like in 2019when he said: '' Who is the enemy of NATO?...Russia is no longer anenemy...Russia is also geographically a neighbor and it is a reality onceagain, and it is also a partner'...It is a power with which we work on certainsubjects, on which we advance ''.
On the opposite spectrum of consistency, however, is the United States'--whose Supreme Socialist Leader Joe Biden afew months ago branded President Putina '' soulless killer '', and whose Pentagon branded Russia their most feared '' existential threat '''--but this weeksaw US National Security Advisor JakeSullivan meeting with Security Council Secretary NikolaiPatrushev to arrange a face-to-face sit down between President Putin and socialist leader Biden scheduled for 16 June '--then yesterdaysaw Pentagon Press Secretary John Kirbystating: '' Nobody's labeled Russia the enemy... that's not the phrasethat we would use to refer to Russia ''.
As to what caused this head-spinning move by the United States to suddenly try and make peace with Russia, though, was socialist leader Biden and the Pentagon being overcome with terror this week when Chinese President Xi Jinping '' sent his most trusted foreign policy aide '' Yang Jiechito hold urgent meetings with PresidentPutin, along with top Russian military, intelligence and foreign policyexperts'--a terror also striking NewZealand, who as a member of the ''Five Eyes'' alliance withAmerica knows its soon coming fate,and is why their Foreign Minister NanaiaMahuta '' has just warned that their tiny nation could soon find itselfin the center of a storm of anger from China in only a matter of time ''.
What the head of China's CentralForeign Affairs Commission, and a specialist in American affairs, Director Jiechi hasbeen revealing in the Kremlin overthe past few days is exactly why the official position of the Chinese Communist Party is thatthe true origin of the COVID-19 pandemic is from a laboratory at Fort Detrick,a US Army base housing a virology facility in Maryland '-- a bioweapon sent to China during the Wuhan military games inOctober-2019 '--whose USArmy participates in the Wuhanmilitary games were medically cleared to go to China at Fort Belvoir in Fairfax-Virginia'--medical clearancessigned by US Army Colonel EdwardMcDaniel Jr , M.D.'--but beyond shockinglyyesterday, saw Colonel-Doctor McDaniel and his US Army physician wife BrendaMcDaniel assassinated in cold blood in front of their Springfield-Virginia homelocated about 14-miles southwest of Washington, D.C.
In the hours preceding the assassination of these two US Army doctors, it was stunningly revealed that socialist leader Biden had secretly ended a State Department investigation into theorigins of COVID-19 '--but when discovered saw Biden quickly ordering US intelligence agencies to report to him in90-days where COVID-19 originated '--that was joined by the White House declaring: '' We Haven't Ruled Out' Possibility That Pandemic From ChinaWas Deliberately Unleashed '''--though most astoundinglyto notice, was Biden entrusting this investigation to the exact same spiesthat foisted upon the American people their Russiagate lies '--theeffect of which will see over half of the American people not believing asingle thing these corrupt spies say, and as best explained by the Wall Street Journal, that factuallynotes: '' Democrats and the media will deny this to their graves, butthe wellsprings of American politics have been poisoned for years by theRussia-collusion narrative ''.
Also immediately following the assassination of these two US Army doctors was leftist socialmedia giant Facebook suddenly announcing that it will stop banning claims COVID-19is man-made '--that was even more astoundingly followed by the US Senate approving with unanimous consent a bill that wouldrequire the Biden and the Director of National Intelligence to declassifyintelligence on the origins of COVID-19 .
With the United States now infull protection mode spinning the world's head off as they rapidly shift theirpositions on Russia and the originsof COVID-19, however, China isn't prepared to go down withouta fight, as evidenced by their just published state article '' U.S. Elites Degenerate Further in Morality, and Fauci Is Oneof Them '''--a Dr.Anthony Fauci who 30-years-ago was openly accused of genocide ,and today the evidence continues to grow that he is themastermind behind the creation COVID-19 '--and is notablebecause former top US Armyintelligence official General MichaelFlynn has just cryptically stated: '' The people in this country are demanding answers'...I believe wewhat we are going to find out is that this was a weaponized operation by the Nation of China with some collaboration with other countries ''.
As to whom '' collaborated '' with elementswithin China to create and spread COVID-19 for the purpose of destroying President Donald Trump and allowingsocialist leader Biden to seizepower this transcript shows the Kremlinis attempting to fully understand'--an attempt at understanding that in the pastfew hours saw Chinese Foreign Ministryspokesman Zhao Lijian declaring: '' I want to emphasize that the Fort Detrick base is full ofsuspicions'...There are more than 200 biological laboratories in the United Statesspreading around the world'...How many secrets are there? '''--thatwas quickly joined by the Chinesegovernment making an official statement saying: '' Out of a sense of responsibility towards the health ofmankind, Beijing supports a comprehensive study of all early cases of COVID-19found worldwide, and a thorough investigation into some secretive bases andbiological laboratories all over the world'...Which will be a full, transparentand evidence-based investigation, and shall get to the bottom to makeeverything clear ''.
With both China and the United States knowing that Russia will accept nothing less than afull accounting of who created COVID-19,and the perpetrators of this crime against humanity being brought to trialbefore the entire world, it was no wonder that President Xi sent his most trusted aide to the Kremlin this week and socialist leader Biden plead for an urgent face-to-face meeting as soon as possiblewith President Putin'--powerfulcountries freely able to present their evidence without fear or favor, but bothof whom know the fierce retribution that awaits those who seek to deceive'--buteven with the United States knowingthis grave reality, this transcript's final section shows SecurityCouncil Members' unrestrained fury over socialist leader Biden and the leftist US corporate media establishment stillkeeping suppressed from the Americanpeople the biggest story in the world about '' The Drug That Cracked Covid '''--a drugcalled '' Ivermectin '' that's broken the back of the COVID-19 pandemic in India and inMexico City reduced hospitalizations by as much as 76% --whichleads to questions being asked why people are still needlessly dying in America when they don't have to. [Note: Some words and/or phrases appearing in quotesin this report are English language approximations of Russian words/phraseshaving no exact counterpart.]
May 27, 2021 (C) EU and US all rights reserved.Permission to use this report in its entirety is granted under the condition itis linked to its original source at WhatDoesItMean.Com. Freebase content licensedunder CC-BY and GFDL.
[ Note :Many governments and their intelligence services actively campaign against the informationfound in these reports so as not to alarm their citizens about the manycatastrophic Earth changes and events to come, a stance that the Sisters of Sorcha Faal strongly disagree with in believing that it is every human being's right toknow the truth. Due to our mission's conflicts with that of those governments,the responses of their 'agents' has been a longstandingmisinformation/misdirection campaign designed to discredit us, and others likeus, that is exampled in numerous places, including HERE .]
[ Note: The WhatDoesItMean.com website was created for anddonated to the Sisters of Sorcha Faal in 2003 by a small group of Americancomputer experts led by the late global technology guru Wayne Green (1922-2013) tocounter the propaganda being used by the West to promote their illegal 2003invasion of Iraq.]
[ Note: The word Kremlin (fortress inside a city) as used inthis report refers to Russian citadels, including in Moscow, having cathedrals wherein femaleSchema monks (Orthodox nuns) reside, many of whom are devoted to the mission ofthe Sisters of Sorcha Faal.]
Mysterious Mock Attack Joins Trump In New Jersey'--Putin Notices And Warns: ''We'llKnock Out Your Teeth''
History Knows American Future: ''Bright Light'...Loud Noise'...Unobstructed View''
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EPA Orders Shutdown Of St. Croix Refinery After Oil "Rains Down" On The Island | ZeroHedge
Wed, 02 Jun 2021 13:16
It was literally raining oil in St. Croix a couple weeks ago - and not in the good "newly discovered oil"-type way most people know from movies and TV.
The oil falling from the sky was the result of a "flare incident" that took place Limetree Bay refinery; the incident shot oil up into the sky and it was carried west by the wind before raining down on parts of the island, according to CNN.
As a result of the incident, the US Environmental Protection Agency ordered an emergency, 60-day shutdown of the plant, citing an "imminent risk" to public health, the report says. The incident sent sulfur dioxide and hydrogen sulfide into the air. 58 year old resident Dyline Thomas said: "The smell was so strong, like sulfur, like rotten eggs."
As a result of the "incident", she said she had an upset stomach, running nose and sore throat.
The release of oil has the island reconsidering whether or not its economic future is worth keeping the refinery on the island. While it has provided jobs and revenue for the island's battered economy, residents are starting to question whether the "price is too high".
Jennifer Valiulis, the executive director of the St. Croix Environmental Association, told CNN: "We are at a crossroads. We have an opportunity to examine what we want our economy to look like, what we want St. Croix to be in a world that's moving away from fossil fuels as its primary energy source."
The island had its first refinery - responsible for helping its citizens raise their quality of life - open in 1966, managed by Hess. The same petroleum refinery paid $5.3 million in fines in 2011 for environmental violations. It then filed for bankruptcy and shut down before being re-opened via a grant issued by the Trump administration. It produces about 200,000 barrels of oil per day.
Virginia Clairmont, who runs a nonprofit working to revitalize the town of Frederiksted on the island's western end, has spoken out about the refinery: "If you talk about it, you'll be attacked for trying to deprive other people of jobs."
Covid-19 also struck a blow to the island, crippling its cruise industry just years after Hurricanes Irma and Maria "devastated" the island.
The restart of the plant created 400 full time jobs and will generate about $7 million in annual tax revenue.
Local senator Nellie Rivera-O'Reilly pushed for the re-opening of the plant. She told CNN: "As a business owner now, I see the benefits of the refinery, or any employer of that magnitude, remaining viable on the island of St. Croix."
But the EPA received "hundreds of calls and emails" complaining about the plant since it reopened. Tysha Henry, who grew up on St. Croix, said smells from the plant woke her up at night: "It felt like I was going to asphyxiate or something. I will not be going back home as long as this smell is there,"
EPA Administrator Michael Regan said of the decision to shut down the plant: "This already overburdened community has suffered through at least four recent incidents that have occurred at the facility, and each had an immediate and significant health impact on people and their property."
Speaking about the spill, Rivera-O'Reilly concluded: "These things happen in these types of industries. The thing to do is to make sure we learn and put in place measures to prevent this from happening."
Police launch manhunt for 20-year-old suspect in killing of Va. Army colonel, wife - The Washington Post
Wed, 02 Jun 2021 13:02
Two men have been charged in connection with the shooting and killing of a husband and wife '-- both of whom had obtained the rank of colonel in the Army '-- in the front yard of their home in Springfield, Fairfax County police said Thursday.
D'Angelo Strand, 19, and Ronnie Keandre Marshall, 20, were taken into custody on two counts each of second-degree murder and firearms violations Thursday, following a manhunt that stretched across Fairfax County and the D.C. area.
Police identified the victims of Wednesday morning's shooting as Edward McDaniel Jr., 55, an Army doctor, and Brenda McDaniel, 63, a retired Army colonel and nurse. Their son and another person were at the home when the shooting occurred, police said.
Springfield husband and wife shot and killed in front yard of home, police say
Fairfax County Police Chief Kevin Davis said at a news conference Thursday evening that the motive for the slayings was a dispute, but its exact nature was under investigation. He said the two men charged worked with a relative of the victims but declined to say where.
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''We've lost two brave, dedicated, lifelong servants to our community .'‰.'‰. and for what?'' Davis said. ''That's what's got us shaking our heads.''
Fairfax County police put out a plea for the public's help late Wednesday in locating a light-colored Nissan that was seen leaving the scene of the shooting in the Newington Forest neighborhood.
Police said that car was spotted shortly after 7:20 a.m. Thursday at a business in Lorton. Officers arrived and the operator of the vehicle, Strand, of Fort Washington, was taken into custody, police said. The car was seized and is being searched for evidence.
Shortly after 2 p.m., Fairfax County police officers and U.S. marshals spotted Marshall, of D.C., near the intersection of Janna Lee Avenue and Richmond Highway in Fairfax County and took him into custody, police said.
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Both suspects are being held at the Fairfax County jail. Neither man was listed in court records yet, so it could not be determined whether they had attorneys. The gun used in the slayings has not been located, police said.
The shooting occurred in the 8000 block of Flint Street around 9:20 a.m. Wednesday, police said. Davis said Wednesday that the McDaniels were gunned down at ''point-blank range'' and called the killing ''in cold blood.''
Davis said Thursday the action that led to the killings began Monday when one of the suspects arrested in the shooting came to the McDaniels' house. There was a dispute and police were called for an attempted burglary. That incident was under investigation when the slayings occurred.
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Edward McDaniel was a doctor of internal medicine at Fort Belvoir Community Hospital, where he was also the director of executive medicine, Army officials said. He had served in the Army since 1995.
Felice McDaniel, his mother, said he had served two stints overseas in Iraq and was scheduled to retire from the Army in November, although he planned to continue working as a doctor.
She said her son was inspired to go into medicine after a high school friend suffered from mental illness. She said Edward grew up in Los Angeles and recounted how as a child he would ask her what she wanted when he got his allowance.
''They loved their country. They loved their service. They loved the people who were their patients,'' Felice McDaniel said.
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Lennie Enzel, a retired colonel with the Army Nurse Corps and Brenda McDaniel's superior when she was assigned to William Beaumont Army Medical Center in El Paso, wrote in a Facebook message to The Post that Brenda was an accomplished medical professional, who was selected to the prestigious post of White House nurse during the Clinton administration.
''She was one of the brightest, kindest, most professional Army Nurses with whom I ever had the honor to serve as evidenced by her tour as a White House Nurse,'' Enzel wrote.
Army officials said Brenda McDaniel served in the Army from 1983 to 2009 and retired as a colonel.
Army officials said her military awards included the Legion of Merit, which recognizes ''exceptionally meritorious conduct in the performance of outstanding services and achievements.'' Her awards also indicated at least two deployments overseas.
Dan Lamothe and Julie Tate contributed to this report.
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In the Garden of Beasts: Love and Terror in Hitler's Berlin - Erik Larson - Google Books
Wed, 02 Jun 2021 00:24
Erik Larson was born in Brooklyn on January 3, 1954. He graduated Summa Cum Laude from the University of Pennsylvania and went to graduate school at Columbia University. Larson worked for the Wall Street Journal and then began writing non-fiction books. He is the bestselling author of the National Book Award finalist and Edgar Award-winning, The Devil in the White City, which has been optioned for a feature film by Leonardo DiCaprio. He also wrote In the Garden of the Beasts, Issac's Storm, Thunderstruck and The Naked Consumer. Larson has taught non-fiction writing at San Francisco State University, the Johns Hopkins Writing Seminars, and the University of Oregon.
Excelsior | Definition of Excelsior by Merriam-Webster
Wed, 02 Jun 2021 00:19
Onward and Upward With Excelsior In 1778 the state of New York adopted a coat of arms incorporating the motto ''Excelsior,'' Latin for ''Higher.'' Decades later, the motto sparked the imagination of the young Henry Wadsworth Longfellow, and in 1842 he used it as the title of an allegorical poem of doomed idealism. The poem begins, ''The shades of night were falling fast, / As through an Alpine village passed / A youth, who bore, 'mid snow and ice, / A banner with the strange device, / Excelsior!'' and follows the young man as he forges upward on his inscrutable mission, ignoring all warnings, before eventually perishing in the snow. It became so popular that, in its wake, the word was adopted as a brand name by numerous businesses; one manufactured wood shavings for use as packing material, and the term is still used for shavings today. But though Longfellow was an eminent linguist, he, like the founders of New York, failed to reflect that the adjective excelsior was perhaps less appropriate to his purpose than the adverb sursum (''upwards''). But the world hasn't minded--and certainly not the great comic-book artist Stan Lee, who for decades closed his popular magazine columns and speeches with the heartening exclamation.
History and Etymology for excelsiorNoun
trade name, from Latin, higher, comparative of excelsus high, from past participle of excellere
Trump Reportedly Claiming He Will Be 'Reinstated' as US President 'by August' - Sputnik International
Tue, 01 Jun 2021 23:51
US21:17 GMT 01.06.2021Get short URL
The former US president, Donald Trump, who lost the most recent White House race to Joe Biden, has refused to accept the outcome of the November 2020 election, continuing to make claims that Biden's victory is the result of massive "voter fraud".
Ex-US President Donald Trump, according to NY Times journalist Maggie Haberman, has been telling "a number of people" that he will gain back his title of US president "by August".
"Trump has been telling a number of people he's in contact with that he expects he will get reinstated by August (no that isn't how it works but simply sharing the information)," Haberman tweeted, attaching a video of a CNN report on ex-national security adviser Michael Flynn appearing to suggest a Myanmar-like coup in the US.Haberman went on to note that it was not "happening in a vacuum", pointing at how Trump "faced the possibility of an indictment from the Manhattan DA". The journalist also said that the former president has been "laser focused" on election audits.
It isn't happening in a vacuum. It is happening as he faced the possibility of an indictment from the Manhattan DA.
'-- Maggie Haberman (@maggieNYT) June 1, 2021'‹Earlier on Monday, Flynn, speaking at a QAnon conference in Texas, appeared to voice support for a Myanmar-style coup to happen in the United States, stating that it "should happen". The video quickly went viral and prompted a backlash from many, with some observers pointing at reports suggesting that QAnon believers back the idea of a coup similar to Myanmar's taking place in the US and placing Trump back in the White House.
Flynn, however, quickly denied allegations that he supports a coup in the US, writing on Telegram that he "does not and have not at any time called for any action of that sort".
"Let me be VERY CLEAR '' There is NO reason whatsoever for any coup in America, and I do not and have not at any time called for any action of that sort", Flynn wrote. "I am no stranger to media manipulating my words and therefore let me repeat my response to a question asked at the conference: There is no reason it (a coup) should happen here (in America)."Flynn, Trump's first of five national security advisers during his four-year term, shares the former president's belief that he won the 2020 presidential election. Flynn pled guilty to lying to the FBI following allegations of contact with Russian diplomats during the 2016 election, but later withdrew his plea. Trump pardoned his former national security adviser in December 2020.
The former US president has refused to accept the results of the 2020 White House election, continuing to claim that US President Joe Biden's victory is the result of what he and his supporters believe to be "massive election fraud". Back on 6 January, when a violent mob that included Trump supporters stormed the US Capitol to prevent the certification of the election results, Trump was accused of inciting the insurrection and impeached a second time by House Democrats based on the accusations.
Acquitted later by the Senate, the former president was ousted by mainstream social media platforms including Twitter and Facebook. Trump denied involvement in inciting the deadly Capitol riot.
Drinking Too Much Is an American Problem - The Atlantic
Tue, 01 Jun 2021 23:50
A little alcohol can boost creativity and strengthen social ties. But there's nothing moderate, or convivial, about the way many Americans drink today.
Photograph by Chelsea Kyle; Prop Stylist: Amy Elise Wilson; Food Stylist: Sue LiThis article was published online on June 1, 2021.
F ew things are more American than drinking heavily. But worrying about how heavily other Americans are drinking is one of them.
The Mayflower landed at Plymouth Rock because, the crew feared, the Pilgrims were going through the beer too quickly. The ship had been headed for the mouth of the Hudson River, until its sailors (who, like most Europeans of that time, preferred beer to water) panicked at the possibility of running out before they got home, and threatened mutiny. And so the Pilgrims were kicked ashore, short of their intended destination and beerless. William Bradford complained bitterly about the latter in his diary that winter, which is really saying something when you consider what trouble the group was in. (Barely half would survive until spring.) Before long, they were not only making their own beer but also importing wine and liquor. Still, within a couple of generations, Puritans like Cotton Mather were warning that a ''flood of RUM'' could ''overwhelm all good Order among us.''
George Washington first won elected office, in 1758, by getting voters soused. (He is said to have given them 144 gallons of alcohol, enough to win him 307 votes and a seat in Virginia's House of Burgesses.) During the Revolutionary War, he used the same tactic to keep troops happy, and he later became one of the country's leading whiskey distillers. But he nonetheless took to moralizing when it came to other people's drinking, which in 1789 he called ''the ruin of half the workmen in this Country.''
Hypocritical though he was, Washington had a point. The new country was on a bender, and its drinking would only increase in the years that followed. By 1830, the average American adult was consuming about three times the amount we drink today. An obsession with alcohol's harms understandably followed, starting the country on the long road to Prohibition.
What's distinctly American about this story is not alcohol's prominent place in our history (that's true of many societies), but the zeal with which we've swung between extremes. Americans tend to drink in more dysfunctional ways than people in other societies, only to become judgmental about nearly any drinking at all. Again and again, an era of overindulgence begets an era of renunciation: Binge, abstain. Binge, abstain.
Right now we are lurching into another of our periodic crises over drinking, and both tendencies are on display at once. Since the turn of the millennium, alcohol consumption has risen steadily, in a reversal of its long decline throughout the 1980s and '90s. Before the pandemic, some aspects of this shift seemed sort of fun, as long as you didn't think about them too hard. In the 20th century, you might have been able to buy wine at the supermarket, but you couldn't drink it in the supermarket. Now some grocery stores have wine bars, beer on tap, signs inviting you to ''shop 'n' sip,'' and carts with cup holders.
Actual bars have decreased in number, but drinking is acceptable in all sorts of other places it didn't used to be: Salons and boutiques dole out cheap cava in plastic cups. Movie theaters serve alcohol, Starbucks serves alcohol, zoos serve alcohol. Moms carry coffee mugs that say things like This Might Be Wine , though for discreet day-drinking, the better move may be one of the new hard seltzers, a watered-down malt liquor dressed up'--for precisely this purpose'--as a natural soda.
Even before COVID-19 arrived on our shores, the consequences of all this were catching up with us. From 1999 to 2017, the number of alcohol-related deaths in the U.S. doubled, to more than 70,000 a year'--making alcohol one of the leading drivers of the decline in American life expectancy. These numbers are likely to get worse: During the pandemic, frequency of drinking rose, as did sales of hard liquor. By this February, nearly a quarter of Americans said they'd drunk more over the past year as a means of coping with stress.
Explaining these trends is hard; they defy so many recent expectations. Not long ago, Millennials were touted as the driest generation'--they didn't drink much as teenagers, they were ''sober curious,'' they were so admirably focused on being well'--and yet here they are day-drinking White Claw and dying of cirrhosis at record rates. Nor does any of this appear to be an inevitable response to 21st-century life: Other countries with deeply entrenched drinking problems, among them Britain and Russia, have seen alcohol use drop in recent years.
In the evolutionary hunger games, the drunk apes beat the sober ones.Media coverage, meanwhile, has swung from cheerfully overselling the (now disputed) health benefits of wine to screeching that no amount of alcohol is safe, ever; it might give you cancer and it will certainly make you die before your time. But even those who are listening appear to be responding in erratic and contradictory ways. Some of my own friends'--mostly 30- or 40-something women, a group with a particularly sharp uptick in drinking'--regularly declare that they're taking an extended break from drinking, only to fall off the wagon immediately. One went from extolling the benefits of Dry January in one breath to telling me a funny story about hangover-cure IV bags in the next. A number of us share the same (wonderful) doctor, and after our annual physicals, we compare notes about the ever nudgier questions she asks about alcohol. ''Maybe save wine for the weekend?'' she suggests with a cheer so forced she might as well be saying, ''Maybe you don't need to drive nails into your skull every day?''
What most of us want to know, coming out of the pandemic, is this: Am I drinking too much? And: How much are other people drinking? And: Is alcohol actually that bad?
The answer to all these questions turns, to a surprising extent, not only on how much you drink, but on how and where and with whom you do it. But before we get to that, we need to consider a more basic question, one we rarely stop to ask: Why do we drink in the first place? By we, I mean Americans in 2021, but I also mean human beings for the past several millennia.
Let's get this out of the way: Part of the answer is ''Because it is fun.'' Drinking releases endorphins, the natural opiates that are also triggered by, among other things, eating and sex. Another part of the answer is ''Because we can.'' Natural selection has endowed humans with the ability to drink most other mammals under the table. Many species have enzymes that break alcohol down and allow the body to excrete it, avoiding death by poisoning. But about 10 million years ago, a genetic mutation left our ancestors with a souped-up enzyme that increased alcohol metabolism 40-fold.
This mutation occurred around the time that a major climate disruption transformed the landscape of eastern Africa, eventually leading to widespread extinction. In the intervening scramble for food, the leading theory goes, our predecessors resorted to eating fermented fruit off the rain-forest floor. Those animals that liked the smell and taste of alcohol, and were good at metabolizing it, were rewarded with calories. In the evolutionary hunger games, the drunk apes beat the sober ones.
But even presuming that this story of natural selection is right, it doesn't explain why, 10 million years later, I like wine so much. ''It should puzzle us more than it does,'' Edward Slingerland writes in his wide-ranging and provocative new book, Drunk: How We Sipped, Danced, and Stumbled Our Way to Civilization, ''that one of the greatest foci of human ingenuity and concentrated effort over the past millennia has been the problem of how to get drunk.'' The damage done by alcohol is profound: impaired cognition and motor skills, belligerence, injury, and vulnerability to all sorts of predation in the short run; damaged livers and brains, dysfunction, addiction, and early death as years of heavy drinking pile up. As the importance of alcohol as a caloric stopgap diminished, why didn't evolution eventually lead us away from drinking'--say, by favoring genotypes associated with hating alcohol's taste? That it didn't suggests that alcohol's harms were, over the long haul, outweighed by some serious advantages.
Versions of this idea have recently bubbled up at academic conferences and in scholarly journals and anthologies (largely to the credit of the British anthropologist Robin Dunbar). Drunk helpfully synthesizes the literature, then underlines its most radical implication: Humans aren't merely built to get buzzed'--getting buzzed helped humans build civilization. Slingerland is not unmindful of alcohol's dark side, and his exploration of when and why its harms outweigh its benefits will unsettle some American drinkers. Still, he describes the book as ''a holistic defense of alcohol.'' And he announces, early on, that ''it might actually be good for us to tie one on now and then.''
Slingerland is a professor at the University of British Columbia who, for most of his career, has specialized in ancient Chinese religion and philosophy. In a conversation this spring, I remarked that it seemed odd that he had just devoted several years of his life to a subject so far outside his wheelhouse. He replied that alcohol isn't quite the departure from his specialty that it might seem; as he has recently come to see things, intoxication and religion are parallel puzzles, interesting for very similar reasons. As far back as his graduate work at Stanford in the 1990s, he'd found it bizarre that across all cultures and time periods, humans went to such extraordinary (and frequently painful and expensive) lengths to please invisible beings.
In 2012, Slingerland and several scholars in other fields won a big grant to study religion from an evolutionary perspective. In the years since, they have argued that religion helped humans cooperate on a much larger scale than they had as hunter-gatherers. Belief in moralistic, punitive gods, for example, might have discouraged behaviors (stealing, say, or murder) that make it hard to peacefully coexist. In turn, groups with such beliefs would have had greater solidarity, allowing them to outcompete or absorb other groups.
Around the same time, Slingerland published a social-science-heavy self-help book called Trying Not to Try. In it, he argued that the ancient Taoist concept of wu-wei (akin to what we now call ''flow'') could help with both the demands of modern life and the more eternal challenge of dealing with other people. Intoxicants, he pointed out in passing, offer a chemical shortcut to wu-wei'--by suppressing our conscious mind, they can unleash creativity and also make us more sociable.
At a talk he later gave on wu-wei at Google, Slingerland made much the same point about intoxication. During the Q&A, someone in the audience told him about the Ballmer Peak'--the notion, named after the former Microsoft CEO Steve Ballmer, that alcohol can affect programming ability. Drink a certain amount, and it gets better. Drink too much, and it goes to hell. Some programmers have been rumored to hook themselves up to alcohol-filled IV drips in hopes of hovering at the curve's apex for an extended time.
His hosts later took him over to the ''whiskey room,'' a lounge with a foosball table and what Slingerland described to me as ''a blow-your-mind collection of single-malt Scotches.'' The lounge was there, they said, to provide liquid inspiration to coders who had hit a creative wall. Engineers could pour themselves a Scotch, sink into a beanbag chair, and chat with whoever else happened to be around. They said doing so helped them to get mentally unstuck, to collaborate, to notice new connections. At that moment, something clicked for Slingerland too: ''I started to think, Alcohol is really this very useful cultural tool.'' Both its social lubrications and its creativity-enhancing aspects might play real roles in human society, he mused, and might possibly have been involved in its formation.
He belatedly realized how much the arrival of a pub a few years earlier on the UBC campus had transformed his professional life. ''We started meeting there on Fridays, on our way home,'' he told me. ''Psychologists, economists, archaeologists'--we had nothing in common'--shooting the shit over some beers.'' The drinks provided just enough disinhibition to get conversation flowing. A fascinating set of exchanges about religion unfolded. Without them, Slingerland doubts that he would have begun exploring religion's evolutionary functions, much less have written Drunk.
Which came first, the bread or the beer? For a long time, most archaeologists assumed that hunger for bread was the thing that got people to settle down and cooperate and have themselves an agricultural revolution. In this version of events, the discovery of brewing came later'--an unexpected bonus. But lately, more scholars have started to take seriously the possibility that beer brought us together. (Though beer may not be quite the word. Prehistoric alcohol would have been more like a fermented soup of whatever was growing nearby.)
For the past 25 years, archaeologists have been working to uncover the ruins of G¶bekli Tepe, a temple in eastern Turkey. It dates to about 10,000 B.C.'--making it about twice as old as Stonehenge. It is made of enormous slabs of rock that would have required hundreds of people to haul from a nearby quarry. As far as archaeologists can tell, no one lived there. No one farmed there. What people did there was party. ''The remains of what appear to be brewing vats, combined with images of festivals and dancing, suggest that people were gathering in groups, fermenting grain or grapes,'' Slingerland writes, ''and then getting truly hammered.''
Over the decades, scientists have proposed many theories as to why we still drink alcohol, despite its harms and despite millions of years having passed since our ancestors' drunken scavenging. Some suggest that it must have had some interim purpose it's since outlived. (For example, maybe it was safer to drink than untreated water'--fermentation kills pathogens.) Slingerland questions most of these explanations. Boiling water is simpler than making beer, for instance.
G¶bekli Tepe'--and other archaeological finds indicating very early alcohol use'--gets us closer to a satisfying explanation. The site's architecture lets us visualize, vividly, the magnetic role that alcohol might have played for prehistoric peoples. As Slingerland imagines it, the promise of food and drink would have lured hunter-gatherers from all directions, in numbers great enough to move gigantic pillars. Once built, both the temple and the revels it was home to would have lent organizers authority, and participants a sense of community. ''Periodic alcohol-fueled feasts,'' he writes, ''served as a kind of 'glue' holding together the culture that created G¶bekli Tepe.''
Things were likely more complicated than that. Coercion, not just inebriated cooperation, probably played a part in the construction of early architectural sites, and in the maintenance of order in early societies. Still, cohesion would have been essential, and this is the core of Slingerland's argument: Bonding is necessary to human society, and alcohol has been an essential means of our bonding. Compare us with our competitive, fractious chimpanzee cousins. Placing hundreds of unrelated chimps in close quarters for several hours would result in ''blood and dismembered body parts,'' Slingerland notes'--not a party with dancing, and definitely not collaborative stone-lugging. Human civilization requires ''individual and collective creativity, intensive cooperation, a tolerance for strangers and crowds, and a degree of openness and trust that is entirely unmatched among our closest primate relatives.'' It requires us not only to put up with one another, but to become allies and friends.
As to how alcohol assists with that process, Slingerland focuses mostly on its suppression of prefrontal-cortex activity, and how resulting disinhibition may allow us to reach a more playful, trusting, childlike state. Other important social benefits may derive from endorphins, which have a key role in social bonding. Like many things that bring humans together'--laughter, dancing, singing, storytelling, sex, religious rituals'--drinking triggers their release. Slingerland observes a virtuous circle here: Alcohol doesn't merely unleash a flood of endorphins that promote bonding; by reducing our inhibitions, it nudges us to do other things that trigger endorphins and bonding.
Over time, groups that drank together would have cohered and flourished, dominating smaller groups'--much like the ones that prayed together. Moments of slightly buzzed creativity and subsequent innovation might have given them further advantage still. In the end, the theory goes, the drunk tribes beat the sober ones.
But this rosy story about how alcohol made more friendships and advanced civilization comes with two enormous asterisks: All of that was before the advent of liquor, and before humans started regularly drinking alone.
Photograph by Chelsea Kyle; Prop Stylist: Amy Elise Wilson; Food Stylist: Sue Li The early Greeks watered down their wine; swilling it full-strength was, they believed, barbaric'--a recipe for chaos and violence. ''They would have been absolutely horrified by the potential for chaos contained in a bottle of brandy,'' Slingerland writes. Human beings, he notes, ''are apes built to drink, but not 100-proof vodka. We are also not well equipped to control our drinking without social help.''
Distilled alcohol is recent'--it became widespread in China in the 13th century and in Europe from the 16th to 18th centuries'--and a different beast from what came before it. Fallen grapes that have fermented on the ground are about 3 percent alcohol by volume. Beer and wine run about 5 and 11 percent, respectively. At these levels, unless people are strenuously trying, they rarely manage to drink enough to pass out, let alone die. Modern liquor, however, is 40 to 50 percent alcohol by volume, making it easy to blow right past a pleasant social buzz and into all sorts of tragic outcomes.
From the September 2016 issue: Caitlin Flanagan on how helicopter parenting can cause binge drinking
Just as people were learning to love their gin and whiskey, more of them (especially in parts of Europe and North America) started drinking outside of family meals and social gatherings. As the Industrial Revolution raged, alcohol use became less leisurely. Drinking establishments suddenly started to feature the long counters that we associate with the word bar today, enabling people to drink on the go, rather than around a table with other drinkers. This short move across the barroom reflects a fairly dramatic break from tradition: According to anthropologists, in nearly every era and society, solitary drinking had been almost unheard'‘of among humans.
The social context of drinking turns out to matter quite a lot to how alcohol affects us psychologically. Although we tend to think of alcohol as reducing anxiety, it doesn't do so uniformly. As Michael Sayette, a leading alcohol researcher at the University of Pittsburgh, recently told me, if you packaged alcohol as an anti-anxiety serum and submitted it to the FDA, it would never be approved. He and his onetime graduate student Kasey Creswell, a Carnegie Mellon professor who studies solitary drinking, have come to believe that one key to understanding drinking's uneven effects may be the presence of other people. Having combed through decades' worth of literature, Creswell reports that in the rare experiments that have compared social and solitary alcohol use, drinking with others tends to spark joy and even euphoria, while drinking alone elicits neither'--if anything, solo drinkers get more depressed as they drink.
Even drinking in bars has become less social in recent years. Striking up conversations with strangers has become almost taboo.Sayette, for his part, has spent much of the past 20 years trying to get to the bottom of a related question: why social drinking can be so rewarding. In a 2012 study, he and Creswell divided 720 strangers into groups, then served some groups vodka cocktails and other groups nonalcoholic cocktails. Compared with people who were served nonalcoholic drinks, the drinkers appeared significantly happier, according to a range of objective measures. Maybe more important, they vibed with one another in distinctive ways. They experienced what Sayette calls ''golden moments,'' smiling genuinely and simultaneously at one another. Their conversations flowed more easily, and their happiness appeared infectious. Alcohol, in other words, helped them enjoy one another more.
This research might also shed light on another mystery: why, in a number of large-scale surveys, people who drink lightly or moderately are happier and psychologically healthier than those who abstain. Robin Dunbar, the anthropologist, examined this question directly in a large study of British adults and their drinking habits. He reports that those who regularly visit pubs are happier and more fulfilled than those who don't'--not because they drink, but because they have more friends. And he demonstrates that it's typically the pub-going that leads to more friends, rather than the other way around. Social drinking, too, can cause problems, of course'--and set people on a path to alcohol-use disorder. (Sayette's research focuses in part on how that happens, and why some extroverts, for example, may find alcohol's social benefits especially hard to resist.) But solitary drinking'--even with one's family somewhere in the background'--is uniquely pernicious because it serves up all the risks of alcohol without any of its social perks. Divorced from life's shared routines, drinking becomes something akin to an escape from life.
Southern Europe's healthy drinking culture is hardly news, but its attributes are striking enough to bear revisiting: Despite widespread consumption of alcohol, Italy has some of the lowest rates of alcoholism in the world. Its residents drink mostly wine and beer, and almost exclusively over meals with other people. When liquor is consumed, it's usually in small quantities, either right before or after a meal. Alcohol is seen as a food, not a drug. Drinking to get drunk is discouraged, as is drinking alone. The way Italians drink today may not be quite the way premodern people drank, but it likewise accentuates alcohol's benefits and helps limit its harms. It is also, Slingerland told me, about as far as you can get from the way many people drink in the United States.
Americans may not have invented binge drinking, but we have a solid claim to bingeing alone, which was almost unheard-of in the Old World. During the early 19th century, solitary binges became common enough to need a name, so Americans started calling them ''sprees'' or ''frolics'''--words that sound a lot happier than the lonely one-to-three-day benders they described.
In his 1979 history, The Alcoholic Republic, the historian W. J. Rorabaugh painstakingly calculated the stunning amount of alcohol early Americans drank on a daily basis. In 1830, when American liquor consumption hit its all-time high, the average adult was going through more than nine gallons of spirits each year. Most of this was in the form of whiskey (which, thanks to grain surpluses, was sometimes cheaper than milk), and most of it was drunk at home. And this came on top of early Americans' other favorite drink, homemade cider. Many people, including children, drank cider at every meal; a family could easily go through a barrel a week. In short, Americans of the early 1800s were rarely in a state that could be described as sober, and a lot of the time, they were drinking to get drunk.
Rorabaugh argued that this longing for oblivion resulted from America's almost unprecedented pace of change between 1790 and 1830. Thanks to rapid westward migration in the years before railroads, canals, and steamboats, he wrote, ''more Americans lived in isolation and independence than ever before or since.'' In the more densely populated East, meanwhile, the old social hierarchies evaporated, cities mushroomed, and industrialization upended the labor market, leading to profound social dislocation and a mismatch between skills and jobs. The resulting epidemics of loneliness and anxiety, he concluded, led people to numb their pain with alcohol.
The temperance movement that took off in the decades that followed was a more rational (and multifaceted) response to all of this than it tends to look like in the rearview mirror. Rather than pushing for full prohibition, many advocates supported some combination of personal moderation, bans on liquor, and regulation of those who profited off alcohol. Nor was temperance a peculiarly American obsession. As Mark Lawrence Schrad shows in his new book, Smashing the Liquor Machine: A Global History of Prohibition, concerns about distilled liquor's impact were international: As many as two dozen countries enacted some form of prohibition.
Yet the version that went into effect in 1920 in the United States was by far the most sweeping approach adopted by any country, and the most famous example of the all-or-nothing approach to alcohol that has dogged us for the past century. Prohibition did, in fact, result in a dramatic reduction in American drinking. In 1935, two years after repeal, per capita alcohol consumption was less than half what it had been early in the century. Rates of cirrhosis had also plummeted, and would remain well below pre-Prohibition levels for decades.
The temperance movement had an even more lasting result: It cleaved the country into tipplers and teetotalers. Drinkers were on average more educated and more affluent than nondrinkers, and also more likely to live in cities or on the coasts. Dry America, meanwhile, was more rural, more southern, more midwestern, more churchgoing, and less educated. To this day, it includes about a third of U.S. adults'--a higher proportion of abstainers than in many other Western countries.
What's more, as Christine Sismondo writes in America Walks Into a Bar, by kicking the party out of saloons, the Eighteenth Amendment had the effect of moving alcohol into the country's living rooms, where it mostly remained. This is one reason that, even as drinking rates decreased overall, drinking among women became more socially acceptable. Public drinking establishments had long been dominated by men, but home was another matter'--as were speakeasies, which tended to be more welcoming.
After Prohibition's repeal, the alcohol industry refrained from aggressive marketing, especially of liquor. Nonetheless, drinking steadily ticked back up, hitting pre-Prohibition levels in the early '70s, then surging past them. Around that time, most states lowered their drinking age from 21 to 18 (to follow the change in voting age)'--just as the Baby Boomers, the biggest generation to date, were hitting their prime drinking years. For an illustration of what followed, I direct you to the film Dazed and Confused.
Drinking peaked in 1981, at which point'--true to form'--the country took a long look at the empty beer cans littering the lawn, and collectively recoiled. What followed has been described as an age of neo-temperance. Taxes on alcohol increased; warning labels were added to containers. The drinking age went back up to 21, and penalties for drunk driving finally got serious. Awareness of fetal alcohol syndrome rose too'--prompting a quintessentially American freak-out: Unlike in Europe, where pregnant women were reassured that light drinking remained safe, those in the U.S. were, and are, essentially warned that a drop of wine could ruin a baby's life. By the late 1990s, the volume of alcohol consumed annually had declined by a fifth.
And then began the current lurch upward. Around the turn of the millennium, Americans said To hell with it and poured a second drink, and in almost every year since, we've drunk a bit more wine and a bit more liquor than the year before. But why?
One answer is that we did what the alcohol industry was spending billions of dollars persuading us to do. In the '90s, makers of distilled liquor ended their self-imposed ban on TV advertising. They also developed new products that might initiate nondrinkers (think sweet premixed drinks like Smirnoff Ice and Mike's Hard Lemonade). Meanwhile, winemakers benefited from the idea, then in wide circulation and since challenged, that moderate wine consumption might be good for you physically. (As Iain Gately reports in Drink: A Cultural History of Alcohol, in the month after 60 Minutes ran a widely viewed segment on the so-called French paradox'--the notion that wine might explain low rates of heart disease in France'--U.S. sales of red wine shot up 44 percent.)
But this doesn't explain why Americans have been so receptive to the sales pitches. Some people have argued that our increased consumption is a response to various stressors that emerged over this period. (Gately, for example, proposes a 9/11 effect'--he notes that in 2002, heavy drinking was up 10 percent over the previous year.) This seems closer to the truth. It also may help explain why women account for such a disproportionate share of the recent increase in drinking.
Throughout history, drinking has provided a social and psychological service. At a moment when friendships seem more attenuated than ever, maybe it can do so again.
Although both men and women commonly use alcohol to cope with stressful situations and negative feelings, research finds that women are substantially more likely to do so. And they're much more apt to be sad and stressed out to begin with: Women are about twice as likely as men to suffer from depression or anxiety disorders'--and their overall happiness has fallen substantially in recent decades.
In the 2013 book Her Best-Kept Secret, an exploration of the surge in female drinking, the journalist Gabrielle Glaser recalls noticing, early this century, that women around her were drinking more. Alcohol hadn't been a big part of mom culture in the '90s, when her first daughter was young'--but by the time her younger children entered school, it was everywhere: ''Mothers joked about bringing their flasks to Pasta Night. Flasks? I wondered, at the time. Wasn't that like Gunsmoke?'' (Her quip seems quaint today. A growing class of merchandise now helps women carry concealed alcohol: There are purses with secret pockets, and chunky bracelets that double as flasks, and'--perhaps least likely of all to invite close investigation'--flasks designed to look like tampons.)
From the April 2015 issue: Gabrielle Glaser on the irrationality of Alcoholics Anonymous
Glaser notes that an earlier rise in women's drinking, in the 1970s, followed increased female participation in the workforce'--and with it the particular stresses of returning home, after work, to attend to the house or the children. She concludes that women are today using alcohol to quell the anxieties associated with ''the breathtaking pace of modern economic and social change'' as well as with ''the loss of the social and family cohesion'' enjoyed by previous generations. Almost all of the heavy-drinking women Glaser interviewed drank alone'--the bottle of wine while cooking, the Baileys in the morning coffee, the Poland Spring bottle secretly filled with vodka. They did so not to feel good, but to take the edge off feeling bad.
Men still drink more than women, and of course no demographic group has a monopoly on either problem drinking or the stresses that can cause it. The shift in women's drinking is particularly stark, but unhealthier forms of alcohol use appear to be proliferating in many groups. Even drinking in bars has become less social in recent years, or at least this was a common perception among about three dozen bartenders I surveyed while reporting this article. ''I have a few regulars who play games on their phone,'' one in San Francisco said, ''and I have a standing order to just refill their beer when it's empty. No eye contact or talking until they are ready to leave.'' Striking up conversations with strangers has become almost taboo, many bartenders observed, especially among younger patrons. So why not just drink at home? Spending money to sit in a bar alone and not talk to anyone was, a bartender in Columbus, Ohio, said, an interesting case of ''trying to avoid loneliness without actual togetherness.''
Last August, the beer manufacturer Busch launched a new product well timed to the problem of pandemic-era solitary drinking. Dog Brew is bone broth packaged as beer for your pet. ''You'll never drink alone again,'' said news articles reporting its debut. It promptly sold out. As for human beverages, though beer sales were down in 2020, continuing their long decline, Americans drank more of everything else, especially spirits and (perhaps the loneliest-sounding drinks of all) premixed, single-serve cocktails, sales of which skyrocketed.
Not everyone consumed more alcohol during the pandemic. Even as some of us (especially women and parents) drank more frequently, others drank less often. But the drinking that increased was, almost definitionally, of the stuck-at-home, sad, too-anxious-to-sleep, can't-bear-another-day-like-all-the-other-days variety'--the kind that has a higher likelihood of setting us up for drinking problems down the line. The drinking that decreased was mostly the good, socially connecting kind. (Zoom drinking'--with its not-so-happy hours and first dates doomed to digital purgatory'--was neither anesthetizing nor particularly connecting, and deserves its own dreary category.)
As the pandemic eases, we may be nearing an inflection point. My inner optimist imagines a new world in which, reminded of how much we miss joy and fun and other people, we embrace all kinds of socially connecting activities, including eating and drinking together'--while also forswearing unhealthy habits we may have acquired in isolation.
But my inner pessimist sees alcohol use continuing in its pandemic vein, more about coping than conviviality. Not all social drinking is good, of course; maybe some of it should wane, too (for example, some employers have recently banned alcohol from work events because of concerns about its role in unwanted sexual advances and worse). And yet, if we use alcohol more and more as a private drug, we'll enjoy fewer of its social benefits, and get a bigger helping of its harms.
Let's contemplate those harms for a minute. My doctor's nagging notwithstanding, there is a big, big difference between the kind of drinking that will give you cirrhosis and the kind that a great majority of Americans do. According to an analysis in The Washington Post some years back, to break into the top 10 percent of American drinkers, you needed to drink more than two bottles of wine every night. People in the next decile consumed, on average, 15 drinks a week, and in the one below that, six drinks a week. The first category of drinking is, stating the obvious, very bad for your health. But for people in the third category or edging toward the second, like me, the calculation is more complicated. Physical and mental health are inextricably linked, as is made vivid by the overwhelming quantity of research showing how devastating isolation is to longevity. Stunningly, the health toll of social disconnection is estimated to be equivalent to the toll of smoking 15 cigarettes a day.
To be clear, people who don't want to drink should not drink. There are many wonderful, alcohol-free means of bonding. Drinking, as Edward Slingerland notes, is merely a convenient shortcut to that end. Still, throughout human history, this shortcut has provided a nontrivial social and psychological service. At a moment when friendships seem more attenuated than ever, and loneliness is rampant, maybe it can do so again. For those of us who do want to take the shortcut, Slingerland has some reasonable guidance: Drink only in public, with other people, over a meal'--or at least, he says, ''under the watchful eye of your local pub's barkeep.''
After more than a year in relative isolation, we may be closer than we'd like to the wary, socially clumsy strangers who first gathered at G¶bekli Tepe. ''We get drunk because we are a weird species, the awkward losers of the animal world,'' Slingerland writes, ''and need all of the help we can get.'' For those of us who have emerged from our caves feeling as if we've regressed into weird and awkward ways, a standing drinks night with friends might not be the worst idea to come out of 2021.
This article appears in the July/August 2021 print edition with the headline ''Drinking Alone.''
Will the Excelsior Pass, New York's Vaccine Passport, Catch On? '' DNyuz
Tue, 01 Jun 2021 23:48
On the Upper East Side in Manhattan, a well-heeled crowd flashed it to get into a socially distanced dance performance at the Park Avenue Armory. In Chelsea, people showed it to attend a John Mulaney stand-up set at City Winery. And in Troy, N.Y., patrons are using it to enter an intimate, speakeasy-style bar that only admits vaccinated guests.
This magic ticket is New York State's Excelsior Pass, which was introduced in March as the first and only government-issued vaccine passport in the country, accessible, for now, only to people who have been vaccinated in the state.
Officials are hoping that it can help New Yorkers feel confident about the safety of businesses and jump-start a statewide economy that is still reeling from losses experienced during the pandemic. But in order for that to happen, they will need more people and businesses to start using it and vaccine passports to become more universally accepted.
Though it is basically just a QR code on your phone that indicates your vaccine status, the pass, and vaccine passports more generally, have become a political flash point among conservatives and others who say the passports violate privacy concerns.
About 1.1 million Excelsior Passes had been downloaded onto phones and computers as of last week, according to the state. But so far, 9.1 million New Yorkers have been fully vaccinated.
Officials are hopeful that the pass will catch on more widely.
Eric Piscini, the vice president of emerging business networks at I.B.M., which developed the Excelsior Pass for the state, said New York was in discussions with other states so the pass could be used by out-of-state residents in New York and by New Yorkers elsewhere.
''In the application space, when you reach a million people, that's a pretty good threshold to pass,'' Mr. Piscini said. ''That is a really good indication that people find value in this.''
Nationally, a range of states including Georgia, Alabama, Arizona and Florida have already banned the use of vaccine passports, presenting the bans as measures to protect individual privacy and vaccination choice.
In New York, some lawmakers are backing new legislation that would provide additional privacy protections.
But though major sports venues and a growing number of smaller New York businesses are embracing using the app, the vast majority of businesses are not requiring any proof of vaccination to enter. (The state would not say how many businesses had signed up.)
For those that take the Excelsior Pass, paper vaccine cards must also be accepted as a form of proof, the state said.
Some businesses '-- especially those catering to adult audiences, like arts venues '-- are jumping into the world of verification. Aside from accepting the Excelsior Pass, City Winery in Chelsea, for example, also uses the CLEAR Health Pass as a way to verify health and vaccination status. Gov. Andrew M. Cuomo has encouraged the move toward fully vaccinated crowds by permitting businesses to disregard social distancing if everyone is vaccinated.
But civic technology experts warn that the passes can be gamed relatively easily, just like the paper vaccine card itself.
It took Albert Fox Cahn, executive director of the Surveillance Technology Oversight Project, a nonprofit watchdog group, just 11 minutes to download someone else's Excelsior Pass using information they had posted on social media and Google searches, he said. Many people have posted pictures of their vaccination cards, which include a person's name, birthday, date of vaccination and type of shot.
And each pass can be uploaded to a limitless number of devices, or printed out and copied. The Excelsior Pass, which cost the state $2.5 million to develop, contains no biometric data for privacy reasons, so it needs to be compared against an ID, an extra step that, in practice, sometimes isn't taken.
''We need to realize that as much as we want a magic piece of software to be able to tell us whether the person next to us is vaccinated, these apps really can't,'' Mr. Cahn said. ''At the end of the day, it's largely built on trust.''
At the City Winery on Wednesday, outdoor hosts sometimes asked for ID when people flashed their Excelsior Pass or paper vaccination cards to gain entry, but sometimes they didn't. At the Armory, Covid compliance officers in face shields carefully checked IDs, but they just eyeballed the pass's QR code, instead of scanning it to double-check its veracity.
There is no law mandating such steps be taken.
''We trust our audience,'' said Michael Dorf, the chief executive of City Winery, adding that his employees use their discretion to make those choices.
Accessibility is another worry. New York's vaccine rollout was marred by a heavy reliance on a complex internet appointment system, which gave tech-savvy people an advantage. Many older New Yorkers and those without good internet access struggled.
Now those same people face another technological hurdle if the pass becomes popular. Noel Hidalgo, executive director of BetaNYC, a nonprofit public interest technology organization, said he didn't think the state should be investing millions in a vaccine passport at a time when more time and effort could be spent on things like helping improve vaccination rates among Black and Hispanic New Yorkers and figuring out how people could quickly replace a lost or damaged paper card.
''Why are we focusing on providing a tech tool to a small group of New Yorkers who are digitally literate and understand how to get access?'' he asked.
Delays in entering data and data entry mistakes are also limiting who gets the pass. About 4 percent of people who tried to get passes were unable to do so, said Jennifer Givner, a state spokeswoman.
The pass pulls its information from the state and city immunization databases. If the information is entered incorrectly '-- for example, with misspellings or a wrong initial '-- the pass cannot be found.
I.B.M. recently added a phone number check to the identification field of the app to make it easier to find someone's vaccination. Only four of the five fields '-- including first and last name, date of birth and ZIP code '-- need to match for someone to get a pass.
A thread on Reddit dedicated to helping people who could not get passes noted that sometimes putting in an old ZIP code seemed to work.
''Yeah, for me it was a ZIP code I hadn't used in 14 years,'' one user wrote on the thread.
People who can't get a pass can fill out a complaint form and call a state hotline, but for the most part, the organization that vaccinated them has to correct the data, which is not always easy. The Excelsior Pass also does not have access to federal vaccination data, so people who got their vaccines at veterans' hospitals, like John Taylor, a 77-year-old Vietnam War veteran who lives in Pleasant Valley, N.Y., are out of luck.
''I had it laminated,'' said Mr. Taylor of his paper vaccine card. ''I'm just going to forget about the pass.''
State officials emphasized that the paper card could always be used, so the Excelsior Pass was not essential. Mr. Cuomo himself recently said that he still shows his paper card.
Outside shows at the Park Avenue Armory and City Winery on recent days, it seemed that about half of the patrons waiting in line to enter flashed their Excelsior Passes to prove vaccination and that the rest used their cards or photos of their cards. Both venues had additional alternatives for unvaccinated guests, such as rapid testing on site, or accepted proof of recent negative coronavirus tests.
''I'm proud of it,'' Scott Hernandez, 42, said of his Excelsior Pass as he waited to see if there was room for him and friends to have dinner at the winery. ''There needs to be more education about it.''
But the extent of social acceptance of the Excelsior Pass may vary around the state. In more conservative areas, the blowback can be severe.
In Auburn, N.Y., a tiny five-table chocolate store, Gretchen's Confections and Cafe, was inundated with social media hate from around the country after photos of a sign asking people to be vaccinated to sit indoors went viral. The store decided to take down its sign, and it now welcomes everyone.
''It is very polarizing,'' said Gretchen Christenson, the owner. ''They have been calling us Hitler and fascists, 'Segregation Cafe.' I think the number of people against it is tiny, but they are just extra loud and threatening.''
And when Matt Baumgartner announced that one of his bars, the Berlin Lounge in Troy, N.Y., would allow only vaccinated guests because of its small size and lack of outdoor space, he was also hit with social media hate.
In both cases, loyal customers rallied in support, and the lounge and the shop have been doing well in recent weeks.
''I'm someone who very strongly who believes in the vaccine, and part of me feels like getting to visit more places is kind of a reward,'' Mr. Baumgartner said.
The post Will the Excelsior Pass, New York's Vaccine Passport, Catch On? appeared first on New York Times.
Fauci's Emails with Chinese CDC Director: 'We Will Get Through Together'
Tue, 01 Jun 2021 20:37
Dr. Anthony Fauci and Chinese Center for Disease Control and Prevention Director George Gao's email exchanges were exposed Tuesday by the Washington Post, depicting a cozy relationship with his Chinese counterpart.
''I saw the Science interview, how could I say such a word 'big mistake' about others? That was journalist's wording. Hope you understand,'' Gao wrote to Fauci March 28, 2020.
''Lets work together to get the virus out of the earth,'' he added.
''I understand completely. No problem,'' Fauci responded. ''We will get through this together.''
On April 8, 2020, Gao wrote, ''I saw some news (hope it is fake) that [you] are being attacked by some people. Hope you are well under such a irrational situation.''
Fauci wrote back three days later. ''Thank you for your kind note. All is well despite some crazy people in this world.''
The Post obtained emails from a Freedom of Information Act request, exposing Fauci's working relationship with China early in the pandemic. This is despite former President Donald Trump pointing to intelligence that said China was responsible for the coronavirus outbreak.
The Post wrote about the 866-page discovery:
The released emails show that Fauci indeed tried to answer many queries, sometimes hitting ''send'' well after midnight. And even as Trump ratcheted up attacks on China for not containing the virus after it was first discovered there, Fauci sought to maintain ties with Gao, a well-regarded Chinese scientific leader '-- and Gao with him.
Meanwhile, Dr. Anthony Fauci admitted May 25 the National Institutes of Health (NIH) funded the Wuhan lab, but he still denies gain of function research support in relation to the origin of the flu.
Sen. Rand Paul (R-KY) stated May 25 that Dr. Fauci committed perjury May 12 over his gain of function comments related to Communist China's lab.
Paul was asked on Real America's Voice, ''Do you believe he [Fauci] perjured himself?''
''Absolutely,'' Paul said. ''He lied to the American people.''
Paul demanded on May 26 Fauci to be ''made to testify under oath'' about whether the National Institute of Allergy and Infectious Diseases funded the Wuhan Institute of Virology's gain of function research.
Democrats have not called for Fauci's firing but have supported demands for an investigation into the origins of the Chinese coronavirus in a move that could perjure Fauci.
''As we analyze what went wrong and what we can do in the future, we have to have answers to these questions, too,'' Sen. Tim Kaine (D-VA), Hillary Clinton's running mate, stated May 26. ''And I think you're going to see Congress addressing some of these matters as well. We've got to get to the bottom of it.''
''Understanding the origin and whether there was any nefarious activity in China is all part of that,'' Kaine said.
However, several Republicans demanded Fauci's firing on May 26 over his flip-flopping on Wuhan Lab funding, two days before the House Judiciary and Oversight Committee Republicans launched a probe into the NIH's Wuhan Lab grant.
Reps. James Comer (R-KY) and Jim Jordan (R-OH), ranking members of the House Oversight Committee and Judiciary Committee respectively, dispatched a letter to the director of the NIH, Dr. Francis Collins, raising ''concerns that EcoHealth Alliance knew of the Chinese Communist Party's attempts to cover-up the origins of the COVID-19 pandemic and failed to act or to inform the U.S. government.''
Snowden Drops A BOMB: Joe Biden 'Deeply Involved' In NSA Op That Illegally Spies On European Leaders '' enVolve
Tue, 01 Jun 2021 20:18
According to a new bomb dropped by Edward Snowden, President Joe Biden was a part of a diabolical NSA program that spied on European politicians, including some of our strongest allies, with the help of Denmark.
A European media investigation revealed that German Chancellor Angela Merkel and President Frank Walter-Steinmeier were among those illegally spied on by the NSA with the participation and support of the Danish Defense Intelligence Service (FE).
Rt.com reports: The US spying on not only its own citizens, but also leaders in foreign countries is an accusation that came to light in 2013, mostly thanks to documents leaked by former NSA contractor-turned-whistleblower '' though he remains a fugitive in the US '' Edward Snowden. Snowden's leaks specifically revealed Merkel's private cell phone had been monitored by US authorities.
The new revelations come as a result of multiple European news outlets '' including Danish state broadcaster DR, German NDR, Swedish SVT, Norwegian NRK and French Le Monde among others '' obtaining access to internal reports and information from Danish Secret Service sources.
According to the report, the NSA used Danish agents to target politicians in Germany, Sweden, Norway, the Netherlands, France, and even the Danish finance industry. The Danish government is said to have known about the collaboration for years and compelled the FE leadership to resign in 2020 when an internal probe revealed the full nature of the relationship. They did not, however, inform any European Union allies of the results.
The spying was primarily done through hijacking Danish electronic communications systems as the country has landing stations for subsea internet cables between numerous countries, such as Germany and Sweden. By using politicians' and officials' phone numbers, authorities were able to pull texts and phone calls, while those being spied on were none the wiser.
Snowden, who made his revelations about the NSA while Biden was vice president, says the current president is ''well-prepared'' to answer the accusations and that there should be a requirement of ''full disclosure'' from both Denmark and the US.
''Biden is well-prepared to answer for this when he soon visits Europe since, of course, he was deeply involved in this scandal the first time around,'' he tweeted. ''There should be an explicit requirement for full public disclosure not only from Denmark, but their senior partner as well.''
Biden is well-prepared to answer for this when he soon visits Europe since, of course, he was deeply involved in this scandal the first time around.
There should be an explicit requirement for full public disclosure not only from Denmark, but their senior partner as well. https://t.co/TJL7gr6dy8
'-- Edward Snowden (@Snowden) May 30, 2021
In response to explosive reports, Norway's Defence Minister Frank Bakke-Jensen said they were ''taking the allegations seriously,'' while Sweden's Defence Minister Peter Hultqvist said he ''demanded full information on these things.'' Neither the NSA nor the Danish Defence Intelligence Service have issued a comment yet.
Former German opposition leader and Merkel rival, Peer Steinbr¼ck, who also reportedly had his communications monitored, told German broadcaster ARD that he considers the situation to be a ''scandal.''
''It is grotesque that friendly intelligence services are indeed intercepting and spying on top representatives of other countries,'' he said.
How the biggest-ever PSA campaign is pitching the vaccine
Tue, 01 Jun 2021 20:16
By Jeff Beer 10 minute ReadYou can almost hear the needle on the record, as Billie Holiday's ''I'll Be Seeing You'' plays. An older woman looks out the window. We see the pictures of her family, her grandkids, sitting in frames and stuck to the fridge. A crayon drawing of two kids wearing masks reads, ''We miss you Grandma.'' The woman goes through her own version of the Mr. Rogers routine (putting on a comfy sweater and slippers) before anxiously looking out the window again. When the doorbell finally does ring, it's not an Amazon or grocery delivery'--it's her family. She opens the door, and after a moment of brief hesitation the kids run in for a long-awaited hug.
The look of love mixed with relief on the woman's face as her grandchildren's arms wrap around her shoulders, as well as that on her daughter's face as she's watching it happen, are what the Ad Council is aiming to convey with this new public-service announcement. It's part of the organization's marketing effort to encourage people to get vaccinated for COVID-19, its biggest-ever PSA campaign at about $52 million, plus $500 million in donated media ad space.
''We have to do everything we can to educate people in order to move them from vaccine hesitancy to vaccine confidence,'' says Ad Council CEO Lisa Sherman. ''This is our moonshot.''
Advertising is typically all about the sell: Persuading us that we need something, and this brand or another is the answer. They make us laugh, they make us cry'--all for us to buy. PSA campaigns are government- or corporate-funded efforts to use these same tools of persuasion to raise awareness and promote safe behavior around a particular societal ill or issue. Just Say No. Don't Drink and Drive. Love Has No Labels. Sometimes these efforts become a part of culture themselves.
This is your brain on ads.
While past issue campaigns have been important and timely, the pandemic brought with it an unprecedented level of both urgency and difficulty. First, the Ad Council had to convey the importance of measures to slow the spread'--such as masks and social distancing'--and then to answer many people's perfectly reasonable questions about vaccines that have been rolled out in record time.
The last time the Ad Council worked on a vaccine campaign, it was for polio in the 1950s, a much simpler media environment, when trust in public institutions was far higher. According to Pew Research in December 2020, 60% of people polled said they would likely get vaccinated, still leaving 40% of Americans to be convinced. The Ad Council's data told it that 30% of Americans definitely planned to be vaccinated, 20% were absolutely not getting it, and 50% categorized their approach as ''wait and see.'' This latter cohort is the target audience.
Although the ''wait and see'' crowd is the key, within that statistic lies another challenge. Black and Latinx communities, among the most vulnerable to the virus, are also the most distrustful and hesitant to take the vaccine. Not only because of specific events such as the Tuskegee Experiment, but also the result of a lifetime of inequality in healthcare. Now multiple organizations and corporations have launched a loosely coordinated, all-out advertising blitz to make a convincing case. Can it mollify people's fears and sufficiently answer their questions to help make America safe again?
GETTING STARTEDLast March, just a week after the World Health Organization declared the coronavirus a global pandemic, the Ad Council launched its first COVID-19-related PSA. The organization partnered with the Centers for Disease Control and the U.S. Department of Health and Human Services to create an ongoing campaign to give people information on how to keep safe, with a focus on wearing masks or face coverings and practicing social distancing. ''We really wanted to ground everything in facts and in science so people could be assured that our information was accurate and vetted,'' says Sherman.
By fall 2020, as the reality of a vaccine rollout began to set in, Sherman says the organization was concerned about reports on the levels of hesitancy that people had about taking the vaccine. It teamed up with a new organization called the COVID Collaborative'--a coalition of experts and institutions across health, education, and the economy'--that not only organized a 24-hour livestream event with Oprah, Julia Roberts, Deepak Chopra, Questlove, and more celebrities back in May but also raised $100 million for vulnerable communities and frontline workers.
''Our role is we're bringing the science, the experts, and all these organizations like the NAACP [and] state leaders [are] all working with us to ensure this campaign really is effective at achieving its objectives,'' says COVID Collaborative cofounder and CEO John Bridgeland.
What they've found through research is that the best tool for an effective campaign is locality. Sure, the big PSAs with the nice stories'--or even ones such as assembling Presidents Obama, Bush, and Clinton to get their shots'--are helpful, but the real progress will be made in getting the message across to people through those they are close to. That can be everyone from their local news anchor to their doctor, pastor, or community leader.
IT'S UP TO YOUTo lead the strategy and creative for its vaccine campaign, the Ad Council brought in San Francisco-based agency Pereira O'Dell last December. Sherman says the organization approached this with three general guiding principles: First, science and data had to drive everything. Second, it had to combine the Ad Council's typical national reach with a more local approach. And third, there had to be a coordinated approach between agency partners, rather than a patchwork method where everyone goes out and does their own thing.
For Pereira O'Dell cofounder and creative chairman PJ Pereira, the challenge was to find an approach that would respect people's hesitancy, while empowering them to make the right choice. The tagline they landed on? ''It's up to you.''
''We didn't want to take an approach that was a badge of approval like 'I took it' or 'I got vaccinated,''' says Pereira. ''That sounds like 'I'm better than you.' If you're leaning no, you immediately cause the program to fail. Switching it to 'It's up to you,' we're leaning into a precious part of the American identity, which is our independence, the freedom to make our own choices. So the approach here is, 'It's up to you, but let me give you some facts.'''
In order to make that message as effective as possible, in particular to specific communities, Pereira O'Dell brought on two more agency partners by year's end: Miami-based Alma DDB to focus on the Latinx community, and Washington, D.C.-based Joy Collective for work tailored for the Black community.
''We weren't going to find a silver-bullet message here that worked for everyone,'' says Pereira. ''We had to find something that would allow us to approach from different angles. It was about finding an emotional attitude rather than specific wording. What we did was try to find an architecture that was flexible enough for different partners to take and join the effort, and there is alignment on the idea of being respectful and empathetic to people's hesitancy.''
When Luis Miguel Messianu, creative chairman and CEO of Alma DDB, first heard the tagline and theme of ''It's up to you,'' he loved the colloquial nature of it, but he quickly realized that the phrase itself really fell short when translated directly to Spanish. So they worked on a solution not only to capture the essence of the phrase but also to add a few additional layers. Their answer had to work linguistically, but more important, it had to translate culturally across all different Spanish-speaking nationalities.
They landed on ''De ti depende.''
''It really communicates the collective aspect of our community and choice in a really empathetic way,'' says Messianu. ''It really captures that sense of empowerment [and] motivates without being pushy. So we felt this is relevant to a Hispanic audience, given the correlation with the dependence and family focus. Not only in this country, but in many instances it connects to the mother country. A lot of our audience has family in Mexico, Colombia, Argentina, and Brazil. It has a very direct connection with the collective aspect, the multigenerational component, and across a variety of geographies.''
In adapting the campaign for a Black American audience, Joy Collective founder and CEO Kelli Richardson wanted to make sure that the campaign and its tagline didn't feel like it was foisting another burden on the Black community. She and her team instead focused on rooting the images and messaging in very familial experiences and the desire to get back some of what has been lost. The ads feature images of HBCU homecoming, family cookouts, and barbershops. The agency is also creating messages featuring well-known pastors from across the country, talking about the importance of getting the facts.
''It started with having a deep understanding of what it means to be Black in America today, and the history of this country,'' says Richardson. ''Things like the Tuskegee Experiment, and the distrust of the medical profession, with only 5% of doctors in this country being Black. There are huge obstacles to overcome in the Black community, so we wanted to say it's okay to have questions. It's okay to be concerned. We understand. Showing empathy towards that distrust, but then saying let's connect.''
MANY PLAYERS, ONE GOALAnother aspect of the vaccine-ad push that makes it unprecedented is how there are multiple, parallel efforts that aren't related. In order to give the general public confidence in the vaccine it would be producing, Moderna hired award-winning agency TBWA\Chiat\Day Los Angeles in October to transform its public image, as much as it had one, beyond an R&D company and into a trusted brand.
Meanwhile, up in the Bronx, New York, the healthcare network Montefiore has been working to instill vaccine confidence in its community of patients'--starting with its own 50,000-employee team. Now the company is working on a consumer brand campaign on vaccine confidence that will launch sometime in April or May.
Pfizer launched its ''Science Wins'' campaign last April, but it wasn't about selling anything or promoting its vaccine development over any other, which is restricted by the FDA's emergency-use authorization, which allowed the company's vaccine to be approved so quickly. Instead, Pfizer's campaign was a confident rallying cry in the race to find a vaccine. Last week, on March 11, the company launched a 44-minute documentary on the National Geographic channel, created with the network, documenting the epic process it took to create a vaccine so quickly.
''Everything we're doing is about instilling vaccine confidence,'' says Sally Susman, Pfizer's executive VP and chief corporate affairs officer, in explaining the company's reason to get the story out now. ''The people in the story, these aren't the top brass of the company. They're the people doing the work on the ground. And like any story, the closer you get to the ground, the more you feel its truth.''
MORE VACCINES, MORE ADSBecause President Biden announced last week that all Americans should have access to the vaccine by May 1, the coalition of marketers, advertisers, and media behind the Ad Council campaign knows that this is only the beginning. Linda Yaccarino, chairman of global advertising and partnerships at NBCUniversal, says the degree of coordination and cooperation between so many, often competing, private-sector partners'--including Ad Council collaborators Verizon, Walmart, Comcast, and Salesforce'--to promote vaccine education ''is nothing short of extraordinary.''
And she doesn't expect it to be a single campaign.
''We're quite sure this message will morph over time,'' says Yaccarino. ''It's not going to be a one-and-done, a month or two campaign. We expect this will go on for well over a year, and I'm sure it'll take on different iterations of what the messaging is.''
The Ad Council has its campaign, while partners have been given the flexibility to create their own work but using the ''It's up to you'' tagline and framework. The hope is that this approach will produce more ways to connect with people, particularly on the local and cultural levels. The collective effect of this, plus the work of Pfizer, Moderna, and an impending White House campaign on the Johnson & Johnson vaccine, is ideally to cover as many hesitancy bases as possible.
Already the push appears to have gained a more favorable response to the very public backlashes against protective measures such as face masks and social distancing. Experts tell Fast Company that the biggest difference between those two campaigns may be that masks and other measures are seen as defensive moves, whereas the vaccine not only gives the impression of being proactive but also brings with it the sense of a light at the end of the tunnel.
The unprecedented nature of this work, from its scale and subject to the number of partners contributing, reflects the sheer importance and urgency of the message. Those involved are also anxious to see the lessons it will provide.
''This is all uncharted territory,'' says Alma's Messianu. ''It will create a new benchmark.''
Proud Father of My Two Sons: "INDIAN BAR ASSOCIATION SERVES LEGAL NOTICE UPON D'..." - No Agenda Social
Tue, 01 Jun 2021 16:12
INDIAN BAR ASSOCIATION SERVES LEGAL NOTICE UPON DR. SOUMYA SWAMINATHAN, THE CHIEF SCIENTIST, WORLD HEALTH ORGANISATION
A legal notice is served by Indian Bar Association (IBA) upon Dr. Soumya Swaminathan, the Chief Scientist at the World Health Organisation (WHO) on May 25, 2021 for her act of spreading disinformation and misguiding the people of India, in order to fulfil her agenda.
https:// indianbarassociation.in/wp-con tent/uploads/2021/05/IBA-PRESS-RELEASE-MAY-26-2021.pdf
@ adam I'm assuming this to be legit.
World's Largest Meat Supplier Crippled by Cyberattack
Tue, 01 Jun 2021 16:10
A major cyberattack has reportedly crippled the world's largest meat processing company, JBS. The company reports an ''organized cybersecurity attack'' has severely hampered its operations in the U.S. and Australia.
NBC News reports that thousands of meat workers in Australia are out of work for a second day this week after a cyberattack has crippled the largest meat supplier in the world, JBS. The company is also Australia's largest meat and food processing company with 47 facilities across the country including abattoirs, feedlots, and meat processing sites. JBS employs around 1,100 people.
JBS USA said in a statement from Greeley, Colorado, on Monday that it was the target of an ''organized cybersecurity attack,'' affecting some of its servers supporting its North American and Australian IT systems.
The statement said: ''The company's backup servers were not affected and it is actively working with an Incident Response firm to restore its systems as soon as possible.'' Australian Agriculture Minister David Littleroud said that the government and Australian Federal Police were working with JBS to resolve the issue and track down those responsible.
Littleproud stated: ''Despite the fact that JBS accounts for around 20 percent of our processing production here in Australia, we're not expecting there to be significant impacts on exports so long as this isn't a protracted shutdown'...We're also working with JBS right here in Australia to make sure that we can get some limited capacity up and going in the next couple of days. JBS have been very proactive in that.''
Littleproud stated that it was too early to determine whether it was a ransomware attack or who might be responsible for the hack. Australian staff at JSB learned of the hack when they were turned away from their workplace on Monday.
JBS exports around 70 per cent of what it produces in Australia but Australia and New Zealand account for only 4 percent of the company's global revenue. Several consignments of cattle in Queensland state were canceled at short notice and cattle trucks were returned around due to the attack. ''We had to send them up on Sunday afternoon and then we got the message in the morning that they'd have to cancel the train because the meat works was going to be shutting for an indefinite amount of time,'' Queensland cattle rancher Colin Baker stated. ''We had a wasted day . . . because mustering the cattle, sorting them out and then trucking them up there and then we had to bring them home today and let them all go again,'' Baker added.
Lucas Nolan is a reporter for Breitbart News covering issues of free speech and online censorship. Follow him on Twitter @LucasNolan or contact via secure email at the address lucasnolan@protonmail.com
JBS Cyber Hack: Meat Supplier Shuts Down Some Slaughterhouses After Attack - Bloomberg
Tue, 01 Jun 2021 16:08
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Killer Drone 'Hunted Down' a Human Target Without Being Told To: UN
Tue, 01 Jun 2021 15:44
A deadly drone "hunted down" a human target without being instructed to do so, a UN report says. The incident took place during clashes in Libya last year, the Daily Star reported. Experts are sounding the alarm about the lack of regulation around using "killer robots." See more stories on Insider's business page. A "lethal" weaponized drone "hunted down a human target" without being told to, likely for the first time, according to a UN report seen by the New Scientist.
In the March 2020 incident, a Kargu-2 quadcopter autonomously attacked a person during a conflict between Libyan government forces and a breakaway military faction, led by the Libyan National Army's Khalifa Haftar, the Daily Star reported.
The Turkish-built Kargu-2, a deadly attack drone designed for asymmetric warfare and anti-terrorist operations, targeted one of Haftar's soldiers while he tried to retreat, according to the paper.
The drone, which can be directed to detonate on impact, was operating in a "'highly effective' autonomous mode that required no human controller," the New York Post reported.
"The lethal autonomous weapons systems were programmed to attack targets without requiring data connectivity between the operator and the munition: in effect, a true 'fire, forget and find' capability," the report from the UN Security Council's panel of experts on Libya said.
Read more: Etsy is awash with illicit products it claims to ban, from ivory to dangerous weapons and mass-produced good
This is likely the first time drones have attacked humans without instructions to do so, Zak Kallenborn, a national-security consultant who specializes in unmanned systems and drones, confirmed in the report.
Kallenborn has concerns about the future of autonomous drones. "How brittle is the object recognition system?" he said in the report. "How often does it misidentify targets?"
Jack Watling, a researcher on land warfare at the Royal United Services Institute, told the New Scientist that the incident demonstrates the "urgent and important" need to discuss the potential regulation of autonomous weapons.
Human Rights Watch has called for an end to so-called "killer robots" and is campaigning for a "preemptive ban on the development, production, and use of fully autonomous weapons," according to a report by the nonprofit.
Can new technology solve a trillion-pound garbage problem?
Tue, 01 Jun 2021 15:19
Ragpickers search for reusable items from a heap of garbage, at Sevapura dumping yard in Jaipur,Rajasthan, India, Wednesday, April 07, 2021.
NurPhoto | NurPhoto | Getty Images
Humans generate a remarkable amount of garbage: over 2 billion tonnes per year, according to the World Bank, or approximately 4.5 trillion pounds annually. And that figure is going to grow. Global garbage is expected to reach 3.4 billion tonnes by 2050.
Even if you could figure out where to put that much garbage, it's going to leak dangerous greenhouse gasses that contribute to climate change. Solid waste landfills are the third-largest source of methane emissions in the United States, according to the most recent data available from the Environmental Protection Agency. In 2019, landfills released 15% of methane emissions, which is equivalent to emissions from more than 21.6 million passenger cars driven for one year.
Recycling is no panacea. And furthermore, there's a wide gap between what's possible to be recycled and what actually is recycled. Dry recyclables such as plastic, paper and cardboard, metal and glass are equal to 38% of municipal waste, according to data in the World Bank's What a Waste 2.0 report. Meanwhile, only 13.5% of those dry recyclables are actually recycled globally.
Technology companies are trying to tackle the garbage problem from multiple directions, improving recycling processes and creating new materials to make single-use products that are compostable.
The U.S. waste industry can use the help. Richer countries do a better job of recycling than poorer countries, but the United States isn't near the top of the list, recycling 34.6% of its garbage. While poor countries on average only recycle 3.7% and many don't recycle at all or don't have data, some of the best rates are in Europe and especially among some of the smallest territories, such as The Faroe Islands, a self-governing archipelago which is part of the Kingdom of Denmark, which is No. 1 in the world, recycling 67% of its garbage.
Recycling cost, profits, and automation"The basic principles of recycling are the collection, sorting, manual and or mechanical processing, and then delivery of the required quality of recycled materials to manufacturing industries," Ross Bartley, the trade and environment director at the Brussels, Belgium-headquartered Bureau of International Recycling, told CNBC. "Even in industrialized countries, manual sorting may be necessary and that can be complemented, and maybe replaced, by automated sorting systems using suitable technologies."
Automated sorting happens with magnets, flotation, wind sifters (to separate light and heavy materials), and cameras, among other techniques, according to Bartley, and such equipment can be bought off the shelf and integrated into recycling plants.
But key questions include how much the separation equipment costs, the all-in running costs per tonne of processed materials, and what is the added value to each of the separated streams of materials. In other words: "When is it profitable?" Bartley said.
Matanya Horowitz, the founder and CEO of AMP Robotics, which ranked No. 25 on this year's CNBC Disruptor 50 list, got his big recycling idea after visiting a materials recovery facility (MRF) '-- the destination for residential and commercial recyclables '-- and learned not only how demanding work conditions are, but how inefficient the process can be.
More coverage of the 2021 CNBC Disruptor 50Horowitz was looking for applications of robotics technology that could be improved. He got his doctorate at California Institute of Technology and when he was there, he worked on several Defense Advanced Research Projects Agency (DARPA) challenges. "That helped me understand what was working well in robotics and what remained a challenge," he told CNBC.
It was clear to Horowitz that computer vision could improve the work of sorting garbage for recycling. In July 2014, Horowitz launched AMP Robotics and has raised $77.8 million and has almost 130 employees. In April 2020, AMP Robotics announced it had processed more than one billion recyclable objects in a year.
A primary challenge for AMP Robotics is that sorting garbage is endlessly complex. "Recycling is a tough business to be in," Horowitz says. "You can't control the materials you're processing, and there are all kinds of odd contaminants that people put in their recycling bins. The result is that you have to build exceptionally tough and high-performance pieces of equipment."
AMP Robotics uses robotics and artificial intelligence to sort recycling.
Photo courtesy AMP Robotics
He's aware of the historic insufficiencies of recycling. "These materials (plastics, metals, paper) all have true value. The problem is that the cost of sorting erodes away that value," Horowitz says. "If you reduce the cost of sorting, the margin you can extract on all those materials increases and you naturally find an incentive to capture that material. That's precisely what our technology does, and how we go about our mission of enabling a world without waste."
Horowitz is optimistic. "A quote I've always liked is, 'Any sufficiently advanced technology is indistinguishable from magic,'" he said.
Consumer brands can help increase the success of the recycling supply chain, too, according to Steve Alexander, the president and CEO of the Association of Plastic Recyclers, by designing packaging that can be recycled.
A label on a soda bottle that has a lot of adhesive or ink may not be consistent with other recyclable designs in the soda bottle category, and might in the fact contaminate that stream.
"Even though it's been separated as a soda bottle, or water bottle, it still could contaminate," Alexander tells CNBC. "It all comes down to design. The first thing we have to do is ensure the products we buy be compatible with recycling."
Brands are being pushed to be better and more transparent about their package recyclability by consumer demand. "It's on the goodwill right now of the consumer brand company," Alexander says, but there's interest in governmental regulation mandating consumer brand package design.
Making single-use, compostable packagingTroy Swope, the CEO of Footprint, a technology company focused on eliminating single-use plastics through development and manufacturing of compostable containers, says to focus on improving recycling for plastics is chasing the wrong solution.
"Just to be real clear: Recycling is a joke when it comes to plastic," Swope said. "It's one of the biggest lies we've ever been told."
Swope pointed to CarbonLite Holdings, a large plastic bottle recycler that filed for bankruptcy protection in March. "Without value, no matter what we do to infrastructure... if nobody wants it at the end, nature can't digest it, it doesn't mean anything. It has no value," he said.
Troy Swope, a co-founder and CEO of Footprint
Photo courtesy Footprint
Just to be real clear: Recycling is a joke when it comes to plastic.
Arizona-headquartered Footprint, which ranked No. 45 on this year's CNBC Disruptor 50 list, is focused on making compostable single-use products from cellulose, plant-based materials, such as a recycled cardboard box, wood fibers and agricultural waste. The goal is for all products to be biodegradable or compostable in 90 days or less.
And they're doing so at scale. "We're going to deliver close to a billion units this year, probably just under a billion units from three factories," Swope told CNBC.
Current Footprint customers include McDonalds, SweetGreen and Conagra Brands.
"Next year, we will sell billions of units," Swope said.
Footprint has three factories currently, one in Arizona, another in South Carolina and a third in Mexico. It is in the process of building a research center in the Netherlands and a manufacturing facility in Poland.
Questioning the environmental impact"I think recycling, and I say this as a recycling company, is not the answer to garbage," said Tom Szaky, CEO of recycling company Terracycle and zero-waste packaging company Loop, in a recent CNBC Evolve livestream event. "It's an answer to the symptom of garbage, maybe the best way to manage waste, but I think we have to go much deeper and enable an economy where garbage doesn't exist."
Indeed, that's a plug for Szaky's company, Loop, which has consumer brands partners collaborate to make "reusability, ideally, as disposability."
But it also gets at a nuance of the garbage problem which David Allaway, a senior policy analyst at the Oregon Department of Environmental Quality Materials Management Program in Portland, Oregon, covered in a report questioning the environmental impact of recycling.
"In this country, most of the impacts of consumer goods and single-use items and packaging '' whether it be in toxics, climate change, water depletion, habitat disruption, or other impacts '' is not a result of disposal. Rather, it is a consequence of supply chains, manufacturing and production," Allaway tells CNBC. "And, as our research showed, items that are 'recyclable' and 'compostable' are not necessarily better for the environment or result in lower human health impacts than functionally equivalent items that are not 'recyclable' or 'compostable.'"
That is not to say that recyclability and composability are necessarily unhelpful.
Items with these popular attributes could be less impactful, and some of them are less impactful, but recyclability and composability are inconsistent predictors of environmental goodness, according to his work, which summarized roughly 17 years of international research on the topic.
For example, elemental mercury is very recyclable but a bad neurotoxin, and whale blubber is compostable but still not a raw material that is desirable.
"Simply knowing that an item is 'recyclable' or 'compostable' tells us surprisingly little about the actual impacts on human health and the environment, or the trade-offs between different materials," Allaway said.
There also are downstream effects of waste decomposition.
"Biodegradable is a great solution in countries that lack solid waste management infrastructure, but in this country, where most of our non-recovered waste goes to landfill, biodegradable means that the material will decompose and produce methane, which is a powerful greenhouse gas," Allaway said.
He cautions that promoting these popular attributes such as "recyclable" and "compostable" is a common marketing strategy that plays to popular wisdom, "which is always popular, but not always wise."
What's most important, in his view, is that producers quantify the total environmental impact of a good with a life cycle assessment. Otherwise, Allaway says, society has no way of knowing whether any of these efforts are steering us in the direction of actual sustainability, or just "feel-good" shifts in pollution involving visible, obvious forms, such as plastic in the oceans.
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Meet the Scientists Bringing Extinct Species Back From the Dead - WSJ
Tue, 01 Jun 2021 14:38
The pigeons are outwardly unremarkable. Thirteen birds, ages two weeks to three months, occupy a coop at an animal research facility west of Melbourne, Australia. They're descendants of the common rock pigeon, recognizable denizens of city squares and park benches'--with one small but crucial distinction. These are the first pigeons in history with reproductive systems that contain the Cas9 gene, an essential component of the Crispr gene-editing tool. The squabs of this flock will be born with the Cas9 gene in every one of their cells, allowing scientists to edit their offspring with DNA from the extinct passenger pigeon. Those birds, if everything goes to plan, will be the first live animals edited with traits from a species that no longer exists. The flock was created by Ben Novak, an American scientist who has spent the past six years working obsessively on a process known as de-extinction. His goal: to bring back a bird that disappeared from the face of the Earth in 1914.
Over the past six years, new gene-editing technology has given us previously unimaginable control over genetics. The Crispr-Cas9 system consists of two main parts: an RNA guide, which scientists program to target specific locations on a genome, and the Cas9 protein, which acts as molecular scissors. The cuts trigger repairs, allowing scientists to edit DNA in the process. Think of Crispr as a cut-and-paste tool that can add or delete genetic information. Crispr can also edit the DNA of sperm, eggs and embryos'--implementing changes that will be passed down to future generations. Proponents say it offers unprecedented power to direct the evolution of species.
In January 2013 scientists published papers demonstrating that, for the first time, they had successfully edited human and animal cells using Crispr. The news sparked fears of so-called designer babies edited for traits like intelligence and athleticism, something scientists stay is still far off because of the complexity of those traits. But editing of embryos for research is already under way. In the past 18 months, researchers in the U.S. and China successfully edited disease-causing mutations in viable human embryos not intended for implant or birth.
The technology is widely used in animals. Crispr has produced disease-resistant chickens and hornless dairy cattle. Scientists around the world routinely edit the genes in mice for research, adding mutations for human diseases such as autism and Alzheimer's in a search of possible cures. Crispr-edited pigs contain kidneys that scientists hope to test as transplants in humans.
Crispr has been discussed as a de-extinction tool since its earliest days. In March 2013 the conservation group Revive & Restore co-organized the first TedXDeExtinction conference in Washington, D.C. Revive & Restore was co-founded by Stewart Brand, the creator of the counterculture Whole Earth Catalog and a vocal advocate for a passenger pigeon revival.
At the conference, George Church, a Crispr pioneer and geneticist at Harvard Medical School, laid out a scientific roadmap for reviving a species. Church focused not on the passenger pigeon but on his own pet project, the woolly mammoth. Scientists, Church explained, had partially sequenced the mammoth's genome using DNA extracted from ancient bones and other remains. Armed with that information, they could use Crispr to edit DNA from the Asian elephant, the mammoth's closest living relative. Through genetic cutting and pasting, physical and behavioral traits of the mammoth'--its namesake coat and ability to withstand subzero temperatures'--could be added to living elephant cells.
The idea that woolly mammoths might once again roam the Earth made headlines around the world. But in his talk, titled ''Hybridizing With Extinct Species,'' Church said that the intended result of his de-extinction experiment was not a genetic facsimile of the mammoth. With enough mammoth DNA, Church explained, a Crispr-edited Asian elephant would become something else entirely: a modern hybrid that looked and behaved like a mammoth but shared DNA with a living species.
For many in the audience that day, an idea straight out of science fiction suddenly seemed plausible. ''Crispr put de-extinction on the plate,'' says Novak, who spoke at the TedXDeExtinction conference and directs the passenger pigeon project for Revive & Restore.
The passenger pigeon has a cultlike following'--a global network of ''pigeoners'' that includes scientists, conservationists, ornithologists, pigeon breeders, poultry geneticists and avid birders eager to see the species revived. Even among these obsessives, Novak's passion stands out. Of the 1,500 stuffed passenger pigeons in museums and private collections, he has personally viewed 497.
He understands that his obsession is difficult for most people to understand. He has a hard time explaining it himself. Novak grew up in a town of 200 people in North Dakota. Long before he could read, he was fascinated by the idea of extinction, digging unsuccessfully for fossils in his backyard. ''I was an odd child,'' he says.
In eighth grade, Novak was working on a science-fair project on the dodo bird when he discovered that the species was essentially ''a giant extinct pigeon.'' Nothing prepared him for the rush he felt when, at age 14, he came across photos of a passenger pigeon while flipping through a National Audubon Society book. ''I thought it was a gorgeous bird,'' Novak says.
Male passenger pigeons were particularly colorful, with red breasts, feet and legs and iridescent pink patches that glistened on the sides of their throats. The birds traveled in flocks that could number three billion, and were known for their grace and speed, flying at up to 60 miles per hour. Novak read histories that described passenger pigeon flocks so large, they darkened the skies for days as they passed overhead. These massive flocks played an important ecological role, breaking branches to allow sunlight to rejuvenate forests and enriching the soil with their excrement. The birds were prized for their meat; hunters could see the flocks approaching from miles away. The population went into steep decline in the late 1800s and never recovered.
The last known passenger pigeon'--a bird named Martha'--died in captivity at a Cincinnati zoo in 1914. Her demise sparked the passing of modern conservation laws to protect other endangered species in the U.S. Shortly after her death, Martha was frozen and shipped to the Smithsonian Institution in Washington, D.C., to be stuffed. She's no longer on display, but Novak has, of course, seen her. ''Martha is in bad shape,'' he says. Written history and degraded taxidermy intensified Novak's desire to revive the species. ''No one can tell me what a passenger pigeon was like in real life,'' he says. ''I feel robbed of history.''
The first step was to sequence the passenger pigeon genome. The project was led by Beth Shapiro, a professor of ecology and evolutionary biology at the University of California, Santa Cruz and the author of the book ''How to Clone a Mammoth.'' Shapiro's lab studies the DNA of extinct animals, extracting fragments from bones and other remains, some dating back hundreds of thousands of years. Novak joined the lab in 2013 to work on the passenger pigeon project; Revive & Restore funded his work.
Sequencing an extinct species' genome is no easy task. When an organism dies, the DNA in its cells begins to degrade, leaving scientists with what Shapiro describes as ''a soup of trillions of tiny fragments'' that require reassembly. For the passenger pigeon project, Shapiro and her team took tissue samples from the toe pads of stuffed birds in museum collections. DNA in the dead tissue left them with tantalizing clues but an incomplete picture. To fill in the gaps, they sequenced the genome of the band-tailed pigeon, the passenger pigeon's closest living relative.
By comparing the genomes of the two birds, researchers began to understand which traits distinguished the passenger pigeon. In a paper published last year in ''Science,'' they reported finding 32 genes that made the species unique. Some of these allowed the birds to withstand stress and disease, essential traits for a species that lived in large flocks. They found no genes that might have led to extinction. ''Passenger pigeons went extinct because people hunted them to death,'' Shapiro says.
In 2014, Shapiro taught a graduate class on de-extinction and asked each student to make a case for bringing one animal back from the dead. Extinct flightless birds'--the moa of New Zealand and the dodo'--were favorites, along with the Yangtze River dolphin. Some students cited an animal's ecological importance or value to tourism. Others mentioned the role humans played in the extinction of a species'--a cornerstone of Stewart Brand's argument for reviving the passenger pigeon.
According to Shapiro, none of these arguments justifies de-extinction. ''What's the point of bringing something back if we don't know why it went extinct?'' she asks. ''Or if we do know why it went extinct but haven't fixed the problem?''
The dodo, she says, exemplifies the latter issue. The flightless bird, native to the Indian Ocean island of Mauritius, nested on the ground and laid only one egg at a time. Settlers who arrived in 1638 brought cats, rats and pigs that devoured dodo eggs. ''There is no point in bringing the dodo back,'' Shapiro says. ''Their eggs will be eaten the same way that made them go extinct the first time.''
Revived passenger pigeons could also face re-extinction. The species thrived in the years before European settlement of North America, when vast forests supported billions of birds. Those forests have since been replaced by cities and farmland. ''The habitat the passenger pigeons need to survive is also extinct,'' Shapiro says.
Her interest in the bird was rooted in conservation rather than de-extinction. Understanding the exact cause of species' extinction can help scientists protect living animals and ecosystems. Shapiro argues that passenger pigeon genes related to immunity could help today's endangered birds survive. ''I wanted to study the passenger pigeon,'' Shapiro says. ''Ben wanted to bring the passenger pigeon back to life.''
But what does it mean to bring an extinct species back? Andre E.R. Soares, a scientist who helped sequence the passenger pigeon genome, says most people will accept a lookalike as proof of de-extinction. ''If it looks like a passenger pigeon and flies like a passenger pigeon, if it has the same shape and color, they will consider it a passenger pigeon,'' Soares says.
Shapiro says that's not enough. Eventually, she says, gene-editing tools may be able to create a genetic copy of an extinct species, ''but that doesn't mean you are going to end up with an animal that behaves like a passenger pigeon or a woolly mammoth.'' We can understand the nature of an extinct species through its genome, but nurture is another matter. With no living woolly mammoths or passenger pigeons to model social behavior, who will teach these genetic replicas how to behave like their kind?
''We are going to need a new biology and new names for all this,'' Soares says.
Church concedes that there are obstacles to de-extinction, not the least of which is public apprehension. But the history of science, he says, is filled with ideas that start out sounding far-fetched, raise complex ethical issues and over time move toward social acceptance. ''The more unknowns there are, the more intense the disagreement,'' he says. He points to in vitro fertilization, now a routine reproductive technology that has led to the birth of millions of children. When IVF was first proposed, people worried about the ethics, repercussions and possible risks. ''As soon as Louise Brown was born in 1978 and completely normal, the disagreement disappeared,'' Church says.
In almost every country, the process of de-extinction requires approval from governments, academic committees and the public along the way. To inject the Cas9 gene into his birds, Novak needed permission from the Office of the Gene Technology Regulator in Australia as well as ethics and animal welfare committees. He'll need another round of approvals to breed and edit the next generation of his pigeons.
In the meantime, Novak is steadily building the flock. In May he injected 19 eggs with the Cas9 gene, but only two pigeons survived hatching. In August, 11 squabs survived from 46 eggs. Novak and a small team of scientists plan to repeat the process until they have 22 pairs of birds for breeding. They're considering which passenger pigeon traits to add first, combing through the sequencing data for the genes associated with the extinct bird's distinctive coloring and preference for life in large flocks. After he determines how passenger pigeon DNA manifests in the rock pigeons, Novak hopes to edit the band-tailed pigeon, the passenger pigeon's closest living relative, with as many of the extinct bird's defining traits as possible. Eventually, he says, he'll have a hybrid creature that looks and acts like a passenger pigeon (albeit with no parental training) but still contains band-tailed pigeon DNA. These new-old birds will need a name, which their human creator has already chosen: Patagioenas neoectopistes, or ''new wandering pigeon of America.''
Write to Amy Dockser Marcus at amy.marcus@wsj.com
The Canadian theology professor Dr. Pierre Gilbert during a lecture in 1995 warned of a coming mandatory vaccine containing liquid crystals that, when exposed to magnetic frequencies, turn vaccine recipients into ''zombies.'' '' SURVIVAL BLOG
Tue, 01 Jun 2021 14:27
In a 2016 experiment, synthesized proteins were inserted into a VIRUS, where they were injected into brains of mice to ultimately control the reward/motivation centers of brain using magnetic fields.
A theology professor in 1995 warned of mandatory vaccines containing magnetized particles that would turn recipients ''into zombies.''
Scientists developed a new method of controlling certain nerve cells of the brain to manipulate behaviors '-- and it's delivered via viral injection.
This presentation PROOVES WITHOUT DOUBT that America is in for a major fight that will put you and your family in the firing line, literally'... So make sure you watch this presentation while it's still online'...
The reason why you should pay attention now is that is because these techniques don't come from books, they're taken from actual 21st century warzones, from lawless states where social chaos is the name of the game'... '... and where not having enough time or money to prepare doesn't stop real-world preppers from creating virtually impenetrable defenses for their families.
In 2016, researchers at the University of Virginia in Charlottesville genetically engineered a magnetized protein, called Magneto, which is inserted into a virus that's injected into an animal's brain to manipulate neural activity under the remote influence of magnetic fields'....
Neuroscientist Steve Ramirez of Harvard University, left, who uses optogenetics to manipulate memories in the brains of mice, says the mind control study is ''badass''.
''Previous attempts [using magnets to control neuronal activity] needed multiple components for the system to work '' injecting magnetic particles, injecting a virus that expresses a heat-sensitive channel, [or] head-fixing the animal so that a coil could induce changes in magnetism,'' he explains. ''The problem with having a multi-component system is that there's so much room for each individual piece to break down.''
This remarkable study is notable given anecdotally reported strange side effects with the COVID-19 vaccine involving magnetism.
It's also worth pointing out that Canadian theology professor Dr. Pierre Gilbert (above) during a lecture in 1995 warned of a coming mandatory vaccine containing liquid crystals that, when exposed to magnetic frequencies, turn vaccine recipients into ''zombies.''
''In the biological destruction there are the organized tempests on the magnetic fields,'' Gilbert said. ''What will follow is a contamination of the bloodstreams of mankind, creating intentional infections.''
''This will be enforced via laws that will make vaccination mandatory,'' he continued. ''And these vaccines will make possible to control people.''
''The vaccines will have liquid crystals that will become hosted in the brain cells, which will become micro-receivers of electromagnetic fields where waves of very low frequencies will be sent.''
''And through these low frequency waves people will be unable to think, you'll be turned into a zombie.''
''Don't think of this as a hypothesis. This has been done. Think of Rwanda,'' he added, suggesting this technology was behind the 1994 Rwandan genocide.
Related '' See the banned videos here.
In this short VIDEO, I will unearth A lost super-food will bulletproof you against any food shortage or famine. It's a food that vanished with the Incas over 6 centuries ago
In the next crisis these lost skills will be more valuable than gold, food supplies and survival equipment combined. These skills have been tested and proven to work for centuries.
Here is just a small glimpse of what you'll find in this massive 300-page sequel (in color) to The Lost Ways:
A lost super-food will bulletproof you against any food shortage or famine. It's a food that vanished with the Incas over 6 centuries ago. This mysterious dish was just recently rediscovered by NASA who has been giving away rations of it to our brave men and women in their month-long space missions. The Incas stored it in pit holes for up to 10 years, ate it year-round, and actually used it to survive a 4 year long super-drought that wiped out their southern neighbors. So, if it managed to save the Incas centuries ago and it still works for our astronauts today, you can bet your last dollar it will keep you and your family well fed in any crisis. And the best part is that you probably already have the ingredients in your kitchen right now.Published by Jack Metir
Jack Metir - served four tours during the Iraq War, As a member of the 4th Infantry Division.View all posts by Jack Metir
PublishedMay 19, 2021May 19, 2021
Vatican Revises Church Law in Wake of Sex Abuse, Financial Scandals...
Tue, 01 Jun 2021 14:10
ROME'--The Vatican on Tuesday unveiled an updated version of the Catholic Church's penal code to reflect scandals over clerical sex abuse and financial corruption that have shaken the church in recent years, expanding the types of offenses as well as potential culprits and victims.
The new penal code broadens the categories of persons who can be punished for sex abuse to include laypeople and nuns, but doesn't provide for the automatic defrocking of abusive priests as some campaigners have demanded.
Though mostly a collection of legislation established by popes over the past three decades, it places greater emphasis than the previous code, published in 1983, on the obligation to enforce penalties, stating that bishops are required to take punitive action when warnings or other measures are inadequate to do justice or reform the guilty.
In a decree instituting the revisions, Pope Francis wrote that charity and discipline are intimately related and that the proper remedy for immoral behavior ''is not only exhortations or suggestions.''
The revised code reclassifies the sexual abuse of minors by clergy among ''crimes against the life, dignity and freedom of man,'' rather than violations of the ''special obligations'' of clergy, as stated in the 1983 code.
The new classification means that the law will also cover abuse committed by lay church employees and members of religious orders who are not priests.
The classification covers not only abuse of a minor but also of a vulnerable adult. Another novelty in the new code is a prohibition of grooming minors or vulnerable adults to take part in making pornography.
Advocates for sex-abuse victims have long demanded that the church define abuse as a crime against children, rather than a violation of priestly celibacy.
But critics are likely to be unsatisfied with the revised language, which still describes abuse as ''an offense against the sixth commandment,'' which prohibits adultery.
''Describing child sexual abuse as the canonical crime of 'adultery' is wrong and minimizes the criminal nature of abuse inflicted on child victims. A canonical crime relating to child sexual abuse should be clearly identified as a crime against the child,'' said a report published last November by the Independent Inquiry into Child Sexual Abuse, sponsored by the U.K. government.
In March, the Catholic Bishops' Conference of England and Wales asked the Vatican to rewrite the law to remove the reference to the sixth commandment.
Bishop Juan Ignacio Arrieta, secretary of the Pontifical Council for Legislative Texts, told reporters on Tuesday that removing that reference would have been a departure from tradition and could have caused confusion about the meaning of the law.
Scandals over clerical sex abuse have been a crisis for the Catholic Church for the past two decades. In 2019, Pope Francis enacted new rules to make bishops more accountable for abuse and its coverup by facilitating allegations by the public. But critics say the process lacks the crucial element of oversight by laypeople.
The revised code doesn't provide for automatic dismissal of abusers from the priesthood, another demand of anti-abuse activists, providing for such dismissal only ''where the case calls for it.''
Some other revisions published Tuesday relate to financial crimes, specifically forbidding the sale of church assets ''without the prescribed consultation, consent, or permission.''
The Vatican's costly investment in a building in London's Chelsea district has triggered multiple investigations and in 2019 led to the suspension of several Vatican employees, including a senior financial supervisor.
Cardinal Giovanni Becciu, who oversaw the original investment, resigned from his Vatican post and renounced his rights as a cardinal at the request of Pope Francis last September. The Vatican hasn't said whether his resignation was linked to the London deal. Cardinal Becciu has denied wrongdoing.
The revised code also includes a law against women's ordination, specifying automatic excommunication for anyone ''who attempts to confer a sacred order on a woman, and the woman who attempts to receive the sacred order.'' Another update explicitly forbids the recording of confessions.
Write to Francis X. Rocca at francis.rocca@wsj.com
Iatrogenesis - Wikipedia
Tue, 01 Jun 2021 13:40
Ancient Greek painting in a vase, showing a physician (
iatros)
bleeding a patient
Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence.[1][2][3] First used in this sense in 1924,[1] the term was introduced to sociology in 1976 by Ivan Illich, alleging that industrialized societies impair quality of life by overmedicalizing life.[4] Iatrogenesis may thus include mental suffering via medical beliefs or a practitioner's statements.[4][5][6] Some iatrogenic events are obvious, like amputation of the wrong limb, whereas others, like drug interactions, can evade recognition. In a 2013 estimate, about 20 million negative effects from treatment had occurred globally.[7] In 2013, an estimated 142,000 persons died from adverse effects of medical treatment, up from an estimated 94,000 in 1990.[8]
Iatrogenic avenues [ edit ] Risk associated with medical interventions [ edit ] Adverse effects of prescription drugsOveruse of drugs (causing, for example, antibiotic resistance in bacteria)Prescription drug interactionMedical errors [ edit ] Incorrect prescription, perhaps due to illegible handwriting or computer typosFaulty procedures, techniques, information, methods, or equipmentNegligenceHospital-acquired infectionsCauses and consequences [ edit ] Medical error and negligence [ edit ] Iatrogenic conditions necessarily result from medical errors, such as mistakes made in surgery, or the prescription or dispensing of the wrong therapy, such as a drug. In fact, intrinsic and sometimes adverse effects of a medical treatment are iatrogenic. For example, radiation therapy and chemotherapy '-- necessarily aggressive for therapeutic effect '' frequently produce such iatrogenic effects as hair loss, hemolytic anemia, diabetes insipidus, vomiting, nausea, brain damage, lymphedema, infertility, etc. The loss of function resulting from the required removal of a diseased organ is iatrogenic, as in the case of diabetes consequential to the removal of all or part of the pancreas.
The incidence of iatrogenesis may be misleading in some cases. For example, a ruptured aortic aneurysm is fatal in most cases; the survival rate for treatment of a ruptured aortic aneurysm is under 25%. Patients who die during or after an operation will still be considered iatrogenic deaths, but the procedure itself remains a better bet than the 100% probability of death if left untreated.
Other situations may involve actual negligence or faulty procedures, such as when pharmacotherapists produce handwritten prescriptions for drugs.
Adverse effects [ edit ] A very common iatrogenic effect is caused by drug interaction, i.e., when pharmacotherapists fail to check for all medications a patient is taking and prescribe new ones that interact agonistically or antagonistically (thereby potentiating or attenuating the intended therapeutic effect). Such situations can cause significant morbidity and mortality. Adverse reactions, such as allergic reactions to drugs, even when unexpected by pharmacotherapists, are also classified as iatrogenic.
The evolution of antibiotic resistance in bacteria is iatrogenic as well.[9] Bacterial strains resistant to antibiotics have evolved in response to the overprescription of antibiotic drugs.[10]
Certain drugs are toxic in their own right in therapeutic doses because of their mechanism of action. Alkylating antineoplastic agents, for example, cause DNA damage, which is more harmful to cancer cells than regular cells. However, alkylation causes severe side-effects and is actually carcinogenic in its own right, with potential to lead to the development of secondary tumors. In a similar manner, arsenic-based medications like melarsoprol, used to treat trypanosomiasis, can cause arsenic poisoning.
Adverse effects can appear mechanically. The design of some surgical instruments may be decades old, hence certain adverse effects (such as tissue trauma) may never have been properly characterized.
Psychiatry [ edit ] In psychiatry, iatrogenesis can occur due to misdiagnosis (including diagnosis with a false condition, as was the case of hystero-epilepsy[11]). An example of a partially iatrogenic condition due to common misdiagnosis is bipolar disorder, especially in pediatric patients.[12] Other conditions such as somatoform disorder and chronic fatigue syndrome are theorized to have significant sociocultural and iatrogenic components.[13] Posttraumatic stress disorder is hypothesized to be prone to iatrogenic complications based on treatment modality.[14] Even use of antipsychotic drugs leads to loss of brain mass[15][16]
The psychiatric treatment of some conditions and populations, such as substance abuse,[17] and antisocial youths[18] are regarded as carrying significant risks for iatrogenesis. At the other end of the spectrum, dissociative identity disorder is considered by a minority of theorists to be a wholly iatrogenic disorder with the bulk of diagnoses arising from a tiny fraction of practitioners.[11][19]
The degree of association of any particular condition with iatrogenesis is unclear and in some cases controversial. The over-diagnosis of psychiatric conditions (with the assignment of mental illness terminology) may relate primarily to clinician dependence on subjective criteria.[citation needed ] The assignment of pathological nomenclature is rarely a benign process and can easily rise[clarification needed ] to the level of emotional iatrogenesis, especially when no alternatives outside of the diagnostic naming process have been considered. Many former patients come to the conclusion that their difficulties are largely the result of the power relationships inherent in psychiatric treatment, which has led to the rise of the anti-psychiatry movement.[citation needed ]
Iatrogenic poverty [ edit ] Meessen et al. used the term "iatrogenic poverty" to describe impoverishment induced by medical care.[20] Impoverishment is described for households exposed to catastrophic health expenditure[21] or to hardship financing.[22] Every year, worldwide, over 100,000 households fall into poverty due to health care expenses. A study reported that in the United States in 2001, illness and medical debt caused half of all personal bankruptcies.[23] Especially in countries in economic transition, the willingness to pay for health care is increasing, and the supply side does not stay behind and develops very fast. But the regulatory and protective capacity in those countries is often lagging behind. Patients easily fall into a vicious cycle of illness, ineffective therapies, consumption of savings, indebtedness, sale of productive assets, and eventually poverty.
Social and cultural iatrogenesis [ edit ] The 20th-century social critic Ivan Illich broadened the concept of medical iatrogenesis in his 1974 book Medical Nemesis: The Expropriation of Health[24] by defining it at three levels.
First, clinical iatrogenesis is the injury done to patients by ineffective, unsafe, and erroneous treatments as described above. In this regard, he described the need for evidence-based medicine 20 years before the term was coined.[25]Second, at another level social iatrogenesis is the medicalization of life in which medical professionals, pharmaceutical companies, and medical device companies have a vested interest in sponsoring sickness by creating unrealistic health demands that require more treatments or treating non-diseases that are part of the normal human experience, such as age-related declines. In this way, aspects of medical practice and medical industries can produce social harm in which society members ultimately become less healthy or excessively dependent on institutional care. He argued that medical education of physicians contributes to medicalization of society because they are trained predominantly for diagnosing and treating illness, therefore they focus on disease rather than on health. Iatrogenic poverty (above) can be considered a specific manifestation of social iatrogenesis.Third, cultural iatrogenesis refers to the destruction of traditional ways of dealing with, and making sense of, death, suffering, and sickness. In this way the medicalization of life leads to cultural harm as society members lose their autonomous coping skills. It is worth noting that in these critiques "Illich does not reject all benefits of modern society but rejects those that involve unwarranted dependency and exploitation."[26]Epidemiology [ edit ] Globally it is estimated that 142,000 people died in 2013 from adverse effects of medical treatment, an increase of 51 percent from 94,000 in 1990.[8] In the United States, estimated deaths per year include:[27][28][29][30]
12,000 due to unnecessary surgery7,000 due to medication errors in hospitals20,000 due to other errors in hospitals80,000 due to nosocomial infections in hospitals106,000 due to non-error, negative effects of drugsBased on these figures, iatrogenesis may cause as many as 225,000 deaths per year in the United States (excluding recognizable error). An earlier Institute of Medicine report estimated 230,000 to 284,000 iatrogenic deaths annually.[27]
History [ edit ] Evidence demonstrating the advent of
pathological anatomy in 1823 Vienna (left vertical line) correlated with incidence of fatal childbed fever. The onset of chlorine handwash in 1847 is noted (right vertical line). For comparison, rates for Dublin maternity hospital, which had no pathological anatomy (
view rates).
Semmelweis 1861.
The term iatrogenesis means brought forth by a healer, from the Greek ἰαÏρός (iatros, "healer") and Î"ένεσις (genesis, "origin"); as such, in its earlier forms, it could refer to good or bad effects.
Since at least the time of Hippocrates, people have recognized the potentially damaging effects of medical intervention. "First do no harm" (primum non nocere) is a primary Hippocratic mandate in modern medical ethics. Iatrogenic illness or death caused purposefully or by avoidable error or negligence on the healer's part became a punishable offense in many civilizations.[31]
The transfer of pathogens from the autopsy room to maternity patients, leading to shocking historical mortality rates of puerperal fever (also known as "childbed fever") at maternity institutions in the 19th century, was a major iatrogenic catastrophe of the era. The infection mechanism was first identified by Ignaz Semmelweis.[32]
With the development of scientific medicine in the 20th century, it could be expected that iatrogenic illness or death might be more easily avoided. Antiseptics, anesthesia, antibiotics, better surgical techniques, evidence-based protocols and best practices continue to be developed to decrease iatrogenic side effects and mortality.
See also [ edit ] References [ edit ] ^ a b "Iatrogenic", Merriam-Webster.com, Merriam-Webster, Inc., accessed 27 Jun 2020. ^ "John O. Barr & Timothy L. Kauffman, "Iatrogenesis in older adults", in Timothy L. Kauffman, Ron Scott, John O. Barr & Michael L. Moran, eds., A Comprehensive Guide to Geriatric Rehabilitation, 3rd edn. (Edinburgh: Churchill Livingstone/Elsevier, 2014)". doi:10.1016/B978-0-7020-4588-2.00056-5. ^ "Intervention Mistakes and How to Avoid Them". Addiction Helper. 11 December 2014 . Retrieved 3 February 2021 . ^ a b "iatrogenesis", A Dictionary of Sociology, Encyclopedia.com. updated 31 May 2020. ^ David Kuhl, What Dying People Want: Practical Wisdom for the End of Life (New York: PublicAffairs, 2002), p 55. ^ Paul F. Lazarsfeld, "Working with Merton", in Lewis A. Cosar, ed., The Idea of Social Structure: Papers in Honor of Robert K. Merton (New Brunswick, NJ: Transaction Publishers, 2012 / New York: Harcourt Brace Jovanovich, 1975), indexing "iatrogenesis", esp. pp 328''329. ^ Global Burden of Disease Study 2013, Collaborators (22 August 2015). "Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990''2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 386 (9995): 743''800. doi:10.1016/s0140-6736(15)60692-4. PMC 4561509 . PMID 26063472. ^ a b GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990''2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 385 (9963): 117''71. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604 . PMID 25530442. ^ Finland M (1979). "Emergence of antibiotic resistance in hospitals, 1935''1975". Rev. Infect. Dis. 1 (1): 4''22. doi:10.1093/clinids/1.1.4. PMID 45521. ^ Llor, Carl; Bjerrum, Lars (16 October 2014). "Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem". Therapeutic Advances in Drug Safety. SAGE Publicatio. 5 (6): 229''241. doi:10.1177/2042098614554919. ISSN 2042-0986. PMC 4232501 . PMID 25436105. ^ a b Spanos, Nicholas P. (1996). Multiple Identities & False Memories: A Sociocognitive Perspective. American Psychological Association (APA). ISBN 1-55798-340-2. ^ Pruett Jr, John R.; Luby, Joan L. (2004). "Recent Advances in Prepubertal Mood Disorders: Phenomenology and Treatment". Current Opinion in Psychiatry. 17 (1): 31''36. doi:10.1097/00001504-200401000-00006. S2CID 145069868 . Retrieved 4 May 2008 . ^ Abbey, S.E. (1993). "Somatization, illness attribution and the sociocultural psychiatry of chronic fatigue syndrome". Ciba Found Symp. Novartis Foundation Symposia. 173: 238''52. doi:10.1002/9780470514382.ch14. ISBN 9780470514382. PMID 8491101. ^ Boscarino, JA (2004). "Evaluation of the Iatrogenic Effects of Studying Persons Recently Exposed to a Mass Urban Disaster" (PDF) . Archived from the original (PDF) on 25 June 2008 . Retrieved 4 May 2008 . ^ Ho, Beng-Choon; Andreasen, Nancy C.; Ziebell, Steven; Pierson, Ronald; Magnotta, Vincent (February 2011). "Long-term Antipsychotic Treatment and Brain Volumes". Archives of General Psychiatry. 68 (2): 128''137. doi:10.1001/archgenpsychiatry.2010.199. ISSN 0003-990X. PMC 3476840 . PMID 21300943. ^ Donald C. Goff, M. D. (4 May 2011). "Antipsychotics and the Shrinking Brain". Psychiatric Times . Retrieved 5 June 2020 . ^ Moos, R.H. (2005). "Iatrogenic effects of psychosocial interventions for substance use disorders: prevalence, predictors, prevention". Addiction. 100 (5): 595''604. doi:10.1111/j.1360-0443.2005.01073.x. PMID 15847616. ^ Weiss, B.; Caron, A.; Ball, S.; Tapp, J.; Johnson, M.; Weisz, J.R. (2005). "Iatrogenic effects of group treatment for antisocial youths". Journal of Consulting and Clinical Psychology. 73 (6): 1036''1044. doi:10.1037/0022-006X.73.6.1036. PMC 4024049 . PMID 16392977. ^ Braun, B.G. (1989). "Iatrophilia and Iatrophobia in the diagnosis and treatment of MPD (Morose Parasitic Dynamism)". Dissociation. 2 (2): 43, 161''2, 165''6, 171''2 passim. hdl:1794/1425. ^ Meessen, B.; Zhenzhong, Z.; Van Damme, W.; Devadasan, N.; Criel, B.; Bloom, G. (2003). "Iatrogenic poverty". Tropical Medicine & International Health. 8 (7): 581''4. doi:10.1046/j.1365-3156.2003.01081.x . PMID 12828538. ^ Xu; Evans, DB; Carrin, G; Aguilar-Rivera, AM; Musgrove, P; Evans, T; et al. (2007). "Protecting Households from Catastrophic Health Spending". Health Affairs. 26 (4): 972''83. doi:10.1377/hlthaff.26.4.972 . PMID 17630440. ^ Kruk; Goldmann, E.; Galea, S.; et al. (2009). "Borrowing And Selling To Pay For Health Care in Low- And Middle-Income Countries" (PDF) . 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PMID 1599594. ^ Phillips DP, Christenfeld N, Glynn LM (February 1998). "Increase in US medication-error deaths between 1983 and 1993". Lancet. 351 (9103): 643''4. doi:10.1016/S0140-6736(98)24009-8. PMID 9500322. S2CID 10122133. ^ Lazarou J, Pomeranz BH, Corey PN (April 1998). "Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies". JAMA. 279 (15): 1200''5. doi:10.1001/jama.279.15.1200. PMID 9555760. ^ Jason A Wolf; Heather Hanson; Mark J Moir; Len Friedman; Grant T Savage, eds. (12 July 2011). Organization Development in Healthcare: Conversations on Research and Strategies. Advances in Health Care Management Series #10. Emerald Group Pub. p. 292. ISBN 978-0-85724-709-4. ^ Hanninen, O; Farago, M.; Monos, E. (1983). "Ignaz Philipp Semmelweis, the prophet of bacteriology". Infection Control and Hospital Epidemiology. 4 (5): 367''370. doi:10.1017/S0195941700059762. JSTOR 30142576. PMID 6354955. External links [ edit ] Patient Safety Network (US)
French Open - Wikipedia
Tue, 01 Jun 2021 13:26
French Open Tennis Championships
The French Open (French: Internationaux de France de Tennis), also called Roland-Garros (French: [ʁÉ--lɑ̃ Éaʁos] ), is a major tennis tournament held over two weeks at the Stade Roland-Garros in Paris, France, beginning in late May each year.[b] The tournament and venue are named after the French aviator Roland Garros. The French Open is the premier clay court tennis championship tournament in the world. Calender-wise it is the second of the four annual Grand Slam tournaments,[3] the other three being the Australian Open, Wimbledon and the US Open. The French Open is currently the only Grand Slam tournament held on clay. Before 1975, the French Open was the lone non-grass major tournament.[4] Between the seven rounds needed for a championship, the clay surface characteristics (slower pace, higher bounce), and the best-of-five-set men's singles matches, the French Open is arguably the most physically demanding tennis tournament in the world.[5][6]
History [ edit ] Officially named in French Internationaux de France de Tennis (the "French International of Tennis" in English),[7][8] the tournament is referred to in English as the "French Open" and alternatively as "Roland Garros", which is the designation used by the tournament itself in all languages.[9] (The stadium and tournament are both hyphenated as Roland-Garros because French spelling rules dictate that in the name of a place or event named after a person, the elements of the name are joined together with a hyphen.[10])
In 1891 the Championnat de France, which is commonly referred to in English as the French Championships, began. They were only open to tennis players who were members of French clubs. The first winner was H. Briggs, a Briton who resided in Paris and was a member of the Club Stade Fran§ais. In the final he defeated P. Baigneres in straight sets.[11] The first women's singles tournament, with four entries, was held in 1897. The mixed doubles event was added in 1902 and the women's doubles in 1907. This "French club members only" tournament was played until 1924, using four different venues during that period:
Societ(C) de Sport de Žle de Puteaux, in Puteaux, Žle-de-France (next to the Seine river); played on the club's ten sand grounds laid out on a bed of rubble. 1891, 1893, 1894 (men's singles), 1895 (men's singles), 1897 (women's singles), 1902 (women's singles and mixed doubles), 1905 (women's singles and mixed doubles), 1907 (men's singles, women's singles, mixed doubles) editions.The Croix-Catelan of the Racing Club de France (club founded in 1882 which initially had two lawn-tennis courts with four more grass courts opened some years later, but due to the difficulty of maintenance, they were eventually transformed into clay courts) in the Bois de Boulogne, Paris. Played on grass (pelouse) and later on clay. 1892, 1894 (men's doubles), 1895 (men's doubles), 1897 (women's singles), 1901 (men's doubles), 1903 (men's doubles and mixed doubles), 1904, 1907 (men's doubles), 1908, 1910''1914, 1920''1924 editions.Tennis Club de Paris (club founded in 1895 which initially had four indoor wood courts and five outdoor clay courts), at 71, Boulevard Exelmans in the Auteuil neighborhood, Paris. Initially had four indoor wood courts and five outdoor clay courts. 1896, 1897 (men's singles), 1898, 1899, 1900, 1901 (men's and women's singles), 1902 (men's singles), 1903 (men's singles and women's singles), 1905 (men's singles) and 1906 editions.Soci(C)t(C) Athl(C)tique de la Villa Primrose in Bordeaux, on clay. Only played in 1909.In the period of 1915''1919, no tournament was organized due to World War I.
In 1925, the French Championships became open to all amateurs internationally and was designated a major championship by the International Lawn Tennis Federation. It was held at the Stade Fran§ais in Saint-Cloud (site of the previous World Hard Court Championships) in 1925 and 1927, on clay courts. In 1926 the Croix-Catelan of the Racing Club de France hosted the event in Paris, site of the previous French club members only tournament, also on clay.
Another clay court tournament, called the World Hard Court Championships, is sometimes considered the true precursor to the modern French Open as it admitted international competitors. This was held at Stade Fran§ais in Saint-Cloud, from 1912 to 1914, 1920, 1921 and 1923, with the 1922 event held in Brussels, Belgium. Winners of this tournament included world No. 1s such as Tony Wilding from New Zealand (1913, 1914) and Bill Tilden from the US (1921). In 1924 there was no World Hard Court Championships due to tennis being played at the Paris Olympic Games.
After the Mousquetaires or Philadelphia Four (Ren(C) Lacoste, Jean Borotra, Henri Cochet, and Jacques Brugnon) won the Davis Cup on American soil in 1927, the French decided to defend the cup in 1928 at a new tennis stadium at Porte d'Auteuil. The Stade de France had offered the tennis authorities three hectares of land with the condition that the new stadium must be named after the World War I aviator hero Roland Garros.[12] The new Stade de Roland Garros (whose central court was renamed Court Philippe Chatrier in 1988) hosted that Davis Cup challenge. On May 24, 1928 the French International Championships moved there, and the event has been held there ever since.[13]
During World War II, the tournament was not held in 1940 and from 1941 through 1945 it took place on the same grounds, but those events are not recognized by the French governing body, the F(C)d(C)ration Fran§aise de Tennis.[14] In 1946 and 1947, the French Championships were held after Wimbledon, making it the third Grand Slam event of the year. In 1968, the French Championships became the first Grand Slam tournament to go open, allowing both amateurs and professionals to compete.[13]
Since 1981, new prizes have been presented: the Prix Orange (for the player demonstrating the best sportsmanship and cooperative attitude with the press), the Prix Citron (for the player with the strongest character and personality) and the Prix Bourgeon (for the tennis player revelation of the year). In another novelty, since 2006 the tournament has begun on a Sunday, featuring 12 singles matches played on the three main courts. Additionally, on the eve of the tournament's opening, the traditional Benny Berthet exhibition day takes place, where the profits go to different charity associations. In March 2007, it was announced that the event would provide equal prize money for both men and women in all rounds for the first time.[15]In 2010, it was announced that the French Open was considering a move away from Roland Garros as part of a continuing rejuvenation of the tournament.[16] Plans to renovate and expand Roland Garros have put aside any such consideration, and the tournament remains in its long time home.
Expansion in the early 21st century [ edit ] Court Philippe Chatrier during the 2013 French Open.
From 2004 to 2008, plans were developed to build a covered stadium with a roof, as complaints continued over delayed matches.[17][18][19] Various proposals were put forward to expand the facility or to move the French Open to a completely new, 55-court venue outside of Paris city limits. In 2011 the decision was taken to maintain the tournament within its existing venue.[20][21] The expansion project called for a new stadium to be built alongside the historical Auteuil's greenhouses and expansion of old stadiums and the tournament village.[22] A wide-ranging project to overhaul the venue was presented in 2011, including building a roof over Court Philippe-Chatrier, demolishing and replacing Court No. 1 with a grassy hill for outdoors viewing, and geographical extension of the venue eastward into the Jardin des Serres d'Auteuil.[23]
Legal opposition from environmental defence associations and other stakeholders delayed the works for several years as litigation ensued.[24] In particular, the city council voted in May 2015 against the expansion project, but on 9 June 2015 Paris Mayor Anne Hidalgo announced the signing of the construction permits, with work scheduled to begin in September of that year and conclude in 2019.[25][26] In December 2015, the Administrative Court of Paris once again halted renovation work, but the French Tennis Federation won the right to proceed with the renovation on appeal.[27]
Renovation work finally commenced at the close of the 2018 edition of the tournament. Redeveloped seating and a retractable roof was constructed for Court Philippe-Chatrier and the new 5,000-seat Court Simonne-Mathieu was opened, having been named after France's second-highest achieving female tennis player, and noted for its innovative use of greenhouse encasing architecture.[28] The renewal of the venue has been generally well received by the players and the public.[29] The 2020 edition of the tournament, which was the first to be assisted by the roof over Philippe-Chatrier, was postponed to late September and early October and was played in front of limited spectators, due to the COVID-19 pandemic.[30] Floodlights were also installed over each of the courts in the precinct, allowing the tournament to facilitate night matches for the first time.[31]
Surface characteristics [ edit ] Clay courts slow down the ball and produce a high bounce when compared with grass courts or hard courts. For this reason, clay courts take away some of the advantages of big servers and serve-and-volleyers, which makes it hard for these types of players to dominate on the surface. For example, Pete Sampras, known for his huge serve and who won 14 Grand Slam titles, never won the French Open '' his best result was reaching the semi-finals in 1996. Many other notable players have won multiple Grand Slam events but have never won the French Open, including John McEnroe, Frank Sedgman, John Newcombe, Venus Williams, Stefan Edberg, Boris Becker, Lleyton Hewitt, Jimmy Connors, Louise Brough, Virginia Wade or Martina Hingis; McEnroe and Edberg lost their sole French Open finals appearances in five sets.
On the other hand, players whose games are more suited to slower surfaces, such as Rafael Nadal, Bj¶rn Borg, Ivan Lendl, Mats Wilander, Justine Henin and Chris Evert, have found great success at this tournament. In the Open Era, the only male players who have won both the French Open and Wimbledon, played on faster grass courts, are Rod Laver, Jan KodeÅ, Bj¶rn Borg, Andre Agassi, Rafael Nadal, Novak Djokovic and Roger Federer. Borg's French Open'--Wimbledon double was achieved three times consecutively (1978, 1979, 1980) and regarded by Wimbledon officials as "the most difficult double in tennis".[32] The feat took 28 years to be repeated and was done 3 times consecutively, twice by Rafael Nadal (2008, 2010) and once by Roger Federer (2009).[33]
Rankings points and prize money [ edit ] When a player makes it to the indicated round, they receive the points and money listed (provided they don't make it to a further round).
Point distribution [ edit ] Men and women often receive different point values based on the rules of their respective tours.
Senior EventsWinnerFinalistSemifinalsQuarterfinalsRound of 16Round of 32Round of 64 Round of 128 Men's Singles20001200720360180904510 Women's Singles 13007804302401307010Men's Doubles1000600360180900'--'-- Women's Doubles 65039021512010'--'--Wheelchair EventsWinnerFinalistSemifinalsQuarterfinalsSingles800500375100 Quad Singles 375 / 100'-- Doubles 800500100'-- Quad Doubles 100'--'--Prize money [ edit ] For 2018, the prize money purse was increased to '‚¬39,197,000.[34]
EventWinnerFinalistSemifinalsQuarterfinalsRound of 16Round of 32Round of 64Round of 128Q3Q2Q1Singles'‚¬2,200,000'‚¬1,120,000'‚¬560,000'‚¬380,000'‚¬222,000'‚¬130,000'‚¬79,000'‚¬40,000'‚¬21,000'‚¬11,000'‚¬6,000Doubles'‚¬560,000'‚¬280,000'‚¬139,000'‚¬76,000'‚¬41,000'‚¬22,000'‚¬11,000N/AN/AN/AN/AMixed Doubles'‚¬120,000'‚¬60,000'‚¬30,000'‚¬17,000'‚¬9,500'‚¬4,750N/AN/AN/AN/AN/AWheelchair Singles'‚¬35,000'‚¬17,500'‚¬8,500'‚¬4,500N/AN/AN/AN/AN/AN/AN/A Wheelchair Doubles '‚¬10,000'‚¬5,000'‚¬3,000N/AN/AN/AN/AN/AN/AN/AN/ADoubles prize money is per team.Champions [ edit ] Champions lists [ edit ] Men's Singles, winners of the Coupe des Mousquetaires.[c]Women's Singles, winners of the Coupe Suzanne Lenglen.[d]Men's Doubles, winners of the Coupe Jacques Brugnon.Women's Doubles, winners of the Coupe Simone Mathieu.Mixed Doubles, winners of the Coupe Marcel Bernard.All champions (Open Era)The trophies, designed and made by Maison Mellerio dits Meller, are all made of pure silver with finely etched decorations on their side. Each new singles winner gets his or her name written on the base of the trophy. Winners receive custom-made pure silver replicas of the trophies they have won.[35]
Current champions [ edit ] Most recent finals [ edit ] Records [ edit ] RecordEraPlayer(s)Num.YearsMen since 1891Most singles titlesOpen Era Rafael Nadal132005''2008, 2010''2014, 2017''2020Pre-Open Era Henri Cochet41926, 1928, 1930, 1932 Note: Also won World Hard Court Championships in 1922.French Championships* Max Decugis81903''1904, 1907''1909, 1912''1914Most consecutive singles titlesOpen Era Rafael Nadal52010''2014Pre-Open Era Frank Parker Jaroslav Drobn½ Tony Trabert Nicola Pietrangeli21948''1949 1951''1952 1954''1955 1959''1960French Championships* Paul Aym(C)41897''1900Most doubles titlesOpen Era Daniel Nestor Max Mirnyi42007 with Mark Knowles, 2010 with Nenad Zimonjić, 2011, 2012 with Max Mirnyi. 2005, 2006 with Jonas Bj¶rkman, 2011, 2012 with Daniel Nestor.Pre-Open Era Roy Emerson61960, 1962 with Neale Fraser, 1961 with Rod Laver, 1963 with Manuel Santana, 1964 with Ken Fletcher, 1965 with Fred Stolle.French Championships* Max Decugis131902''1909, 1911''1914, 1920[36]Most consecutive doubles titlesOpen Era Daniel Nestor32010''2012Pre-Open Era Roy Emerson61960''1965French Championships* Maurice Germot101906''1914, 1920[36]Most mixed doubles titlesFrench Open Ken Fletcher Jean-Claude Barclay31963''1965 with Margaret Court.1968, 1971, 1973 with Fran§oise D¼rr.French Championships* Max Decugis71904''1906, 1908''1909, 1914 and 1920 with Suzanne Lenglen.Most titles (singles, doubles, mixed)French Open Rafael Nadal132005''2008, 2010''2014, 2017''2020 (13 singles)French Championships* Max Decugis281902''1920 (8 singles, 13 doubles, 7 mixed)Women since 1897Most singles titlesOpen Era Chris Evert71974''1975, 1979''1980, 1983, 1985''1986French Championships* Suzanne Lenglen61920''1923, 1925''1926 Note: Also won World Hard Court Championships in 1914, 1921''1923.Most consecutive singles titlesOpen Era / Monica Seles Justine Henin31990''1992 2005''2007French Championships* Jeanne Matthey Suzanne Lenglen41909''1912 1920''1923Most doubles titlesOpen Era / Martina Navratilova71975 with Chris Evert, 1982 with Anne Smith, 1984''1985, 1987, 1988 with Pam Shriver, 1986 with Andrea Temesvri.French Championships* Simonne Mathieu61933, 1934 with Elizabeth Ryan, 1936''1937, 1938 with Billie Yorke, 1939 with Jadwiga JÄdrzejowska.Most consecutive doubles titlesOpen Era / Martina Navratilova Gigi Fernndez
51984''1987, 1988 with Pam Shriver, 1986 with Andrea Temesvri. 1991 with Jana Novotn, 1992''95 with Natasha Zvereva.
French Championships* Fran§oise D¼rr51967''1971Most mixed doubles titlesOpen Era Fran§oise D¼rr31968, 1971, 1973 with Jean-Claude Barclay.French Championships* Suzanne Lenglen71914, 1920 with Max Decugis, 1921''1923, 1925, 1926 with Jacques Brugnon.Most titles (singles, doubles, mixed)Open Era / Martina Navratilova111974''1988 (2 singles, 7 doubles, 2 mixed)French Championships* Suzanne Lenglen151919''1926 (6 singles, 2 doubles, 7 mixed)MiscellaneousUnseeded championsMen: Marcel Bernard Mats Wilander Gustavo Kuerten Gast"n Gaudio1946 1982 1997 2004Women: Margaret Scriven Jeļena Ostapenko Iga Świątek1933 2017 2020Youngest championMen: Michael Chang17 years and 3 months (1989)Women: / Monica Seles16 years and 6 months (1990)Oldest championMen: Andr(C)s Gimeno34 years and 10 months (1972)Women: Zsuzsa K¶rm¶czy33 years and 10 months (1958)French Championships (1891''1924) was only open to the French clubs members. By 1925 it opened itself to international palyers and was renamed to French Open. See WHCC.Ball boys and ball girls [ edit ] At the 2020 French Open, there were 230 "ramasseurs de balles" which in English translates literally as "gatherers of balls". They are aged between 12 and 16 years old, and dress in matching shirts and shorts. The 230 ball boys and ball girls are chosen to take part in the French Open by an application and selection process, which in 2020 had approximately 4,000 applicants from across France.[37][38] Upon selection the ball boys and ball girls participate in preparatory training in the weeks leading up to the French Open to ensure that they are prepared for the day they set foot on the tennis court in front of a global audience.
Television coverage [ edit ] Broadcast rights to the French Open (as of 2018) are as follows:[39]
France [ edit ] France T(C)l(C)visions and Eurosport hold the broadcast rights to the French Open until 2021.
United Kingdom [ edit ] ITV Sport and Eurosport holds broadcasting rights to show the French Open tennis tournaments until 2021.[40] The bulk of the daily coverage is broadcast on ITV4 although both singles finals plus other weekend matches are shown on ITV. John Inverdale hosts the coverage. Commentators include Nick Mullins, Jonathan Overend, Mark Petchey, Sam Smith, Jim Courier, Fabrice Santoro and Anne Keothavong.
Studio presentation for the French Open on Eurosport is hosted by Barbara Schett sometimes joined by Mats Wilander. Commentators include Simon Reed, Chris Bradnam, Nick Lester, Jason Goodall, Jo Durie, Frew McMillan, Arvind Parmar and Chris Wilkinson.
United States [ edit ] NBC's coverage of the French Open began in 1975.[41] Tennis Channel owns pay television rights to the tournament. Coverage of morning window (U.S. time) matches were sub-licensed to ESPN for broadcast by ESPN2 from 2007 through 2015.[42] In August 2015, ESPN announced that it would discontinue its sub-licensing and drop coverage of the French Open beginning in 2016, with network staff citing that because of the structure of the arrangement, its coverage "did not fit our successful model at the other three Majors"'--where ESPN is the exclusive rightsholder.[42] Tennis Channel chose to retain these rights under its new owner Sinclair Broadcast Group, nearly doubling the amount of coverage Tennis Channel will air from Roland Garros.[43][44]
Other than a three-year stint on CBS, NBC has remained the American television network home of the French Open since 1983. Since acquiring rights to the Indianapolis 500 in 2019, NBC's coverage begins on Memorial Day, the second day of the tournament; the network provides coverage windows on the holiday and the second weekend in the afternoon U.S. time. These windows consist of exclusive tape-delayed matches from earlier in the day, but any ongoing matches at the window's start are shown live to their conclusion. The later men's and women's semifinals are broadcast live on NBC in the Eastern Time Zone and tape-delayed in others, but since 2017 these matches are also simulcast on NBCSN to allow nationwide live coverage. Finals are live nationwide.[45]
Other countries and areas [ edit ] Europe '' Eurosport and the Eurosport Player[46] (co-broadcaster in various countries)
Albania '' RTSH[46]Austria '' ORF[46]Belgium '' RTBF[46]Bulgaria '' BNT[46]Croatia '' HRT[46]Cyprus '' CyBC[46]Czech Republic '' Česk Televize[46]Estonia '' Postimees TV[46]Finland '' Yle[46]Georgia '' Silknet[46]Greece '' ERT[46]Ireland '' Eir Sport 1[46]Montenegro '' RTCG[46]Russia '' RTRS[46]Slovakia '' Mark­za[46]Slovenia '' RTV Slovenija[46]Switzerland '' SRG SSR[46]Americas '' ESPN[46] (except Brazil & Canada)
Argentina '' Televisi"n Pºblica Argentina[46]Brazil '' BandSports[46]Canada '' RDS (French) & TSN (English)[46]Caribbean '' ESPN Caribbean[46]United States '' NBCSN and The Tennis ChannelAfrica
North Africa and Middle East '' beIN Sports[46]Southern Africa '' SuperSport[46]Asia [ edit ] Oceania [ edit ] Australia '' Nine Network and Stan Sport[68]New Zealand '' Sky Sport[46]Fiji & Pacific Islands '' Fox Sports[46]See also [ edit ] Lists of championsList of French Open champions (Open Era, all events)List of French Open men's singles championsList of French Open women's singles championsList of French Open men's doubles championsList of French Open women's doubles championsList of French Open mixed doubles championsList of French Open singles finalists during the open era, records and statisticsOther Grand Slam tournamentsAustralian OpenWimbledonUS OpenNotes [ edit ] References [ edit ] ^ "Un si¨cle d'histoire". Roland-Garros Official Website (in French). ^ "French Open 2020 Purse Money (Revealed)". sportekz.com. 24 September 2020. ^ Clarey, Christopher (30 June 2001). "Change Seems Essential to Escape Extinction: Wimbledon: World's Most Loved Dinosaur". International Herald Tribune. Archived from the original on 16 October 2007 . Retrieved 20 July 2007 . ^ Monte Burke (30 May 2012). "What Is The Most Prestigious Grand Slam Tennis Tournament?". Forbes . Retrieved 25 June 2013 . That survey asked 108 top players to rank the four Slams in order of prestige. The ranking went as follows: 1. Wimbledon 2. French Open 3. U.S. Open 4. Australian Open ^ Clarey, Christopher (26 May 2006). "In a year of change at Roland Garros, the winners may stay the same". International Herald Tribune. Archived from the original on 16 October 2007 . Retrieved 8 August 2007 . ^ "French Open '' Countdown: Borg's view on RG". Eurosport. 22 May 2008 . Retrieved 22 May 2008 . [dead link ] Alt URL ^ "Un si¨cle d'histoire". rolandgarros.com. ^ "Britannica: French Open" . Retrieved 22 February 2021 . ^ Christopher Clarey (23 May 2013). "A Puzzler in Paris: French Open or Roland Garros?". The New York Times. ^ Ramat, Aurel (1994). Le Ramat typographique. ‰ditions Charles Corlet. p. 63. ISBN 2854804686. ^ "Event Guide / History / Past Winners 1891''2008". rolandgarros.com. Archived from the original on 13 May 2012 . Retrieved 3 July 2009 . ^ Evan Gershkovich (10 June 2017). "Who was Roland Garros? The fighter pilot behind the French Open". The New York Times. ^ a b "Roland Garros: a venue open all year long. Past Winners and Draws". ftt.fr. Archived from the original on 8 August 2007 . Retrieved 7 August 2007 . ^ Henry D. Fetter (6 June 2011). "The French Open During World War II: A Hidden History". The Atlantic. ^ "Roland Garros Awards Equal Pay". WTA Tour. 16 March 2007. Archived from the original on 23 June 2007 . Retrieved 20 July 2007 . ^ "French Open could move away from Roland Garros in Paris". BBC News. 16 March 2007 . Retrieved 20 July 2007 . ^ "Roland Garros set for roof" . Retrieved 29 March 2015 . ^ "French Open Adds Day; Clay Stays the Same" . Retrieved 29 March 2015 . ^ "Only 13 matches completed before rain halts play" . Retrieved 29 March 2015 . ^ Christopher Clarey (28 May 2013). "Renovation Plans in Limbo, Roland Garros Faces Future". The New York Times. ^ Andrew Roberts (14 February 2011). "French Open Tennis Will Stay in Paris at Upgraded Roland Garros". Bloomberg. ^ "Modernising Roland Garros stadium". F(C)d(C)ration Fran§aise de Tennis (FFT). Archived from the original on 10 August 2015. ^ "Projet de nouveau stade Roland-Garros | CNDP '' Commission nationale du d(C)bat public". www.debatpublic.fr . Retrieved 2 June 2019 . ^ "Extension de Roland-Garros: retour devant la justice". Francetvsport (in French) . Retrieved 2 June 2019 . ^ Kamakshi Tandon (29 May 2015). "Paris city council votes against French Open expansion project". Tennis.com. ^ "Roland Garros Revamp Gets Green Light". NDTV. 10 June 2015. Archived from the original on 4 March 2016 . Retrieved 11 June 2015 . ^ "French Federation to Appeal against Roland Garros´ Modernization suspension!". Tennis World. 26 March 2016. ^ "Court Simonne-Mathieu stunning new addition to Roland Garros". The Independent. 26 May 2019 . Retrieved 2 June 2019 . ^ " " Un (C)crin extraordinaire" : le court Simonne-Mathieu de Roland-Garros fait l'unanimit(C) chez les joueurs et spectateurs". Franceinfo (in French). 2 June 2019 . Retrieved 2 June 2019 . ^ Christopher Clarey (27 September 2020). "New for This Pandemic French Open: Fall Weather and Lights". The New York Times. ^ "French Open lights up as another tradition dies". tennishead.net. 21 September 2020. ^ Atkin, Ronald. "Wimbledon Legends '' Bjorn Borg". Wimbledon.com. Archived from the original on 11 February 2012 . Retrieved 4 February 2012 . ^ "Nadal: Roland Garros-Wimbledon double no longer that tough". Tennis.com . Retrieved 30 January 2019 . ^ "Press Release 2018 French Open Prize Money Increase to over '‚¬39 million" (PDF) . 22 March 2018. ^ "An A to Z of Roland Garros". rolandgarros.com. F(C)d(C)ration Fran§aise de Tennis (FFT). Archived from the original on 2 April 2015. ^ a b "French Open winners". Roland Garros . Retrieved 2 February 2015 . ^ Edworthy, Sarah (2 June 2019). "Day in the Life: Ball Kids". Roland-Garros Official Website . Retrieved 2 June 2019 . ^ Guedon, Claire (4 October 2020). "Luka, 14 ans, un Dr´mois ramasseur de balles Roland-Garros". France Bleu (in French) . Retrieved 4 October 2020 . ^ "Channels Broadcasting French Open 2018 Live on TV & Online" . Retrieved 3 March 2018 . ^ "French Open to stay on ITV until 2021". ITV Press Centre. 6 June 2014 . Retrieved 8 June 2014 . ^ Fang, Ken (23 May 2013). "NBC Begins Coverage of The 2013 French Open This Sunday". Fang's Bites. Archived from the original on 8 December 2013 . Retrieved 26 May 2013 . ^ a b "ESPN drops the French Open, NBCSN could step in". Awful Announcing . Retrieved 3 August 2015 . ^ Umstead, R. Thomas (14 March 2016). "Tennis Channel Extends French Open Pay TV Rights". Multichannel News . Retrieved 16 March 2016 . ^ Ourand, John & Kaplan, Daniel, - (3 August 2015). "ESPN bids French Open adieu after 13 years". Sports Business Journal . Retrieved 16 March 2016 . CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link) ^ "French Open TV Schedule 2018". Sports Media Watch. 19 May 2016. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa "Broadcasters". Roland-Garros. 31 January 2020 . Retrieved 31 January 2020 . ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ https://www.rolandgarros.com/en-us/broadcasters ^ Perry, Kevin (12 November 2020). "STAN and NINE become new Australian home of Wimbledon and French Open Tennis". TV Blackbox . Retrieved 11 April 2021 . External links [ edit ] Official website (in French) Roland Garros on France2 (in French) Roland Garros on ina.fr : more than 600 hours of audio/visual archivesPhotos of Roland GarrosFrench Open '' All winners and runners-up. Reference book Coordinates: 48°50'²49.8'"N 2°14'²57.3'"E >> / >> 48.847167°N 2.249250°E >> / 48.847167; 2.249250
OFFICIAL LICENSEES - Roland-Garros - The 2021 Roland-Garros Tournament official site
Tue, 01 Jun 2021 13:26
OFFICIAL LICENSEES OF ROLAND-GARROS 2021 COLLECTION
Amazon devices will soon automatically share your Internet with neighbors | Ars Technica
Tue, 01 Jun 2021 13:23
WHAT COULD POSSIBLY GO WRONG? '-- Amazon's experimental wireless mesh networking turns users into guinea pigs. Dan Goodin - May 29, 2021 7:10 pm UTC
If you use Alexa, Echo, or any other Amazon device, you have only 10 days to opt out of an experiment that leaves your personal privacy and security hanging in the balance.
On June 8, the merchant, Web host, and entertainment behemoth will automatically enroll the devices in Amazon Sidewalk. The new wireless mesh service will share a small slice of your Internet bandwidth with nearby neighbors who don't have connectivity and help you to their bandwidth when you don't have a connection.
By default, Amazon devices including Alexa, Echo, Ring, security cams, outdoor lights, motion sensors, and Tile trackers will enroll in the system. And since only a tiny fraction of people take the time to change default settings, that means millions of people will be co-opted into the program whether they know anything about it or not. The Amazon webpage linked above says Sidewalk "is currently only available in the US."
The webpage also states:
What is Amazon Sidewalk?
Amazon Sidewalk is a shared network that helps devices work better. Operated by Amazon at no charge to customers, Sidewalk can help simplify new device setup, extend the low-bandwidth working range of devices to help find pets or valuables with Tile trackers, and help devices stay online even if they are outside the range of their home wifi. In the future, Sidewalk will support a range of experiences from using Sidewalk-enabled devices, such as smart security and lighting and diagnostics for appliances and tools.
How will Amazon Sidewalk impact my personal wireless bandwidth and data usage?
The maximum bandwidth of a Sidewalk Bridge to the Sidewalk server is 80Kbps, which is about 1/40th of the bandwidth used to stream a typical high definition video. Today, when you share your Bridge's connection with Sidewalk, total monthly data used by Sidewalk, per account, is capped at 500MB, which is equivalent to streaming about 10 minutes of high definition video.
Why should I participate in Amazon Sidewalk?
Amazon Sidewalk helps your devices get connected and stay connected. For example, if your Echo device loses its wifi connection, Sidewalk can simplify reconnecting to your router. For select Ring devices, you can continue to receive motion alerts from your Ring Security Cams and customer support can still troubleshoot problems even if your devices lose their wifi connection. Sidewalk can also extend the working range for your Sidewalk-enabled devices, such as Ring smart lights, pet locators or smart locks, so they can stay connected and continue to work over longer distances. Amazon does not charge any fees to join Sidewalk.
Amazon has published a white paper detailing the technical underpinnings and service terms that it says will protect the privacy and security of this bold undertaking. To be fair, the paper is fairly comprehensive, and so far no one has pointed out specific flaws that undermine the encryption or other safeguards being put in place. But there are enough theoretical risks to give users pause.
Advertisement Wireless technologies like Wi-Fi and Bluetooth have a history of being insecure. Remember
WEP, the encryption scheme that protected Wi-Fi traffic from being monitored by nearby parties? It was widely used for four years before researchers exposed flaws that made decrypting data relatively easy for attackers. WPA, the technology that replaced WEP, is much more robust, but it
also has a
checkered history.
Bluetooth has had its
share of
similar vulnerabilities over the years, too, either in the Bluetooth standard or in the way it's implemented in various products.
If industry-standard wireless technologies have such a poor track record, why are we to believe a proprietary wireless scheme will have one that's any better?
The omnipotent juggernautNext, consider the wealth of intimate details Amazon devices are privy to. They see who knocks on our doors, and in some homes they peer into our living rooms. They hear the conversations we're having with friends and family. They control locks and other security systems in our home.
Extending the reach of all this encrypted data to the sidewalk and living rooms of neighbors requires a level of confidence that's not warranted for a technology that has never seen widespread testing.
Last, let's not forget who's providing this new way for everyone to share and share alike. As independent privacy researcher Ashkan Soltani puts it: ''In addition to capturing everyone's shopping habits (from amazon.com) and their internet activity (as AWS is one of the most dominant web hosting services)... now they are also effectively becoming a global ISP with a flick of a switch, all without even having to lay a single foot of fiber.''
Advertisement Amazon's decision to make Sidewalk an opt-out service rather than an opt-in one is also telling. The company knows the only chance of the service gaining critical mass is to turn it on by default, so that's what it's doing. Fortunately, turning Sidewalk off is relatively painless. It involves:
Opening the Alexa appOpening More and selecting SettingsSelecting Account SettingsSelecting Amazon SidewalkTurning Amazon Sidewalk OffNo doubt, the benefits of Sidewalk for some people will outweigh the risks. But for the many, if not the vast majority of users, there's little upside and plenty of downside. Amazon representatives didn't respond to a request for comment.
Tay Anderson to step back from 'everyday' duties but keep voting - Chalkbeat Colorado
Tue, 01 Jun 2021 12:57
Denver school board member Tay Anderson said Sunday he would step back from ''everyday board functions'' until an outside firm hired by the school district completes an investigation into sexual assault allegations against him.
In a separate statement, the school board clarified that Anderson will still vote on key matters, including the selection of a new superintendent, which is set to happen June 3. A Denver Public Schools spokesperson said Anderson's stepping back means Anderson will not attend school or district meetings with staff or students.
''These unsubstantiated false allegations have caused a great deal of trauma to our entire district, and our students deserve better,'' Anderson wrote on Twitter on Sunday. ''These false claims have put my family and I in harm's way, and now as a father and son, I must protect those I love first, therefore I will be stepping back from everyday board functions until the completion of the independent investigation.''
Anderson announced his decision two days after the school board announced it was aware of new allegations against him.
''Director Tay Anderson's fellow DPS board members agree with his decision to step back from routine board functions and events until the conclusion of the investigation authorized by the board on April 6,'' the board members wrote in a statement Sunday night.
''Director Anderson will continue to vote on necessary matters before the board including the hiring of a new superintendent.''
In addition to meetings, Denver school board members often attend events at district schools. In recent weeks, Anderson has attended high school graduations, and he was at an in-person press conference at South High School Wednesday to announce the selection of the next superintendent.
Anderson is under investigation by an outside firm hired by Denver Public Schools. The district launched the investigation after the civil rights group Black Lives Matter 5280 said in March that a woman came to them to report that Anderson had sexually assaulted her.
Separate from that accusation, former members of anti-gun violence group Never Again Colorado said that Anderson engaged in inappropriate behavior when he was the group's president in 2018.
Then this week, Denver parent Mary-Katherine Brooks Fleming testified before a Colorado legislative committee that 62 young people, nearly all of them current Denver high school students, came to her starting in August seeking help and protection from a specific man ''in a position of trust.'' She said they had experienced abuse ranging from unwanted touching to violent rape.
Brooks Fleming did not name Anderson in her testimony, but on Friday, the Denver school board said it was aware of allegations of sexual abuse and that those allegations were against Anderson. The Denver Police Department said it has spoken to Brooks Fleming but has not heard directly from any victims.
Also on Sunday, the Colorado High School Democrats, a group that Anderson once chaired, called for him to resign.
''Director Anderson has lost the confidence of the students and families of his school district,'' current High School Democrats Chair Spencer Wilcox said in a statement. ''Students, including our many members in DPS, should not have to be afraid of one of their school board members. He must resign.''
Anderson has consistently denied all allegations against him. He said Sunday that he expects to be cleared and return to all his duties.
Under state law, a school board seat is considered vacant if the person elected or appointed to that seat submits a letter of resignation or if they miss three consecutive regular meetings. However, a school board can vote to approve additional absences by the missing member.
It's not clear that the change in Anderson's duties would result in any absences, considering that he will continue to vote.
The Denver school board said the investigation into Anderson remains open.
The board said it encourages anyone with information to email the group conducting the investigation, the Denver-based Investigations Law Group, at interviews@ilgdenver.com.
Why delaying the 21 June unlocking is such a political headache for Boris Johnson
Tue, 01 Jun 2021 12:56
Should the 21 June unlocking be delayed? Some scientists and medical experts are urging Boris Johnson to push back the date of England's unlocking, so that the vaccine programme could be more advanced '' particularly so that all over-50s have received not one, but two jabs '' before the final wave of freedoms are permitted.
Others believe that the impact of the vaccine programme is such that the consequence of a more transmissible virus on people's health and NHS capacity would be small. (The Times has an excellent read-through of the various positions.)
The most important area of scientific consensus is this: we'll have a better idea of whether or not England is in a position to go ahead with the 21 June unlocking on 14 June than we do today, and that the biggest priority is to push on with the vaccination programme.
But the politics are considerably more fraught. Large numbers of Conservative MPs have a "this far, no further" position as far as lockdowns are concerned, and as far as they are concerned, the 21 June date has to be met.
[See also: Can Matt Hancock survive? Here are two reasons why he might]
Many more note if the Delta variant is delaying the United Kingdom's lockdown, then the blame for that has to be located at the Prime Minister's door: he kept India off the red list for the best part of a fortnight, his government still hasn't established meaningful central quarantine or adequate compensation for self-isolation, and so on.
And others fear that, whatever the science, a delay to 21 June will do irrevocable damage to the government's standing: that it would, at a stroke, puncture the feel-good factor around unlocking, and break the public's appetite for extending the benefit of the doubt to Boris Johnson and his administration.
The bigger picture is this: while our own vaccine roll-out proceeds at great speed and efficiency, throughout the United Kingdom in general but in Wales in particular, a global pandemic can't be defeated by a British vaccine programme. If we don't have a global vaccination programme, then we don't have an enduring way to escape the Covid-19 era: a disease that has already killed more than three million people worldwide, and that without global vaccination programmes will retain the ability to paralyse life as we know it in the United Kingdom as well as overseas.
[See also: Boris Johnson's biggest asset is that most people never want to think about Covid-19 again]
'EU werkt aan digitale portemonnee-app voor hele Unie' | RTL Nieuws
Tue, 01 Jun 2021 11:29
Alles erin 3 uur 9 minuten geleden Aangepast: 2 uur 53 minuten geleden
De Europese Unie werkt aan een digitale portemonnee voor alle 27 EU-lidstaten, die bij alle overheden in de EU zou zijn te gebruiken.
Het zou gaan om een app die al je betalingsinformatie opslaat en die bij elke instantie van elk EU-land gebruikt kan worden, schrijft The Financial Times. De app is onder andere met een vingerafdruk of oogscan te gebruiken.
De bedoeling is dat EU-burgers er ook belangrijke papieren zoals hun rijbewijs in kunnen opslaan. De app wordt niet verplicht, maar zou extra veiligheid bieden. Volgens de FT maakt de EU vandaag meer details bekend.
DigID Nieuwe identiteitskaarten hebben chip met inlogfunctie DigiD
Regels nog op te stellenDe EU is van plan om regels op te stellen zodat bedrijven die toegang hebben tot de digitale portemonnee, die data niet voor andere doeleinden kunnen gebruiken. Er wordt nog gediscussieerd over de technische kant van het verhaal.
FT verwacht dat het systeem over een jaar bruikbaar is. Er bestaat al een EU-brede digitale ID, maar die is slechts door 19 EU-landen ge¯mplementeerd. Ze werken daarin ook niet goed samen.
Deze nieuwe laptop van LG is vederlicht:
Altijd weten wat er speelt?Download de gratis RTL Nieuws-app en blijf op de hoogte.
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Ex-Trump Lawyer Sidney Powell Tells QAnon Crowd Trump Can Be 'Reinstated' As President
Tue, 01 Jun 2021 04:19
Sidney Powell Tom Williams/CQ-Roll Call, Inc via Getty Images Former Trump attorney Sidney Powell told the audience at a QAnon conference that Trump could be inaugurated and "reinstated" as president. Powell wore a leather biker vest adorned with a slew of pro-Trump and religious patches. Powell, who previously represented Trump in his efforts to overturn the 2020 election, is a longtime promoter of the QAnon conspiracy theory. See more stories on Insider's business page. Sidney Powell, former President Donald Trump's ex-attorney, told the audience at a QAnon conference on Saturday that President Joe Biden should be removed from office and Trump should be "reinstated" as president.
Powell, who's filed dozens of unsuccessful lawsuits attempting to overturn 2020 election results, falsely told the crowd that Trump could still be inaugurated, but he wouldn't get credit for "time lost."
"He can simply be reinstated," she said, eliciting cheers from the Dallas crowd.
"A new inauguration day is set and Biden is told to move out of the White House. And President Trump should be moved back in. I'm sure there's not going to be credit for time lost, unfortunately, because the Constitution sets the date for inauguration, but he should definitely get the remainder of his term and make the most of it."
Powell, a longtime promoter of the QAnon conspiracy theory, wore a leather biker vest adorned with political and religious patches, including one that read "MAGA" and another with, "No God No Peace Know God Know Peace." Dominion Voting Systems filed a $1.3 billion defamation lawsuit against Powell earlier this year, accusing her of helping push "a viral disinformation campaign" that spread dangerous lies about the election and the company.
The three-day conference, called For God & Country: Patriot Roundup, featured other prominent Trump world figures, including Trump's former national security adviser, Michael Flynn, Texas Republican Rep. Louie Gohmert, and chairman of the Texas Republican Party, Allen West.
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Alarming Casualty Rates for mRNA Vaccines Warrant Urgent Action
Tue, 01 Jun 2021 04:17
Alarming Casualty Rates for mRNA Vaccines Warrant Urgent Action By F. William Engdahl19 May 2021 Image: Author: Bicanski on Pixnio. License: Personal & commercial use (CC0) https://pixnio.com/media/injection-medication-needles-syringe-vaccination# includes link to license
As official government data is emerging in Europe and the USA on the alarming numbers of deaths and permanent paralysis as well as other severe side effects from the experimental mRNA vaccines, it is becoming clear that we are being asked to be human guinea pigs in an experiment that could alter the human gene structure and far worse. While mainstream media ignores alarming data including death of countless healthy young victims, the politics of the corona vaccine is being advanced by Washington and Brussels along with WHO and the Vaccine Cartel with all the compassion of a mafia ''offer you can't refuse.''
The alarming EMA Report
On May 8 the European Medicines Agency (EMA) an agency of the European Union (EU) in charge of the evaluation and supervision of medical products, using the data base EudraVigilance which collects reports of suspected side effects of medicines including vaccines, published a report that barely warranted mention in major mainstream media. Through May 8, 2021 they had recorded 10,570 deaths and 405,259 injuries following injections of four experimental COVID-19 shots: COVID-19 mRNA VACCINE of MODERNA (CX-024414); COVID-19 mRNA VACCINE of PFIZER-BIONTECH; COVID-19 VACCINE of ASTRAZENECA (CHADOX1 NCOV-19); and Johnson & Johnson's Janssen COVID-19 VACCINE (AD26.COV2.S).
A detailed analysis of each vaccine gives the following: The Pfizer-BioNTech mRNA gene-edited vaccine resulted in the largest fatalities'' 5,368 deaths and 170,528 injuries or nearly 50% of the total for all four. The Moderna mRNA vaccine was second with 2,865 deaths and 22,985 injuries. That is to say, the only two gene manipulated mRNA experimental vaccines, Pfizer-BioNTech and Moderna, accounted for 8,233 deaths of the total registered deaths of 10,570. That's 78% of all deaths from the four vaccines currently in use in the EU.
And among the serious side effects or injuries recorded by the EMA, for the two mRNA vaccines which we focus on in this article, for the Pfizer ''experimental'' vaccine, most reported injuries included blood and lymphatic system disorders including deaths; cardiac disorders including deaths; musculoskeletal and connective tissue disorders; respiratory, thoracic and mediastinal disorders, and vascular disorders. For the Moderna mRNA vaccine, most serious injuries or causes of death included blood and lymphatic system disorders; cardiac disorders; musculoskeletal and connective tissue disorders; disorders of the central nervous system.
Note that these are only the most serious injuries related to those two genetically manipulated mRNA vaccines. The EMA also notes that it is believed that only a small percent of actual vaccine deaths or serious side effects, perhaps only 1% to 10%, are reported for various reasons. Officially more than 10,000 persons have died after receiving the coronavirus vaccines since January, 2021 in the EU. That is a horrifying number of vaccine-related deaths, even if the true numbers are far greater.
CDC as well
Even the US Centers for Disease Control (CDC) a notoriously political and corrupt agency with for-profit ties to vaccine makers, in its official Vaccine Adverse Event Reporting System (VAERS), shows a total of 193,000 ''adverse events'' including 4,057 deaths, 2,475 permanent disabilities, 25,603 emergency room visits, and 11,572 hospitalizations following COVID-19 injections between December 14, 2020 and May 14, 2021. That included the two mRNA vaccines, Pfizer and Moderna, and the far less prevalent J&J Janssen vaccine. Of the reported deaths, 38% occurred in people who became ill within 48 hours of being vaccinated. The official US vaccine-related death toll is greater in just 5 months than all the vaccine-related deaths from the past 20 years combined. Yet the major media worldwide and the US Government virtually bury the alarming facts.
Some 96% of the fatal results were from the Pfizer and Moderna vaccines, the two variants funded and promoted by the Gates Foundation and Tony Fauci's NIAID with the experimental mRNA genetic technology. Moreover, Dr. Tony Fauci, the US Biden Administration vaccine czar and his NIAID Vaccine Research Center co-designed the Moderna mRNA vaccine and gave Moderna and Pfizer each $6 billion to produce it. That's also a blatant conflict of interest as Fauci and his NIAID are allowed to financially benefit from their patent earnings in the vaccine under a curious US law. The NIAID developed the coronavirus spike proteins for the development of SARS-CoV-2 mRNA vaccines using taxpayer money. They licensed it to Moderna and Pfizer.
''never seen in nature'...''
In a tragic sense, the experience with reactions to the two unprecedented mRNA experimental vaccines since rollout in unprecedented speed ''warp speed'' as the US Government called it, is only now beginning to be seen, in real trials of human guinea pigs. Few realize that the two mRNA vaccines use genetic manipulations that never before have been used in humans. And under the cover of urgency, US and EU health authorities waived normal animal trials and did not even approve the safety, but gave an ''emergency use authorization.'' Moreover, the vaccine makers were made 100% exempt from damage litigation.
The general public was reassured of the vaccine safety when Pfizer and Moderna published reports of 94% and 95% ''efficacy'' of these vaccines. NIAID's Fauci was quick to call it ''extraordinary'' in November 2020, and Warp Speed was off and running as was the stock price of Pfizer and Moderna.
Peter Doshi, Associate Editor of the British Medical Journal pointed to a huge flaw in the 90+% reports for efficacy of Moderna and Pfizer vaccines. He noted that the percentages are relative, in relation to the select small healthy young test group, and not absolute as in real life. In real life we want to know how effective the vaccine is among the large general population. Doshi points to the fact that Pfizer excluded over 3400 ''suspected COVID-19 cases'' that were not included in the interim analysis. Moreover individuals ''in both Moderna and Pfizer trials were deemed to be SARS-CoV-1- (the 2003 Asian SARS virus) positive at baseline, despite prior infection being grounds for exclusion,'' Doshi notes. Both companies refused to release their raw data. Pfizer in-house scientists did their tests. In short 95% is what Pfizer or Moderna claim. We are told, ''Trust us.'' A more realistic estimate of the true efficacy of the two vaccines for the general public, using data supplied by the vaccine makers to the FDA, shows the Moderna vaccine at the time of interim analysis demonstrated an absolute risk reduction of 1.1%, while the Pfizer vaccine absolute risk reduction was 0.7%. That is very poor.
Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, says, ''Ideally, you want an antiviral vaccine to do two things . . . first, reduce the likelihood you will get severely ill and go to the hospital, and two, prevent infection and therefore interrupt disease transmission.'' As Doshi notes, none of the trials were ''designed to detect a reduction in any serious outcome such as hospital admissions, use of intensive care, or deaths. Nor are the vaccines being studied to determine whether they can interrupt transmission of the virus.'' Moderna's chief medical officer even admitted that, ''Our trial will not demonstrate prevention of transmission.''
Possible effects of mRNA vaccines
In a major new study just published in the International Journal of Vaccine Theory, Practice and Research, Dr. Stephanie Seneff, senior scientist at the MIT Computer Science and Artificial Intelligence Laboratory, and Dr. Greg Nigh, Naturopathic oncology specialist, analyze in detail the possible pathways in which the experimental mRNA vaccines of Pfizer and Moderna could be causing such adverse effects in the vaccinated. First they point out that both the Pfizer and Moderna gene-edited vaccines are highly unstable: ''Both are delivered through muscle injection, and both require deep-freeze storage to keep the RNA from breaking down. This is because, unlike double-stranded DNA which is very stable, single-strand RNA products are apt to be damaged or rendered powerless at warm temperatures and must be kept extremely cold to retain their potential efficacy.'' Pfizer recommends minus 70' Celsius.
The authors point out that to keep the mRNA from breaking down before it could produce protein, both vaccine makers substitute methyl-pseudouridine to stabilize RNA against degradation, allowing it to survive long enough to produce adequate amounts of protein antigen. The problem they point out is that, ''This form of mRNA delivered in the vaccine is never seen in nature, and therefore has the potential for unknown consequences'... manipulation of the code of life could lead to completely unanticipated negative effects, potentially long term or even permanent. ''
PEG Adjuvants and Anaphylactic Shock
For various reasons to avoid using aluminum adjuvants to boost the antibody response, both mRNA vaccines use polyethylene glycol, or PEG, as adjuvant. This has consequences. The authors point out, '''...both mRNA vaccines currently deployed against COVID-19 utilize lipid-based nanoparticles as delivery vehicles. The mRNA cargo is placed inside a shell composed of synthetic lipids and cholesterol, along with PEG to stabilize the mRNA molecule against degradation.''
PEG has been shown to produce anaphylactic shock or severe allergenic reactions. In studies of prior non-mRNA vaccines, anaphylactic shock reactions occurred in 2 cases per million vaccinations. With the mRNA vaccines initial monitoring revealed that, ''anaphylaxis occurred at a rate of 247 per million vaccinations. This is more than 21 times as many as were initially reported by the CDC. The second injection exposure is likely to cause even larger numbers of anaphylactic reactions.'' One study noted, ''PEG is a high-risk 'hidden' allergen, usually unsuspected, and can cause frequent allergic reactions due to inadvertent re-exposure.'' Among such reactions are included life-threatening cardiovascular collapse.
This is far from all the undeclared risks of the experimental mRNA coronavirus vaccines.
Antibody-Dependent Enhancement
Antibody-Dependent Enhancement (ADE) is an immunological phenomenon. Seneff and Nigh note that, ''ADE is a special case of what can happen when low, non-neutralizing levels of'... antibodies against a virus are present at the time of infection. These antibodies might be present due to'... prior vaccination against the virus'...'' The authors suggest that in the case of both Pfizer and Moderna mRNA vaccines, ''non-neutralizing antibodies form immune complexes with viral antigens to provoke excessive secretion of pro-inflammatory cytokines, and, in the extreme case, a cytokine storm causing widespread local tissue damage.''
To be clear, normally cytokines are part of the body's immune response to infection. But their sudden release in large quantities, a cytokine storm, can cause multisystem organ failure and death. Our innate immune system undergoes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines.
The authors add that pre-existing ''antibodies, induced by prior vaccination, contribute to severe pulmonary damage by SARS-CoV in macaques'...'' Another cited study shows that the much more diverse range of prior exposures to coronaviruses such as seasonal flu experienced by the elderly might predispose them to ADE upon exposure to SARS-CoV-2.'' This is a possible explanation for the high incidence of post-mRNA vaccination deaths among elderly.
The vaccine makers have a clever way of denial as to the toxicity of their mRNA vaccines. As Seneff and Nigh state, ''it is not possible to distinguish an ADE manifestation of disease from a true, non-ADE viral infection.'' But they make the telling point, ''In this light it is important to recognize that, when diseases and deaths occur shortly after vaccination with an mRNA vaccine, it can never be definitively determined, even with a full investigation, that the vaccine reaction was not a proximal cause. ''
The authors make numerous other alarming points including emergence of auto-immune diseases such as Celiac disease, a disease of the digestive system that damages the small intestine and interferes with the absorption of nutrients from food. Also Guillain-Barr(C) syndrome (GBS) that causes progressive muscle weakness and paralysis. Additionally, Immune thrombocytopenia (ITP) in which a person has unusually low levels of platelets '-- the cells that help blood to clot'' could occur following vaccination ''through the migration of immune cells carrying a cargo of mRNA nanoparticles via the lymph system into the spleen'... ITP appears initially as petechiae or purpura on the skin, and/or bleeding from mucosal surfaces. It has a high risk of fatality through haemorrhaging and stroke.''
These examples are indicative of the fact that we are literally exposing the human race via untested experimental gene edited mRNA vaccines to incalculable dangers which in the end may exceed by far any potential risk of damage from something which has been called SARS-Cov-2. Far from the much-touted miracle substance proclaimed by WHO, Gates, Fauci and others, the Pfizer, Moderna and other possible mRNA vaccines clearly hold potentially tragic and even catastrophic unforeseen consequences. Little wonder some critics believe it is a disguised vehicle for human eugenics.
F. William Engdahl is strategic risk consultant and lecturer, he holds a degree in politics from Princeton University and is a best-selling author on oil and geopolitics, exclusively for the online magazine''New Eastern Outlook''
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Landlords and restaurant bosses say furlough is destroying work ethic and must end now
Tue, 01 Jun 2021 03:58
PUB and restaurant bosses are demanding Chancellor Rishi Sunak ends furlough '' to combat a spiralling recruitment crisis.
They are so short-staffed, some have been offering £1,000 joining-up bonuses to coax back uncertain workers.
7
David Wilson says many workers in the hospitality industry have no desire to come back Credit: Andy Kelvin / Kelvin Media They blame the £63billion government pay scheme, as would-be recruits prefer to stay home and take state cash.
The Sun on Sunday can reveal UK-wide there are 700,000 job vacancies, including 188,000 in hospitality alone where more than 250,000 remain on furlough.
The scheme does not stop until the end of September, amid uncertainty over the economy.
But experts fear some have now lost the will to work. Professor Len Shackleton, from the Institute of Economic Affairs, said: ''Furlough has been a great success but has gone on for far too long.
''We should wind it up and get back to reality. We should not be holding back new businesses which need workers in a vain attempt to keep old businesses alive.''
Furlough began in March last year to stop firms laying off staff, or collapsing, during lockdown.
7
David Wilson says he has advertised for roles and had no success Credit: Andy Kelvin / Kelvin MediaSome 11.5million workers have been furloughed, with 4.2million still on the handout at the end of March this year. It has helped keep unemployment at around five per cent.
A Treasury spokesman said: ''Furlough means two million fewer people will have lost their jobs.
"We went long with furlough to avoid a cliff edge and ensure as many jobs as possible are protected.''
But it is down to employers to stop the payouts, by ceasing to apply for the state to pay 80 per cent of a worker's wages.
Meanwhile, trade body UK Hospitality says 15 per cent of its workers, or around 270,000, are reluctant to come off furlough, over fears of another lockdown.
7
Jamie Rogers is offering £1,000 incentives to try and attract new staff Credit: ApexUK Hospitality's chief executive Kate Nicholls said: ''Furlough is still essential, helping to make sure jobs are protected over the summer.
''But it could be tightened up to ensure it is not masking problems in our economy and protecting jobs that are no longer there.
''Lots of people are trying to recruit and in some parts of the country there are vacancies that they cannot fill.''
How the furlough scheme works
THE Coronavirus Job Retention Scheme, also known as furlough, began in March 2020 and is due to end at the end of September this year.
The scheme provides grants that cover 80 per cent of an employee's wages up to a maximum of £2,500 per month.
To apply, employers have only to agree in writing that the worker has been furloughed, and they can furlough staff for any amount of time and any work pattern, while still being able to claim the grant for the hours not worked.
Employees cannot continue working for the company during the time they are furloughed but are free to undertake training or even second jobs.
The scheme does, however, cover only employees recruited on or before March 2 this year, and from July 1 the grant will be reduced each month.
The scheme is not cost-free because employers still have to cover national insurance and pension outlays.
Small business owner Jamie Rogers is now so desperate, he is offering a £1,000 bonus to anyone who will work for him until September.
His Twenty Seven by Jamie Rogers restaurant in Kingsbridge, Devon, is losing thousands of pounds a day because he is short of chefs, bartenders and waiters.
Jamie, 30, said: ''Right now I only have 15 staff and need 20 to be fully operational. We are turning away bookings every day.
"It's impossible to find good staff and restaurants are offering double wages to bring people in.
''I call on the Chancellor to end furlough now because enough is enough and we are going to be facing a huge problem by winter.''
7
Jamie Rogers says he needs five more staff or he will keep having to turn away bookings Credit: ApexEmployers say one clear fault is that they cannot apply for furlough for new staff they have taken on after March 2 this year, even if they are forced back into lockdown.
So workers are turning down job offers as they are nervous about losing the possible future benefit.
A second issue is that people on furlough are allowed to take a second job, and maybe double their income, so have little interest in their old employment restarting.
There are similar stories across Europe, too, as lack of staff hampers the reopening of hotels, restaurants and bars. Some owners are raining money to attract workers, creating inflationary pressures.
7
Rishi Sunak has been urged to end the furlough scheme Credit: AFPIn the US and Israel, high unemployment benefits have been blamed for people staying away from work.
Back in the UK, Hugh Osmond, founder of restaurant group Various Eateries, with around a dozen locations across the country, has even heard stories of workers claiming furlough in the UK despite starting new jobs overseas in countries such as Italy and France.
Hugh, 59, said: ''Furlough has been a godsend for the hospitality industry but now we want people back to work and it's causing chaos.
''It's a perfect storm because furlough is giving people many reasons not to return to work or find a new job. It's time to end furlough, 100 per cent.''
The system is also rife with abuse and HMRC is investigating more than 21,000 cases of alleged furlough fraud, with firms claiming for people they no longer have on the books.
7
David Wilson fears many overseas workers cannot or will not return to the UK Credit: Andy Kelvin / Kelvin MediaDavid Wilson, 56, has run his Calypso restaurant in Blackburn for ten years and has now got into a staffing crisis.
The dad of two had to furlough five workers and although he has taken them back, he is still short-staffed.
He said: ''We've advertised but haven't had any joy and it's a real worry. There are lots of people who have worked in hospitality for years but have no interest in coming back.
''Hospitality relies heavily on workers from overseas but during the pandemic many have flown home and sadly aren't returning.''
Tory MP David Jones last night said: ''Furlough has been a huge success, keeping business ticking over and maint-aining jobs for individuals.
Furlough has saved businesses but leaders say it needs to end''But this seems to be having some unintended consequences, which I am fully aware of from speaking to business, particularly the hospitality industry.
''Many workers have been using the past 15 months, while on furlough, to retrain and learn new skills. There are now fears these people will leave their jobs in hospitality and find another industry for employment.''
Greg Mulholland, director of the Campaign for Pubs, said: ''The reality of furlough for pubs, especially those run by independent publicans, is that it has and is keeping pub staff in jobs, which is important.
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''But it is not helping the pub as a business '-- indeed furlough is yet another cost on top of the other ongoing ones of rent, mortgage and bills.
''The issue for pubs and hospitality at the moment is the acute shortage of staff.
''Many are struggling to recruit, which will have an impact on pubs '-- including over bank holiday weekend.''
The curse of free money
By Douglas Murray
DO you still feel like going into work?
Plenty of people have got used to life at home and we are about to find out whether the last year has changed our idea of what a working day should actually be.
In the US, some in charge are starting to get worried about this. In the last year Americans got a set of stimulus cheques from the government.
Free money, basically, to keep the economy going. But it seems a lot of Americans are very keen to stay working from home.
In a story that is cropping up across the land, bosses in the US claim they can't get people to fill the jobs they have vacant.
One employer in Dallas said this week that despite offering wages of up to $30 (£21) an hour, he can't find anyone willing to turn up to work.
The average weekly unemployment benefit is now well over $600 (£420), with some states paying $700 (£490). The average weekly minimum wage is roughly $450 (£317).
The question now is will it be the same story here in Britain? As the economy starts to reopen, we are about to find out.
Chancellor Rishi Sunak has kept extending his generous furlough scheme.
It has worked brilliantly and meant that a lot of people who might have lost their jobs have been able to keep them.
That scheme is thought to have helped around 11million people. In March it was again extended '-- to October this year.
That means many people will have spent 18 months with most of their salary paid by the Government.
But is the deal they've had going to prove, like in America, to have been a bit too generous? Has furlough left people with less incentive to seek work?
Most of those on the scheme have spent the last year and more being paid 80 per cent of their usual salary.
That 20 per cent sounds like a big cut until you take out a number of things.
Nobody on the scheme has had to pay their commuting bills, car or public transport costs.
They've been able to get all their meals more cheaply at home, and many other outgoings (not least the ones from going out) have gone.
From the beginning of the Sunak scheme there were people who worried that the 80 per cent figure was too high.
Will people want to go back to work? Some will, of course. But many will find normal working life a drudgery after this.
Fighting through the traffic, spending less time with the family, seeing colleagues you don't much care for.
For many people this and much more means working life might not look so good.
You can understand why some on furlough look to October with dread.
So this country, like America, is going to have a big test in front of it.
We need our economy not just to sluggishly grind into gear but to roar back into gear.
For this country to pull through we have to positively roar back, not sidle back.
Will we be able to do it? You'd hope so. There are benefits to everyone when people work hard for their earnings.
But a little bit of me worries that this country might have lost its work ethic.
And that we're going to need a rude awakening to get us back into gear.
Furloughed barman scoops £100k on a £2 National Lottery scratchcard after tough year
Alex Berenson on Twitter: "BOOM. The media may have ignored Saturday's huge London protests, but the British gov't paid attention. Vaccine passports are done in the UK. Presumably it will now go the soft coercion route the US prefers (at least in stat
Tue, 01 Jun 2021 00:00
Alex Berenson : BOOM.The media may have ignored Saturday's huge London protests, but the British gov't paid attention. Vaccine pa'... https://t.co/3QsZQWPHVo
Mon May 31 01:57:39 +0000 2021
CNN Loses Nearly 70% Of Its Viewers Since Trump Left Office | The Daily Caller
Mon, 31 May 2021 21:18
Ratings from Neilsen Media Research reported Tuesday indicated that CNN lost 67% of its total viewers since January, when Donald Trump left the White House.
During the primetime hours of 8:00 p.m. '' 11:00 p.m. (EST), CNN lost around 65% of its total viewers since January. In the critical 25-54 age demographic, the network lost 71% of its viewers for both the day and primetime.
CNN's drop in viewers is larger than its competitors, but all major cable news shows have experienced a drop. MSNBC had the second-largest drop in viewership since January, losing 49% of its total viewership between January and May. In the 25-54 age demographic, the network lost 63% of its viewers. During primetime hours, MSNBC lost 42% of its total viewers and 58% of viewers between the ages of 25 and 54.
Cable News Ratings Sunday May 23
Average Viewers 4 pm to Midnight Demo | Total 1'ģ@FoxNews 119,875 822,875 2'ģ@CNN 120,000 558,125 3'ģ@MSNBC 49,750 396,000
Primetime 1'ģFox News 129,000 1,015,333 2'ģCNN 163,667 708,333 3'ģMSNBC 47,667 383,333 pic.twitter.com/YfqfRoNNG8
'-- RoadMN (@RoadMN) May 25, 2021
Fox News had the least substantial drop out of all networks, losing 12% of its total viewers and 15% of viewers between the ages of 25-54 between January and May. (RELATED: CNN Condemns 'Abhorrent' Pro-Hitler Tweets From Freelance Contributor, Says He Will Not Work With Company In 'Any Capacity' Again)
CNN's New Day has taken a major hit in ratings. The show had its least-watched week of the year so far with 461,000 total viewers and 108,000 viewers between the ages of 25 and 54, and it has averaged less than 500,000 viewers for the past four consecutive weeks.
Fox News reached its 14th consecutive week at the number one spot for cable news viewers, with 2.1 million viewers during primetime and an average of 1.2 million viewers for the day.
Next generation COVID vaccines to be cheaper, easier, more protective
Mon, 31 May 2021 12:43
The COVID-19 vaccines are among the best ever created. They're safe and more than 90% effective at preventing any disease, and even more so at blocking serious illness and death.
Now drug companies are trying to make them even better.
Some future shots will be more effective against certain variants of the SARS-CoV-2 virus that causes COVID-19. Others are aiming to cover several types of severe respiratory viruses, including the first SARS, which caused outbreaks between 2002 and 2004, or even all viruses in the larger coronavirus family.
Companies are testing vaccines that won't need to be kept cold, won't require two shots, will have fewer side effects, can be produced more efficiently and can be delivered without needles to make them easier to provide in rural areas and the developing world.
"There's a long history within vaccinology of second-generation vaccines being multiply improved over first-generation vaccines. That's just the way things go," said Scot Roberts, chief scientific officer of Altimmune, a biotech based in Gaithersburg, Maryland, that is developing an inhaled vaccine.
None of these second-generation COVID-19 vaccines will be ready until at least later this summer, and many, including Altimmune's, not until early next year at the soonest. No single vaccine will have all the desired attributes, a number of experts said.
But with potentially every one of Earth's nearly 8 billion inhabitants needing one or two initial doses and potentially boosters, there's plenty of room for different approaches, a number of experts said.
"Depth and breadth" is what vaccinologist, pharmacist, and public-health leader John Grabenstein said he wants in a second-generation vaccine. He expects protection against a number of different variants and respiratory diseases and, ideally, a decade or more between shots.
The jury is still out on how long the current vaccines will last '' or whether we'll even need boosters at all, said Scott Hensley, a viral immunologist at the University of Pennsylvania Perelman School of Medicine. "Time will tell," he said.
But most companies investing in COVID-19 vaccines are presuming '' even banking on the idea '' that regular boosters will be necessary.
Stanley Erck, president and CEO of Novavax, which plans to release its vaccine's effectiveness data soon, said his company's studies in monkeys show that giving a booster dose a year after initial vaccination yields "spectacular results."
"I think we're going to want to do that with humans," he said. "This isn't going to go away from a commercial point of view anytime in the future."
Expected need for boosters
COVID-19 will not be a pandemic forever, but the virus that causes it will probably be around indefinitely, like the flu, said Dr. Paul Offit, director of the Vaccine Education Center at Children's Hospital of Philadelphia.
"Are we going to need to give a vaccine as long as this virus exists in the world? I think the answer to that question is yes," Offit said. "So you're talking about decades, I would imagine."
The problem is not with current vaccines, which are better than anyone would have predicted. "This is the most amazing scientific achievement in my lifetime," Offit said. "And I'm old. My lifetime includes the polio vaccine."
But viruses change, immunity fades and there's always room for improvement, he said.
To understand the how long immunity lasts, researchers generally look at antibodies in the blood, which begin to dwindle a few months after infection and to a lesser extent, vaccination. The immune system has a second line of defense, so-called T cells, which aren't as easily studied, said Dr. Betty Diamond, an immunologist and rheumatology expert at the Feinstein Institutes for Medical Research in New York.
"If those are good, we may be protected for lots longer than the antibodies suggest," Diamond said.
Leaders in the vaccine race aren't waiting around until protection wanes. They're already experimenting with the best ways to make boosters.
It's not clear yet which approach will be the most effective, but several companies, including Moderna, are testing whether people are better protected if they receive an additional dose of the same vaccine, or a shot tailored to one or more of the variants now circulating.
Moderna, the maker of one of the three COVID-19 vaccines authorized for use in the U.S., also is using artificial intelligence and machine learning to try to predict future mutations that could cause problems and design vaccines to address them, said Melissa J. Moore, Moderna's chief scientific officer for platform research.
It's not yet clear how many different variants and viruses the mRNA vaccines like Moderna's can protect against simultaneously, but Moore thinks she can make at least six vaccines in one, and maybe 10. Some could cover SARS-CoV-2 variants, along with several flu strains and other respiratory viruses.
Any revised Moderna vaccine also will include a lower dose than the original, Moore said. The company went with a high dose in its initial vaccine to guarantee effectiveness, but now, she said the company is confident the dose can come down, reducing side effects without compromising protection.
One of Moderna's co-founders, MIT professor Robert Langer, also is known for his research on microneedles, tiny Band-Aid-like patches that can deliver medications without the pain of a shot. Moderna has said nothing about future delivery plans, but it seems conceivable the company might try to combine the two technologies to provide a booster that doesn't require an injection.
Other next-gen efforts
Both Moderna's vaccine and one by Pfizer-BioNTech, which were the first authorized in the U.S., were rapidly made, highly effective and based on a technology called messenger RNA. But a German company, CureVac, which started working in mRNA years before the others, is trying to catch up and maybe leap ahead in the booster market.
CureVac's initial effectiveness and safety data is due out any day, but the company already is focused on its second-generation vaccine, which it expects to be ready for market by the end of this year at the latest, said Mariola Fotin-Mleczek, the company's chief technology officer.
The second version of the CureVac vaccine will trigger a higher immune response than the first at a lower dose, and won't have the cold storage issues of the other mRNA vaccines, Fotin-Mleczek said. It's still unclear whether one or two doses will be needed for long-term protection, she said.
CureVac's vaccine should be appealing to low- and moderate-income countries, she said, because its low dose will keep it relatively inexpensive and storage requirements will make it easy to distribute.
By putting out the first-generation vaccine this summer, the company hopes to have any production issues worked out by the time the second version is ready later this year, she said.
Counting on at least some long-term need for boosters, GlaxoSmithKline is contributing to three vaccines made by other companies, including CureVac, getting "several shots on goal," as Roger Connor, president of GlaxoSmithKline Global Vaccines put it. GSK makes a so-called adjuvant, which can be added to a vaccine to make it work more effectively at a lower dose.
GSK and another partner, Medicago, a biopharmaceutical company based in Quebec City, Canada, recently released mid-stage clinical data suggesting their plant-derived vaccine is safe and potentially effective against COVID-19.
Growing vaccines in plants can be easier and enable more predictable scale-up of vaccine production, Connor said.
GSK also is pairing with Sanofi for a vaccine that launched a definitive trial Thursday to prove safety and effectiveness. That trial, which will include 35,000 adult volunteers from the U.S., Asia, Africa, and Latin America, will be conducted in two phases, the first testing against the original virus and the second against a variant first seen in South Africa.
The pair hope their vaccine can be used as a first-line priming dose, but also plan to test it as a booster for people who have already been vaccinated, because, Connor said, "it's too soon to tell what will be needed."
No needles
Several companies are working on vaccines that can be delivered without the needles that send shivers down some people's spines.
A nasal spray makes sense, proponents say, because COVID-19 is transmitted through aerosols and droplets that can enter the body via the nose and then travel into the respiratory tract. This area is lined with mucus and building up what's called mucosal immunity should prevent infection with the virus.
A vaccine delivered through the nose is also likely to avoid side effects '' like fever and muscle aches '' that can accompany shots in the arm, said Altimmune's Roberts. In trials of intranasal flu vaccines, he said, side effects were so mild that there was no difference seen between the active vaccine and a saline placebo.
An inhaled vaccine with limited side effects also will be useful for protecting younger children, who aren't yet eligible for COVID-19 vaccines, Roberts said. Children, who, of course, hate shots, are less likely to fall seriously ill from COVID-19, so reducing side effects improves the vaccine's risk-benefit ratio for them.
A vaccine like the one his company is developing also will have advantages in countries without many financial resources, he said. Altimmune's vaccine won't require freezing or even refrigeration for weeks at a time, and can be delivered without a highly trained medical professional, he said.
The company expects to release early-stage trial data next month and, if all goes well, to apply for Food and Drug Administration approval early next year. Altimmune is testing both one and two doses, but hopes that one will be enough, Roberts said.
While most vaccines target the distinctive "spike" protein on the outside of the SARS-CoV-2 virus, a candidate COVID-19 vaccine from ImmunityBio includes a second target on the virus, hoping to avoid problems with variants and to stimulate more of a long-term T cell response.
The Culver City, California-based company is trying four different delivery routes '' a shot, an under-the-tongue droplet, a pill and a nasal spray '' and envisions mixing and matching, according to the company. Maybe an injection will be followed by a nasal spray to reduce both the chance of infection and the potential spread of the virus through the respiratory tract.
A trial approved last week will test the vaccine as a booster for previously vaccinated South African health care workers, according to a company press release.
Hensley, of Penn, said the future will depend on how much the virus changes over time and how long immunity from the first generation of vaccines lasts.
"If I was a betting man, I would say that we're not going to need a booster in the fall," he said. "Will we need a booster in five years? Maybe."
It makes sense for companies to invest money and research into next-generation vaccines, but the more immediate issue is providing the already available vaccines to more people, he said. "We have a real, tangible solution to what's presented to us now and it's just a matter of getting the vaccine out there."
Contact Karen Weintraub at kweintraub@usatoday.com.
Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.
View Notice - Public Contracts Scotland
Mon, 31 May 2021 11:40
Section I: Contracting authority I.1) Name and addressesScottish Police Authority
1 Pacific Quay, 2nd Floor
Glasgow
G51 1DZ
UK
Contact person: Alison McElroy
E-mail: Alison.McElroy@scotland.pnn.police.uk
NUTS: UKM82
Internet address(es)
Main address: http://www.spa.police.uk
Address of the buyer profile: https://www.publiccontractsscotland.gov.uk/search/Search_AuthProfile.aspx?ID=AA19762
I.2) Joint procurementThe contract is awarded by a central purchasing body
I.3) CommunicationThe procurement documents are available for unrestricted and full direct access, free of charge at:
https://www.publiccontractsscotland.gov.uk
Additional information can be obtained from the abovementioned address
Tenders or requests to participate must be sent electronically to:
https://www.publiccontractsscotland.gov.uk
Electronic communication requires the use of tools and devices that are not generally available. Unrestricted and full direct access to these tools and devices is possible, free of charge, at:
https://www.publiccontractsscotland.gov.uk
I.4) Type of the contracting authorityBody governed by public law
I.5) Main activityPublic order and safety
Section II: ObjectII.1) Scope of the procurement II.1.1) TitleDisaster Victim Identification Shelters
Reference number: PROC-21-1017
II.1.2) Main CPV code35200000
II.1.3) Type of contractSupplies
II.1.4) Short descriptionPolice Scotland are looking to purchase shelters for Disaster Victim Identification purposes, in the event of a Mass Fatality incident.
II.1.5) Estimated total value Value excluding VAT: 115 000.00 GBP
II.1.6) Information about lots This contract is divided into lots: No
II.2) Description II.2.2) Additional CPV code(s)35200000
II.2.3) Place of performanceNUTS code:
UKM82
Main site or place of performance:
Delivery Glasgow - for use Scotland-wide
II.2.4) Description of the procurementPolice Scotland are looking to award a contract to a single supplier for various styles of Disaster Victim Identification Shelters, for use in the event of a Mass Fatality incident.
II.2.5) Award criteriaCriteria below:
Quality criterion: Quality / Weighting: 60
Price / Weighting: 40
II.2.7) Duration of the contract, framework agreement or dynamic purchasing system Duration in months: 24
This contract is subject to renewal: No
II.2.9) Information about the limits on the number of candidates to be invited II.2.10) Information about variants Variants will be accepted: No
II.2.11) Information about options Options: No
II.2.13) Information about European Union funds The procurement is related to a project and/or programme financed by European Union funds: No
Section III: Legal, economic, financial and technical informationIII.1) Conditions for participation III.1.2) Economic and financial standingSelection criteria as stated in the procurement documents
III.1.3) Technical and professional abilitySelection criteria as stated in the procurement documents
III.2) Conditions related to the contractSection IV: ProcedureIV.1) Description IV.1.1) Type of procedure Open procedure
IV.1.8) Information about Government Procurement Agreement (GPA) The procurement is covered by the Government Procurement Agreement: Yes
IV.2) Administrative information IV.2.2) Time limit for receipt of tenders or requests to participate Date: 27/05/2021
Local time: 12:00
IV.2.4) Languages in which tenders or requests to participate may be submittedEN
IV.2.7) Conditions for opening of tenders Date: 27/05/2021
Local time: 13:00
Place:
Police Scotland premises
Information about authorised persons and opening procedure:
Alison McElroy, Procurement Officer - opening electronically
Section VI: Complementary informationVI.1) Information about recurrence This is a recurrent procurement: No
VI.3) Additional informationNOTE: To register your interest in this notice and obtain any additional information please visit the Public Contracts Scotland Web Site at https://www.publiccontractsscotland.gov.uk/Search/Search_Switch.aspx?ID=654417.
The buyer has indicated that it will accept electronic responses to this notice via the Postbox facility. A user guide is available at https://www.publiccontractsscotland.gov.uk/sitehelp/help_guides.aspx.
Suppliers are advised to allow adequate time for uploading documents and to dispatch the electronic response well in advance of the closing time to avoid any last minute problems.
(SC Ref:654417)
VI.4) Procedures for reviewVI.5) Date of dispatch of this notice19/05/2021
Information added to the notice since publication.
Additional information added to the notice since it's publication. No further information has been uploaded. Commodity CategoriesCommodity Categories35200000Police equipmentSecurity, fire-fighting, police and defence equipment45216129Protective sheltersConstruction work for buildings relating to law and order or emergency services and for military buildings Delivery LocationsDelivery Locations130Aberdeen & North-East100All Scotland160Edinburgh & Lothians150Glasgow & Strathclyde120Highlands and Islands170Scotland South140Tayside, Central & Fife
Texas Legislature Online - 87(R) Text for SB 7
Mon, 31 May 2021 11:24
VersionBillFiscal NoteAnalysisWitnessListSummary ofCmte ActionIntroducedSenate Committee ReportEngrossedHouse Committee ReportConference Committee Report* Fiscal Impact Statements (View description of impact statement types) Bill VersionImpact Type Introduced Criminal Justice Policy Senate Committee Report Criminal Justice Policy Engrossed Criminal Justice Policy House Committee Report Criminal Justice Policy*Source: Legislative Reference Library
1,000 Lawyers and 10,000 Doctors Have Filed a Lawsuit for Violations of the Nuremberg Code
Mon, 31 May 2021 04:06
by Sven-Allan Johansson; auto translated from Swedish by SD
Background to the new Nuremberg Trials 2021:
A large team of more than 1,000 lawyers and over 10,000 medical experts, led by Dr. Reiner Fuellmich, has initiated legal proceedings against the CDC, WHO and the Davos Group for crimes against humanity.
Fuellmich and his team present the incorrect PCR test and the order for doctors to describe any comorbidity death as a Covid death '' as fraud.
The PCR test was never designed to detect pathogens and is almost 100% inaccurate at 35 cycles. All PCR tests monitored by the CDC are set at 37 to 45 cycles. The CDC acknowledges that tests over 28 cycles are not allowed for a positive reliable result.
This invalidates over 90% of the alleged Covid cases / ''infections'' detected by the use of this incorrect test.
In addition to the incorrect tests and fraudulent death certificates, the ''experimental'' vaccine itself violates Article 32 of the Geneva Convention.
Under Article 32 of the 1949 Geneva Convention, ''mutilation and medical or scientific experiments not required for the medical treatment of a protected person'' are prohibited.
According to Article 147, conducting biological experiments on protected persons is a serious breach of the Convention.
David Icke: We Must Demand Nuremberg Trials For All The 'Covid' Perpetrators
The ''experimental'' vaccine violates all 10 Nuremberg codes '' which carry the death penalty for those who try to break these international laws:1) Provides immunity to the virus
This is a ''leaky'' gene therapy that does not provide immunity to Covid and claims that they reduce the symptoms, but double-vaccinated are now 60% of patients who need ER or ICU with covid infections.
2) Protects the recipients from getting the virus
This gene therapy does not provide immunity and the double vaccine can still catch and spread the virus.
3) Reduces deaths due to viral infection
This gene therapy does not reduce deaths from the infection. Double-vaccinated people infected with Covid have also died.
4) Reduces the circulation of the virus
This gene therapy still allows the virus to spread because it gives zero immunity to the virus.
5) Reduces the transmission of the virus
This gene therapy still allows transmission of the virus because it does not confer immunity to the virus.
The following violations of the Nuremberg Code apply:
Nuremberg Code # 1: Voluntary consent is important
No person should be forced to take a medical experiment without informed consent.
Many media, political and non-medical people urge people to take the injection.
They do not provide information about the negative effects or dangers of this gene therapy. All you hear from them is '' ''safe and effective'' and ''the benefits outweigh the risks.''
Countries use blockades, coercion and threats to force people to take this vaccine or are banned from participating in free society under the mandate of a vaccine pass or Green Pass.
During the Nuremberg trials, the media were also prosecuted and members were killed for lying to the public, along with many of the doctors and Nazis found guilty of crimes against humanity.
Nuremberg Code # 2: Yields with fruitful results that cannot be produced by other means
As mentioned above, gene therapy does not meet the criteria for a vaccine and does not offer immunity to the virus. There are other medical treatments that give fruitful results against Covid, such as Ivermectin, vitamin D, vitamin C, zinc and strengthened immune system for flu and colds.
Nuremberg Code # 3: Basic experiments as a result of animal experiments and natural history disease
This gene therapy skipped animal experiments and went directly to human experiments.
In mRNA research used by Pfizer '' a candidate study on mRNA with rhesus macaques monkeys using BNT162b2 mRNA and in that study all monkeys developed pneumonia but the researchers considered the risk low because these were young healthy monkeys from 2-4 years of age.
Israel has used Pfizer and the International Court of Justice has accepted a requirement that 80% of recipients with pneumonia should be injected with this gene therapy.
Despite this alarming development, Pfizer continued to develop its mRNA for Covid, without animal testing.
Nuremberg Code # 4: Avoid all unnecessary suffering and injury
Since the launch of the experiment and listed under the CDC VAERS reporting system, over 4,000 deaths and 50,000 vaccine injuries have been reported in the United States. In the EU, more than 7,000 deaths and 365,000 vaccine injuries have been reported. This is a serious violation of this code.
Nuremberg Code # 5: No experiment should be performed if there is reason to believe that injury or death will occur
See No. 4, based on fact-based medical data, this gene therapy causes death and injury. Previous research on mRNA also shows several risks that have been ignored for this current experimental gene experiment. A 2002 study of SARS-CoV-1 nail proteins showed that they cause inflammation, immunopathology, blood clots and inhibit Angiotensin 2 expression. This experiment forces the body to produce this nail protein that inherits all these risks.
Nuremberg Code # 6: The risk should never exceed the benefit
Covid-19 has a recovery rate of 98-99%. Vaccine damage, death, and adverse side effects of mRNA gene therapy far outweigh this risk.
The use of ''leaky'' vaccines was banned for agricultural use by the US and the EU due to the Marek Chicken study which shows ''hot viruses'' and variants appear'... make the disease even more deadly.
Nevertheless, this has been ignored for human use by the CDC aware that the risk of new, more deadly variants arises from leaky vaccinations. The CDC is fully aware that the use of leaky vaccines facilitates the emergence of hotter (more deadly) strains. Yet they have ignored this when it comes to humans
Nuremberg Code # 7: Preparations must be made for even remote possibilities of injury, disability or death
No preparations were made. This gene therapy skipped animal experiments. The pharmaceutical companies' own clinical phase 3 studies will not end until 2022/2023. These vaccines were approved in an emergency
Use only action to force on a misinformed public. They are NOT FDA approved.
Nuremberg Code # 8: Experiments must be carried out by scientifically qualified persons
Politicians, the media and actors who claim that this is a safe and effective vaccine are not qualified. Propaganda is not medical science.
Many stores such as Walmart & drive-through vaccine centers are not qualified to administer experimental medical gene therapies to the uninformed public.
Nuremberg Code # 9: Everyone must have the freedom to end the experiment at any time
Despite the call from over 85,000 doctors, nurses, virologists and epidemiologists '' the experiment does not end. In fact, there are currently many attempts to change laws to enforce vaccine compliance.
This includes mandatory and mandatory vaccinations. Experimental ''sprayers'' are planned every six months without using the growing number of deaths and injuries already caused by this experiment.
These update images will be administered without any clinical trials. Hopefully, this new Nuremberg trial will put an end to this crime against humanity.
Nuremberg Code # 10: The researcher must terminate the experiment at any time if there is a probable cause for injury or death
It is clear from statistical reporting data that this experiment leads to death and injury. But not all politicians, pharmaceutical companies and so-called experts make any attempt to stop this gene therapy experiment from harming a misinformed public.
Legal proceedings are progressing, evidence has been gathered and a large growing group of experts is sounding the alarm.
WO2020060606 CRYPTOCURRENCY SYSTEM USING BODY ACTIVITY DATA
Sun, 30 May 2021 22:24
Abstract (EN)Human body activity associated with a task provided to a user may be used in a mining process of a cryptocurrency system. A server may provide a task to a device of a user which is communicatively coupled to the server. A sensor communicatively coupled to or comprised in the device of the user may sense body activity of the user. Body activity data may be generated based on the sensed body activity of the user. The cryptocurrency system communicatively coupled to the device of the user may verify if the body activity data satisfies one or more conditions set by the cryptocurrency system, and award cryptocurrency to the user whose body activity data is verified.
(FR)L'activit(C) du corps humain associ(C)e une tche fournie un utilisateur peut ªtre utilis(C)e dans un processus de minage d'un syst¨me de cryptomonnaie. Un serveur peut fournir une tche un dispositif d'un utilisateur qui est coupl(C) de mani¨re communiquer avec le serveur. Un capteur coupl(C) de mani¨re communiquer avec un dispositif de l'utilisateur ou compris dans ce dernier peut d(C)tecter l'activit(C) corporelle de l'utilisateur. Des donn(C)es d'activit(C) corporelle peuvent ªtre g(C)n(C)r(C)es sur la base de l'activit(C) corporelle d(C)tect(C)e de l'utilisateur. Le syst¨me de cryptomonnaie de la pr(C)sente invention coupl(C) de mani¨re communiquer avec le dispositif de l'utilisateur peut v(C)rifier si les donn(C)es d'activit(C) corporelle satisfont une ou plusieurs conditions d(C)finies par le syst¨me de cryptomonnaie, et attribuer une cryptomonnaie l'utilisateur dont les donn(C)es d'activit(C) corporelle sont v(C)rifi(C)es.
Will Covid-19 Vaccination Disqualify You From Life Insurance? Here Are The Claims
Sun, 30 May 2021 22:19
Posts on social media are now claiming that receiving the Covid-19 vaccine will jeopardize your life ... [+] insurance benefits because the vaccines are "experimental," even though they have already received emergency use authorization from the U.S. Food and Drug Administration. (Photo by JOSEPH PREZIOSO/AFP via Getty Images)
AFP via Getty ImagesWhat does getting a Covid-19 vaccine have to do with life insurance?
Well, neither rhymes with the word ''porcupine.'' But some on social media are claiming another link between the two: that receiving a Covid-19 vaccination may actually prevent you from receiving life insurance coverage.
Wait how could this possibly be? Aren't the vaccines supposed to supposed to save lives by preventing deaths from Covid-19 coronavirus infections? Wouldn't this be a good thing for life insurance companies? Don't life insurance companies want you to live in the same way that auto insurance companies don't want you to drive your car into the ocean? Why then are there posts on social media like the tweet that said, ''Insurance company's won't pay out on life insurance if you die from the covid vaccine.......what does that tell ya'' from @snowdevil8:
Keep in mind that many such tweets happen to be from fairly anonymous Twitter accounts. For example, @snowdevil8 has on its bio is ''Snow Geese and Divers yes please, Die hard #MnTwins fan #Trump2020 #MAGA.'' So perhaps the only way to tell who this may be is to go around asking people, ''do you like snow geese, divers, and Donald Trump, not necessarily in that order? Oh, and who's your favorite baseball team?''
The ''explanation'' being provided by some social media posts is that the Covid-19 vaccines are supposedly ''experimental.'' For example, there's the tweet that said, ''just so you are aware many have died from the covid vaccine, and if you have life insurance you cannot collect it, because the vaccine is deemed experimental, therefore you are not covered if you die from the vaccine #covidscam #insurance #scam #vaccineskill #fooledyou,'' from @canolivemusic:
As you can see, this tweet was a bit like a non-alcoholic drink: it didn't really offer any proof. Making statements like ''many have died from the covid vaccine'' without offering actual numbers and supporting evidence would be a bit like saying, ''many have died from snow geese and the Minnesota Twins,'' or perhaps, ''many have died from snow geese who are Minnesota Twins,'' without further clarification. That would be a somewhat fowl and foul statement.
In fact, there have been enough such tweets and posts on other social media platforms like Parler to prompt the Canadian Life and Health Insurance Association (CLHIA) to issue a statement that included the following line: ''Contrary to misinformation being shared on-line, receiving a Covid-19 vaccine will have no effect on the ability to obtain coverage or benefits from life insurance or supplementary health insurance.'' The statement continued by saying that ''Canada's life and health insurers stress that vaccination is one of the most effective ways to protect yourself and others from serious illness and death from Covid-19.''
The US Food and Drug Administration (FDA) has issued emergency use authorizations to three Covid-19 ... [+] vaccines. (Photo by BRENDAN SMIALOWSKI/AFP via Getty Images)
AFP via Getty ImagesIf you are receiving the Pfizer/BioNTech, Moderna, or Johnson & Johnson Covid-19 vaccines, you are not receiving what's still considered by the U.S. Food and Drug Administration (FDA) to be an ''experimental'' vaccine. Instead, you are receiving a vaccine that has already earned emergency use authorization (EUA) from the FDA. That means that the FDA has reviewed the pre-clinical and clinical trial data on these vaccines and determined that the benefits of the vaccines significantly outweigh any risks and unknowns about the vaccines.
Of course, all of this doesn't mean that there aren't Covid-19 vaccines out there that are still at the ''experimental'' or ''investigational'' stage. There are also plenty of scams out there. Therefore, be careful should someone offer you something called ''shhhh, this is a Covid-19 vaccine'' or ''the special super duper tiara vaccine'' or the ''hey-this-is-still-a-experimental-vaccine-vaccine.'' Make sure that you know the type of vaccine that you are getting and that it's at a legitimate vaccination location. Proper locations shouldn't be offering you a combination vaccination, waxing, and decaf latte deal.
This certainly isn't the first time social media posts have offered misinformation and disinformation about vaccines. Tying an available vaccine with life insurance benefits may be a relatively new one though. It's not clear how many of the social media posts are from actual human beings versus bots or what the actual sources and their agendas may be. There are many reasons why some person or some bot may spread Covid-19 vaccine misinformation, ranging from inadvertently passing something along to ''let's try to decrease confidence in the government or health care so that you can listen to us instead,'' whoever us may be. Listening to a social media post from someone who is not a real expert can be akin to walking on the sidewalk and getting advice from trash cans.
If you are still worried that the Covid-19 vaccine will somehow jeopardize your life insurance, here's an idea. Try calling your insurance company directly or maybe even several insurance companies. Ask them if getting the vaccine will affect your life insurance coverage in any way. Or contact an insurance expert. Look for someone who has real credentials and puts more on his, her, or its profile than just something related to fowl and foul balls.
Full coverage and live updates on the Coronavirus
Nobel Prize Winner Warns Vaccines Facilitate Development of Deadlier COVID Variants, Urges Public to Reject Jabs - The New American
Sun, 30 May 2021 21:19
France's Luc Montagnier / AP ImagesLuc Montagnier, a French virologist and recipient of the 2008 Nobel Prize in Medicine for his discovery of the human immunodeficiency virus (HIV), has recently exposed the dangers of the COVID-19 vaccines. Montagnier discussed the issue in an interview with Pierre Barn(C)rias of Hold-Up Media earlier this month, which was exclusively translated from French into English for RAIR Foundation USA.
The vaccines don't stop the virus, argues the prominent virologist, they do the opposite '-- they ''feed the virus,'' and facilitate its development into stronger and more transmittable variants. These new virus variants will be more resistant to vaccination and may cause more health implications than their ''original'' versions.
During the interview, professor Montagnier referred to the vaccine program for the coronavirus as an ''unacceptable mistake.'' Mass vaccinations are a ''scientific error as well as a medical error,'' he said. ''The history books will show that, because it is the vaccination that is creating the variants.'' Montagnier explained that ''there are antibodies, created by the vaccine,'' forcing the virus to ''find another solution'' or die. This is where the variants are created. It is the variants that ''are a production and result from the vaccination.''
Montagnier details that the mutation and strengthening of the virus occurs owing to the phenomenon known as Antibody Dependent Enhancement (ADE). ADE is a mechanism that increases the ability of a virus to enter cells and cause a worsening of the disease. ADE occurs when the antibodies generated during an immune response recognize and bind to a pathogen, but they are unable to prevent infection. Instead, these antibodies act as a ''Trojan horse,'' allowing the pathogen to get into cells and exacerbate the immune response.
In America, routinely recommended vaccines do not cause ADE. If they did, they would be removed from circulation. Phase III clinical trials of new vaccines are designed to uncover frequent or severe side effects before the vaccine is approved for use. Typically, it takes 2-4 years to assess whether a vaccine is safe, but with COVID-19 vaccines, manufacturers are spending around six months or less for testing.
According to the Cambridge University, ADE occurs in SARS-CoV-1, MERS, HIV, Zika, and Dengue virus infection and vaccination.
Data from around the world confirms ADE occurs in SARS-CoV-2, which causes COVID-19, says Montagnier. ''You see it in each country, it's the same: the curve of vaccination is followed by the curve of deaths. I'm following this closely and I am doing experiments at the Institute with patients who became sick with Corona after being vaccinated.''
In a medical documentary Hold Up: Return of the Chaos, released in France on November 11, 2020, Montagnier rejected the then-upcoming vaccine against COVID, saying he will not be vaccinated. ''My conscience tells me not to,'' he said. Montagnier also addressed his French colleagues, urging them ''to uphold their [medical] titles as doctors, not as the sheep.''
The movie discusses the origins of the virus, criticizes harmful and irrational mask mandates as well as lockdowns, quarantines, abuses of government overreach, and explores effective COVID treatments such as hydroxychloroquine. The video was banned on YouTube, possibly because the creators imply the World Economic Forum used the pandemic to establish world dominance as a part of a global plan that is known as the Great Reset.
Montagnier has been a vocal critic of the mass vaccination campaign. In a letter to the President and Judges of the Supreme Court of the State of Israel, which unrolled the world's speediest and the most massive vaccination campaign, Montagnier urged for its suspension:
''I would like to summarize the potential dangers of these vaccines in a mass vaccination policy.
1. Short-term side effects: these are not the normal local reactions found for any vaccination, but serious reactions involve the life of the recipient such as anaphylactic shock linked to a component of the vaccine mixture, or severe allergies or an autoimmune reaction up to cell aplasia.
2. Lack of vaccine protection:
2.1 Induction of facilitating antibodies '' the induced antibodies do not neutralize a viral infection, but on the contrary facilitate it depending on the recipient. The latter may have already been exposed to the virus asymptomatically. A low level of naturally induced antibodies may compete with the antibodies induced by the vaccine.
2.2 The production of antibodies induced by vaccination in a population highly exposed to the virus will lead to the selection of variants resistant to these antibodies. These variants can be more virulent or more transmissible. This is what we are seeing now. An endless virus-vaccine race that will always turn to the advantage for the virus.
3. Long-term effects: Contrary to the claims of the manufacturers of messenger RNA vaccines, there is a risk of integration of viral RNA into the human genome. Indeed, each of our cells has endogenous retroviruses with the ability to reverse transcriptase from RNA into DNA. Although this is a rare event, its passage through the DNA of germ cells and its transmission to future generations cannot be excluded.
''Faced with an unpredictable future, it is better to abstain.''
Earlier last year, Montagnier presented a powerful case proving that SARS-CoV2 could only be a genetically engineered coronavirus, therefore the vaccine strategy should be based on that fact.
As reported by French Soir, in his television interview of April 17, 2020, Montagnier drew attention to the presence of at least half a dozen mini-sequences of the HIV virus grouped together in a short segment of the SARS-Cov2 genome. This observation was published by the mathematician Jean-Claude Perez in February 2020 under the title ''Synthetic origin of Covid-19 and Evolution.'' These mini-sequences, researchers believe, could be exogenous information elements (EIA), that is, they can have genetic significance. They assert that this unmistakable presence of concentrated EIAs, in relation to HIV but also with the Yoeli Plasmodium parasite, the agent responsible for malaria, would not be natural and therefore would require an adequate strategy to develop a safe and effective vaccine. Montagnier and Perez explain the scientific challenges and complexity to develop vaccines against HIV and malaria, both of which still have no vaccines to combat infection.
Montagnier argues the coronavirus had escaped in an ''industrial accident,'' while Chinese scientists at the Wuhan city laboratory were trying to develop a vaccine against HIV.
Back in April 2020, Montagnier urged people to refuse vaccines against COVID-19 when they become available, because ''instead of preventing the infection, they [would] accelerate infection.'' Today, the newly occurring variants of SARS-CoV-2 that affect vaccinated people prove his thesis. In this case, mass vaccination may cause a new, more deadly wave of pandemic.
The same thesis is shared by the Belgium virologist Vanden Bossche, who is also calling for a halt to the mass-vaccination programs. He believes that if the jabs are not halted, they could lead to the evolution of stronger and stronger variants of the virus until a ''supervirus'' takes hold and wipes out huge numbers of people.
Biden's $6T budget includes multimillion-dollar transportation projects in Austin | kvue.com
Sun, 30 May 2021 20:22
The projects are among 25 rail, BRT and streetcar projects in 12 states recommended to receive a share of $2.5 billion in competitive funding.
AUSTIN, Texas '-- On Friday, U.S. Transportation Secretary Pete Buttigieg announced President Joe Biden's 2022 budget includes $36.1 million for the construction of two new Bus Rapid Transit projects in Austin.
According to the U.S Department of Transportation, the projects are among 25 rail, BRT and streetcar projects in 12 states recommended to receive a share of $2.5 billion in competitive funding through the Federal Transit Administration's Capital Investment Grant program.
''Across the country, communities are seeking to expand public transit as a way to create economic opportunity, improve safety, advance equity, reduce congestion and pollution, and lower the cost of living for their residents,'' said Buttigieg. ''These capital projects will improve life in 25 communities and are the start of what we hope will be a once-in-a-generation investment to modernize and expand public transit across the country.''
The first recommended BRT project in Austin is a 12-mile, 23-station corridor-based BRT between Downtown Austin and the Exposition Center in northeast Austin worth $17.81 million. Transit along this corridor will be by 10 40-foot electric buses and four 60-foot articulated electric buses.
The second project in Austin, a 14-mile, 19-station corridor-based BRT along Pleasant Valley Road between northeast Austin and southeast Austin, is worth $18.28 million. Transit along this BRT will include 12 40-foot electric buses and four 60-foot articulated electric buses.
Both projects will include near-level boarding stations with platforms, shelters, shade panels, benches, solar lighting, off-vehicle fare collection and mobile ticket validators.
According to the U.S Department of Transportation, these projects will create hundreds of construction and operations-related jobs and help communities in Austin expand transportation options to improve access and mobility for residents.
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Apple's M1 Chip Has a Fascinating Flaw | WIRED
Sun, 30 May 2021 20:19
Apple's new M1 CPU has a flaw that creates a covert channel that two or more malicious apps'--already installed'--can use to transmit information to each other, a developer has found.
Ars Technica
This story originally appeared on Ars Technica, a trusted source for technology news, tech policy analysis, reviews, and more. Ars is owned by WIRED's parent company, Cond(C) Nast.
The surreptitious communication can occur without using computer memory, sockets, files, or any other operating system feature, developer Hector Martin said. The channel can bridge processes running as different users and under different privilege levels. These characteristics allow for the apps to exchange data in a way that can't be detected'--or at least without specialized equipment.
Martin said that the flaw is mainly harmless because it can't be used to infect a Mac and it can't be used by exploits or malware to steal or tamper with data stored on a machine. Rather, the flaw can be abused only by two or more malicious apps that have already been installed on a Mac through means unrelated to the M1 flaw.
Still, the bug, which Martin calls M1racles, meets the technical definition of a vulnerability. As such, it has come with its own vulnerability designation: CVE-2021-30747.
"It violates the OS security model," Martin explained in a post published Wednesday. "You're not supposed to be able to send data from one process to another secretly. And even if harmless in this case, you're not supposed to be able to write to random CPU system registers from userspace either."
Other researchers with expertise in CPU and other silicon-based security agreed with that assessment.
"The discovered bug cannot be used to infer information about any application on the system," said Michael Schwartz, one of the researchers who helped discover the more serious Meltdown and Spectre vulnerabilities in Intel, AMD, and ARM CPUs. "It can only be used as a communication channel between two colluding (malicious) applications."
He went on to elaborate:
The vulnerability is similar to an anonymous "post office box", it allows the two applications to send messages to each other. This is more or less invisible to other applications, and there is no efficient way to prevent it. However, as no other application is using this "post office box", no data or metadata of other applications is leaking. So there is the limitation, that it can only be used as a communication channel between two applications running on macOS. However, there are already so many ways for applications to communicate (files, pipes, sockets, ...), that one more channel doesn't really impact the security negatively. Still, it is a bug that can be abused as an unintended communication channel, so I think it is fair to call it a vulnerability.
A covert channel might be of more consequence on iPhones, Martin said, because it could be used to bypass sandboxing that's built into iOS apps. Under normal conditions, a malicious keyboard app has no means to leak key presses because such apps have no access to the Internet. The covert channel could circumvent this protection by passing the key presses to another malicious app, which in turn would send it over the Internet.
Even then, the chances that two apps would pass Apple's review process and then get installed on a target's device are farfetched.
The flaw stems from a per-cluster system register in ARM CPUs that's accessible by EL0, a mode that's reserved for user applications and hence has limited system privileges. The register contains two bits that can be read or written to. This creates the covert channel, since the register can be accessed simultaneously by all cores in the cluster.
Martin wrote:
A malicious pair of cooperating processes may build a robust channel out of this two-bit state, by using a clock-and-data protocol (e.g., one side writes 1x to send data, the other side writes 00 to request the next bit). This allows the processes to exchange an arbitrary amount of data, bound only by CPU overhead. CPU core affinity APIs can be used to ensure that both processes are scheduled on the same CPU core cluster. A PoC demonstrating this approach to achieve high-speed, robust data transfer is available here. This approach, without much optimization, can achieve transfer rates of over 1MB/s (less with data redundancy).
Occult Fan on Twitter: "Kirk, add this to your Op Depop. https://t.co/GMPNPReAX9 and this Rudolph Steiner quote: @adamcurry @darkjournalist @mysticinthemoon @WatcherPlanet https://t.co/70MvFFUDjK" / Twitter
Sun, 30 May 2021 20:11
Occult Fan : Kirk, add this to your Op Depop.https://t.co/GMPNPReAX9and this Rudolph Steiner quote:@adamcurry'... https://t.co/wvUdVLFgZa
Sun May 30 17:00:14 +0000 2021
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Wed, 02 Jun 2021 00:00
By Bill Galluccio
June 1, 2021
Moderna has started the process of applying for full FDA approval for its COVID-19 vaccine for people over the age of 18. The drug company will continue to submit trial data to the FDA on a rolling basis over the next several weeks as it waits for the agency to conduct a priority review. The review is expected to take about six months.
"We are pleased to announce this important step in the U.S. regulatory process for a Biologics License Application (BLA) of our COVID-19 vaccine," Moderna CEO St(C)phane Bancel said in a statement. "We look forward to working with the FDA and will continue to submit data from our Phase 3 study and complete the rolling submission."
Moderna said that after two doses, its vaccine is 90% effective at protecting against COVID-19 and more than 95% effective against severe disease for up to six months.
As of June 1, over 124 million doses of Moderna's vaccine have been administered in the United States.
Getting full approval for its vaccine will allow Moderna to continue to market the shot once the pandemic has come to an end. Currently, all three vaccines in the U.S. are being distributed under an emergency use authorization.
Moderna is the second company to apply for a biologics license for its coronavirus vaccine. Pfizer requested full approval for its vaccine last month for people over the age of 16.
Both companies are testing their vaccines in adolescents and children as young as six months.
Photo: Getty Images
Chat About Moderna Applies For Full FDA Approval For Its COVID-19 Vaccine
Canada says it's OK to mix coronavirus vaccine brands - CNN
Tue, 01 Jun 2021 23:58
Ottawa (CNN)Canada has changed its guidelines on mixing doses of Covid-19 vaccines, the country's health agency said Tuesday, and Canadians may get a different type of vaccine for their second shot.
The Public Health Agency of Canada said people who received an AstraZeneca vaccine for the first dose may get either a Pfizer or Moderna vaccine for the second dose. People who received
one of the two mRNA vaccines -- Pfizer's or Moderna's -- may get either of the two brands for the second dose.
It is still optimal, however, to use the same brand of vaccine for
both doses, the country's top doctor said.
"Try and find the same vaccine, the same mRNA vaccine -- but if you can't, for some reason, then consider them interchangeable," Dr. Theresa Tam, Canada's chief public health officer, told a news briefing. "This advice provides provinces and territories with safe and effective options to manage the vaccine programs."
After a slow start, Canada has been vaccinating nearly 1% of its population each day, on average, for the past few weeks.
Supply remains an issue, however, with the Moderna and AstraZeneca vaccines.
Canada's National Advisory Committee on Immunization (NACI) now says people who received a first dose of
the AstraZeneca vaccine may receive a second dose of either AstraZeneca or an mRNA vaccine. It does not recommend that people who got either the Pfizer or Moderna vaccine for the first dose get the AstraZeneca vaccine, which uses a different technology, for the second dose.
The advisory committee says Canadians who received a first dose of an mRNA vaccine, either Pfizer or Moderna, can receive the other mRNA vaccine for their second dose if the same mRNA vaccine "is not readily available."
"NACI has worked to quickly adapt this guidance on the use of Covid-19 vaccines in Canada to ensure optimal protection of Canadians at pace with the ever-changing circumstances during this pandemic," said Tam.
According to Canadian data, as of the last week of May, 13 million Canadians had received at least one dose of the Pfizer vaccine, while 3.5 million had received the Moderna vaccine and nearly 2 million had received the AstraZeneca vaccine.
CNN's Jacqueline Howard contributed to this report.
For Six Trillion Dollars, We're Not Even Getting Universal Health Care?
Tue, 01 Jun 2021 23:53
News This is the second of a series from The Western Journal that will examine in depth some of the big-ticket items the president and Congress are proposing for the 2022 budget, which would be the largest increase since World War II.
On Friday, President Joe Biden submitted his fiscal year 2022 budget request to Congress. Weighing in at an eye-popping $6 trillion, Biden's budget is $1.2 trillion more than the record-setting one submitted by President Donald Trump last year.
One of the big line items of the budget is getting a lot of attention, not for what it contains, but for what is missing '-- health care.
The U.S. spent $1.2 trillion combined for Medicare and Medicaid last year, and The Lancet medical journal estimates a total cost for Medicare for all would be approximately $3 trillion annually.
If the president and Democrats in Congress truly wanted universal health care, now would be the time to enact it. Instead of rolling out health care for all, Biden chose to increase nearly every non-defense-related aspect of the budget.
Taxes Going UpBiden's budget called for corporate tax rates to increase from 21 to 28 percent, and the top tier capital gains tax rate would jump from 28 to 43.4 percent. The amount companies pay around the world averages 23.85 percent. Making it more expensive to do business domestically will certainly not help the retaining jobs on American soil.
And, The Wall Street Journal pointed out that increases to the capital gains tax rate would be applied retroactively '-- in late April. This means that individuals who made trades on the stock market with the assumption that they would be charged 28 percent will now be on the hook for nearly half of their gains.
More for Health Care, but Not Where It CountsShould America have Medicare for all?
Yes: 57% (4 Votes)
No: 43% (3 Votes)
The Centers for Disease Control and Health and Human Services will see major bumps, with $25 billion more for HHS '-- a total of $132 billion. The CDC will see the biggest bump in 20 years, with a total of $8.7 billion.
But universal health care is nowhere in the budget. U.S. Centers for Medicare & Medicaid Services estimated that in 2019, America spent $3.8 trillion or $11,582 per person for health care.
If we are already spending $3.8 trillion on private health care, and the Lancet number of $3 trillion is accurate, why not just make the switch right now?
It sounds like Biden is not the Democrat many voters were hoping for.
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SummaryMore Biographical Information Recent Posts ContactEric Nanneman is a business and technology writer with more than 20 years of investment and banking experience, including stints at Bank of America, Charles Schwab, and Goldwater Bank. He was previously securities registered, holding the Series 7, 63, 9 and 10 FINRA licenses.
Eric Nanneman is a business and technology writer with more than 20 years of investment and banking experience, including stints at Bank of America, Charles Schwab, and Goldwater Bank. He was previously securities registered, holding the Series 7, 63, 9 and 10 FINRA licenses.He graduated from Arizona State and the Pontifical College Josephinum with degrees in English and philosophy. He has one adult son and resides in Phoenix.
Formally ends 'Remain in Mexico' immigration policy...
Tue, 01 Jun 2021 23:53
The Biden administration on Tuesday formally nixed the "Remain in Mexico" program, the latest in a series of moves to dismantle the Trump administration's restrictive immigration policies.
The program, known formally as the Migrant Protection Protocols (MPP), was a cornerstone of Trump's border management policy; it forced potential asylum seekers to stay in Mexico to wait out the result of their case in U.S. immigration court.
In a memo ending the program Tuesday, Homeland Security Alejandro Mayorkas Alejandro MayorkasTSA screens 2 million travelers heading into Memorial Day weekend Biden aims to speed review for families seeking asylum in US Mayorkas says TSA ready for Memorial Day travel: 'People will see lines' MORE said the MPP did not help with enhancing the border management.
The move was first reported by Reuters.
President Biden Joe BidenBill that would mandate Asian-American history lessons in Illinois schools heads to governor's desk Five things to know about the new spotlight on UFOs Biden shows little desire to reverse Trump's Cuba policies MORE paused MPP shortly after taking office on Jan. 20, and has allowed into the country around 11,000 people who were in the program according to Reuters.
The formal end of MPP comes days after the Department of Homeland Security officially banned family separations for prosecutions of illegal border crossings, another Trump administration policy designed to slow the asylum process.
Rep. Bennie Thompson Bennie Gordon ThompsonNew Russian hacks spark calls for tougher Biden actions Democrats plot next move after GOP sinks Jan. 6 probe GOP gambles with Pelosi in opposing Jan. 6 commission MORE (D-Miss.), chairman of the House Committee on Homeland Security, and Rep. Nanette Diaz Barragn (D-Calif), chairwoman of the Homeland Security subcommittee on Border Security, Facilitation, and Operations, released a joint statement Tuesday applauding the announcement.
"This policy was a stain on our nation's history and our longstanding tradition of protecting refugees and asylum seekers," Thompson and Barragn wrote.
''Despite Republican efforts to misrepresent U.S. asylum law and smear those fleeing violence and seeking asylum, we must remember that it is completely legal to come to the U.S. border and seek asylum. While the process has been underway to dismantle MPP and bring asylum seekers in the country, more still needs to be done to help those hurt by the policy and we look forward to working with the Administration on those efforts. We must ensure we have a just and humane asylum processing system,'' they added.
Biden has faced criticism over his immigration policies from both the right and left, from one end for discontinuing Trump's restrictive approach and from the other for not moving quickly enough to dismantle it.But the administration has sped up the pace of reform, drawing praise for moves like the end of MPP, family separations and providing safe haven to Haitian immigrants in the United States.
''This is a huge victory. The forced return policy was cruel, depraved, and illegal, and we are glad that it has finally been rescinded," said Judy Rabinovitz, an attorney for the ACLU who led the organization's legal challenge against MPP.
Still advocates for a return to broad application of asylum law say obstacles remain, including a measure known as Title 42, which allows U.S. border officials to quickly expel anyone crossing the border without authorization '-- including potential asylum seekers '-- under the guise of protecting from the spread of COVID-19."The administration must follow through on this announcement by ensuring that everyone who has been subjected to this policy can now pursue their asylum cases in the United States, in safety and without additional trauma or delay. And it must swiftly move to dismantle the Trump administration's other attacks on the asylum system, including the unconscionable 'Title 42' order,'' said Rabinovitz in a statement.
'--Updated at 5:18 p.m.

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ABC GMA - anchor Ian Pannell - vietnams capital enters lockdown after new variant found (43sec).mp3
ABC Jon Karl explains media's response to lab theory.mp3
Acting premier Victoria finally speaks the truth - The vaccine is our Enemy Gaffe.mp3
amazon streaming MPR.mp3
Bank of America eDD Story KGO.mp3
Biden speech - sprint to get more vaccinated by 4th of July (2min11sec).mp3
Boston Red Sox first pitch thrown out by Dr. Rochelle Walensky -announcement from stadium (37sec).mp3
Bret Weinstein on forbidden treatments.mp3
California report gas prices.mp3
CBS Face the Nation - anchor John Dickerson - Dr. Scott Gottlieb (1) wuhan -title of new book- important to find out for security (1min35sec).mp3
CBS Face the Nation - anchor John Dickerson - Dr. Scott Gottlieb (2) wuhan -do the chinese know the answer (36sec).mp3
CLIMATE Shell lawsuit 2.mp3
CLIMATE Shell lawsuit HAH NPR.mp3
concerts vaccine passport red book.mp3
COVID YEadon 2.mp3
COVID YEadon One.mp3
Dr McCullough on Spike Proteins and Furin Cleavage was Gain of function research.mp3
Dr Michael Yeadon - Variants are bullcrap.mp3
Israel update.mp3
Judge Janine - Virus vaccine gaffe.mp3
Kick their Balls ISO.mp3
Klaus Again with Cyber Pandemic.mp3
Klaus Schwab ESG (CARBON) and a New Mindset for Climate.mp3
Leon Black will retire as CEO of Apollo Global Management.mp3
Matt Hancock Sec State and soc welfare UK - Deny the vaccine spread.mp3
meat packing hack 2.mp3
meat packing hack NPR.mp3
My pleasure ISO.mp3
Naomi Osaka withdrew from the French Open on Monday.mp3
NASA Venus Ask Adam.mp3
NBC Meet the Press - anchor Chuck Todd - Dr. Peter Hotez (1) introduction -credentials (9sec).mp3
NBC Meet the Press - anchor Chuck Todd - Dr. Peter Hotez (2) wuhan -how important is it to know the origin of covid (2min01sec).mp3
NBC Meet the Press - anchor Chuck Todd - Dr. Peter Hotez (3) wuhan -can we do this without china cooperation (1min07sec).mp3
New anti-biden Trump political ad.mp3
NFL Race Norming.mp3
NPR Ads.mp3
NTD - Parents and doctors suing HHS over children shot.mp3
NY AG James asks court to force Kodak CEO to testify on insider trading investigation.mp3
Oklahoma State University educator's statements at a virtual conference of educators.mp3
RFKJ Whitney bess 2.mp3
RFKJ Whitney bess 3.mp3
RFKJ Whitney bess 4.mp3
RFKJ Whitney bess 5.mp3
RFKJ Whitney bess 6.mp3
RFKJ Whitney bess One.mp3
RFKJ Whitney kicker.mp3
Sackler Family scam 2.mp3
Sackler Family scam NPR.mp3
Seattle Police quitting NTD.mp3
Sky News Vaccine messe with gaffe.mp3
SOuthern Australia Chief Health Officer - DOn't touch the ball.mp3
the-vaccine-is-our-enemy.mp3
Trillion dollar infrastructure wrap.mp3
Trudeau all jiddy about getting his shot.mp3
TV Commercial -Johnson & Johnson HIV Exploratory Vaccine Featuring Billy Porter (56sec).mp3
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