Rhiza Labs FluTracker Forum

I crawled out from under the bed. Is it safe to come out!!!!!

And blow me down a man made super death virus.

Geez that flu just keeps on Rollin year after year after year.

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Download references
http://www.nature.com/nature/journal/va ... references

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CDC published a transmitting man made virus (Egypt egret) last year in Virology.

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In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity
Li-Mei Chena, 1,
Ola Blixtb, d, 1, 2,
James Stevensa, c,
Aleksandr S. Lipatova,
Charles T. Davisa,
Brian E. Collinsb, d,
Nancy J. Coxa,
James C. Paulsonb, d, 1,
Ruben O. Donisa, , 1,
a Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, United States
b Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States
c Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States
d Glycan Array Synthesis Core-D, Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States
Received 27 August 2011. Revised 26 September 2011. Accepted 10 October 2011. Available online 5 November 2011.
http://dx.doi.org/10.1016/j.virol.2011.10.006, How to Cite or Link Using DOI

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Commentary

http://www.recombinomics.com/News/05031 ... DC_MM.html

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Suppressed data on mutant H5N1 human-killer virus PUBLISHED

Information wants to be free
By Adam Smith • Get more from this author

Posted in Biology, 3rd May 2012 16:01 GMT
Strains of bird flu that could spread among humans have been created in the lab - and now full details on just how this was done have been published openly, raising fears that the research could be used by terrorists to craft a deadly bio-weapon plague.

Bird flu, or H5N1, has killed more than half of the 600 people it is known to have infected, but it cannot spread easily between people. So Yoshihiro Kawaoka of the University of Wisconsin-Madison set out to find whether H5N1 could evolve in the wild into a form that was transmissible between humans.


Kawaoka’s FBI-approved team first created thousands of mutant versions of H5N1. From these they identified a version that could stick to cells in the human nose and throat and then combined this with the strain from the wild that caused the 2009 pandemic. With this hybrid virus, the scientists infected ferrets and watched for when the virus evolved a strain that could spread through the air and infect healthy ferrets in neighbouring cages.

According to Kawaoka, the study shows that relatively few mutations are required for the virus to acquire the ability to transmit between mammals, including humans. The strain created during Kawaoka’s research is less severe than the one that caused the 2009 pandemic, it is susceptible to Tamiflu and it did not kill any of the ferrets in the experiments.

But there may be further strains not studied that have the ability to evolve transmissibility. In fact, the researchers have already spotted strains with one of the mutations they identified in Egypt. As Laurence Fishburne’s character in Contagion says: “Someone doesn’t need to weaponise the bird flu. The birds are doing that.”

Kawoaka is less dramatic, claiming that the results can help authorities to prevent or prepare for an outbreak.

"This study has significant public health benefits and contributes to our understanding of this important pathogen,” he said. “By identifying mutations that facilitate transmission among mammals, those whose job it is to monitor viruses circulating in nature can look for these mutations so measures can be taken to effectively protect human health."

It is an argument made repeatedly over the past few months by Kawoaka and his colleague Ron Fouchier, a researcher at the Erasmus Medical Center in Rotterdam and author of another blocked bird flu paper. Although Kawaoka’s research is now published, Fouchier’s remains under wraps, even though Science magazine has said it will publish the work. The concerns over the researchers’ studies came from the US National Science Advisory Board for Biosecurity (NSABB).

The body’s decision to block the research kickstarted months of tense discussion between virologists, security experts and journal editors. Last month, the NSABB reversed its controversial decision after Kawaoka and Fouchier amended their papers. “The revised papers had more clarity on risks and benefits,” said the NSABB’s Paul Keim, who added that the board comprises scientists, not “generals and colonels and majors”.

Fouchier admitted at an emergency conference convened in April to discuss the controversy, that most of the extra 1000 words he added to his paper dealt with the level of biosecurity in place during the research.

The Dutch virologist explained that due to the biosecurity conditions in place, if an accident were to happen, “the public won’t be exposed, but the individuals in the laboratory will be”.

http://www.theregister.co.uk/2012/05/03 ... published/

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Formerly Banned Bird Flu Studies Suggests Pandemic

The virus could potentially mutate and spread widely among people.Thu May 3, 2012 11:41 AM ET
Content provided by Jesse Emspak, LiveScience Contributor

THE GIST
Research in the studies detailed how the H5N1 avian (bird) flu virus can morph.
The morphing comes with the possibility that it could spread from person to person.
Debate flared as to whether they should be published at all.

Bird flu can be transmitted between mammals — and possible humans — needing only four mutations to do so, a new study published this week in the journal Nature suggests. But the mutant virus is not deadly, and the work could show virologists how to combat others like it.

The research, by Yoshihiro Kawaoka, professor of virology at the University of Wisconsin-Madison, is one of two studies that already made headlines when bits of the results were made public. That's because the studies outline how to make a more easily transmissible — and deadly — version of H5N1, or avian flu. The other paper, by Ron Fouchier, of the Erasmus Medical Center in the Netherlands, also described a method of breeding a virulent and transmissible flu in ferrets.

NEWS: Chickens Modified to Not Spread Bird Flu

Debate flared as to whether either study should be published at all, because of fears that a terrorist group or hostile government could use it to make biological weapons. This kind of research is classified as "dual use," much like that involving nuclear material. In the end, the National Science Advisory Board on Biosecurity (NSABB), which advises the government on publicly financed research, decided to allow the publication of Kawaoka's work. In the Netherlands, Fouchier was granted an export license, allowing him to submit the work to the journal Science. Fouchier, however, had previously said he would go ahead with publication regardless of a license. [Inside the H5N1 Debate]

What's in H5N1?

Full details of the experiments hadn't been made public until now. On seeing the actual paper, Vincent Racaniello, a professor of microbiology and immunology at Columbia University, called it "a significant piece of work."

NEWS: How Bird Flu Works

"After waiting to read it for so long, it was like eating again after fasting," Racaniello wrote in an email to LiveScience.

Kawaoka was able to create a hybrid flu virus that is transmitted via respiratory droplets, meaning it can spread through the fluid a person (or in this case, a ferret) sneezes out or coughs up. [10 Deadly Diseases That Hopped Across Species]

Two key factors made the virus transmissable. One involved a protein called haemagglutinin, or HA, which is what gives H5N1 its name; the number 5 says what type of haemagglutinin it is. The other involved combining the genes from the H5N1 virus with that of another called H1N1, or swine flu, which caused a pandemic in 2009 in Asia.

The HA protein only connects to a molecule called alpha 2,3 linked sialic acid. Birds carry that receptor in their respiratory and digestive tracts. Humans and other mammals also have it, but it is deeper in the lungs and harder for the virus to reach. Flu viruses like H1N1 that infect humans link to a receptor called alpha 2,6 linked sialic acid, which resides in mammals' respiratory systems.

So the first thing was to change the HA protein into something that would bind to the molecules in a mammalian respiratory tract. To do that, Kawaoka and his team introduced random changes in the "head" of the HA molecule, and looked for ones that would bind to alpha 2,6.

NEWS: Bird Flu Survives in Landfills

Once they found those, they created a hybrid H5N1/H1N1 flu virus, using genes from H1N1. The result was an H5N1 (strictly speaking, it is an H5 HA/ H1N1) with genes that coded for that altered HA protein.

The next step was infecting ferrets, which acted as a stand-in for mammals, including humans. More changes happened in the viral gene as it reproduced in the ferrets. That was expected, as viral RNA often gets altered as it infects a host's cells.



Four little mutations

It turned out the new H5N1 did not transmit well between ferrets, that is, until four key changes had occurred in the HA protein. Three of those changes allowed the virus to live in the ferret's bodies, but it was the fourth — an amino acid called T318I — that kept the HA protein stable so that the virus would bind to the ferret's cells long enough to reproduce and live in the droplets that get spread whenever a ferret sneezes.

While that may sound scary, the virus had other surprises. For instance, the H5N1 hybrid wasn't very deadly; Kawaoka noted in his paper that none of the ferrets died. The researchers also tested an H5N1 vaccine against the virus and found that it was effective, as was Tamiflu.

Racaniello noted that Kawaoka's discovery shows the importance of the stability of HA in transmitting the virus between animals. The results also revealed which genes are important in making an airborne virus, and that the mutations that made the virus bind to animal cells actually made HA less stable until another amino acid, far from the site where the binding happens, changed also.

With that knowledge, scientists now know what to look for. "This is a mechanism we can work on," Racaniello said. "How universal is it [among flu viruses] that stabilizing the HA is needed for transmission? Do we see stabilizing mutations arising in nature?"

While Racaniello supports the publication of the research, not everyone was so enthusiastic. Michael Osterholm, director of the Center for Infectious Disease Research and Policy, which studies bioterrorism threats, has said in the past that H5N1 is more dangerous than people realize, though he voted for publication of Kawaoka's paper when it came before the NSABB. In Fouchier's case, he voted against. [Blockbuster Bioterrorism? 11 Infectious Movies]

In an April 12 letter to Dr. Amy Patterson, the associate director for Science Policy at the National Institutes of Health, Osterholm said that even if H5N1 was not spread in human populations, a terrorist group might try to infect pigs, devastating local livestock industries because people would fear infection from eating them (the viruses aren't transmitted that way in any case).

Also, a virus that escaped to reproduce in pigs might still pose a danger to humans. "I can't think of a worse scenario than having H5N1 virus circulating widely in swine with a critical reassortment likely to occur and human transmission not far off," Osterholm wrote in the letter. Reassortment refers to the natural changes in viral RNA that occur when it is "cooking" in a population.

Kawaoka did not return calls or emails for this story, nor was Osterholm willing to speak.

Fouchier's paper has been submitted; it may appear in the next several weeks. When it does it may reveal more about the inner workings of bird flu.

http://news.discovery.com/human/bird-fl ... 20503.html

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One of two controversial ‘bird flu’ papers is published

By David Brown, Published: May 2

The journal Nature, after much debate and delay, on Wednesday published a paper in which scientists describe how they engineered a part of the deadly H5N1 “bird flu” virus to become more transmissible in mammals.

The research, led by Yoshihiro Kawaoka of the University of Wisconsin, was one of two experiments that a federal advisory panel had asked journals to hold off publishing because the papers might provide a how-to guide for terrorists or mischief-makers. The panel later dropped its objections after it became clear the engineered viruses were less virulent than had been feared.

Since it emerged in Hong Kong in 1997, H5N1 influenza has killed millions of chickens, mostly in Asia. People are rarely infected, but when that happens they are likely to die. Since 2003 there have been 602 human cases and 355 deaths.

In the lab, Kawaoka started with an H5N1 strain that had killed several people in Vietnam in 2004. He isolated the gene for “hemagglutinin,” which is most responsible for contagiousness. He put into it two mutations that allow the flu virus to attach more easily to cells in a person’s throat.

He then combined that doctored gene with the “normal” genes from the strain of H1N1 flue that caused the human flu pandemic in 2009. Two more mutations in hemagglutinin appeared during lab experiments and after ferrets — which stand in for people in flu studies — were infected with the virus.

Together, the four mutations made the engineered virus transmissible through the air, although it didn’t kill the ferrets who caught it, or even make them very sick. Whether “wild” bird flu virus containing them would be both contagious and deadly isn’t known.

However, the experiment has given scientists an idea of what mutations to look out for — which was the purpose of the research from the beginning.

One of the mutations is already widespread in H5N1 strains circulating in the Middle East. Some of those strains also carry a mutation in a different gene that makes growth in human cells easier.

“These viruses may be several steps closer to those capable of efficient transmission in humans and are of concern,” Kawaoka and his colleagues wrote in their Nature article.

A second paper, by Dutch scientist Ron A. M. Fouchier, that made a more contagious bird flu virus using other methods, is awaiting publication at the journal Science.

The National Science Advisory Board for Biosecurity, a panel of independent experts that advises the federal government, in December asked the two journals to hold off publishing the papers while researchers and governments thought about how to handle this kind of research. In late March the board looked at the experiments more closely and said it no longer opposed publication.

http://www.washingtonpost.com/national/ ... story.html

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Study Shows How Bird Flu Could Jump to Humans

Download Complimentary Source PDF

By Michael Smith, North American Correspondent, MedPage Today
Published: May 02, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner






Action Points

Note that a paper published in Nature demonstrated transmissibility between ferrets of a reassortant H1N1 influenza strain with four mutations in an H5N1 hemagglutinin.
Note that while the reassortant virus transmitted easily by respiratory droplets and that ferrets are a good model for human transmission, the virus did not cause a fatal illness in the animals.



A hotly debated study pins down four mutations in a key gene in the highly pathogenic H5N1 avian flu that allow it to adapt to mammals.

The mutations, in the hemagglutinin gene of the avian flu, are enough to make it easily pass among ferrets in droplet form, much as human-adapted flu passes among humans, researchers reported.

But the modified virus – a construct combining the modified H5N1 gene and seven genes from the human H1N1 pandemic flu -- was not lethal to the animals, according to Yoshihiro Kawaoka, PhD, of the University of Wisconsin Madison, and colleagues.

And it remains unclear if a wild-type H5N1 virus that acquired the four mutations would be transmissible among mammals, Kawaoka and colleagues wrote in an online Nature report that was the subject of heated discussion even before it was published.

But Kawaoka and colleagues noted that wild-type H5N1 viruses already exist that contain one of the mutations they found, suggesting that some circulating strains may already be closing in on the ability to transmit easily among humans.

The highly pathogenic H5N1 avian flu is endemic among fowl, but only infects humans rarely, largely because it uses different cellular receptors than human-adapted influenza.

Nonetheless, the avian strain has been worrisome because when it does infect humans it is very often fatal: As of April 12, according to the World Health Organization, there have been 602 human infections, of which 355 have ended in death.

Because of those concerns, Kawaoka and colleagues, as well as researchers led by Ron Fouchier, PhD, of Erasmus Medical Center in Rotterdam in the Netherlands, had been investigating what it would take to make the wild-type H5N1 into a virus that could pass easily among humans.

The answer, according to both groups: Not much.

Their papers -- submitted at roughly the same time to Nature and Science, respectively -- caused a heated debate when a U.S. government review agency suggested they were too dangerous to be published.

The National Science Advisory Board for Biosecurity has since reversed that position and the journal Nature, in an editorial accompanying the Kawaoka paper, argued that the board's initial stand was flawed.

"It is now clear that the committee's original deliberations were too limited, especially given the enormous implications for flu research of a recommendation against publication," the journal argued.

A Science spokesman told MedPage Today that the Fouchier paper is in the peer-review process, but a publication date has not been set.

The Kawaoka group is now reporting that they created chimeric flu viruses, using the H1N1 pandemic flu for most of the genetic material, but adding a modified hemagglutinin gene from the H5N1 avian flu.

The hemagglutinin protein is what determines which animals can be infected by a given strain. In the case of avian flu, the protein binds to cells with what is called an alpha2,3-linked sialic acid receptor; human-adapted flu strains bind to an alpha2,6-linked sialic acid receptor.

Respiratory tract cells in birds have mainly the first form of sialic acid receptor, while mammals, including humans, have mainly the second.

In a series of experiments, the researchers developed chimeric viruses in which the hemagglutinin protein of an H5N1 flu strain was capable of binding to alpha2,6-linked sialic acid receptors. The most potent binding came from a virus with just four mutations in the avian flu-derived hemagglutinin gene.

Kawaoka and colleagues then tested to see how well the modified virus would pass among ferrets -- animals that are regarded as a good model for human influenza infection -- and how deadly the virus would be.

They put six uninfected ferrets in wire cages, each of them next to an infected animal, and found evidence of transmission – by sneezing or coughing, since the ferrets were not in direct contact with each other – in five of the six.

On the other hand, none of the animals in the experiment died, Kawaoka and colleagues reported.

Although suggestive, the finding doesn't prove that only a handful of mutations could turn the wild-type avian flu into something with a broader reach, the researchers cautioned.

Because most of the genes in the modified virus were already human-adapted, they "may have critically contributed" to its transmissibility between animals, they noted.

Also, they said, tests showed that the modified virus was susceptible to oseltamivir (Tamiflu), one of the main anti-flu medications, and that a prototype H5N1 vaccine protected against it.

"Appropriate control measures would be available to combat the transmissible virus described in this study," Kawaoka and colleagues concluded.

Despite the cautions, however, a key implication of the work is that H5N1 flu has the potential to acquire the four mutations reported by Kawaoka and colleagues – and perhaps enough others to make the jump to humans.

"Natural emergence of an H5N1–H1N1 hybrid virus is plausible," argued Hui-Ling Yen, PhD, and Joseph Sriyal Malik Peiris, MD, PhD, both of the University of Hong Kong, in an accompanying News and Views article.

They noted that H5N1 and H1N1 viruses have both been found in pigs and that the two strains have been known to swap genetic material in lab experiments.

But, they argued, the findings also suggest changes to watch for, so that such a virus doesn't take us by surprise.

The debate over the two papers centered on fear that the methods employed by the research teams could be turned to illicit use by terrorists or criminals. Supporters of publication countered that the public health benefits of the research – particularly in helping bird flu surveillance – outweighed any risk.

Indeed, an independent assessment of the risk, commissioned by Nature and accompanying the Kawaoka report, said it would require "an exceptionally competent laboratory" to exploit the work.

And the report "does not provide sufficient information to produce [a] fully competent dangerous pathogen," the unattributed assessment said, concluding that, overall, the risks did not outweigh the benefits of publishing the study.


The study was supported by the Bill & Melinda Gates Foundation, the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Japan Science and Technology Agency, and the National Institute of Allergy and Infectious Diseases.

Kawaoka reported financial links with Chugai Pharmaceuticals, Novartis, Daiichi-Sankyo Pharmaceutical, Toyama Chemical, Wyeth, GlaxoSmithKline. Astellas Inc., Theraclone, Crucell, and FluGen.

The News and Views authors did not report external support or any conflicts.




Primary source: Nature
Source reference:
Imai M, et al "Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets" Nature 2012; DOI: 10.1038/nature10831.

Additional source: Nature
Source reference:
"Publishing risky research" Nature 2012; DOI: 10.1038/485005a.

Additional source: Nature
Source reference:
H-L Yen, Peiris JSM "Bird flu in mammals" Nature 2012; DOI: 10.1038/nature11192.
http://www.medpagetoday.com/InfectiousD ... eFlu/32464

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Amino acid structure of the mutant H5N1's modified protein; the positions of four key virulence-increasing mutations are noted. Image: Imai et al./Nature

After months of controversy, an experiment describing how H5N1 avian influenza can be modified into potentially human-contagious forms was published today.

The study was originally submitted to the journal Nature in 2011. Concern that its details, along with those in a similar, as-yet-unpublished experiment, could be turned to malevolent ends delayed its publication.

Subsequent public controversy resulted in a temporary moratorium on such research that is still ongoing. The uproar, however, is far from over: Flu researchers and biodefense experts continue to argue over the findings’ safety and scientific value.

“Given the possibility of accidental escape from the lab — a not too uncommon event — the risks seem to me enormous, while the benefits are very small,” said Richard Roberts, a Nobel Prize-winning geneticist who now works at New England Biolabs.



Amino acid structure of the mutant H5N1's modified protein; the positions of four key virulence-increasing mutations are noted. Image: Imai et al./Nature

In the study, researchers led by virologist Yoshiro Kawaoka of the University of Wisconsin introduced random genetic mutations to one of the flu virus’ eight genes.

The mutations changed the shape of the protein the gene produced, allowing H5N1 — which until now had great difficulty infecting mammals, including humans — to infect and pass easily between ferrets, an animal commonly used to model human flu pathology. The viruses also attached more easily to human respiratory-tract cells.

The resulting strains were non-lethal to ferrets, and it’s thought they’d be non-lethal to humans as well, though this is obviously untested. Experimental vaccines against naturally occurring H5N1 appeared activated by exposure to the new strains, suggesting a protective effect, though this too remains unproven.

According to the study’s authors and many flu experts, the findings are important in several ways: They prove that it’s indeed possible for H5N1 to evolve to infect humans, they flag several genetic mutations to watch for in naturally evolving strains, and they underscore the need for continued research. The potential hybridization of H5N1 with the H1N1 swine flu of 2009 is especially troubling.

“These findings do not only provide further indication that such a virus may arise naturally; they also pave the way for improved influenza surveillance and pandemic preparedness,” wrote University of Hong Kong virologists Hui-Ling Yen and Malik Peiris, the scientist who first identified SARS, in a commentary accompanying the study.

Over the last several months, objections to the research have frequently been called uninformed or overblown. “Fear needs to be put to rest with solid science and not speculation,” wrote microbiologist Peter Palese of the Mount Sinai School of Medicine in a January commentary in the Proceedings of the National Academy of Sciences.

Hints of that tone remain in an “independent risk assessment” commissioned by Nature, describing how the findings “could be misrepresented by a willful media, in the absence of a knowledgeable public.”


Many prominent virologists are afraid to criticize the findings publicly.Many experts do, however, remain skeptical of the findings’ value.

The mutations identified are indeed interesting, but thousands of other as-yet-unknown mutations may have the same effect, potentially limiting this work’s relevance. It’s uncertain whether naturally occurring mutations would even behave the same way.

Global flu surveillance is also piecemeal and grossly underfunded, making it unlikely that the identity of these experimental mutations can be put to use in the near future.

“I find it rather unlikely that these experiments would have resulted in the discovery of anything useful other than the knowledge that aerosolic transmission was possible,” said Richard Roberts of New England Biolabs.

Virologist Michael Osterholm of the University of Minnesota expressed a similar sentiment in a January editorial in the journal Science. ”The desire to disseminate the entirety of the methods and results of the two H5N1 studies in the general scientific literature will not materially increase our ability to protect the public’s health from a future H5N1 pandemic,” he wrote. Osterholm declined to comment this week.

According to Roberts, many prominent virologists are afraid to criticize the findings publicly for fear of retribution from the National Institutes of Health and other funders that promised the strategy of experimentally making dangerous pathogens more virulent would be safe and valuable.

“That’s certainly not the case,” said Anthony Fauci, director of the National Institutes of Allergy and Infectious Disease, the NIH division that funded the research. “We’re driven by a philosophy of open scientific discourse. Disagreements are one of the fundamental positive aspects of science.”

Images: Imai et al./Nature

Citations: “Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets.” By Masaki Imai, Tokiko Watanabe, Masato Hatta, Subash C. Das, Makoto Ozawa, Kyoko Shinya, Gongxun Zhong, Anthony Hanson, Hiroaki Katsura, Shinji Watanabe, Chengjun Li, Eiryo Kawakami, Shinya Yamada, Maki Kiso, Yasuo Suzuki, Eileen A. Maher, Gabriele Neumann & Yoshihiro Kawaoka. Nature, Vol. 785 No. 7396, May 3, 2012.

“Bird flu in mammals.” By Hui-Ling Yen and Malik Peiris. Nature, Vol. 785 No. 7396, May 3, 2012. Nature, Vol. 785 No. 7396, May 3, 2012.

http://www.wired.com/wiredscience/2012/ ... published/

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