Friday, April 26, 2013

U.S. suspects Syria used chemical weapons, wants proof

By Phil Stewart and David Alexander

WASHINGTON (Reuters) - The White House said on Thursday the Syrian government of President Bashar al-Assad had probably used chemical weapons on a small scale in the country's civil war, but insisted that President Barack Obama needed definitive proof before he would take action.

The disclosure created a quandary for Obama, who has set the use of chemical weapons as a "red line" that Assad must not cross. It triggered calls from some hawkish Washington lawmakers for a U.S. military response, which the president has resisted.

In a shift from a White House assessment just days earlier, U.S. officials said the intelligence community believed with "varying degrees of confidence" that the chemical nerve agent sarin was used by Assad's forces against rebel fighters. But it noted that "the chain of custody is not clear."

While Obama has declared that the deployment of chemical weapons would be a game-changer and has threatened unspecified consequences if it happened, his administration is moving carefully - saying it is mindful of the lessons of the start of the Iraq war more than a decade ago.

Then, the George W. Bush administration used inaccurate intelligence to justify the invasion of Iraq in pursuit of nuclear, chemical and biological weapons that turned out not to exist.

"Given the stakes involved and what we have learned from our own recent experiences, intelligence assessments alone are not sufficient - only credible and corroborated facts that provide us with some degree of certainty will guide our decision-making," Miguel Rodriguez, White House director of the office of legislative affairs, said in a letter to lawmakers.

One senior U.S. defense official told reporters, "We have seen very bad movies before," where intelligence was perceived to have driven policy decisions that later, in the cold light of day, were proven wrong.

The term "varying degrees of confidence" used to describe the assessment of possible chemical weapons use in Syria usually suggests debate within the U.S. intelligence community about the conclusion, the defense official noted.

The White House said the evaluation that Syria probably used chemical weapons was based in part on "physiological" samples. But a White House official, briefing reporters on condition of anonymity, repeatedly declined to say what that evidence was. Nor is it clear who supplied it.

Chemical weapons experts say sarin, a nerve agent, can be detected in human tissue, blood, urine and hair samples, or in nearby soil or even leaves. But the chemical can dissipate within days or weeks, depending on ambient heat, wind and other factors.

Iraq is said to have used sarin 25 years ago in an attack on the Kurdish city of Halabja during the Iran-Iraq war. More recently, the agent was used in the 1994 attack by a religious cult on riders of the Tokyo subway system.

In Syria, U.S. officials said the scale of the use of sarin appeared limited. Nobody is "seeing any mass casualties" from the possible use of chemical weapons in Syria, one U.S. intelligence official noted.

The United States has resisted being dragged militarily into Syria's conflict and is providing only non-lethal aid to rebels trying to overthrow Assad. Washington is worried that weapons supplied to the rebels could end up in the hands of al Qaeda-linked fighters.

But acknowledgement of the U.S. intelligence assessment appeared to move the United States closer - at least rhetorically - to some sort of action in Syria, military or otherwise.

A White House official told reporters that "all options are on the table in terms of our response" and said the United States, which has been criticized for not doing enough to halt the bloodshed, would consult with its allies.

The official said the U.S. military was preparing for a range of "different contingencies," but declined to give specifics. Options available to Obama could include everything from air strikes to commando raids to setting up a Libya-style "no-fly" zone, either unilaterally or in cooperation with allies.

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But Obama appeared intent on deflecting pressure for swift action by stressing the need for a comprehensive U.N. investigation on the ground in Syria - something Assad has blocked from going forward.

Syria's deputy foreign minister, Faisal Mekdad, in an interview with Reuters, dismissed Western and Israeli claims that government forces had used chemical weapons and said it was a "big lie" that Syria was preventing the U.N. probe.

Assad has clung to power despite repeated U.S. calls for him to step down. More than 70,000 people have been killed in the revolt against his family's decades-long autocratic rule. A military stalemate has set in, but Assad has still been able to rely on support from Russia and Iran.

"The reality is that as a country we can't declare red lines and then do nothing when they are crossed. Eventually we have to do something," said Ariel Ratner, a former Middle East adviser in the State Department and now a fellow at the Truman National Security Project.

The Obama administration's sudden disclosure caught many off guard. It came just two days after Defense Secretary Chuck Hagel and other U.S. officials appeared to play down an Israeli assessment that there had been repeated use of chemical weapons in Syria.

France and Britain have also concluded that evidence suggests chemical arms have been used in Syria's conflict.

"The intelligence community has been assessing information for some time on this issue and the decision to reach this conclusion was made within the past 24 hours," Hagel said.

The White House said it wanted to provide a "prompt response" to a query on Wednesday from lawmakers about whether Syria had used chemical weapons. The legislators' letter to Obama cited the assessments by Israel, France and Britain.

Republican Senator John McCain of Arizona, one of the leading advocates of deeper U.S. involvement in the Syrian conflict, said the intelligence assessment demanded a response.

"The president of the United States said that if Bashar Assad used chemical weapons, it would be a game-changer, that it would cross a red line," he said. "I think it's pretty obvious that red line has been crossed."

Democratic Senator Dianne Feinstein, head of the Senate Intelligence Committee, voiced concern that the public acknowledgement of the U.S. intelligence assessment could embolden Assad and may prompt him to calculate "he has nothing more to lose."

"Syria has the ability to kill tens of thousands with its chemical weapons. The world must come together to prevent this by unified action," she said.

In Brussels, the NATO alliance was "concerned by reports of the possible use of chemical weapons," an official said.

"As NATO has said in the past, any use of these weapons would be completely unacceptable and a clear breach of international law, and if any side uses these weapons we would expect a reaction from the international community," the official said.

Patriot missile interceptors that NATO has sent to Turkey, a member of the alliance which borders Syria, would "help ensure the protection of Turkey against any missile attack, whether the missiles carry chemical weapons or not," the official added.

(Additional reporting by Matt Spetalnick, Roberta Rampton, Patricia Zengerle and Tabassum Zakaria; Editing by Warren Strobel and Peter Cooney)

Source: http://news.yahoo.com/u-suspects-syria-used-chemical-weapons-wants-proof-034431157.html

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'American Idol' Recap: Angie Miller Steals The Show And 'Snatches Some Wigs'

Judges sang Miller's praises for all three of her performances Wednesday night.
By Adam Graham

Source: http://www.mtv.com/news/articles/1706306/american-idol-final-four-angie-miller.jhtml

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Link between inherited endocrine tumor syndrome and much-studied cell pathway

Apr. 24, 2013 ? A mutation in a protein called menin causes a hereditary cancer syndrome called MEN1 (multiple endocrine neoplasia type 1). Individuals with MEN1 are at a substantially increased risk of developing neuroendocrine tumors, including cancer of the pancreatic islet cells that secrete insulin.

Yet knowing these connections and doing something to improve fighting the syndrome are two different things. Researchers still did not exactly understand how menin mutations lead to MEN1 syndrome, and more importantly, what molecular pathways might be dysregulated by menin mutations and thus can be targeted to improve therapy against this type of cancer. Now, researchers at the Perelman School of Medicine at the University of Pennsylvania have found that pathway, which may lead to a new treatment for patients with MEN1 and sporadic endocrine tumors.

A research team led by Xianxin Hua, MD, PhD, associate professor of Cancer Biology at the Abramson Family Cancer Research Institute, report in Cancer Research that menin suppresses signaling in the much-studied Hedgehog pathway in endocrine organs. Menin mutations lead to increased Hedgehog signaling and cell proliferation. They found that inhibiting proteins in the Hedgehog network using drugs reduces growth of tumors in an animal model of human MEN1 syndrome.

Unlike many cancer-associated proteins, menin is neither an enzyme nor a signaling receptor. Instead, the team discovered that menin works by physically interacting with a second protein, PRMT5. The menin-PRMT5 complex binds to the promoter of the Gas1 gene, where PRMT5 (an enzyme that adds methyl groups to histone proteins) functions as an epigenetic inhibitor, tamping down gene transcription. The GAS1 protein promotes Hedgehog signaling, and thus by inhibiting Gas1 expression, menin and PRMT5 effectively dial down the pathway's tendency towards cell proliferation.

"This study uncovered a new layer of regulation of pro-proliferative genes by menin via the Hedgehog signaling pathway," Hua says. "These pro-replication genes are regulated through GAS1 and PRMT5."

Discovering the link between menin and Hedgehog was serendipitous, says Hua. Using microarray analysis, his team found that loss of menin results in increased expression of the Gas1 gene. Separately, other groups reported that GAS1 mediates Hedgehog signaling. That knowledge gave Hua's team the missing piece of information required to identify menin's normal cellular function. "We found menin linked to Hedgehog signaling by suppressing expression of GAS1, leading to the suppression of Hedgehog signaling in endocrine tissue."

Significantly, Hua's team found that menin mutant proteins associated with MEN1 cancer in patients were impaired in their ability to interact with PRMT5, and thus, in adding the methyl chemical group to the Gas1 promoter gene. What's more, treating a mouse model of human MEN1 syndrome with a Hedgehog pathway inhibitor called Erivedge (FDA-approved in 2012 for metastatic or locally advanced basal cell carcinoma) reduced proliferation of tumor cells and blood insulin levels. That, says Hua, suggests a potential new treatment for patients with MEN1 syndrome, and also likely for sporadic endocrine tumors, some 40 percent of which also contain menin mutations

"Because we show in this mouse tumor model that we can significantly suppress proliferation of tumor cells in pancreatic islets and that we can reduce the higher insulin levels with a drug, which was just clinically approved to be safe, that naturally raises the question of whether, in patients who have mutation in this gene or enhanced Hedgehog signaling, this drug can improve patient symptoms to reduce tumor progression or insulinemia," Hua asks.

First author and postdoctoral fellow in the Hua lab Buddha Gurung, PhD, adds "the possibilities of translating these findings into a viable therapeutic option is extremely exciting."

Co-authors include Zijie Feng, Daniel V. Iwamoto, and Austin Thiel of the Abramson Family Cancer Research Institute; Guanghui Jin of Xiamen University, Fujian, China; Chen-Min Fan of the Carnegie Institution for Science, Baltimore, MD; and Jessica M.Y. Ng and Tom Curran of the Children's Hospital of Philadelphia.

The research was supported by Caring for Carcinoid Foundation and the National Cancer Institute (R01-CA-113962, 548 R01-DK085121; R01 DK084963).

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The above story is reprinted from materials provided by University of Pennsylvania School of Medicine.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. B. Gurung, Z. Feng, D. V. Iwamoto, A. Thiel, G. Jin, C.-M. Fan, J. M. Y. Ng, T. Curran, X. Hua. Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome. Cancer Research, 2013; 73 (8): 2650 DOI: 10.1158/0008-5472.CAN-12-3158

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/PXF7RToyLqk/130424125836.htm

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Thursday, April 25, 2013

Epigenetic changes shed light on biological mechanism of autism

Apr. 23, 2013 ? Scientists from King's College London have identified patterns of epigenetic changes involved in autism spectrum disorder (ASD) by studying genetically identical twins who differ in autism traits.

The study, published in Molecular Psychiatry, is the largest of its kind and may shed light on the biological mechanism by which environmental influences regulate the activity of certain genes and in turn contribute to the development of ASD and related behaviour traits.

ASD affects approximately 1 in 100 people in the UK and involves a spectrum of disorders which manifest themselves differently in different people. People with ASD have varying levels of impairment across three common areas: deficits in social interactions and understanding, repetitive behaviour and interests, and impairments in language and communication development.

Evidence from twin studies shows there is a strong genetic component to ASD and previous studies suggest that genes that direct brain development may be involved in the disorder. In approximately 70% of cases, when one identical twin has ASD, so does the other. However, in 30% of cases, identical twins differ for ASD. Because identical twins share the same genetic code, this suggests non-genetic, or epigenetic, factors may be involved.

Epigenetic changes affect the expression or activity of genes without changing the underlying DNA sequence -- they are believed to be one mechanism by which the environment can interact with the genome. Importantly, epigenetic changes are potentially reversible and may therefore provide targets for the development of new therapies.

The researchers studied an epigenetic mechanism called DNA methylation. DNA methylation acts to block the genetic sequences that drive gene expression, silencing gene activity. They examined DNA methylation at over 27,000 sites across the genome using samples taken from 50 identical twin pairs (100 individuals) from the UK Medical Research Council (MRC) funded Twins Early Development Study (TEDS): 34 pairs who differed for ASD or autism related behaviour traits, 5 pairs where both twins have ASD, and 11 healthy twin pairs.

Dr Chloe Wong, first author of the study from King's College London's Institute of Psychiatry, says: "We've identified distinctive patterns of DNA methylation associated with both autism diagnosis and related behaviour traits, and increasing severity of symptoms. Our findings give us an insight into the biological mechanism mediating the interaction between gene and environment in autism spectrum disorder."

DNA methylation at some genetic sites was consistently altered for all individuals with ASD, and differences at other sites were specific to certain symptom groups. The number of DNA methylation sites across the genome was also linked to the severity of autism symptoms suggesting a quantitative relationship between the two. Additionally, some of the differences in DNA methylation markers were located in genetic regions that previous research has associated with early brain development and ASD.

Professor Jonathan Mill, lead author of the paper from King's College London's Institute of Psychiatry and the University of Exeter, says: "Research into the intersection between genetic and environmental influences is crucial because risky environmental conditions can sometimes be avoided or changed. Epigenetic changes are potentially reversible, so our next step is to embark on larger studies to see whether we can identify key epigenetic changes common to the majority of people with autism to help us develop possible therapeutic interventions."

Dr Alycia Halladay, Senior Director of Environmental and Clinical Sciences from Autism Speaks who funded the research, says: "This is the first large-scale study to take a whole genome approach to studying epigenetic influences in twins who are genetically identical but have different symptoms. These findings open the door to future discoveries in the role of epigenetics -- in addition to genetics -- in the development of autism symptoms."

The study was funded by Autism Speaks, Medical Research Council UK (MRC) and the Brain and Behavior Research Foundation (NARSAD). The twins were selected from the Twins Early Development Study (TEDS) which is funded by the MRC with additional support from the US National Institutes of Health.

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Story Source:

The above story is reprinted from materials provided by King's College London.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. C C Y Wong, E L Meaburn, A Ronald, T S Price, A R Jeffries, L C Schalkwyk, R Plomin, J Mill. Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits. Molecular Psychiatry, 2013; DOI: 10.1038/mp.2013.41

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/5SSPuYtQGZA/130423091113.htm

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Wednesday, April 24, 2013

Binge eating curbed by deep brain stimulation in animal model, Penn study shows

Binge eating curbed by deep brain stimulation in animal model, Penn study shows [ Back to EurekAlert! ] Public release date: 24-Apr-2013
[ | E-mail | Share Share ]

Contact: Kim Menard
kim.menard@uphs.upenn.edu
215-662-6183
University of Pennsylvania School of Medicine

PHILADELPHIA - Deep brain stimulation (DBS) in a precise region of the brain appears to reduce caloric intake and prompt weight loss in obese animal models, according to a new study led by researchers at the University of Pennsylvania. The study, reported in the Journal of Neuroscience, reinforces the involvement of dopamine deficits in increasing obesity-related behaviors such as binge eating, and demonstrates that DBS can reverse this response via activation of the dopamine type-2 receptor.

"Based on this research, DBS may provide therapeutic relief to binge eating, a behavior commonly seen in obese humans, and frequently unresponsive to other approaches," said senior author Tracy L. Bale, PhD, associate professor of neuroscience in Penn's School of Veterinary Medicine's Department of Animal Biology and in the Perelman School of Medicine's Department of Psychiatry. DBS is currently used to reduce tremors in Parkinson's disease and is under investigation as a therapy for major depression and obsessive-compulsive disorder.

Nearly 50 percent of obese people binge eat, uncontrollably consuming palatable highly calorie food within a short period of time. In this study, researchers targeted the nucleus accumbens, a small structure in the brain reward center known to be involved in addictive behaviors. Mice receiving the stimulation ate significantly less of the high fat food compared to mice not receiving DBS. Following stimulation, mice did not compensate for the loss of calories by eating more. However, on days when the device was turned off, binge eating resumed.

Researchers also tested the long-term effects of DBS on obese mice that had been given unlimited access to high-fat food. During four days of continuous stimulation, the obese mice consumed fewer calories and, importantly, their body weight dropped. These mice also showed improvement in their glucose sensitivity, suggestive of a reversal of type 2 diabetes.

"These results are our best evidence yet that targeting the nucleus accumbens with DBS may be able to modify specific feeding behaviors linked to body weight changes and obesity," Bale added.

"Once replicated in human clinical trials, DBS could rapidly become a treatment for people with obesity due to the extensive groundwork already established in other disease areas," said lead author Casey Halpern, MD, resident in the Department of Neurosurgery of the Perelman School of Medicine at the University of Pennsylvania.

###

The study was funded by the National Institutes of Health (DA022605 and HL091911). In addition to Drs. Bale and Halpern, Penn experts include Anand Tekriwal from the College of Arts and Sciences, John Wolf from Neurosurgery and Jeffrey Keating from Neurology. They were joined by colleagues in Psychology at the University of Buffalo.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.


[ Back to EurekAlert! ] [ | E-mail | Share Share ]

?


AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.


Binge eating curbed by deep brain stimulation in animal model, Penn study shows [ Back to EurekAlert! ] Public release date: 24-Apr-2013
[ | E-mail | Share Share ]

Contact: Kim Menard
kim.menard@uphs.upenn.edu
215-662-6183
University of Pennsylvania School of Medicine

PHILADELPHIA - Deep brain stimulation (DBS) in a precise region of the brain appears to reduce caloric intake and prompt weight loss in obese animal models, according to a new study led by researchers at the University of Pennsylvania. The study, reported in the Journal of Neuroscience, reinforces the involvement of dopamine deficits in increasing obesity-related behaviors such as binge eating, and demonstrates that DBS can reverse this response via activation of the dopamine type-2 receptor.

"Based on this research, DBS may provide therapeutic relief to binge eating, a behavior commonly seen in obese humans, and frequently unresponsive to other approaches," said senior author Tracy L. Bale, PhD, associate professor of neuroscience in Penn's School of Veterinary Medicine's Department of Animal Biology and in the Perelman School of Medicine's Department of Psychiatry. DBS is currently used to reduce tremors in Parkinson's disease and is under investigation as a therapy for major depression and obsessive-compulsive disorder.

Nearly 50 percent of obese people binge eat, uncontrollably consuming palatable highly calorie food within a short period of time. In this study, researchers targeted the nucleus accumbens, a small structure in the brain reward center known to be involved in addictive behaviors. Mice receiving the stimulation ate significantly less of the high fat food compared to mice not receiving DBS. Following stimulation, mice did not compensate for the loss of calories by eating more. However, on days when the device was turned off, binge eating resumed.

Researchers also tested the long-term effects of DBS on obese mice that had been given unlimited access to high-fat food. During four days of continuous stimulation, the obese mice consumed fewer calories and, importantly, their body weight dropped. These mice also showed improvement in their glucose sensitivity, suggestive of a reversal of type 2 diabetes.

"These results are our best evidence yet that targeting the nucleus accumbens with DBS may be able to modify specific feeding behaviors linked to body weight changes and obesity," Bale added.

"Once replicated in human clinical trials, DBS could rapidly become a treatment for people with obesity due to the extensive groundwork already established in other disease areas," said lead author Casey Halpern, MD, resident in the Department of Neurosurgery of the Perelman School of Medicine at the University of Pennsylvania.

###

The study was funded by the National Institutes of Health (DA022605 and HL091911). In addition to Drs. Bale and Halpern, Penn experts include Anand Tekriwal from the College of Arts and Sciences, John Wolf from Neurosurgery and Jeffrey Keating from Neurology. They were joined by colleagues in Psychology at the University of Buffalo.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.


[ Back to EurekAlert! ] [ | E-mail | Share Share ]

?


AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.


Source: http://www.eurekalert.org/pub_releases/2013-04/uops-bec042413.php

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The Logos of Terrorist Organizations Predictably Love Using Guns

In a book called Branding Terror, Francesco Trivini Bellini and former United Nations counter-terrorism analyst Artur Beifuss compiled the logos and brand identities of terrorist organizations "from al-Qaeda to the Real IRA" and analyzed them as they would any logo. It's fascinating to approach the identity of the terrorists from a graphic design perspective. More »
    


Source: http://feeds.gawker.com/~r/gizmodo/full/~3/bqZg1pIjS0Y/the-logos-of-terrorist-organizations-predictably-love-using-guns

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Download How to Build and Repair Concrete, Brickwork, and Stone ...

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