3 Episode 54 - The Internet of Insecure Robots (IoIR) MWC, the government's digital strategy and pesky hackable robots By play.acast.com Published On :: Fri, 03 Mar 2017 16:32:09 GMT The gang muck in to discuss the hottest tech topics of the week (as is tradition). Deputy Editor of Macworld UK David Price asks Jim Martin what was hot at MWC, where phones are birthed or something. Then Techworld Online Editor Thomas MacAuley chats about the government's digital strategy. First question: does it have one? Finally Tamlin Magee, Computerworld UK's Online Editor explains how to hack a robot and why people will almost certainly use this for EVIL. Thanks for listening. See acast.com/privacy for privacy and opt-out information. Full Article tech pod technology podcast mwc phones digital strategy robots hacking
3 Episode 63 - The Internet of the French (IotF) New Surface Pro and Netflix vs Cannes By play.acast.com Published On :: Fri, 26 May 2017 11:15:53 GMT This week we dive into the new Surface Pro with Digital Arts' Neil Bennett. Who is it for and is it that different to the last one? And are 2 in 1 devices really the future of computing? Then Techworld's Scott Carey, fresh back from Cannes, discusses why the French film industry booed at a Netflix film - why was it there in the first place? Is the film industry being that affected by tech giants like Amazon? Tech Advisor's Dom Preston chimes in to let us know. Finally, we all quickly nerded out about Alien: Covenant. Mild spoiler alert! See acast.com/privacy for privacy and opt-out information. Full Article technology film tech funny
3 Episode 65 - The Internet of flops (IoF) E3 and the fall of Uber By play.acast.com Published On :: Fri, 16 Jun 2017 09:42:49 GMT Games! Tech Advisor's Lewis Painter and Dom Preston school Henry Burrell and Techword's Scott Carey on the haps from E3. What does E3 stand for? What is a rabbid? Which games have eagles in them? All the issues. Scott then talks us through Uber's latest mishaps, which by now are not funny - will the company survive the mess its CEO has led it into? See acast.com/privacy for privacy and opt-out information. Full Article tech technology tech podcast pod podcast mario metroid e3 uber travis kalanick gaming games
3 Episode 70 - The Internet of tricky surnames (IoTS) Uber's new CEO and new phone chat By play.acast.com Published On :: Fri, 01 Sep 2017 09:17:10 GMT Scott Carey necessarily tries to get his pronunciation game on fleek to deliver the latest Uber news - there's a new CEO in town, and it isn't a woman. Should it have been? He tells Henry Burrell what's next for the company. Then roles are reversed as Henry updates Scott on the Galaxy Note 8, LG V30 and September 12's very own iPhone 8 - will it be called that? Will anyone spend £1,000 on it? See acast.com/privacy for privacy and opt-out information. Full Article pod podcast tech technology iphone 8 iphone apple uber samsung note 8 galaxy note 8
3 Episode 71: The Internet of iPhone X (IoiX) Plus Apple Watch 3 and Apple TV announcements By play.acast.com Published On :: Wed, 13 Sep 2017 15:41:20 GMT This week it is all about Apple as the company announces its eagerly awaited iPhone X and iPhone 8/8 Plus smartphones, a new Apple watch (yawn) and Apple TV news. Macworld UK editor Karen Haslam is our host this week, as she chats to a distinctly unconvinced Dominic Preston about the latest iPhone, followed by David Price on the Apple Watch Series 3, which he likes but not as much as its predecessor. Then everyone piles in together to discuss the quite-good iPhone 8, the quite-late Apple TV 4K, and all the rest of the evening's festivities. See acast.com/privacy for privacy and opt-out information. Full Article
3 Episode 73 - The Internet of Electric Sheep (IoES) Facebook's blunder, the new Kindle and Blade Runner 2049 By play.acast.com Published On :: Fri, 13 Oct 2017 11:48:50 GMT Episode 73 sees David Price lead Scott Carey, Miriam Harris and Henry Burrell into a critique of Mark Zuckerberg's decision to go into a VR tour of Puerto Rico. Disaster tourism at its finest/worst.Henry then discusses the new Kindle Oasis, which for the firs time is waterproof - but very expensive and quietly released.Finally we all chip in to ask why Blade Runner 2049 is quite so overtly sexist in its portrayal of women. There be spoilers. See acast.com/privacy for privacy and opt-out information. Full Article
3 Episode 78 - The Internet of the pod before Christmas (IotPBC) iMac Pro, Netflix's Twitter misstep and Apple buys Shazam By play.acast.com Published On :: Fri, 15 Dec 2017 11:00:00 GMT Once more for 2017 as Henry Burrell, Karen Khan and Scott Carey bid farewell to this wonderful year (ahem) with musings on Apple's sexy new iMac Pro. Who is it for, how much is it and does this mean there is no Mac Pro in 2018?We then tackle Netflix's Twitter shaming of its users and why Spotify got away with it earlier in the year. How comfortable are we all when we realise how much data companies really have on us?In light of this, Apple bought Shazam - most likely for the data sets as much as the tech and the talent. What form will it take in Apple as another UK tech company is acquired? See acast.com/privacy for privacy and opt-out information. Full Article
3 Episode 83 - The Internet of White Rings (IoWR) HomePod, Kingdom Come: Deliverance and no spoiler Black Panther chat By play.acast.com Published On :: Fri, 16 Feb 2018 00:00:00 GMT Scott Carey assembles half the Tech Advisor squad to chat about the HomePod's great audio and then all the things that make it a tabloid headline. Jim Martin lets us know if Apple ruined his oak and/or pine.Lewis Painter chats us through Kingdom Come: Deliverance and all the wacky things you can do in its slow paced but huge world. Dom Preston then lets us know - without spoilers - just how good Black Panther is, Marvel's latest marvel (hopefully). See acast.com/privacy for privacy and opt-out information. Full Article
3 Episode 87 - The Internet of Snoozing (IoS) New Gmail features, 'Chat' and AMD By play.acast.com Published On :: Fri, 27 Apr 2018 14:49:25 GMT A double Google header as Henry Burrell leads Scott Carey and Sean Bradley down the tech rabbit hole. Alphabet's most famous outlet has redesigned Gmail for desktop, but what does that mean for businesses and consumers. Will anyone notice?Then what is Chat? Not Google Chat or Android Chat, mind - just Chat. Will the Google-led initiative really transform text messaging on Android or is it doomed to forever to be a fragmented mess?Sean then talks us through the latest AMD processors to challenge Intel. Intel hasn't had the best of year's after Apple announced it is going solo. Is there a change afoot? See acast.com/privacy for privacy and opt-out information. Full Article
3 Episode 91 - The Internet of Dub Dub (IoDD) WWDC and E3 By play.acast.com Published On :: Thu, 14 Jun 2018 14:13:21 GMT We're back this week to bring you all the hot news from E3 and some cooler takes on everything Apple announced at its WWDC developer conference a few weeks back.To help us do that Macworld UK editor Karen Khan runs through all the iOS and macOS Mojave updates Apple users can look forward to later this year.Then Tech Advisor staff writer Sean Bradley is on hand for a whistlestop tour of all of the big gaming announcements from E3 in LA so far, including Gears of War, Death Stranding and The Last Of Us 2.See you next week! See acast.com/privacy for privacy and opt-out information. Full Article
3 Episode 93 - The Internet of Newsworthy Stuff (IoNS) Uber in London, FB crypto and BlackBerry Key2 By play.acast.com Published On :: Fri, 29 Jun 2018 09:53:21 GMT With Germany out of the World Cup what better way to celebrate than with a triptych of tech news'n'views? Henry Burrell hears from Scott Carey on Uber's London license while Sean Bradley explains why Facebook banned, and then allowed, cryptocurrency ads.Henry then shows off the new BlackBerry and a collection of other phones that Scott finds insulting and ridiculous. See acast.com/privacy for privacy and opt-out information. Full Article
3 Episode 103 - The Internet of Dystopia (IoD) Skirting the line between fact and fiction By play.acast.com Published On :: Fri, 21 Sep 2018 11:04:13 GMT It's a pop culture episode this week as we do a deep dive into dystopian fiction. Scott Carey is your host as he chats to Dominic Preston and Tamlin Magee about the best novels, films, TV shows and video games set in dystopian universes.We talk about how the world is closer to fiction than ever before, and how this impacts the way we think about fictional dystopias, and end on a positive note to discuss our favourite utopian fiction too. See acast.com/privacy for privacy and opt-out information. Full Article
3 Episode 104 - The Internet of Circles (IoC) RIP Google+, Pixel 3 and new tech in films By play.acast.com Published On :: Fri, 12 Oct 2018 14:46:35 GMT This week our host Scott Carey catches up on the Google+ breach news and the final demise of the doomed social media network before being joined by consumer technology editor at Tech Advisor, Henry Burrell, to talk about Google's latest batch of smartphones: the Pixel 3 and Pixel 3 XL.Then Techworld reporter Tamlin Magee joins to talk about the technology-related films screening during the London Film Festival this month and his hopes for more utopian tech-flecked stories in the future. See acast.com/privacy for privacy and opt-out information. Full Article
3 Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro [Research Articles] By feedproxy.google.com Published On :: 2020-03-10T13:30:31-07:00 Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM’s catalytic activity in cultured cells, a mechanism which differs from that of functional inhibitors of ASM (FIASMAs). We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASMpromoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro. When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo. Full Article
3 The lncRNA Gm15622 stimulates SREBP-1c expression and hepatic lipid accumulation by sponging the miR-742-3p in mice [Research Articles] By feedproxy.google.com Published On :: 2020-03-30T14:36:26-07:00 Excessive lipid deposition is a hallmark of nonalcoholic fatty liver disease (NAFLD). Although much has been learned about the enzymes and metabolites involved in NAFLD, few studies have focused on the role of long non-coding RNAs (lncRNAs) in hepatic lipid accumulation. Here, using in vitro and in vivo models of NAFLD, we found that the lncRNA Gm15622 is highly expressed in the liver of obese mice fed a high-fat diet (HFD) and in murine liver (AML-12) cells treated with free fatty acids. Investigating the molecular mechanism in the liver-enriched expression of Gm15622 and its effects on lipid accumulation in hepatocytes and on NAFLD pathogenesis, we found that Gm15622 acts as a sponge for the microRNA miR-742-3p. This sponging activity increased the expression of the transcriptional regulator sterol regulatory element–binding transcription factor 1c (SREBP-1c) and promoted lipid accumulation in the liver of the HFD mice and AML-12 cells. Moreover, further results indicated that metformin suppresses Gm15622 and alleviates NAFLD-associated lipid deposition in mice. In conclusion, we have identified an lncRNA Gm15622–miR-742-3p–SREBP-1c regulatory circuit associated with NAFLD in mice, a finding that significantly advances our insight into how lipid metabolism and accumulation are altered in this metabolic disorder. Our results also suggest that Gm15622 may be a potential therapeutic target for managing NAFLD. Full Article
3 America's Coronavirus Response Is Shaped By Its Federal Structure By feedproxy.google.com Published On :: Mon, 16 Mar 2020 09:00:36 +0000 16 March 2020 Dr Leslie Vinjamuri Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme @londonvinjamuri Google Scholar The apparent capacity of centralized state authority to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. 2020-03-16-Coronavirus-America.jpg Harvard asked its students to move out of their dorms due to the coronavirus risk, with all classes moving online. Photo by Maddie Meyer/Getty Images. As coronavirus spreads across the globe, states grapple to find the ideal strategy for coping with the global pandemic. And, in China, Singapore, South Korea, the US, the UK, and Europe, divergent policies are a product of state capacity and legal authority, but they also reveal competing views about the optimal role of centralized state authority, federalism, and the private sector.Although it is too soon to know the longer-term effects, the apparent capacity of centralized state authority in China, South Korea and Singapore to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. America’s response is being shaped by its federal structure, a dynamic private sector, and a culture of civic engagement. In the three weeks since the first US case of coronavirus was confirmed, state leaders, public health institutions, corporations, universities and churches have been at the vanguard of the nation’s effort to mitigate its spread.Images of safety workers in hazmat suits disinfecting offices of multinational corporations and university campuses populate American Facebook pages. The contrast to the White House effort to manage the message, downplay, then rapidly escalate its estimation of the crisis is stark.Bewildering responseFor European onlookers, the absence of a clear and focused response from the White House is bewildering. By the time President Donald Trump declared a national emergency, several state emergencies had already been called, universities had shifted to online learning, and churches had begun to close.By contrast, in Italy, France, Spain and Germany, the state has led national efforts to shutter borders and schools. In the UK, schools are largely remaining open as Prime Minister Boris Johnson has declared a strategy defined by herd immunity, which hinges on exposing resilient populations to the virus.But America has never shared Europe’s conviction that the state must lead. The Center for Disease Control and Prevention, the leading national public health institute and a US federal agency, has attempted to set a benchmark for assessing the crisis and advising the nation. But in this instance, its response has been slowed due to faults in the initial tests it attempted to rollout. The Federal Reserve has moved early to cut interest rates and cut them again even further this week.But states were the real first movers in America’s response and have been using their authority to declare a state of emergency independent of the declaration of a national emergency. This has allowed states to mobilize critical resources, and to pressure cities into action. After several days delay and intense public pressure, New York Governor Andrew Cuomo forced New York City Mayor Bill de Blasio to close the city’s schools.Declarations of state emergencies by individual states have given corporations, universities and churches the freedom and legitimacy to move rapidly, and ahead of the federal government, to halt the spread in their communities.Washington state was the first to declare a state of emergency. Amazon, one of the state’s leading employers, quickly announced a halt to all international travel and, alongside Microsoft, donated $1million to a rapid-response Seattle-based emergency funds. States have nudged their corporations to be first movers in the sector’s coronavirus response. But corporations have willingly taken up the challenge, often getting ahead of state as well as federal action.Google moved rapidly to announce a move allowing employees to work from home after California declared a state of emergency. Facebook soon followed with an even more stringent policy, insisting employees work from home. Both companies have also met with World Health Organization (WHO) officials to talk about responses, and provided early funding for WHO’s Solidarity Response Fund set up in partnership with the UN Foundation and the Swiss Philanthropy Foundation.America’s leading research universities, uniquely positioned with in-house public health and legal expertise, have also been driving preventive efforts. Just days after Washington declared a state of emergency, the University of Washington became the first to announce an end to classroom teaching and move courses online. A similar pattern followed at Stanford, Harvard, Princeton and Columbia - each also following the declaration of a state of emergency.In addition, the decision by the Church of the Latter Day Saints to cancel its services worldwide followed Utah’s declaration of a state of emergency.The gaping hole in the US response has been the national government. President Trump’s declaration of a national emergency came late, and his decision to ban travel from Europe but - at least initially - exclude the UK, created uncertainty and concern that the White House response is as much driven by politics as evidence.This may soon change, as the House of Representatives has passed a COVID-19 response bill that the Senate will consider. These moves are vital to supporting state and private efforts to mobilize an effective response to a national and global crisis.Need for public oversightIn the absence of greater coordination and leadership from the centre, the US response will pale in comparison to China’s dramatic moves to halt the spread. The chaos across America’s airports shows the need for public oversight. As New York State Governor Cuomo pleaded for federal government support to build new hospitals, he said: ‘I can’t do it. You can’t leave it to the states.'When it comes to global pandemics, we may be discovering that authoritarian states can have a short-term advantage, but already Iran’s response demonstrates that this is not universally the case. Over time, the record across authoritarian states as they tackle the coronavirus will become more apparent, and it is likely to be mixed.Open societies remain essential. Prevention requires innovation, creativity, open sharing of information, and the ability to inspire and mobilize international cooperation. The state is certainly necessary, but it is not sufficient alone. Full Article
3 Let's Emerge From COVID-19 with Stronger Health Systems By feedproxy.google.com Published On :: Thu, 26 Mar 2020 09:33:28 +0000 26 March 2020 Robert Yates Director, Global Health Programme; Executive Director, Centre for Universal Health @yates_rob Heads of state should grasp the opportunity to become universal health heroes to strengthen global health security 2020-03-26-Health-Protest A "Big Insurance: Sick of It" rally in New York City. Photo by Mario Tama/Getty Images. As the COVID-19 pandemic presents the greatest threat to human health in over a century, people turn to their states to resolve the crisis and protect their health, their livelihoods and their future well-being.How leaders perform and respond to the pandemic is likely to define their premiership - and this therefore presents a tremendous opportunity to write themselves into the history books as a great leader, rescuing their people from a crisis. Just as Winston Churchill did in World War Two.Following Churchill’s advice to “never let a good crisis go to waste”, if leaders take decisive action now, they may emerge from the COVID-19 crisis as a national hero. What leaders must do quickly is to mitigate the crisis in a way which has a demonstrable impact on people’s lives.Given the massive shock caused by the pandemic to economies across the world, it is not surprising that heads of state and treasury ministers have implemented enormous economic stimulus packages to protect businesses and jobs – this was to be expected and has been welcome.National heroes can be madeBut, in essence, this remains primarily a health crisis. And one obvious area for leaders to act rapidly is strengthening their nation’s health system to stop the spread of the virus and successfully treat those who have fallen sick. It is perhaps here that leaders have the most to gain - or lose - and where national heroes can be made.This is particularly the case in countries with weak and inequitable health systems, where the poor and vulnerable often fail to access the services they need. One major practical action that leaders can implement immediately is to launch truly universal, publicly-financed health reforms to cover their entire population – not only for COVID-19 services but for all services.This would cost around 1-2% GDP in the short-term but is perfectly affordable in the current economic climate, given some of the massive fiscal stimuluses already being planned (for example, the UK is spending 15% GDP to tackle COVID-19).Within one to two years, this financing would enable governments to implement radical supply side reforms including scaling up health workforces, increasing the supply of essential medicines, diagnostics and vaccines and building new infrastructure. It would also enable them to remove health service user fees which currently exclude hundreds of millions of people worldwide from essential healthcare. Worldwide these policies have proven to be effective, efficient, equitable and extremely popular.And there is plenty of precedent for such a move. Universal health reform is exactly what political leaders did in the UK, France and Japan as post-conflict states emerging from World War Two. It is also the policy President Kagame launched in the aftermath of the genocide in Rwanda, as did Prime Minister Thaksin in Thailand after the Asian Financial Crisis in 2002, and the Chinese leadership did following the SARS crisis, also in 2003.In China’s case, reform involved re-socialising the health financing system using around 2% GDP in tax financing to increase health insurance coverage from a low level of one-third right up to 96% of the population.All these universal health coverage (UHC) reforms delivered massive health and economic benefits to the people - just what is needed now to tackle COVID-19 - and tremendous political benefits to the leaders that implemented them.When considering the current COVID-19 crisis, this strategy would be particularly relevant for countries underperforming on health coverage and whose health systems are more likely to be overwhelmed if flooded with a surge of patients, such as India, Pakistan, Bangladesh, Myanmar, Indonesia and most of sub-Saharan Africa, where many governments spend less than 1% of their GDP on health and most people have to buy services over the counter.But also the two OECD countries without a universal health system – the United States and Ireland – are seeing the threat of COVID-19 already fuelling the debate about the need to create national, publicly-financed health system. And the presidents of South Africa, Kenya and Indonesia have already committed their governments to eventually reach full population coverage anyway, and so may use this crisis to accelerate their own universal reforms. Although difficult to predict which leaders are likely to grasp the opportunity, if some of these countries now fast-track nationwide UHC, at least something good will be coming from the crisis, something which will benefit their people forever. And ensuring everyone accesses the services they need, including public health and preventive services, also provides the best protection against any future outbreaks becoming epidemics.Every night large audiences are tuning in to press briefings fronted by their heads of state hungry for the latest update on the crisis and to get reassurance that their government’s strategy will bring the salvation they desperately need. To truly improve health security for people across the world, becoming UHC heroes could be the best strategic decision political leaders ever make. Full Article
3 COVID-19: America's Looming Election Crisis By feedproxy.google.com Published On :: Wed, 08 Apr 2020 08:31:53 +0000 8 April 2020 Dr Lindsay Newman Senior Research Fellow, US and the Americas Programme @lindsayrsnewman LinkedIn Planning now is essential to ensure the legitimacy of November’s elections is not impacted by COVID-19, as vulnerabilities are becoming ever more apparent if voting in person is restricted. 2020-04-08-COVID-US-election Roadside voting in Madison, Wisconsin in April 2020. Because of coronavirus, the number of polling places was drastically reduced. Photo by Andy Manis/Getty Images. The COVID-19 epidemic has hit every aspect of American life. The upcoming November general elections will not be immune to the virus’ impact and may be scheduled to happen while the pandemic remains active, or has returned.There is a danger the epidemic forces change to the way voting takes place this fall, amplifying risks around election security and voter suppression that ultimately undermine the integrity of the elections.This is further highlighted by the US Supreme Court’s last-minute ruling along ideological lines to restrict an extension on the absentee voting period in the Wisconsin Democratic presidential primary despite the level of infections in the state, forcing voters into a trade-off between their health and their right to vote. The US could be thrown into a political crisis in addition to the health and economic crises it already faces.Bipartisan sentimentWhile France, Chile and Bolivia have already postponed elections in the wake of COVID-19, there is a bipartisan sentiment that the US elections should be held as scheduled on the Tuesday after the first Monday in November. This is enshrined not only in America’s sense of itself – having weathered elections during a civil war, a world war and heightened terrorist alert before – but also in its federal law since 1845.Despite increasing appetite for federal elections to go ahead in November, there are serious vulnerabilities, which are already becoming visible as connections are drawn between mail-in voting and voter fraud, greater voter access and disadvantages for the Republican party, and city polling closures and Democratic voter suppression.Concerns around voting access have gained the most attention. If voting in-person is untenable or risky (especially for vulnerable health populations), voters must have alternative means to cast ballots.During negotiations for the Coronavirus Aid, Relief, and Economic Security (CARES) Act, the Democratic caucus in the House of Representatives proposed $4 billion in state election grants and a nationally-mandated period for early voting and no-excuse absentee voting.But the final CARES Act sidestepped the access question and stripped funding to $400 million for election security grants to ‘prevent, prepare for, and respond to coronavirus, domestically or internationally, for the 2020 Federal election cycle’. Without knowing exactly what is in store from a cyber-threat perspective, the actual cost for basic election security upgrades is estimated to be $2.1billion. And that is a pre-COVID-19 calculation.With social-distanced voters likely to be getting more election information than ever from social media, information security is critical to prevent influence from untrustworthy sources. And opportunities for cyber intrusions are likely to increase as states transition to greater virtual registration, plus absentee and mail-in balloting.This will open new doors on well-documented, existing voter suppression efforts. With the Supreme Court clawing back the Voting Rights Act in 2013 - allowing certain states to make changes to election and voting laws without federal pre-clearance - heightened election security requirements, such as exact match campaigns and voter purges, have been used to justify voter suppression.As more vote remotely in the remaining primaries (many now rescheduled for 2 June) and the November general elections, the added burden on states around verification will only increase temptation to set aside ‘non-compliant’ ballots. Especially as some in the Republican Party, including Donald Trump, have advocated a contested view that higher turnout favours the Democratic Party.A fundamental principle of US democracy is that losers of elections respect the result, but history shows that election results have been contested. In 2000, it took weeks for a result to be confirmed in the presidential election. More recently, in the 2018 race for governor in Georgia, allegations of voter suppression raised questions about the validity of the eventual result.Without proper access, security, and verification the electoral process – whenever it takes place – will become vulnerable to questions of integrity. The federal response to the initial spread of COVID-19 saw costly delays which pushed the US into a public health crisis and economic contraction.Any narrative thread of election illegitimacy with November’s elections will further pull apart the fabric of a country already frayed by coronavirus. Federal and state authorities must start planning now for how the US will hold elections in the midst - or immediate aftermath - of COVID-19. Full Article
3 Coronavirus Vaccine: Available For All, or When it's Your Turn? By feedproxy.google.com Published On :: Mon, 04 May 2020 15:39:19 +0000 4 May 2020 Professor David Salisbury CB Associate Fellow, Global Health Programme LinkedIn Despite high-level commitments and pledges to cooperate to ensure equitable global access to a coronavirus vaccine, prospects for fair distribution are uncertain. 2020-05-04-Vaccine-COVID-Brazil Researcher in Brazil working on virus replication in order to develop a vaccine against the coronavirus. Photo by DOUGLAS MAGNO/AFP via Getty Images. When the H1N1 influenza pandemic struck in 2009, some industrialized countries were well prepared. Many countries’ preparedness plans had focused on preparing for an influenza pandemic and based on earlier alerts over the H5N1 ‘bird flu’ virus, countries had made advanced purchase or ‘sleeping’ contracts for vaccine supplies that could be activated as soon as a pandemic was declared. Countries without contracts scrambled to get supplies after those that already had contracts received their vaccine.Following the 2009 pandemic, the European Union (EU) developed plans for joint-purchase vaccine contracts that any member state could join, guaranteeing the same price per dose for everyone. In 2009, low-income countries were unable to get the vaccine until manufacturers agreed to let 10 per cent of their production go to the World Health Organization (WHO).The situation for COVID-19 could be even worse. No country had a sleeping contract in place for a COVID-19 vaccine since nobody had anticipated that the next pandemic would be a coronavirus, not an influenza virus. With around 80 candidate vaccines reported to be in development, choosing the right one will be like playing roulette.These candidates will be whittled down as some will fail at an early stage of development and others will not get to scale-up for manufacturing. All of the world’s major vaccine pharmaceutical companies have said that they will divert resources to manufacture COVID-19 vaccines and, as long as they choose the right candidate for production, they have the expertise and the capacity to produce in huge quantities.From roulette to a horse raceOur game now changes from roulette to a horse race, as the probability of winning is a matter of odds not a random chance. Countries are now able to try to make contracts alone or in purchasing consortia with other states, and with one of the major companies or with multiple companies. This would be like betting on one of the favourites.For example, it has been reported that Oxford University has made an agreement with pharmaceutical company AstraZeneca, with a possibility of 100 million doses being available by the end of 2020. If the vaccine works and those doses materialize, and are all available for the UK, then the UK population requirements will be met in full, and the challenge becomes vaccinating everyone as quickly as possible.Even if half of the doses were reserved for the UK, all those in high-risk or occupational groups could be vaccinated rapidly. However, as each major manufacturer accepts more contracts, the quantity that each country will get diminishes and the time to vaccinate the at-risk population gets longer.At this point, it is not known how manufacturers will respond to requests for vaccine and how they will apportion supplies between different markets. You could bet on an outsider. You study the field and select a biotech that has potential with a good production development programme and a tie-in with a smaller-scale production facility.If other countries do not try to get contracts, you will get your vaccine as fast as manufacturing can be scaled up; but because it is a small manufacturer, your supplies may take a long time. And outsiders do not often win races. You can of course, depending on your resources, cover several runners and try to make multiple contracts. However, you take on the risk that some will fail, and you may have compromised your eventual supply.On April 24, the WHO co-hosted a meeting with the president of France, the president of the European Commission and the Bill & Melinda Gates Foundation. It brought together heads of state and industry leaders who committed to ‘work towards equitable global access based on an unprecedented level of partnership’. They agreed ‘to create a strong unified voice, to build on past experience and to be accountable to the world, to communities and to one another’ for vaccines, testing materials and treatments.They did not, however, say how this will be achieved and the absence of the United States was notable. The EU and its partners are hosting an international pledging conference on May 4 that aims to raise €7.5 billion in initial funding to kick-start global cooperation on vaccines. Co-hosts will be France, Germany, Italy, the United Kingdom, Norway and Saudi Arabia and the priorities will be ‘Test, Treat and Prevent’, with the latter dedicated to vaccines.Despite these expressions of altruism, every government will face the tension between wanting to protect their own populations as quickly as possible and knowing that this will disadvantage poorer countries, where health services are even less able to cope. It will not be a vote winner to offer a share in available vaccine to less-privileged countries.The factories for the biggest vaccine manufacturers are in Europe, the US and India. Will European manufacturers be obliged by the EU to restrict sales first to European countries? Will the US invoke its Defense Production Act and block vaccine exports until there are stocks enough for every American? And will vaccine only be available in India for those who can afford it?The lessons on vaccine availability from the 2009 influenza pandemic are clear: vaccine was not shared on anything like an equitable basis. It remains to be seen if we will do any better in 2020. Full Article
3 WITHDRAWN: Extraordinary apolipoprotein oxidation in chronic hepatitis C and liver cirrhosis [13. Other] By feedproxy.google.com Published On :: 2007-09-05T09:37:40-07:00 Withdrawn by Author. Full Article
3 Metabolic profiling in colorectal cancer reveals signature metabolic shifts during tumorigenesis [13. Other] By feedproxy.google.com Published On :: 2010-02-10T02:51:33-08:00 Colorectal cancer (CRC) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor, and thus is an useful model for studying metabolic shift. In the present study, we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC. Colonic tissues including tumor, polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors were elevated, suggesting higher energy needs for increased cellular proliferation. In contrast, significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis. In addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric acid concentration, suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC. Further, there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors. It appears that to gain a growth advantage, cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment. Full Article
3 Translating Divergent Environmental Stresses into a Common Proteome Response through Hik33 in a Model Cyanobacterium [Research] By feedproxy.google.com Published On :: 2017-05-12T06:53:48-07:00 The histidine kinase Hik33 plays important roles in mediating cyanobacterial response to divergent types of abiotic stresses including cold, salt, high light (HL), and osmotic stresses. However, how these functions are regulated by Hik33 remains to be addressed. Using a hik33-deficient strain (hik33) of Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found that Hik33 depletion induces differential protein expression highly similar to that induced by divergent types of stresses. This typically includes downregulation of proteins in photosynthesis and carbon assimilation that are necessary for cell propagation, and upregulation of heat shock proteins, chaperons, and proteases that are important for cell survival. This observation indicates that depletion of Hik33 alone mimics divergent types of abiotic stresses, and that Hik33 could be important for preventing abnormal stress response in the normal condition. Moreover, we found the majority of proteins of plasmid origin were significantly upregulated in hik33, though their biological significance remains to be addressed. Together, the systematically characterized Hik33-regulated cyanobacterial proteome, which is largely involved in stress responses, builds the molecular basis for Hik33 as a general regulator of stress responses. Full Article
3 HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV [Research] By feedproxy.google.com Published On :: 2020-04-21T08:36:14-07:00 Assembly factors play a critical role in the biogenesis of mitochondrial respiratory chain complexes I-IV where they assist in the membrane insertion of subunits, attachment of co-factors, and stabilization of assembly intermediates. The major fraction of complexes I, III and IV are present together in large molecular structures known as respiratory chain supercomplexes. A number of assembly factors have been proposed as required for supercomplex assembly, including the hypoxia inducible gene 1 domain family member HIGD2A. Using gene-edited human cell lines and extensive steady state, translation and affinity enrichment proteomics techniques we show that loss of HIGD2A leads to defects in the de novo biogenesis of mtDNA-encoded COX3, subsequent accumulation of complex IV intermediates and turnover of COX3 partner proteins. Deletion of HIGD2A also leads to defective complex IV activity. The impact of HIGD2A loss on complex IV was not altered by growth under hypoxic conditions, consistent with its role being in basal complex IV assembly. While in the absence of HIGD2A we show that mitochondria do contain an altered supercomplex assembly, we demonstrate it to harbor a crippled complex IV lacking COX3. Our results redefine HIGD2A as a classical assembly factor required for building the COX3 module of complex IV. Full Article
3 Wheat, Farmer's Woes By feedproxy.google.com Published On :: Mon, 06 Apr 2020 16:15:42 +0000 1 February 2008 , Number 3 Oliver Walston Farms at Thriplow Farm, Cambridgeshire Walston.jpg Full Article
3 Moscow's Domestic Policy: Russian Roulette By feedproxy.google.com Published On :: Wed, 15 Apr 2020 11:20:12 +0000 1 October 2008 , Number 4 Russia’s military action in Georgia was driven by Moscow’s domestic agenda. Foreign policy has become a tool of collective control back home. While the ‘ruling tandem’ has gained popularity, the new consensus does not provide for modernisation. Will the predatory state reform or collapse? Lilia Shevtsova Senior Associate, Carnegie Moscow Centre bear copy.jpg Full Article
3 Chemical, Biological, Radiological and Nuclear Terrorism: Tomorrow's Threat By feedproxy.google.com Published On :: Mon, 27 Apr 2020 13:23:42 +0000 1 March 2007 , Number 11 In early November, the retiring head of Britain’s Security Service MI5, Dame Eliza Manningham-Buller, warned that the danger of a terror attack was ‘serious’ and ‘growing’, with as many as thirty plots underway. Traditional terrorism of the sort practised by the Irish Republican Army has given way to the possibility, if not the expectation, that groups such as Al Qaeda might make use of chemical, biological, radiological and nuclear weapons and materials in an attack in Britain. So what are the dangers? GettyImages-200457787-001 copy.jpg Syrian Special Forces in gas masks, Saudi Arabia 1990 Full Article
3 It's a man's world: carnal spectatorship and dissonant masculinities in Islamic State videos By feedproxy.google.com Published On :: Thu, 07 May 2020 08:41:04 +0000 7 May 2020 , Volume 96, Number 3 Manni Crone Read Online Islamic State videos have often been associated with savage violence and beheadings. An in-depth scrutiny however reveals another striking feature: that female bodies are absent, blurred or mute. Examining a few Islamic State videos in depth, the article suggests that the invisibility of women in tandem with the ostentatious visibility of male bodies enable gendered and embodied spectators to indulge in homoerotic as well as heterosexual imaginaries. In contrast to studies on visual security and online radicalization which assert that images affect an audience, this article focuses on the interaction between video and audience and argues that spectators are not only rational and emotional but embodied and gendered as well. Islamic State videos do not only attract western foreign fighters through religious–ideological rhetoric or emotional impact but also through gendered forms of pleasure and desire that enable carnal imagination and identification. The article probes the analytical purchase of carnal aesthetics and spectatorship. Full Article
3 Soundscapes of war: the audio-visual performance of war by Shi'a militias in Iraq and Syria By feedproxy.google.com Published On :: Thu, 07 May 2020 09:16:54 +0000 7 May 2020 , Volume 96, Number 3 Helle Malmvig Read online This article sets out to bring sound and music to the field of visual studies in International Relations. It argues that IR largely has approached the visual field as if it was without sound; neglecting how audial landscapes frame and direct our interpretation of moving imagery. Sound and music contribute to making imagery intelligible to us, we ‘hear the pictures’ often without noticing. The audial can for instance articulate a visual absence, or blast visual signs, bring out certain emotional stages or subjects’ inner life. Audial frames steer us in distinct directions, they can mute the cries of the wounded in war, or amplify the sounds of joy of soldiers shooting in the air. To bring the audial and the visual analytically and empirically together, the article therefore proposes four key analytical themes: 1) the audial–visual frame, 2) point of view/point of audition, 3) modes of audio-visual synchronization and 4) aesthetics moods. These are applied to a study of ‘war music videos’ in Iraq and Syria made and circulated by Shi'a militias currently fighting there. Such war music videos, it is suggested, are not just artefacts of popular culture, but have become integral parts of how warfare is practiced today, and one that is shared by soldiers in the US and Europe. War music videos are performing war, just as they shape how war is known by spectators and participants alike. Full Article
3 How images frame China's role in African development By feedproxy.google.com Published On :: Thu, 07 May 2020 09:21:23 +0000 7 May 2020 , Volume 96, Number 3 George Karavas Read online Political leaders, policy-makers and academics routinely refer to development as an objective process of social change through the use of technical, value-free terms. Images of poverty and inequality are regularly presented as evidence of a world that exists ‘out there’ where development unfolds. This way of seeing reflects the value of scientific forms of knowledge but also sits in tension with the normative foundations of development that take European modernization and industrialization as the benchmark for comparison. The role images play in this process is often overlooked. This article argues that a dominant mode of visuality based on a Cartesian separation between subject and object, underpinning the ascendance of European hegemony and colonialism, aligns with the core premises of orthodox development discourse. An example of how visual representations of development matter is presented through images of Africa–China relations in western media sources. Using widely circulated images depicting China's impact on African development in western news media sources as an example of why visual politics matters for policy-making, the article examines how images play a role in legitimizing development planning by rendering associated forms of epistemological and structural violence ‘invisible to the viewer’. Full Article
3 Let's talk about the interregnum: Gramsci and the crisis of the liberal world order By feedproxy.google.com Published On :: Thu, 07 May 2020 09:34:15 +0000 7 May 2020 , Volume 96, Number 3 Read online Milan Babic The liberal international order (LIO) is in crisis. Numerous publications, debates and events have time and again made it clear that we are in the midst of a grand transformation of world order. While most contributions focus on either what is slowly dying (the LIO) or what might come next (China, multipolarity, chaos?), there is less analytical engagement with what lies in between those two phases of world order. Under the assumption that this period could last years or even decades, a set of analytical tools to understand this interregnum is urgently needed. This article proposes an analytical framework that builds on Gramscian concepts of crisis that will help us understand the current crisis of the LIO in a more systematic way. It addresses a gap in the literature on changing world order by elaborating three Gramsci-inspired crisis characteristics—processuality, organicity and morbidity—that sketch the current crisis landscape in a systematic way. Building on this framework, the article suggests different empirical entry points to the study of the crisis of the LIO and calls for a research agenda that takes this crisis seriously as a distinct period of changing world orders. Full Article
3 Anaïs Marin By feedproxy.google.com Published On :: Wed, 15 Jan 2020 16:52:38 +0000 Associate Fellow, Russia and Eurasia Programme Biography Anaïs Marin is an independent Belarus expert who joined the the Russia and Eurasia programme as an associate fellow in December 2019.An IR scholar specialising on post-Soviet Eurasia, since 2014 she has been investigating the foreign policy of authoritarian regimes (“dictaplomacy”), first as a Marie Curie Fellow (Collegium Civitas, Warsaw), now with a grant from the Polish National Centre for Science (University of Warsaw).Her current research focuses on how Russian “sharp power” impacts European democracy and regional security.Anaïs has been involved in policy expert and advocacy networks on Belarus, and published for various think tanks, notably the Finnish Institute of International Affairs (FIIA, Helsinki) and the EU Institute for Security Studies. She regularly participates in OSCE/ODIHR election observation missions in the region.In 2018 she was appointed UN special rapporteur on human rights in Belarus.She received her PhD and MA from Sciences Po Paris/CERI. Areas of expertise BelarusRussian foreign policyEastern PartnershipEU-Russia relationsEurasian integration Past experience 2019 - presentResearcher, Centre for French Culture, University of Warsaw2015-18Marie Curie Fellow, Collegium Civitas2011-14Researcher, Eastern neighbourhood and Russia programme, Finnish Institute of International Affairs +48 517 808 917 Email LinkedIn Full Article
3 What Putin's Constitutional Shakeup Means By feedproxy.google.com Published On :: Thu, 16 Jan 2020 12:39:30 +0000 16 January 2020 Professor Nikolai Petrov Senior Research Fellow, Russia and Eurasia Programme, Chatham House Google Scholar Nikolai Petrov on the key takeaways from the Russian president's latest move. 2020-01-16-STP.jpg A live broadcast of Vladimir Putin's annual address to the Federal Assembly of the Russian Federation, seen on the Leader Tower screen in St Petersburg. Photo: Getty Images. Vladimir Putin’s proposed constitutional reforms will transform Russia’s political regime and allow him to prolong his grip on power when his fourth presidential term expires in 2024.The proposals suggest that he will not seek another term as president after 2024, but is preparing the ground for retaining power after he leaves the presidency. The changes will introduce checks and balances on his close associates and ensure the country’s judiciary, legislative and executive bodies remain passive.The State Duma, the lower house of parliament, is unlikely to rock the boat with legislative elections approaching in 2021. Former prime minister Dmitry Medvedev’s cabinet has been replaced by an acting government headed by a new prime minister, Mikhail Mishustin. The highest courts will be weakened further by Putin’s proposal to give the president the power to dismiss judges.Most of the proposed changes are vague. Notable specific proposals include the requirement that any presidential candidate must be resident in Russia for a minimum of 25 years prior to the elections, and that anyone who has held a residency permit abroad at any point in their life would not be eligible to run. This is clearly aimed at eliminating political opposition based abroad.While Putin mentioned a popular vote on the constitutional changes (which is not required by law), it is important to note that he didn’t use the term ‘referendum’, which would have mandated that the results be acted upon. Regardless, it is clear that, with no easy foreign policy and military wins in the offing, Putin will seek to boost his legitimacy through a popular vote. The current federal electoral cycle starts next year and will end in 2024 with the presidential election.The key question now is how Putin will maintain control over the siloviki, Russia’s political elite, though he has made this task easier for himself by replacing some of the strongest players with mid-level officers and weakening the authority of those who remain.The proposals to consult with the Federation Council, the upper house of parliament, when appointing siloviki and to keep the president in charge of law enforcement are a smokescreen. Putin will consolidate his power through his leadership at the Security Council and by chairing the State Council. For this reason, Putin is seeking to enshrine the State Council, which was reshaped in 2018 to include senior government ministers, in the constitution. It is too early to be certain of the major beneficiaries of these sweeping reforms, though Sergey Sobyanin, the current mayor of Moscow, is likely to become Putin’s deputy at the State Council. The head of the audit chamber, Alexei Kudrin, and Deputy Chief of Staff Sergei Kiriyenko are also likely to benefit from the changes, after helping to develop Putin’s political and economic strategies prior to the 2018 presidential election.Notably, the audit chamber, headed by Kudrin, will now have the power to check Rostekh, Rosneftegaz and Gazprom, organizations associated with major siloviki figures Sergey Chemezov and Igor Sechin. The role offered to Medvedev – deputy chair of the Security Council – will be newly created: the scope is unclear but it is unlikely that Putin will relinquish any of his influence over the siloviki. Full Article
3 Russia's Imperial Nostalgia: Implications for the West By feedproxy.google.com Published On :: Thu, 16 Jan 2020 14:50:01 +0000 Invitation Only Research Event 31 January 2020 - 11:00am to 12:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Sergei Medvedev, Professor, Faculty of Social Sciences, Higher School of Economics (Moscow) Vladimir Putin’s goal of restoring Russia’s status as a great power has led to an aggressive foreign policy and confrontation with its immediate neighbours as well as Western countries.Sergei Medvedev, author of The Return of the Russian Leviathan, will discuss the forces shaping Russian politics and society today as well as how a nostalgia for empire – still widespread in contemporary Russia - has shaped Moscow’s foreign policy.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Russia and Eurasia Programme, Russian Foreign Policy, The Drivers of Russian Foreign Policy Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
3 Webinar: Russian Disinformation's Golden Moment: Challenges and Responses in the COVID-19 Era By feedproxy.google.com Published On :: Tue, 21 Apr 2020 23:55:01 +0000 Invitation Only Research Event 7 May 2020 - 3:00pm to 4:30pm Event participants Anneli Ahonen, Head, StratCom East Task Force, European External Action ServiceKeir Giles, Senior Consulting Fellow, Russia and Eurasia Programme, Chatham HouseThomas Kent, Adjunct Associate Professor, Harriman Institute, Columbia University; Senior Fellow, the Jamestown FoundationChairs:James Nixey, Programme Director, Russia and Eurasia, Chatham HouseGlen Howard, President, The Jamestown Foundation The COVID-19 pandemic provides the ideal environment for malign influence to thrive as it feeds on fear and a vacuum of authoritative information. What are the current challenges posed by Russian disinformation, and how should Western nations be responding? In this discussion, jointly hosted by the Jamestown Foundation and the Chatham House Russia and Eurasia Programme, the speakers will consider what best practice looks like in safeguarding Western societies against the pernicious effects of disinformation. This event will be held on the record. Department/project Russia and Eurasia Programme, Russia's Domestic Politics Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
3 Virtual Roundtable: Land Reform in Ukraine: Is Zelenskyy's Government Getting it Right? By feedproxy.google.com Published On :: Thu, 07 May 2020 00:05:01 +0000 Invitation Only Research Event 14 May 2020 - 12:00pm to 1:30pmAdd to CalendariCalendar Outlook Google Yahoo Ihor Petrashko, Minister of Economic Development and Trade, UkraineAndriy Dykun, Chair, Ukrainian Agricultural CouncilVadim Tolpeco, Ukrlandfarming PlcChair: Orysia Lutsevych, Research Fellow and Manager, Ukraine Forum, Chatham House Ukraine is known as the ‘breadbasket of Europe’ thanks to its grain exports. On 31 March 2020, the Ukrainian parliament passed a landmark law ending a 19-year ban on the sale of privately owned agricultural land. Due to come into force in July 2021, the law applies to 41.5 million hectares of farmland and economists predict substantial economic gains from this liberalization. This event will discuss the impact of the law on Ukraine’s agricultural sector and food security. How can the government best implement this reform and ensure that small and medium-sized agricultural companies increase their productivity? What does this change mean for Ukraine’s capacity to export grain? Can the country’s food supply withstand crises such as the COVID-19 pandemic? What role could foreign direct investors play in boosting production? This event will be held on the record. Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Department/project Russia and Eurasia Programme, Ukraine Forum Full Article
3 Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Angiopoietin-like protein 3 (ANGPTL3) inhibits lipid clearance and is a promising target for managing cardiovascular disease. Here we investigated the effects of a high-sugar (high-fructose) diet on circulating ANGPTL3 concentrations in rhesus macaques. Plasma ANGPTL3 concentrations increased ~30% to 40% after 1 and 3 months of a high-fructose diet (both P < 0.001 vs. baseline). During fructose-induced metabolic dysregulation, plasma ANGPTL3 concentrations were positively correlated with circulating indices of insulin resistance [assessed with fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR)], hypertriglyceridemia, adiposity (assessed as leptin), and systemic inflammation [C-reactive peptide (CRP)] and negatively correlated with plasma levels of the insulin-sensitizing hormone adropin. Multiple regression analyses identified a strong association between circulating APOC3 and ANGPTL3 concentrations. Higher baseline plasma levels of both ANGPTL3 and APOC3 were associated with an increased risk for fructose-induced insulin resistance. Fish oil previously shown to prevent insulin resistance and hypertriglyceridemia in this model prevented increases of ANGPTL3 without affecting systemic inflammation (increased plasma CRP and interleukin-6 concentrations). ANGPTL3 RNAi lowered plasma concentrations of ANGPTL3, triglycerides (TGs), VLDL-C, APOC3, and APOE. These decreases were consistent with a reduced risk of atherosclerosis. In summary, dietary sugar-induced increases of circulating ANGPTL3 concentrations after metabolic dysregulation correlated positively with leptin levels, HOMA-IR, and dyslipidemia. Targeting ANGPTL3 expression with RNAi inhibited dyslipidemia by lowering plasma TGs, VLDL-C, APOC3, and APOE levels in rhesus macaques. Full Article
3 ANGPTL3, PCSK9, and statin therapy drive remarkable reductions in hyperlipidemia and atherosclerosis in a mouse model [Commentary] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Full Article
3 Lithium ion adduction enables UPLC-MS/MS-based analysis of multi-class 3-hydroxyl group-containing keto-steroids [Methods] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 Steroids that contain a 3-hydroxyl group (3-OH steroids) are widely distributed in nature. During analysis with ESI-MS, they easily become dehydrated while in the protonated form, resulting in the production of several precursor ions and leading to low sensitivity of detection. To address this analytical challenge, here, we developed a method for the quantitation of 3-OH steroids by LC-MS/MS coupled with post-column addition of lithium (Li) ions to the mobile phase. The Li ion has a high affinity for the keto group of steroids, stabilizing their structures during ionization and permitting detection of analytes exclusively as the lithiated form. This not only improved the intensities of the precursor ions, but also promoted the formation of typical lithiated fragment ions. This improvement made the quantitation by multiple reaction monitoring more sensitive and reliable, as evidenced by 1.53–188 times enhanced detection sensitivity of 13 steroids that contained at least one keto and two hydroxyl groups or one keto and one 5-olefinic double bond, among 16 different 3-OH steroids. We deployed our newly developed method for profiling steroids in mouse brain tissue and identified six steroids in one tissue sample. Among these, 16-hydroxyestrone, tetrahydrocorticosterone, and 17α-hydroxypregnenolone were detected for the first time in the mouse brain. In summary, the method described here enables the detection of lithiated steroids by LC-MS/MS, including three 3-OH steroids not previously reported in the mouse brain. We anticipate that this new method may allow the determination of 3-OH steroids in different brain regions. Full Article
3 SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect FA translocation [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:28-07:00 Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement. Full Article
3 Slc43a3 is a regulator of free fatty acid flux [Research Articles] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, increased about 2.5-fold after bariatric surgery. Further investigation demonstrated that Slc43a3 is highly expressed in murine adipose tissue and induced during adipocyte differentiation in primary preadipocytes and in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated FA efflux, while also increasing FA uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased FA uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate FA flux in adipocytes, functioning as a positive regulator of FA efflux and as a negative regulator of FA uptake. Full Article
3 Commentary on SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect fatty acid translocation [Commentaries] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Full Article
3 Problem Notes for SAS®9 - 65939: "ERROR: Unable to transcode data to/from UCS-2 encoding" occurs when you run an SQL query using SAS/ACCESS Interface to ODBC on SAS 9.4M5 with UTF-8 By feedproxy.google.com Published On :: Fri, 8 May 2020 11:20:02 EST When you run an SQL query using SAS/ACCESS Interface to ODBC under the following conditions, you might receive an error: You run SAS 9.4M5 (TS1M5) or SAS 9.4M6 (TS1M6) i Full Article ODBC+SAS/ACCESS+Interface+to+ODBC
3 Problem Notes for SAS®9 - 65938: Incorrect values might be written to Hadoop for columns defined with the BIGINT data type By feedproxy.google.com Published On :: Fri, 8 May 2020 10:20:46 EST Large numeric values consisting of 16 digits in SAS might be incorrect when written to Hadoop for columns defined with the BIGINT data type. This problem was introduced in SAS 9 Full Article HADOOP+SAS/ACCESS+Interface+to+Hadoop
3 Problem Notes for SAS®9 - 35066: When a bulk-loading process fails with "SQL*Loader 2026" error, error message appears as a warning in the SAS log By feedproxy.google.com Published On :: Thu, 7 May 2020 17:15:19 EST If a bulk-loading process fails when you use SAS with SAS/ACCESS Interface to Oracle, you will receive the warning: "WARNING: All or some rows were rejected/discarded.: The actual error is "SQL*Loader-2026: The load was aborted because SQL Full Article ORACLE+SAS/ACCESS+Interface+to+Oracle
3 Problem Notes for SAS®9 - 65834: PROC METADATA returns various errors when the input contains certain multi-byte characters By feedproxy.google.com Published On :: Thu, 7 May 2020 17:12:13 EST The METADATA procedure might return an error similar to one of the following: ERROR: Missing root element definition. Full Article BASE+Base+SAS
3 Problem Notes for SAS®9 - 65899: "ERROR: ORACLE disconnect error: ORA-03135" occurs when SAS disconnects from the Oracle database server By feedproxy.google.com Published On :: Thu, 7 May 2020 08:04:08 EST When you run 32-bit SAS on Windows and disconnect from the Oracle database server, you might see the error: "ERROR: ORACLE disconnect error: ORA-03135: connection lost contact." Full Article ORACLE+SAS/ACCESS+Interface+to+Oracle
3 Problem Notes for SAS®9 - 60332: A SAS 9.4 installation in Update mode notifies you about unwritable files in the "SASHome\SASWebApplicationServer" directory By feedproxy.google.com Published On :: Wed, 6 May 2020 14:49:04 EST When you run SAS Deployment Wizard to install or update SAS 9.4 software, the file system is examined. If any files that the wizard needs to delete are found to be locked, they are reported as unwritable f Full Article BASE+Base+SAS
3 Problem Notes for SAS®9 - 64285: The SCD Type 2 Loader transformation in SAS Data Integration Studio generates "ERROR 22-322: Syntax error, expecting one of the following:..." By feedproxy.google.com Published On :: Wed, 6 May 2020 12:38:17 EST If your business key column is a name literal, like " business key "n, a syntax error occurs when that variable name does not follow standard SAS naming conventions. Full Article DATABUILDER+SAS+Data+Integration+Studio
3 Problem Notes for SAS®9 - 64459: A SAS Data Integration Studio job receives an error that states "The name '; index_name '; has the wrong number of qualifiers" By feedproxy.google.com Published On :: Wed, 6 May 2020 12:37:37 EST An error occurs because of an incorrectly generated CREATE INDEX clause in an SQL query that is sent to DB2 when the DB2 schema value is SESSION . The error message says "The name '; index_name '; has the wrong number of qualifie Full Article DATABUILDER+SAS+Data+Integration+Studio
3 Problem Notes for SAS®9 - 65935: The UNICODE function does not support Numeric Character Representation (NCR) for a surrogate pair By feedproxy.google.com Published On :: Wed, 6 May 2020 09:33:48 EST Using the NCR form of a surrogate pair as an input string to the UNICODE function does not convert the string to the appropriate display character. Full Article BASE+Base+SAS