hr Police watchdog lead defends Chris Kaba decision By www.bbc.com Published On :: Mon, 04 Nov 2024 05:57:38 GMT Sal Naseem tells the BBC he wasn't convinced Mr Kaba presented a sufficient danger to justify being shot. Full Article
hr Watch: How Covent Garden gets its Christmas tree By www.bbc.com Published On :: Tue, 12 Nov 2024 05:33:21 GMT The journey of this year's tree from the West Midlands to the West End ahead of tonight's switch on. Full Article
hr “If the Democrats could fight wars as well as they execute Election Fraud, we would have obliterated all of our many enemies throughout the World, and would have nothing to worry about!” ~ Donald J. Trump By powderedwigsociety.com Published On :: Sun, 29 Aug 2021 14:34:49 +0000 Touché! .@POTUS45: "If the Democrats could fight wars as well as they execute Election Fraud, we would have obliterated all of our many enemies throughout the World, and would have nothing to worry about!" pic.twitter.com/GpMO46zrNQ — Natalie Harp (@NatalieJHarp) August […] The post “If the Democrats could fight wars as well as they execute Election Fraud, we would have obliterated all of our many enemies throughout the World, and would have nothing to worry about!” ~ Donald J. Trump appeared first on Powdered Wig Society. Full Article 2020 presidential election 2020 election fraud afghanistan donald trump
hr McCarthy Threatens Motion To Oust Pelosi If She Attempts Impeachment By hispolitica.com Published On :: Thu, 24 Sep 2020 00:06:37 +0000 House Minority Leader Kevin McCarthy (R-CA) threatened to introduce a motion on the floor to oust House Speaker Nancy Pelosi (D-CA) as speaker if she attempts to impeach President Trump for “following the constitution” to slow down the Supreme Court confirmation process to fill the vacancy for the late Justice Ruth Bader Ginsburg. “I will […] The post McCarthy Threatens Motion To Oust Pelosi If She Attempts Impeachment appeared first on Hispolitica. Full Article U.S. Congress Andy Biggs Freedom Caucus George Stephanopoulos House impeachment Kevin McCarthy mitch mcconnell motion to vacate nancy pelosi president trump Ruth Bader Ginsburg supreme court This Week
hr Princess of Wales to host Christmas carol service again this year By www.bbc.com Published On :: Wed, 13 Nov 2024 06:18:51 GMT The princess has begun to return to some public duties since finishing chemotherapy in September. Full Article
hr 2 Good 2 Bad: Timber's bizarre throw-in fail and a goal of the month? By www.bbc.com Published On :: Mon, 11 Nov 2024 00:04:40 GMT A bizarre throw in from Arsenal's Jurrien Timber, and a goal of the season contender from Brentford's Yoane Wissa feature in this week's '2 Good, 2 Bad' from Match of the Day 2. Full Article
hr velocityconf: @tsantero @garethr No, there's just a lot that goes into producing #velocityconf. Plus the chairs are getting ready for Santa Clara + NY! :) By twitter.com Published On :: Mon, 20 May 2013 16:50:15 +0000 velocityconf: @tsantero @garethr No, there's just a lot that goes into producing #velocityconf. Plus the chairs are getting ready for Santa Clara + NY! :) Full Article
hr Understanding through history By www.readingrockets.org Published On :: Tue, 22 Mar 2022 17:30 EDT War is back in daily headlines. It’s devastating to think about the impact on children here and where the actual fighting is taking place. Full Article
hr How parents can help children with ADHD thrive in friendships By www.kqed.org Published On :: Tue, 11 Jul 2023 13:34:12 EDT Parents of kids with ADHD often say their kids miss social cues, such as when peers are bored, hurt or offended, according to Amori Mikami, a psychology professor at the University of British Columbia in Canada. “It can lead to a lot of outbursts or temper tantrums or whining and complaining or arguing with the friend,” she said. Mikami researches peer relationships, specifically focusing on children with ADHD. Additionally, she developed a parental friendship coaching (PFC) model where parents of elementary school-age kids can learn to support their child in making friends. Full Article
hr Three Benefits of Promoting Digital Goods and Software Products By blog.avangate.com Published On :: Thu, 20 Dec 2018 00:00:00 +0000 Are you dreaming of being your own boss someday, or would you like to bring in extra income? Starting an online business is one of the easiest ways to accomplish this. The biggest challenge of starting an online business can be developing your business plan. If you are struggling to come up with that brilliant […] Full Article
hr News24 | At least 30 killed in Mozambique since start of election violence: HRW By www.news24.com Published On :: Friday Nov 08 2024 18:12:23 Human Rights Watch (HRW) said Friday that at least 30 people have been killed in Mozambique in almost three weeks of crackdowns on protests over a disputed presidential election. Full Article
hr AI labs – Learning unsupervised learning through Robotics By www.opengardensblog.futuretext.com Published On :: Sun, 06 May 2018 17:24:21 +0000 We are launching an AI lab. The goal is to learn unsupervised learning through Robotics (Cobots) Long seen as a poor cousin to supervised learning - with Variational autoencoders, Reinforcement learning and Generative-Adversarial networks , unsupervised learning techniques have moved beyond the limitations of autoencoders. From Oct 2018 to March 2019 , we are running a [...] Full Article BIG DATA FEATURED POSTS LATEST POSTS
hr NASA plans to grow mushroom houses on the moon By boingboing.net Published On :: Tue, 01 Oct 2024 18:37:53 +0000 With NASA's sights on moon bases, the question becomes how do you build shelters for tomorrow's lunar inhabitants? Carting up large amounts of raw materials from Earth is prohibitively expensive. And the only resources on the surface are regolith—lunar dust—and water. — Read the rest The post NASA plans to grow mushroom houses on the moon appeared first on Boing Boing. Full Article Post moon NASA Space
hr Enterprise Software: Saas vs. the Big Three By communicationtransformation.blogspot.com Published On :: Tue, 14 Jul 2009 11:03:00 +0000 Forbes.com published an article by Dan Woods where he describes a battle between the traditional enterprise software providers (Microsoft, SAP, and Oracle) and Saas providers like Salesforce.com and NetSuite.According to Woods, SaaS applications are easier to use because they offer streamlined interfaces that are modeled after successful web consumer sites like Amazon.com, Yahoo!, eBay, Google, etc. These SaaS interfaces were designed to be easily configurable.Traditional enterprise software is not as easy to use because user interfaces are often created before it is known exactly how the software would be used. Customization to the user interface is often done at installation by systems integrators who do not have any actual user behavior on which to base their customizations.The Big Three are well aware of the usability gap between their products and SaaS software, but it is unclear how to solve the problem. Oracle emphasizes Fusion as an integration platform. SAP recently announced an experiment called Blue Ruby that is attempting to adapt Ruby on Rails as a user interface and programming technology for its applications. But is it possible to affordably automate a business starting with a configurable application platform that must be adapted to the specific user interfaces and business processes in a company? The SaaS model starts with a usable interface and a working automation of common processes, and then has the configuration proceed from there. The hosted nature of SaaS removes the deployment barriers.IVT software is the only webcasting and digital asset management applications available both as a SaaS and as a behind-the-firewall installation. With webcasting software, the divide has included the question: should there be proprietary hardware or should the solution be software-only.IVT falls on the software-only side, believing that "black box" proprietary hardware is not scalable and is prone to obsolescence.IVT software on a SaaS basis works with the network infrastructure that already exists, which is one of the competitive advantages we take to the enterprise video battle. Full Article
hr Will These Deranged Celebrities Who Promised To End Their Lives Or Flee The Country If Trump Wins Actually Follow Through? By conservativefiringline.com Published On :: Mon, 11 Nov 2024 00:15:19 +0000 The following article, Will These Deranged Celebrities Who Promised To End Their Lives Or Flee The Country If Trump Wins Actually Follow Through?, was first published on Conservative Firing Line. (Natural News) Similar to what happened in 2016, a host of celebrities and influencers made wild claims that they would leave the country or even end their lives if Donald Trump won another term in the White House. Will any of them actually follow through? Take Rob Reiner, for instance. He promised to “set himself on … Continue reading Will These Deranged Celebrities Who Promised To End Their Lives Or Flee The Country If Trump Wins Actually Follow Through? ... Full Article Politics Bono celebrities Drano kill leave meltdown Midler suicide
hr Trump Scores Three Big Wins Less Than One Day After The Election By clashdaily.com Published On :: Thu, 07 Nov 2024 10:00:34 +0000 While the rest of us were busy cheering (or crying) about the election results, the world kept turning and events continued to unfold at home and around the world. The post Trump Scores Three Big Wins Less Than One Day After The Election appeared first on Clash Daily. Full Article News Clash
hr BOOM: Trump’s Lawyers SAVAGE Letitia James… Threaten PRISON If She Plays More Of Her Games By clashdaily.com Published On :: Fri, 08 Nov 2024 11:05:28 +0000 If anyone could accuse Trump of being on 'defense' during his witch-hunt trials, he's going on full offense now. The post BOOM: Trump’s Lawyers SAVAGE Letitia James… Threaten PRISON If She Plays More Of Her Games appeared first on Clash Daily. Full Article Videos
hr Basecamp has offset our cumulative emissions through 2019 By signalvnoise.com Published On :: Fri, 30 Oct 2020 19:07:02 +0000 Earlier this year, we announced that Basecamp was committing to getting to carbon negative for our cumulative history and moving forward. Today, I want to share an update on that commitment. Note: I edited this post on Nov 5, 2020 to include the prices paid for all carbon offsets and explain a little more about the… keep reading Full Article Uncategorized
hr 30 Years of Non-Maghreb: What next for Algeria-Morocco relations? By www.chathamhouse.org Published On :: Tue, 13 Aug 2024 16:27:13 +0000 30 Years of Non-Maghreb: What next for Algeria-Morocco relations? 10 September 2024 — 2:00PM TO 3:15PM Anonymous (not verified) 13 August 2024 Online Experts discuss Algeria-Morocco relations and implications for regional actors. In 1989, the establishment of the Arab Maghreb Union (UMA) brought a promise of economic integration and strengthening of ties between Algeria, Libya, Mauritania, Morocco and Tunisia for the benefit and prosperity of their societies.Decades on, very little has been accomplished in developing the Maghreb project, and the region remains one of the least integrated in the world, despite significant social and cultural similarities between member countries. The last time the full UMA leadership met was back in 1994, with August 2024 marking 30 years of closed borders between Algeria and Morocco.Relations between the two largest Maghreb countries have deteriorated further since 2020 due to disagreements over issues of Western Sahara, and, most recently, the Abraham Accords, with Algeria cutting diplomatic ties with Morocco in 2021.In this webinar, experts will discuss:Which primary obstacles are hindering Maghreb integration and Algeria-Morocco relations?What are the costs and implications for regional countries?What are the positions of Libya, Tunisia, and Mauritania?What is required for a rapprochement and how can external partners support this? Full Article
hr In conversation with HRH Prince Turki AlFaisal By www.chathamhouse.org Published On :: Fri, 16 Aug 2024 09:27:14 +0000 In conversation with HRH Prince Turki AlFaisal 13 September 2024 — 11:00AM TO 12:00PM Anonymous (not verified) 16 August 2024 Chatham House and Online This event will discuss how the ongoing Gaza war is impacting the region and the role external actors can play to support de-escalation. The Gaza war, now in its tenth month, continues with ever-worsening consequences for Palestinians and no end in sight. The Israeli-Palestinian conflict has also heightened tensions across the Middle East with fears of a broader regional war that would include Iran and aligned groups from the ‘axis of resistance’.Against this backdrop, ceasefire negotiations supported by regional and international mediators, have not amounted to an agreement nor have there been any concrete proposals for a way forward out of the crisis by key actors such as the United States, Gulf countries or other key stakeholders.In this event, His Royal Highness Prince Turki AlFaisal will discuss how the Gaza war and related developments are impacting the Middle East, and will share his views on the role of regional and external actors in supporting de-escalation efforts.The addresses:How are Middle Eastern countries managing regional security and heightened tensions with Iran and aligned groups in Iraq, Lebanon and Yemen?What role are Gulf countries playing in efforts to de-escalate tensions?How can they support short- and long-term planning for a way forward in the Israeli-Palestinian conflict?How are relationships between Middle East countries and external powers such as the United States changing as a result of the Gaza war?In person places for this event are balloted. Confirmations will be sent by email on Monday 9 September at 3pm or a placed on the waiting list. Virtual registrations are confirmed immediately.Individual membership provides you with the complete Chatham House experience, connecting you with a unique global policy community. Find out more about membership. Full Article
hr How can young people in MENA thrive despite economic and political insecurity? By www.chathamhouse.org Published On :: Fri, 30 Aug 2024 12:47:13 +0000 How can young people in MENA thrive despite economic and political insecurity? 24 September 2024 — 2:00PM TO 3:00PM Anonymous (not verified) 30 August 2024 Online Experts share insights on how young people navigate challenges and find opportunities in a changing domestic and regional landscape. Across the Middle East and North Africa young people between the ages of 15 and 29 comprise around 24 per cent of the population in the region. As the complex regional geopolitical developments unfold, the majority of these young people are living in a time of economic and political insecurity, with many, such as Iraqis and Libyans, also growing up during conflict and uncertainty.Enhanced education and employment programs are key opportunities for development and stability in the region. Despite this, limited resources and competing priorities have meant that governments often struggle to deliver competitive educational and employment opportunities and lack the capacity and funding for education reform and active labour market policy development. Key tensions that pit modernity and autonomy against tradition and control continue to frame the education and skills development landscape.This webinar will address:The challenges young people within the MENA region face in different contexts;The role education and employment play in developing skills for 21st century challenges;Spaces for young people to practice citizenship and participate in political processes;Youth’s economic prospects while navigating the tumultuous backdrop of enduring conflict and authoritarianism. Full Article
hr Digital politics threatens democracy and must change By www.chathamhouse.org Published On :: Fri, 13 Jan 2023 16:08:06 +0000 Digital politics threatens democracy and must change Expert comment NCapeling 13 January 2023 Violence in Brazil has again brought into focus the need for technology platforms to prioritize social responsibility to help prevent anti-democratic action. Immediately following the violent storming of Brazil’s congressional building, supreme court, and presidential palace, comparisons to the infamous events of 6 January 2021 in the US came quickly and easily – and with good reason. Both Donald Trump and Jair Bolsonaro built a fervent – albeit inchoate – political base of grievance which included Christian evangelicals, gun enthusiasts, and the disenfranchised. Both cynically spread doubts about the election victories of their successors without evidence. And it has been claimed both incited their supporters to overturn these results. But this list of similarities extend beyond mere politics. The attack on democracy in Brazil was recorded, amplified, coordinated, and funded by exactly the same technologies used by the protesters in the US on 6 January. In Brazil, the main engines of misinformation and insurrection planning were Telegram, Facebook, and WhatsApp, although some election-denying diehards also shifted to Twitter. Tactical use of social media to mobilize and fundraise When Bolsonaro was originally elected in 2018, these platforms were already a medium for promoting disinformation, conspiracy, and fear. But in the lead-up to the violence of 8 January, they became a means by which ‘Bolsonaristas’ raised funding for an attack and mobilized supporters to come to Brasilia – advertising the availability of buses and even free food for marchers – using the Festa da Selma hashtag. Well-intentioned regulation will fall short so long as it is narrowly focused on a never-ending game of ‘content whack-a-mole’ and is hamstrung by powerful voices To avoid detection by authorities, organizers used a simple switch of the letter ‘v’ to ‘m’ so that Selva, meaning ‘jungle’, became Selma – which means ‘party in the jungle’ to those in the know. But the authorities in the Brasilia state of Distrito Federal appeared to care little about preventing the attack anyway. Civil society organizations have warned for decades that policies made in a Silicon Valley boardroom fit poorly to the realities of countries such as Brazil, Somalia, or Myanmar. Content moderation is a near-impossible task at the scale demanded by platforms as vast as those operated by big tech, and automated solutions are far from being a silver bullet as they create as many problems as they solve. Extremism has found an unfettered enabler on mainstream platforms, and an increasingly sprawling network of alternative tech has made such voices resilient to challenge. Platforms such as Gettr, Gab, and Telegram have become go-to platforms for extremist networks when fringe voices find themselves blocked by mainstream platforms. Telegram has come under significant scrutiny for the role it played in the storming of Congress in Brasilia but any number of tools and platforms – each with millions of users – could have achieved similar results. The sordid events in Brasilia are just the latest chapter in digital extremism and conspiracy- mongering which often erupts into anti-democratic violence, and should serve as a reminder of the urgent risks of disinformation and the role digital technology plays in inciting, coordinating, fundraising, and amplifying such events. But the checks on the power of private social media companies are still few and splintered. In Brazil, Supreme Court Justice Alexandre de Moraes, head of the elections tribunal, attempted to crack down on social media, banning users for spreading misinformation in a move which sparked complaints of censorship from Bolsonaro supporters. Following the elections, Moraes has advocated for greater judicial authority to regulate social media – but the justice is only one person and his impartiality is already being challenged given his aggressive pursuit of Bolsonaro supporters posting inflammatory messages. And one justice doing it alone only inflames an already volatile situation. Effective regulation of social media requires an independent body vested with multiparty support and operating under clearly-defined rules and authority. A global movement to find solutions Brazil is not alone in an increasingly frantic search for checks on digital power as dozens of regulatory regimes are springing up around the world. All are premised on platforms being responsible for their own fiefdoms, but few tackle the threat posed to democracy by unchecked corporate power over digital commons. Telegram has come under significant scrutiny for the role it played in the storming of Congress in Brasilia but any number of tools and platforms – each with millions of users – could have achieved similar results Well-intentioned regulation will fall short so long as it is narrowly focused on a never-ending game of ‘content whack-a-mole’ and is hamstrung by powerful voices who see any rules as an attack on freedoms of expression or corporate decision-making. Democracies are traditionally cautious in managing speech, in separating good information from bad information, or in defining acceptable politics. The steady watering down of the UK’s Online Safety Bill, now so thin on disinformation as to be essentially homeopathic, shows that democratic regulation is willing to go only so far in tackling challenges posed by digital politics. Full Article
hr SVB collapse shows interest rate financial stability threat By www.chathamhouse.org Published On :: Wed, 15 Mar 2023 19:39:36 +0000 SVB collapse shows interest rate financial stability threat Expert comment LJefferson 15 March 2023 Governments must resist pressure to relax post-financial crisis regulation, while central banks should moderate their attack on inflation if financial stability is at risk. The collapse of California’s Silicon Valley Bank (SVB) on 10 March has triggered a wave of volatility in global bank equity prices, raised questions about whether US bank regulation and its tech industry funding model are fit for purpose, and forced a rethink on the extent and pace of monetary policy tightening appropriate for the US and other advanced economies. SVB was the US’s 16th largest bank with total assets of $212bn at the end of 2022 and a presence in eight countries around the world, including the UK. Since it was founded 40 years ago, it has maintained a strong focus on the technology sector, claiming recently that nearly half of all US venture-backed technology and life science companies banked with it. Partly as a consequence, some 95 per cent of its deposits came from corporates and hedge funds, far higher than the one-third typical of similarly sized banks. What led to SVB’s collapse? Ironically, SVB’s failure did not result from its core business model of serving a relatively high-risk and fast-growing sector, but rather from a dramatic failure in liquidity management. During the pandemic, SVB saw a very large inflow of corporate deposits. But rather than disincentivizing depositors or investing the funds attracted in assets of matching maturity, it chose to invest them in low credit risk, but long maturity bonds attracted by a small pick-up in return over shorter-term assets. When US interest rates began to rise rapidly in 2022 following Russia’s invasion of Ukraine, the value of SVB’s long-term bond portfolio declined sharply. It was left facing a large capital loss of some $15bn, roughly equivalent to its total shareholder funds. The management attempted to repair SVB’s balance sheet last week by crystalizing some of the loss and raising new capital. But when this failed, the US supervisory authorities had no choice but to step in and close the institution. This action was quickly followed by emergency action from other regulators vis-a-vis SVB subsidiaries and offices around the world. Ironically, SVB’s failure did not result from its core business model of doing business with a relatively high-risk and fast-growing sector, but rather from a dramatic failure in liquidity management. The US entity has formally been taken over by the FDIC and a bridge bank established. All depositors have had their funds guaranteed, going beyond the normal federal deposit insurance limit of $250,000 per customer. However, bond holders and equity holders have been wiped out. The authorities have said that any loss will be covered by the industry as a whole via the FDIC. In the UK, the Bank of England was able to sell the ring-fenced UK subsidiary of SVB to HSBC for £1 over the weekend, so that all its depositors and other liability holders have effectively had their funds guaranteed. In contrast to previous Bank of England rescues (such as Johnson Matthey Bank in 1984, the ‘small banks’ crisis in 1991 and the global financial crisis in 2008-9) no public money has been put at risk. Four key questions SVB’s rapid collapse raises four central questions: First, how was it that the bank was able to take on such a risky interest rate maturity mismatch in its US operations? Maturity transformation is standard banking industry practice, but it is usually closely monitored by regulators who place limits on the extent of interest rate maturity mismatch and require liquidity buffers to offset the risk of deposit flight and forced asset sales. SVB’s very high concentration of corporate deposits as compared to ‘sticky’ retail deposits, means that the risk of deposit flight was unusually high and so the bank should have been more, not less, cautious in its liquidity policy. SVB was classed as a regional bank in the US which means that it did not have to meet international regulatory standards under Basle III. And in 2018, the Trump administration approved legislation removing the post-financial crisis requirement that banks with assets under $250bn submit to stress testing and relaxing liquidity buffer requirements. But it is still hard to understand why regulators allowed SVB to commit such a classic banking error. On Monday, the Federal Reserve ordered an inquiry into what it has correctly described as a regulatory failure. This should look at the role played by all the elements of the oversight system including the auditors, KPMG. In 2018, the Trump administration approved legislation removing a post-financial crisis (regulatory) requirement…but it is still hard to understand why regulators allowed SVB to commit such a classic banking error. Second, does SVB’s failure reflect a much bigger underlying risk in the US banking sector, and potentially other banking systems around the world, built up over the prolonged period of ultra-low interest rates? SVB’s collapse was followed by the failure of the $110bn Signature Bank in New York, as well as sharp falls in US regional bank stock prices – by close of play on 14 March, the S&P Regional Bank Index was down 22 per cent on a week before, with some individual bank stocks seeing much sharper falls. To the extent that banks have been covered by international bank regulatory requirements, the risk of a much broader problem should be limited because stress testing and other regulatory tests would have looked at precisely the scenario that has happened. Even where large market losses have been incurred, capital buffers should be sufficient to cover them. But as SVB has shown, there are some large banks that are seemingly not required to follow international rules, while the latest developments at Credit Suisse indicate that market concerns may still arise when other factors are in play. SVB’s collapse was followed by the failure of the $110bn Signature Bank in New York, as well as sharp falls in US regional bank stock prices. Third, how far, in the light of the potential vulnerability in banking systems, should central banks in advanced countries moderate their efforts to squeeze out inflationary pressures? While inflation already appears to have peaked in many economies and the pace of interest rate rises was expected to slow, inflation is far from vanquished, as recent data in the US has demonstrated. Fourth, does the failure of SVB tell us something new about the financial risks facing the high technology sector? It was remarkable that a single (and not particularly large, by international standards) financial institution could have played such a central role in the tech sector in both the US and UK. Why was this the case and does it reflect special features of the tech/start-up sector (e.g. the need for substantial cash deposits to cover relatively large negative cash flows in the early years of operation, or the need for highly specialized lending expertise). If so, should governments take steps to mitigate such risks, given the outsized importance of this sector in many national economic strategies? Full Article
hr Phosphoproteome Analysis of E. coli Reveals Evolutionary Conservation of Bacterial Ser/Thr/Tyr Phosphorylation By www.mcponline.org Published On :: 2008-02-01 Boris MacekFeb 1, 2008; 7:299-307Research Full Article
hr PaxDb, a Database of Protein Abundance Averages Across All Three Domains of Life By www.mcponline.org Published On :: 2012-08-01 M. WangAug 1, 2012; 11:492-500Technological Innovation and Resources Full Article
hr Extending the Limits of Quantitative Proteome Profiling with Data-Independent Acquisition and Application to Acetaminophen-Treated Three-Dimensional Liver Microtissues By www.mcponline.org Published On :: 2015-05-01 Roland BrudererMay 1, 2015; 14:1400-1410Research Full Article
hr A Multidimensional Chromatography Technology for In-depth Phosphoproteome Analysis By www.mcponline.org Published On :: 2008-07-01 Claudio P. AlbuquerqueJul 1, 2008; 7:1389-1396Research Full Article
hr Development and validation of a high-throughput whole cell assay to investigate Staphylococcus aureus adhesion to host ligands [Microbiology] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 Staphylococcus aureus adhesion to the host's skin and mucosae enables asymptomatic colonization and the establishment of infection. This process is facilitated by cell wall-anchored adhesins that bind to host ligands. Therapeutics targeting this process could provide significant clinical benefits; however, the development of anti-adhesives requires an in-depth knowledge of adhesion-associated factors and an assay amenable to high-throughput applications. Here, we describe the development of a sensitive and robust whole cell assay to enable the large-scale profiling of S. aureus adhesion to host ligands. To validate the assay, and to gain insight into cellular factors contributing to adhesion, we profiled a sequence-defined S. aureus transposon mutant library, identifying mutants with attenuated adhesion to human-derived fibronectin, keratin, and fibrinogen. Our screening approach was validated by the identification of known adhesion-related proteins, such as the housekeeping sortase responsible for covalently linking adhesins to the cell wall. In addition, we also identified genetic loci that could represent undescribed anti-adhesive targets. To compare and contrast the genetic requirements of adhesion to each host ligand, we generated a S. aureus Genetic Adhesion Network, which identified a core gene set involved in adhesion to all three host ligands, and unique genetic signatures. In summary, this assay will enable high-throughput chemical screens to identify anti-adhesives and our findings provide insight into the target space of such an approach. Full Article
hr Identification of a domain critical for Staphylococcus aureus LukED receptor targeting and lysis of erythrocytes [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-11T00:06:21-08:00 Leukocidin ED (LukED) is a pore-forming toxin produced by Staphylococcus aureus, which lyses host cells and promotes virulence of the bacteria. LukED enables S. aureus to acquire iron by lysing erythrocytes, which depends on targeting the host receptor Duffy antigen receptor for chemokines (DARC). The toxin also targets DARC on the endothelium, contributing to the lethality observed during bloodstream infection in mice. LukED is comprised of two monomers: LukE and LukD. LukE binds to DARC and facilitates hemolysis, but the closely related Panton–Valentine leukocidin S (LukS-PV) does not bind to DARC and is not hemolytic. The interaction of LukE with DARC and the role this plays in hemolysis are incompletely characterized. To determine the domain(s) of LukE that are critical for DARC binding, we studied the hemolytic function of LukE–LukS-PV chimeras, in which areas of sequence divergence (divergence regions, or DRs) were swapped between the toxins. We found that two regions of LukE's rim domain contribute to hemolysis, namely residues 57–75 (DR1) and residues 182–196 (DR4). Interestingly, LukE DR1 is sufficient to render LukS-PV capable of DARC binding and hemolysis. Further, LukE, by binding DARC through DR1, promotes the recruitment of LukD to erythrocytes, likely by facilitating LukED oligomer formation. Finally, we show that LukE targets murine Darc through DR1 in vivo to cause host lethality. These findings expand our biochemical understanding of the LukE–DARC interaction and the role that this toxin-receptor pair plays in S. aureus pathophysiology. Full Article
hr Trump and his growing number of European allies threaten the European project By www.chathamhouse.org Published On :: Fri, 08 Nov 2024 14:03:05 +0000 Trump and his growing number of European allies threaten the European project Expert comment LToremark 8 November 2024 With Trump in the White House, a key challenge for Europe will be the growing transatlantic illiberal ties which risk undermining European unity. As the US presidential election result became clear, European leaders followed a similar formula when congratulating President-elect Trump. They offered their congratulations, mentioned previous good working relations with the US (special points for a nod to long-standing relations), and – most importantly – emphasized the need for this to continue for the benefit of the citizens of both their country and the US.The formula was a telling sign of the political bartering most European heads of state expect with Trump back in the White House. The exception, of course, were Trump’s European allies who were simply ecstatic.Transatlantic illiberalismTrump’s growing number of European allies and the increase of illiberalism and populism is perhaps the most worrying development for Europe. In 2016, some of Trump’s counterparts in Europe were Angela Merkel in Germany, Emmanuel Macron in France, Mark Rutte in the Netherlands, and Giuseppe Conte in Italy. Regardless of their record, they were moderates. What European populist leaders have in common is a deep-seated scepticism of the EU and a desire to erode it from within. The picture looks very different today. Anti-war extremist parties Alternative for Germany and the Sahra Wagenknecht Alliance are on the rise in Germany. In France, pro-Russia Marine le Pen has been able to reduce support for Ukraine from €3 billion to €2 billion in the draft French budget. In the Netherlands, the far-right Freedom Party is the biggest coalition partner. In Italy, Prime Minister Georgia Meloni hails from a neo-fascist party. Hungarian Prime Minister Viktor Orbán’s populist and illiberal playbook is being replicated across Europe. Related content Independent Thinking: Is the far-right a threat to the European Union? Meanwhile in Poland, moderate prime minister, Donald Tusk, is experiencing the difficulties of reversing damage done by the previous populist government.What European populist leaders have in common is a deep-seated scepticism of the EU and a desire to erode it from within. And many of these leaders also welcome the return of Trump.It is no coincidence that Orbán scheduled the European Political Community Summit, hosted by Hungary, to take place just days after the US election. The Trump win was an added bonus. This meant European heads of state travelled to Budapest for the summit still reeling from – or rejoicing at – the election result. Orbán would like to position himself as Trump’s man in Europe. He has spent the past four years building ties with the president-elect and the MAGA wing of the Republican party. Trump even namechecked Orbán – a Eurosceptic Putin-supporter – during the presidential debate.Italy’s Meloni, meanwhile, has so far worked with EU institutions and NATO rather than against them: she has supported EU and NATO resolutions for Ukraine and demonstrated opposition to Russia. But this may have been a strategic calculation. She likely looked at her country’s balance sheet and realized she needed the European Commission’s COVID-19 recovery funds. But with the fund coming to an end and given her history of Euroscepticism and pro-Russian views, the transatlantic illiberal ties mean she may now feel emboldened to revise her positions. She is already deploying the illiberal playbook domestically.Policy implications for Europe of a second Trump term Despite some ideological similarities, Trump’s policies will not be good for his European allies. He has threatened to impose 10 to 20 per cent tariffs on all EU imports. For Italy and the Netherlands, the second and fifth largest EU exporters to the US, this would have direct negative impacts on their economies. Despite some ideological similarities, Trump’s policies will not be good for his European allies. Increased tariffs on Chinese goods – Trump has threatened up to 60 per cent – would also have an impact on Europe’s economies. Rerouting of Chinese goods could see China dump overproduction in Europe, one of the few remaining relatively open markets, and make European products compete with cheaper Chinese goods in Europe and on the global market. Neither of these developments are positive for export-led European countries. In France, the EU’s fourth largest exporter to the US, Marine le Pen – previously a strong supporter of Trump – had a notably muted response to his victory due to concerns over a trade war. Related content Independent Thinking: What does Donald Trump’s re-election mean for the world? Even European leaders who might have hoped for a different election outcome may seek to hedge their bets. There are two things that are clear about Trump: he is unpredictable and transactional. It is quite possible that some European states, in particular frontline states with genuine fears over Russia’s imperialist ambitions, will seek to buy Trump’s support through bilateral arms deals – despite their distaste for Trump’s position vis-à-vis Russia. These countries already have some of the highest defence spending in NATO, with Poland, Estonia and Latvia leading the way, so this will not irk Trump – arms deals would simply be an additional insurance premium.Countries rushing to make bilateral deals with the US risks a similar uncoordinated race for American arms deals as during Trump’s first term. This would in turn undermine much-needed European defence industrial cooperation efforts. As the need to reduce dependencies on third countries – even for defence equipment from historically close allies – has become increasingly clear, this would be a problematic development.The silver lining may be that it could galvanize the UK and the EU just enough to take action on UK-EU security and defence cooperation, of which the defence industrial piece is the most essential.Europe disunitedThe transatlantic link between populist, illiberal leaders should be a concern. Trump is no longer isolated in Europe, he is rapidly accumulating allies among European heads of state. These leaders agree on the perceived existential threat posed by migration, the need for so-called ‘traditional family values’ and ‘anti-wokeism’. But beyond that, they share and want to advance an illiberal view of the world, with ramifications from security and global trade to human rights – and directly threatening the European project. Full Article
hr Members’ Christmas drinks By www.chathamhouse.org Published On :: Mon, 11 Nov 2024 12:02:28 +0000 Members’ Christmas drinks 11 December 2024 — 6:00PM TO 8:00PM Anonymous (not verified) 11 November 2024 Chatham House Join us at 10 St James’s Square for a chance to raise a glass with fellow Chatham House members and staff. This evening is a special opportunity to meet fellow Chatham House members and staff around the Christmas tree.Please note this reception is open to members of Chatham House only. Regrettably, we are unable to register non-member guests.The institute occupies a position of respect and trust, and is committed to fostering inclusive dialogue at all events. Event attendees are expected to uphold this by adhering to our code of conduct. Full Article
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hr Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase By www.jlr.org Published On :: 2000-02-01 Jorge H. CapdevilaFeb 1, 2000; 41:163-181Reviews Full Article
hr Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3 By www.jlr.org Published On :: 2000-09-01 Mohamad NavabSep 1, 2000; 41:1495-1508Articles Full Article
hr Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1 By www.jlr.org Published On :: 2000-09-01 Mohamad NavabSep 1, 2000; 41:1481-1494Articles Full Article
hr Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics By www.jlr.org Published On :: 2008-05-01 Vitali MatyashMay 1, 2008; 49:1137-1146Methods Full Article
hr The UK must not sleepwalk into leaving the ECHR By www.chathamhouse.org Published On :: Fri, 17 Mar 2023 18:57:59 +0000 The UK must not sleepwalk into leaving the ECHR Expert comment NCapeling 17 March 2023 Talk of the UK leaving the European Convention on Human Rights (ECHR) keeps rearing its head with little thought for the real impact. Withdrawal from the European Convention on Human Rights (ECHR) has not been firmly ruled out as a potential UK government policy option to allow easier implementation of its controversial new measures to deport asylum seekers to Rwanda. This, in the context of a UK general election looming and tackling the ‘small boats problem’ being one of the five priorities of UK prime minister Rishi Sunak. In recent months, ECHR withdrawal has come up in relation to the UK’s controversial draft Illegal Migration Bill, the (now shelved) bill of rights, and – perhaps most significantly – the Northern Ireland Protocol deal with implications for the Good Friday Agreement. But leaving the ECHR – and likely the Council of Europe – would be counterproductive for the UK’s global leadership. UK values and priorities will be undermined The only other countries in the region outside of the Council of Europe, Russia and Belarus, both had sanctions imposed on them by the UK for their human rights record. Russia was expelled from the Council of Europe in 2022 due to its aggression in Ukraine and, although the UK would be deciding to remove itself from Europe’s oldest and largest intergovernmental human rights body, the optics would not be good. This is especially true considering the UK’s vocal support for Ukraine in international forums, including its intervention in Ukraine’s case against Russia before the International Court of Justice and, potentially, in a separate case against Russia before the European Court of Human Rights itself. If the UK withdraws from the ECHR, the EU would be entitled to terminate important provisions concerning international law enforcement and judicial cooperation in criminal justice matters More significantly and closer to home, the ECHR is a fundamental part of the Good Friday Agreement. It is difficult to argue UK withdrawal would not breach the agreement. As well as risking damage to intercommunal relations, such a breach is likely to significantly harm strategic relations with the US – and President Biden is set to visit Northern Ireland and the Republic of Ireland to mark the 25th anniversary of the Good Friday Agreement. It would also damage relations with the UK’s closest neighbours, Ireland, and the European Union (EU), with whom the prime minister has only recently scored credits for securing the Northern Ireland Protocol deal. If the UK withdraws from the ECHR, the EU would be entitled to terminate important provisions concerning international law enforcement and judicial cooperation in criminal justice matters under Article 692 of the UK-EU Trade and Cooperation Agreement, further isolating the UK from allies who share its legal and other values. Withdrawal would be in the name of sovereignty but with little thought to the practical implications on rights and few perceived gains from doing so. But the idea could easily gain traction by erroneously conflating the Strasbourg court and Council of Europe (of which the UK is a member) with the European Union (which the UK has left). This means leaving the ECHR could easily be confused as a post-Brexit ‘tidy up’ exercise of taking back control from the EU when the reality is the UK would be withdrawing from a completely different regional body. It would also be at odds with the UK’s Integrated Review Refresh which, reassuringly, contains references to the UK’s commitment to the rule of law, ‘respect for the fundamental principles of the UN Charter and international law’, and ‘universal human rights that underpins our democracy’. This would make the UK far less able to champion international law and influence states with long records of human rights violations, and run contrary to UK strategic priorities such as tackling aggression from Russia and China, its support for multilateralism, and its global legal leadership. There are many reasons beyond simply human rights concerns which are preventing migrants being deported to Rwanda All this loss would come for little gain. Before going down this path, there must be a clearer understanding about exactly what concerns there are about the ECHR, and whether they stand up to scrutiny. Are they about UK sovereignty, specific issues about the European Court of Human Rights, or about the rights and obligations contained in the Convention? The latter would raise a far bigger question on the UK’s commitment to other international treaties, such as the International Covenant on Civil and Political Rights and the UN Convention on Rights of the Child, as many ECHR obligations also exist elsewhere in both common law and international law. The need for cool heads and a long-term view The significant concerns surrounding proposals in the Illegal Migration bill have been well-documented, including in relation to obligations under the ECHR and UN Refugee Convention. There are many reasons beyond simply human rights concerns which are preventing migrants being deported to Rwanda, including the fact there are insufficient countries with which the UK has agreements to allow for deportation. Full Article
hr The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm [Computational Biology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Mammalian circadian clocks are driven by transcription/translation feedback loops composed of positive transcriptional activators (BMAL1 and CLOCK) and negative repressors (CRYPTOCHROMEs (CRYs) and PERIODs (PERs)). CRYs, in complex with PERs, bind to the BMAL1/CLOCK complex and repress E-box–driven transcription of clock-associated genes. There are two individual CRYs, with CRY1 exhibiting higher affinity to the BMAL1/CLOCK complex than CRY2. It is known that this differential binding is regulated by a dynamic serine-rich loop adjacent to the secondary pocket of both CRYs, but the underlying features controlling loop dynamics are not known. Here we report that allosteric regulation of the serine-rich loop is mediated by Arg-293 of CRY1, identified as a rare CRY1 SNP in the Ensembl and 1000 Genomes databases. The p.Arg293His CRY1 variant caused a shortened circadian period in a Cry1−/−Cry2−/− double knockout mouse embryonic fibroblast cell line. Moreover, the variant displayed reduced repressor activity on BMAL1/CLOCK driven transcription, which is explained by reduced affinity to BMAL1/CLOCK in the absence of PER2 compared with CRY1. Molecular dynamics simulations revealed that the p.Arg293His CRY1 variant altered a communication pathway between Arg-293 and the serine loop by reducing its dynamicity. Collectively, this study provides direct evidence that allosterism in CRY1 is critical for the regulation of circadian rhythm. Full Article
hr Stop codon read-through of mammalian MTCH2 leading to an unstable isoform regulates mitochondrial membrane potential [Gene Regulation] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3' UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3' UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through–deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential. Full Article
hr Hepatocyte nuclear factor 1{beta} suppresses canonical Wnt signaling through transcriptional repression of lymphoid enhancer-binding factor 1 [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β. Full Article
hr Competing visions of Europe are threatening to tear the union apart By www.chathamhouse.org Published On :: Mon, 10 Feb 2020 16:18:01 +0000 Source The Observer URL https://www.theguardian.com/commentisfree/2018/jul/01/three-competing-visions-of... Release date 01 July 2018 Expert Hans Kundnani In the news type Op-ed Hide date on homepage Full Article
hr The HRDC domain oppositely modulates the unwinding activity of E. coli RecQ helicase on duplex DNA and G-quadruplex [Enzymology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RecQ C-terminal domain, and an auxiliary element helicase and RNaseD C-terminal (HRDC) domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3'-partial duplex and fork DNA with a moderate processivity and periodically patrols on the ssDNA in the 5'-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA-binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms. Full Article
hr The Ukraine war and threats to food and energy security By www.chathamhouse.org Published On :: Wed, 06 Apr 2022 09:17:14 +0000 The Ukraine war and threats to food and energy security 13 April 2022 — 12:00PM TO 1:00PM Anonymous (not verified) 6 April 2022 Online What are the potential impacts on food and energy markets emerging from the situation in Ukraine? Russia and Ukraine are key players in global energy, food, fertilizer and mineral markets. In the first few days after Russia’s invasion, both the threat and reality of resource flows being reduced drove up global prices, and has impacted the day-to-day life of people and businesses around the world. Developing and nutrition-fragile countries across Africa and the Middle East will be hit the hardest – Somalia, for example, is reliant on Russia and Ukraine for 100 per cent of its wheat imports and is currently experiencing its worst drought in years. The potential scale of disruption to food and energy markets increases with every week the war continues. This event launches the Environment and Society programme’s latest briefing paper The Ukraine war and threats to food and energy security: Cascading risks from rising prices and supply disruptions. The panel discusses: The political, socio-economic and resource pressures already faced by the international community prior to Russia’s invasion of Ukraine. Direct and cascading impacts on the complex and interconnected energy, minerals, food and fertilizer markets, and policy or market responses that may exacerbate these impacts. Geopolitical ramifications that will affect the evolution of the conflict, as well as longer-term international cooperation and security. Measures that governments can take to build resilience, both to the ongoing impacts of the situation in Ukraine and to future risks of market disruption and geopolitical upheaval. Full Article
hr The Rohingya Crisis: Three Years On By www.chathamhouse.org Published On :: Wed, 09 Sep 2020 08:05:01 +0000 The Rohingya Crisis: Three Years On 17 September 2020 — 1:30PM TO 2:15PM Anonymous (not verified) 9 September 2020 Online Speakers examine the current situation of the Rohingya people and assess the threat that COVID-19 poses to the health and human rights of refugees and displaced people. It has been three years since a military-led crackdown forced more than 740,000 Rohingya to flee across the border into Bangladesh to escape collective punishment and violence in Myanmar. Most refugees have sought shelter in Bangladesh’s Cox’s Bazar district, where access to clean water is limited, sanitation facilities are lacking, and due to overcrowding, social distancing is impossible. While the number of reported COVID-19 cases has so far been relatively low, testing capacity remains limited and anecdotal reports from humanitarians suggest that COVID-19 has spread extensively through the refugee camps and the Bangladeshi host community. The speakers also consider the different approaches taken by neighbouring states, regional and international organizations in responding to the crisis. What can be done to address the needs of refugees in the short term and how can fundamental human rights be restored and protected during the time of COVID-19? What aid provision has been successfully delivered within Rakhine State and in what ways? Ahead of elections in Myanmar in November, how can the international community persuade the Myanmarese government into positive action? And what would a sustainable solution to the Rohingya crisis look like and what are the competing views over how such a solution should be delivered? This event is held in partnership with The Atlantic Council. Full Article
hr From discrete to continuous: Monochromatic 3-term arithmetic progressions By www.ams.org Published On :: Mon, 21 Oct 2024 15:01 EDT Torin Greenwood, Jonathan Kariv and Noah Williams Math. Comp. 93 (), 2959-2983. Abstract, references and article information Full Article
hr Explaining Wildfires Through Curvature By www.ams.org Published On :: Tue, 17 Oct 2023 10:33:14 -0400 Dr. Valentina Wheeler of University of Wollongong, Australia, shares how her work influences efforts to understand wildfires and red blood cells. In Australia, where bushfires are a concern year-round, researchers have long tried to model these wildfires, hoping to learn information that can help with firefighting policy. Mathematician Valentina Wheeler and colleagues began studying a particularly dangerous phenomenon: When two wildfires meet, they create a new, V-shaped fire whose pointed tip races along to catch up with the two branches of the V, moving faster than either of the fires alone. This is exactly what happens in a mathematical process known as mean curvature flow. Mean curvature flow is a process in which a shape smooths out its boundaries over time. Just as with wildfires, pointed corners and sharp bumps will change the fastest. Full Article