end News24 | US climate action won't end with Trump, envoy tells COP29 By www.news24.com Published On :: Monday Nov 11 2024 19:00:27 Washington's top climate envoy sought to reassure countries at the CO29 talks Monday that Donald Trump's re-election would not end US efforts to tackle global warming. Full Article
end News24 | 'A just and comprehensive peace': Arab-Muslim summit demands end to Israel occupation By www.news24.com Published On :: Tuesday Nov 12 2024 07:00:12 Arab and Muslim leaders demanded that Israel withdraw from occupied Palestinian territories as a precondition for regional peace, while denouncing "shocking" Israeli crimes in war-ravaged Gaza. Full Article
end velocityconf: Free webcast from our friends at @citrix 5/29 http://t.co/IOeY4U0wUP Learn to consolidate 40 load balancers and ADCs into single platform By twitter.com Published On :: Tue, 21 May 2013 15:01:58 +0000 velocityconf: Free webcast from our friends at @citrix 5/29 http://t.co/IOeY4U0wUP Learn to consolidate 40 load balancers and ADCs into single platform Full Article
end velocityconf: New #velocityconf CA program preview is up: http://t.co/rKjf91RXdD @ariyahidayat on End-to-End JS Quality Analysis. By twitter.com Published On :: Thu, 23 May 2013 17:01:13 +0000 velocityconf: New #velocityconf CA program preview is up: http://t.co/rKjf91RXdD @ariyahidayat on End-to-End JS Quality Analysis. Full Article
end velocityconf: @da3mon Sorry! We were just doing some followup with past Velocity attendees. Sorry to intrude. No harm intended. :-( By twitter.com Published On :: Thu, 23 May 2013 20:03:49 +0000 velocityconf: @da3mon Sorry! We were just doing some followup with past Velocity attendees. Sorry to intrude. No harm intended. :-( Full Article
end 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
end Shopify's 25% gain sends Canada's benchmark stock index to all-time highs By markets.businessinsider.com Published On :: Tue, 12 Nov 2024 21:28:37 +0000 Shopify's surge added fuel to Canada's strong market rally, helping its benchmark index cross 25,000 for the first time. Full Article Markets mi-exclusive shopify q3-earnings earnings-season ecommerce shopify-stock earnings canada canadian-stocks
end 2019 Must-Know Trends for Online Business – Live Panel Wrap-up By blog.avangate.com Published On :: Thu, 21 Feb 2019 00:00:00 +0000 We recently hosted an engaging live discussion with industry experts from G2Crowd, Instapage and Subscription Insider, covering trends and growth tips for online businesses. Check out what these leaders had to say about what they learned last year in the software industry, where people are missing opportunities and what’s coming next. Full Article
end News24 | Mozambique on the brink: Violence escalates as youth protests extend beyond Maputo By www.news24.com Published On :: Friday Nov 08 2024 04:45:14 Mozambique is on a knife's edge as young people continue to protest against the outcome of the October elections that extended 49 years of Frelimo rule. Full Article
end News24 | Africa has other friends if Trump won't work with it - Kenya's AU candidate By www.news24.com Published On :: Saturday Nov 09 2024 18:36:48 Kenya's candidate for the top job at the African Union said on Saturday that if US president-elect Donald Trump does not want to work with Africa, the continent has "other friends". Full Article
end Beyond Labels and Agendas: Research Teachers need to Know about Phonics and Phonological Awareness By www.readingrockets.org Published On :: Tue, 10 Jan 2023 16:16:51 EST This article describes the current findings on phonics and phonological awareness instruction. It uses a question & answer format to explore 10 common questions that teachers ask about teaching phonics and phonemic awareness. Here are a few key questions addressed in the article: What are phonics and phonemic awareness? Should phonemic awareness be paired with print and taught together? Should phonological awareness be coordinated with phonics instruction? What is the best sequence for teaching phonics? Full Article
end Factoring In PayPal Fees When Sending Money Using the Goods and Services Option By www.tipsandtricks-hq.com Published On :: Wed, 12 May 2021 00:48:45 +0000 With more and more online marketplaces popping up, many individuals prefer to pay for items, whether they be new or second hand using the PayPal Goods and Services option. The PayPal ‘Goods and Services’ option gives buyers further peace of mind with the PayPal guarantee. If the seller does not provide what they have described, […] The post Factoring In PayPal Fees When Sending Money Using the Goods and Services Option appeared first on Tips and Tricks HQ. Full Article General Shop Admin Tips Paypal paypal donation PayPal Tutorials Transfer Money
end Sneak peek at Super Nintendo World expansion By readwrite.com Published On :: Tue, 12 Nov 2024 12:45:05 +0000 Nintendo has offered an early look at the Donkey Kong expansion to Super Nintendo World in Japan’s Universal Studios. Following… Continue reading Sneak peek at Super Nintendo World expansion The post Sneak peek at Super Nintendo World expansion appeared first on ReadWrite. Full Article Gaming Nintendo
end News24 | 'We already miss him': Brackenfell family looking for missing teen last seen visiting a friend By www.news24.com Published On :: Tuesday Nov 12 2024 19:38:05 A family in Brackenfell, Cape Town, is looking for their missing teenage son, whom they last saw on Saturday morning heading to visit a friend in the area. Full Article
end News24 | Ronald Lamola denies ANC is protecting 'its friend Frelimo' ahead of more protests in Mozambique By www.news24.com Published On :: Tuesday Nov 12 2024 20:00:30 International Relations and Cooperation Minister Ronald Lamola threw diplomacy out the window on Tuesday and responded angrily when he was asked whether South Africa and the ANC were "protecting its friend" Frelimo in troubled Mozambique. Full Article
end Radar Trends to Watch: August 2024 By www.oreilly.com Published On :: Tue, 06 Aug 2024 10:02:43 +0000 July was a big month for model releases: There are new large models from Mistral and Meta, smaller multilingual models from Mistral and DeepL, another Mistral model that specializes in code generation, and a small version of GPT-4o. The security world saw another software supply chain disaster when CrowdStrike released a bad software update that […] Full Article Radar Trends Signals
end Radar Trends to Watch: September 2024 By www.oreilly.com Published On :: Tue, 03 Sep 2024 10:00:09 +0000 This month, we’ll give AI a rest. Alex Russell has finished an excellent series of posts titled “Reckoning.” It’s a must-read for web developers. If you want to understand why our networks and laptops are much faster than they were 15 or 20 years ago, but the web is slower, it comes down to one […] Full Article Radar Trends Signals
end Radar Trends to Watch: October 2024 By www.oreilly.com Published On :: Tue, 01 Oct 2024 09:55:29 +0000 The model release train continues, with Mistral’s multimodal Pixtral 12B, OpenAI’s o1 models, and Roblox’s model for building 3D scenes. We also have another important AI-enabled programming tool: Cursor is an alternative to GitHub Copilot that’s getting rave reviews. Security will never cease to be a problem, but this month seems particularly problematic. The Mirai […] Full Article Radar Trends Signals
end Radar Trends to Watch: November 2024 By www.oreilly.com Published On :: Tue, 05 Nov 2024 11:04:37 +0000 October had many language model releases. The mid-size models, and even the small models, are catching up to frontier models like GPT-4.5o in performance. But the release that blew us all away wasn’t a language model: It was Claude’s computer use API. Computer use allows you to teach Claude how to use a computer: how […] Full Article Radar Trends Signals
end Another emulation project disappears amid Nintendo crackdown By boingboing.net Published On :: Wed, 02 Oct 2024 13:53:28 +0000 Nintendo is cracking down on emulators of its hardware and media depicting their use. First Yuzu was taken down with a lawsuit, and now departs Ryujinx, a similar project that had sought to avoid the legal landmines Yuzu stepped on. — Read the rest The post Another emulation project disappears amid Nintendo crackdown appeared first on Boing Boing. Full Article Post copyright gadgets lawsuits retrogaming tech
end Independent Consultant Chooses WebCaster By communicationtransformation.blogspot.com Published On :: Fri, 30 Sep 2011 23:13:00 +0000 Jan Ozer is a streaming media consultant and frequent contributor to industry magazines and websites on streaming related topics and the author of Video Compression for Flash, Apple Devices and HTML5. This year he reviewed both the MediaPlatform WebCaster platform and the Polycom Accordent Capture Station and Media management System for Streaming Media magazine. Here is a link to the Accordent review, which appeared in the August, 2011 edition of Streaming media magazine: Accordent Capture Station and Media Management System: Review Here is a link to the WebCaster review, which appeared in the June, 2011 edition of Streaming media magazine: MediaPlatform WebCaster Review: A Strong Option for Webcasts We think it is important to note that an independent consultant with recent and intimate knowledge of the two leading webcasting platforms is running his next webcast on the WebCaster platform. You can register to watch his webcast, titled Introduction to Live Event Streaming, which will be broadcast live on Tuesday, October 4, 2:00 - 3:00 PM EST. Click here to register Here is Ozer’s description of the event: “This seminar will introduce attendees to live event streaming. It will start by discussing the technologies underlying live event streaming, like codecs and formats, and how most live event platforms can reach both a desktop player (usually Flash) and Apple and Android devices.” Full Article
end Trends in Housing Affordability: Who Can Currently Afford to Buy a Home? By www.nar.realtor Published On :: Tue, 27 Aug 2024 15:26:37 +0000 Who Can Currently Afford to Buy a Home? With mortgage rates recently falling below 6.5%, there has been an improvement in housing affordability. By: Nadia Evangelou Full Article
end 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
end ‘Utterly Unacceptable’: After Helping Trump Win, Elon Musk Makes Crucial Endorsement For Senate Majority Leader By conservativefiringline.com Published On :: Mon, 11 Nov 2024 06:00:13 +0000 The following article, ‘Utterly Unacceptable’: After Helping Trump Win, Elon Musk Makes Crucial Endorsement For Senate Majority Leader, was first published on Conservative Firing Line. Despite a landslide victory for Donald Trump and his “Make America Great Again” agenda last week, a ferocious battle has suddenly broken out in the U.S. Senate over who will be the chamber’s new leader, with some saying outgoing Majority Leader Mitch McConnell is trying to thwart the plans of the president-elect. “What the hell … Continue reading ‘Utterly Unacceptable’: After Helping Trump Win, Elon Musk Makes Crucial Endorsement For Senate Majority Leader ... Full Article Politics Cornyn McConnell Musk Scott Thune Trump
end Joe Rogan Officially Backs A Candidate… Could Be The Biggest Endorsement Yet By clashdaily.com Published On :: Tue, 05 Nov 2024 10:23:15 +0000 There is a reason Joe Rogan became the world's largest podcaster. He doesn't take his audience -- or his guests -- for granted. He wants MEANINGFUL conversations. The post Joe Rogan Officially Backs A Candidate… Could Be The Biggest Endorsement Yet appeared first on Clash Daily. Full Article News Clash
end EPIC: The ‘Songify’ Trend Of Clipping Speeches To Music Is Back… And AWESOME! By clashdaily.com Published On :: Mon, 11 Nov 2024 11:00:46 +0000 Kamala was right about one thing: this election really DID deliver 'joy'... just not the way she expected. The post EPIC: The ‘Songify’ Trend Of Clipping Speeches To Music Is Back… And AWESOME! appeared first on Clash Daily. Full Article Videos
end Breaking: Republicans Retain Control Over House of Representatives, Handing Trump the Keys to His Agenda By www.westernjournal.com Published On :: Tue, 12 Nov 2024 00:24:13 +0000 Republicans have solidified their control of Washington by retaining control of the House of Representatives. President-elect Donald Trump’s overwhelming victory in the presidential race, coupled with GOP control of the […] The post Breaking: Republicans Retain Control Over House of Representatives, Handing Trump the Keys to His Agenda appeared first on The Western Journal. Full Article News 2024 election Congress Donald Trump House of Representatives Republican Party Republicans U.S. News
end Watch: Oprah Pressed Over Claims That Kamala Harris' Campaign Paid Her $1M for Political Endorsement By www.westernjournal.com Published On :: Tue, 12 Nov 2024 14:35:53 +0000 It was one of the high points in the early days of the Kamala Harris campaign, the honeymoon period where the vice president — newly minted as the Democratic nominee […] The post Watch: Oprah Pressed Over Claims That Kamala Harris' Campaign Paid Her $1M for Political Endorsement appeared first on The Western Journal. Full Article News 2024 election Campaign Campaign finance Celebrities Democrats Hollywood Kamala Harris Oprah Winfrey
end Biden Asked If He'll Get a Hostage Deal by the End of His Term, and His Response Is Telling By www.westernjournal.com Published On :: Tue, 12 Nov 2024 21:08:42 +0000 Legendary Christian writer C.S. Lewis gave us an analogy to help explain otherwise inexplicable moments such as this. Tolerance, Lewis once wrote, “parodies love as flippancy parodies merriment.” In a […] The post Biden Asked If He'll Get a Hostage Deal by the End of His Term, and His Response Is Telling appeared first on The Western Journal. Full Article Commentary Biden administration Donald Trump Fire Hamas Israel Joe Biden Middle East U.S. News
end Sport | Football legend Dalglish lauds Gary Player after golf event: 'Fantastic what he's done for SA' By www.news24.com Published On :: Tuesday Nov 12 2024 12:09:17 Sir Kenny Dalglish hailed nine-time Major champion Gary Player and expressed his delight at Liverpool's position at the top of the Premier League during his visit to South Africa this weekend. Full Article
end Sport | Difference between good and great is handling pressure, says Kaizer Chiefs legend Baloyi By www.news24.com Published On :: Tuesday Nov 12 2024 19:39:57 Former Kaizer Chiefs legend Brian Baloyi says that holding the Kaizer Chiefs No 1 jersey requires a hardened mentality, but he is upbeat over Amakhosi's chances this season. Full Article
end Sport | Springbok injuries: Sacha on the mend, doubt remains over Kitshoff future By www.news24.com Published On :: Wednesday Nov 13 2024 09:30:19 Springbok team doctor Jerome Mampane says that injured utility back Sacha Feinberg-Mngomezulu is recovering well. Full Article
end Newsroom: Insider Intelligence Slashes Ad Spending Forecast for Russia and Eastern Europe Amid Conflict By www.emarketer.com Published On :: Thu, 31 Mar 2022 04:01:00 GMT Total media ad spend in Russia to drop nearly 50%   March 30, 2022 (New York, NY) – Insider Intelligence expects the ongoing war in Ukraine to have a significant […] Full Article
end Investigation: Waste of the Day – New Yorkers Spend $25 Million on Ex-Governor’s Legal Troubles By deneenborelli.com Published On :: Tue, 08 Oct 2024 17:53:10 +0000 Investigation by Jeremy Portnoy originally published by RealClearInvestigations and RealClearWire Topline: The State of New York has spent $25.4 million to defend former Gov. Andrew Cuomo from sexual harassment lawsuits and criminal investigations over the last three years, The New York Times reported this month. Key facts: More than half of the money was spent … Full Article Commentaries News
end The existence of Zariski dense orbits for endomorphisms of projective surfaces By www.ams.org Published On :: Wed, 16 Oct 2024 14:24 EDT Junyi Xie J. Amer. Math. Soc. 38 (), 1-62. Abstract, references and article information Full Article
end Beijing briefing: China’s wish for 2023? An end to lockdown By www.chathamhouse.org Published On :: Tue, 29 Nov 2022 16:12:17 +0000 Beijing briefing: China’s wish for 2023? An end to lockdown The World Today mhiggins.drupal 29 November 2022 Xi Jinping will try to beef up Global South relations in 2023, but weary Chinese and the business sector need pandemic restrictions to end, says Yu Jie. This past year in Chinese politics was capped by a highly anticipated 20th Party Congress in Beijing in October which marked the beginning of General Secretary Xi Jinping’s unprecedented third term. Xi stacked the all-powerful Politburo with male loyalists and left the rest of the world to sift through the implications of his leadership reshuffle. Meanwhile, Xi made headlines at the G20 summit in Indonesia, maintaining a largely positive tone with President Joe Biden and being caught on camera chiding Canada’s Justin Trudeau for leaks after their talks. So, what can we expect Xi to pull out of the hat in 2023, the Chinese Year of the Rabbit? In February and March, the conversations around Beijing dinner tables will focus on the composition of the new central government – the important seats within the Chinese State Council. This body must deliver Xi’s ‘security-oriented’ economic agenda as well as his much-promoted ‘Common Prosperity’ initiative. The ‘Zero-Covid’ strategy has exacerbated youth unemployment and tested the patience of China’s upwardly mobile middle-class Pundits will be paying particular attention to who is put in charge of economic planning, who the new foreign minister might be and who will govern the central bank. I will offer my reading of these tea leaves as the year unfolds. In April and May, speculation may turn to whether China will finally open its borders to foreign visitors and those compatriots who want to be reunited with loved ones after enduring the pandemic lockdown. While some loosening of restrictions began in November 2022, China is still balancing its twin aims of containing the spread of Covid and re-engineering its economy along similar lines to Europe. Beijing’s controversial ‘Zero-Covid’ strategy has intensified economic pressures, exacerbated rising levels of youth unemployment and tested the patience of China’s middle class, which has led to unprecedented civil disobedience. Those not employed by the state have been hit particularly hard. It is difficult to see how China’s economy can crank up again until Beijing reduces its internal restrictions and reconnects with the world. A pivot to the Global South June and July will be prime season for Beijing’s diplomacy with the Global South. Xi recently announced that China would host the third Belt and Road Forum in 2023 – a meeting of heads of states from predominantly developing countries to discuss his flagship foreign affairs initiative. As seen in the Political Report of the 20th Party Congress, Xi has abandoned the ‘new type of great power relations’ language he previously used to describe relations with the US-led western world. In its place, Xi is stressing that China should develop its ties with the Global South through his Global Development and Global Security initiatives which were announced in 2021 and 2022 respectively. These aim to reshape the global governance agenda in multilateral forums and project Beijing’s influence on to the developing world. Sport will dominate throughout August and September. While Beijing’s spending spree on football promotion might have failed to see the national side qualify for the World Cup, its table tennis team has proved invincible and continues to cheer up the nation. I will offer my own verdict on why there is such a stark contrast between the success of the two men’s teams and explain the meaning of sports in modern Chinese society. In October and November, young graduates will begin their careers while new university students start to arrive on campus. Chinese students are constantly subjected to strenuous testing. And like their western peers, they face the inevitable pressures of finding a job, repaying the mortgage and other everyday facts of life. The burnout of China’s Generation Z The term ‘involution’ – neijuan – has been adopted by China’s Generation Z to describe their feelings of burnout at the ever-increasing expectations associated with high performance. Equally, they have strong opinions about their own government as well as western liberal democracies. China’s leaders of the future will come from their ranks so it will be worthwhile spending some time trying to understand what makes them tick. Billions will want a return to normal life without the fear of having the wrong colour – yellow or red – on their Covid health QR code Whatever the Year of the Rabbit holds for China, billions of its people will want to have their life return to normal without the fear of having the wrong colour – yellow or red – on their Covid health QR code. Only a green code shows a person is healthy and free to move around. The Covid threat has hovered over people for three years and as borders reopen, they may be holding their breath. A slowing economy dimming consumer confidence and a precarious international environment make it look even harder for President Xi to pursue the agenda outlined in October 2022. As the Year of the Rabbit dawns, China doesn’t need a Mad Hatter or a March Hare, instead it urgently needs a sound path to economic recovery and a plan to reopen its borders that works for everyone. Full Article
end The endosomal trafficking regulator LITAF controls the cardiac Nav1.5 channel via the ubiquitin ligase NEDD4-2 [Computational Biology] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation. Full Article
end Civilian priorities for ending the war in Sudan By www.chathamhouse.org Published On :: Tue, 08 Oct 2024 08:17:13 +0000 Civilian priorities for ending the war in Sudan 31 October 2024 — 12:30PM TO 1:30PM Anonymous (not verified) 8 October 2024 Chatham House and Online Dr Abdalla Hamdok, former prime minister of Sudan and chairperson of the Coordination of Civil Democratic Forces (Tagadum), will discuss the prospects for conflict resolution in Sudan. The intensification of fighting across Sudan demonstrates that both warring parties and their allies are continuing to pursue an outright military victory in the war, with little regard for the human cost. Diplomatic efforts, including the US-led Geneva talks in August, have produced little progress towards a ceasefire. Meanwhile, the conflict has resulted in widespread devastation, mass displacement, and an escalating hunger crisis.Civilian perspectives on ending the war, their vital efforts in providing lifesaving humanitarian assistance, and the aspiration of many Sudanese for a more inclusive and democratic Sudan, have been sidelined by the interests and actions of the belligerent parties.At this event, Dr Abdalla Hamdok will discuss options for reaching a ceasefire and seeking a peaceful political resolution to the conflict. He will also address the urgent need for an international response to what has become the world’s largest humanitarian crisis.Please note that in-person attendance for this event will be balloted. Guests looking to join in-person must ‘register interest’ in joining. Full confirmations to successful applicants will be sent on Monday 28 October at 15:00.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
end M8R tropomyosin mutation disrupts actin binding and filament regulation: The beginning affects the middle and end [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Dilated cardiomyopathy (DCM) is associated with mutations in cardiomyocyte sarcomeric proteins, including α-tropomyosin. In conjunction with troponin, tropomyosin shifts to regulate actomyosin interactions. Tropomyosin molecules overlap via tropomyosin–tropomyosin head-to-tail associations, forming a continuous strand along the thin filament. These associations are critical for propagation of tropomyosin's reconfiguration along the thin filament and key for the cooperative switching between heart muscle contraction and relaxation. Here, we tested perturbations in tropomyosin structure, biochemistry, and function caused by the DCM-linked mutation, M8R, which is located at the overlap junction. Localized and nonlocalized structural effects of the mutation were found in tropomyosin that ultimately perturb its thin filament regulatory function. Comparison of mutant and WT α-tropomyosin was carried out using in vitro motility assays, CD, actin co-sedimentation, and molecular dynamics simulations. Regulated thin filament velocity measurements showed that the presence of M8R tropomyosin decreased calcium sensitivity and thin filament cooperativity. The co-sedimentation of actin and tropomyosin showed weakening of actin-mutant tropomyosin binding. The binding of troponin T's N terminus to the actin-mutant tropomyosin complex was also weakened. CD and molecular dynamics indicate that the M8R mutation disrupts the four-helix bundle at the head-to-tail junction, leading to weaker tropomyosin–tropomyosin binding and weaker tropomyosin–actin binding. Molecular dynamics revealed that altered end-to-end bond formation has effects extending toward the central region of the tropomyosin molecule, which alter the azimuthal position of tropomyosin, likely disrupting the mutant thin filament response to calcium. These results demonstrate that mutation-induced alterations in tropomyosin–thin filament interactions underlie the altered regulatory phenotype and ultimately the pathogenesis of DCM. Full Article
end FUS contributes to mTOR-dependent inhibition of translation [Signal Transduction] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 The amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)–linked RNA-binding protein called FUS (fused in sarcoma) has been implicated in several aspects of RNA regulation, including mRNA translation. The mechanism by which FUS affects the translation of polyribosomes has not been established. Here we show that FUS can associate with stalled polyribosomes and that this association is sensitive to mTOR (mammalian target of rapamycin) kinase activity. Specifically, we show that FUS association with polyribosomes is increased by Torin1 treatment or when cells are cultured in nutrient-deficient media, but not when cells are treated with rapamycin, the allosteric inhibitor of mTORC1. Moreover, we report that FUS is necessary for efficient stalling of translation because deficient cells are refractory to the inhibition of mTOR-dependent signaling by Torin1. We also show that ALS-linked FUS mutants R521G and P525L associate abundantly with polyribosomes and decrease global protein synthesis. Importantly, the inhibitory effect on translation by FUS is impaired by mutations that reduce its RNA-binding affinity. These findings demonstrate that FUS is an important RNA-binding protein that mediates translational repression through mTOR-dependent signaling and that ALS-linked FUS mutants can cause a toxic gain of function in the cytoplasm by repressing the translation of mRNA at polyribosomes. Full Article
end China: End of the Reform Era By www.chathamhouse.org Published On :: Wed, 30 May 2018 14:30:00 +0000 China: End of the Reform Era 20 July 2018 — 12:30PM TO 1:30PM Anonymous (not verified) 30 May 2018 Chatham House, London The speaker will argue that China’s reform era is ending, and that core factors which characterized it - including political stability, ideological openness and rapid economic growth - are unravelling.Since the 1990s, Beijing’s leaders have firmly rejected any fundamental reform of their authoritarian one-party political system, even as a decades-long boom has reshaped China’s economy and society. On the surface, their efforts have been a success, but Carl Minzner says a closer look at China’s reform era reveals a different truth.He outlines how over the past three decades, a frozen political system has fuelled both the rise of entrenched interests within the Communist Party and the systematic underdevelopment of institutions of governance among state and society at large. Economic gaps have widened, social unrest has worsened and ideological polarization has deepened.The speaker will discuss how China’s leaders are attempting to address these looming challenges, including institutional reforms and a shift back towards single-man rule. The speaker will also consider the question of regime stability given that China’s era of ‘reform and opening up’ is ending and there is now a renewed uncertainty over Beijing’s future.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Full Article
end National security and transatlantic unity top Biden’s agenda By www.chathamhouse.org Published On :: Wed, 01 Feb 2023 14:11:35 +0000 National security and transatlantic unity top Biden’s agenda Expert comment NCapeling 1 February 2023 The timing of the State of the Union address is significant as Joe Biden tries to maintain focus on Ukraine and China while navigating partisanship at home. Although primarily a domestic affair, the president’s remarks in the annual State of the Union (SOTU) telegraph the US’s foreign policy priorities to the rest of the world. They reveal the prism through which the US understands its national security and its role in the world. The 2023 address comes as the first anniversary of the Ukraine invasion rapidly approaches, and the US is also trying to build international support for tough economic measures towards China. Domestically, Republican control of the House of Representatives will exert new pressure on US foreign policy choices. Electoral pressures are also around the corner and Joe Biden should announce soon whether he plans to run for president in 2024. Alliances and partnerships are a driving force for Biden. As pressure to end the war in Ukraine intensifies, maintaining transatlantic unity on Ukraine will be a key priority for the president. And as US electoral politics rise to the fore, ensuring the visibility of Europe’s role as a security provider in its own backyard will be essential. For a US president who sees China and the Indo-Pacific as America’s most significant long-term geopolitical challenge – and the only peer competitor to the US – transatlantic unity on China will also come under pressure. Ukraine, China, and controlling domestic division Republican leaders who now chair key committees in the House of Representatives continue to signal support for Ukraine, and polling shows a majority of US public opinion (54 per cent) favours sending either weapons or air defence systems. But recent polls also reveal a growing gap between Democrat and Republican supporters with a slight majority of Republicans (52 per cent) now opposing further support for Ukraine. Biden’s ability to demonstrate that America and its European partners remain unified in their policy towards Ukraine and Russia will help him ward off partisanship at home. Congressional approval of $45 billion for Ukraine in its end of year spending budget will help the president remain above the fray of partisan politics for now. But if there is an absence of clear signs Ukraine is succeeding in its war aims, the challenge of maintaining domestic support could become more difficult. Bipartisanship is strong on China, Republicans are more singular and hawkish in their approach to China than the US president, and the public support tough measures A greater US focus on China, India, and on the Indo-Pacific in 2023 is also likely. Bipartisanship is strong on China, Republicans are more singular and hawkish in their approach to China than the US president, and the public support tough measures. At a time of war in Europe, the president will place great emphasis on the need to maintain transatlantic unity and to work with a broader coalition of partners in the Indo-Pacific. The groundwork for focus on China has already been laid. Throughout 2022, the Biden administration worked steadily, but quietly, to set out its China policy. Just before Russia’s invasion of Ukraine in February 2022, the US released its new US-Indo Pacific Strategy stressing regional partnerships – especially the Quad and ASEAN – and it’s determination to shape essential norms for the region. It stated boldly – albeit in a document which was largely unnoticed – that the objective is not to change China but to ‘shape the strategic environment in which it operates’, a policy which signifies a clear departure from the more ideological approach pursued by the US during Donald Trump’s final year in office. And in May, the US announced its economic strategy for the region, the Indo-Pacific Economic Framework. Now the terrain for competition with China and alignment with US partners and allies is heavily focused on technology and the daylight between national security and economic strategy in US China policy is rapidly disappearing. Biden’s policy focus of ‘invest (at home), align (with allies and partners), and compete (with China)’ has overshadowed earlier talk of cooperation between the US and China. Those listening carefully to the State of the Union and who have followed US policy will also note the unchallenged hegemony of neoliberalism is rapidly vanishing But as China opens its doors and Europe looks to bolster its economies, the US will have to work far harder to maintain transatlantic unity. Japan and the Netherlands embracing the US adoption of export controls on semiconductor chips is a positive sign, but the US’s economic strategy towards China may present harder choices to come for Europe. If China leans into its diplomacy, the pressure on transatlantic unity will also grow. The new US Congress will only sharpen the president’s tough stance on China. Some Republican leaders still deny climate change and have demonstrated little interest in cooperating with China on debt relief for developing countries. The prospects for addressing critical global challenges appear dim without China’s collaboration, and the UK and Europe should work with the US president and Congress to correct this. President Biden has clearly recognized that diplomacy will be critical in the months ahead. At a time of growing tensions, the potential for misperceptions or misunderstandings to create conflict will also increase, and so a US – and also European – commitment to broadening and deepening diplomacy with China is urgent but it also needs to be patient and sustained. A new American industrial policy? Those listening carefully to the State of the Union and who have followed US policy will also note the unchallenged hegemony of neoliberalism is rapidly vanishing. The American state appeared to be disturbingly absent in the early months of the US pandemic response – but now it is back and, in a surprising turn of events, is being cast as a solution not a problem. Full Article
end Japan’s G7 leadership: Defending the liberal order amid crisis By www.chathamhouse.org Published On :: Mon, 20 Feb 2023 09:22:13 +0000 Japan’s G7 leadership: Defending the liberal order amid crisis 28 February 2023 — 9:00AM TO 10:00AM Anonymous (not verified) 20 February 2023 Online How G7 countries should best respond to global economic and security challenges in order to defend the liberal international order. In May 2023 Japan hosts the G7 summit in Hiroshima, where leaders of the US, UK, Canada, France, Germany and Italy come to discuss the most urgent challenges facing the world. This year’s summit takes place against a backdrop of continued global economic and political instability from the war in Ukraine to intensifying competition between China and the West. The speakers discuss Japanese Prime Minister Fumio Kishida’s priorities at the summit and consider how G7 countries should best respond to global economic and security challenges in order to defend the liberal international order. This event is the third of a three-part series held in partnership with Japan House London. Watch the first event which looked at Africa-Japan relations here, and the second event, on the UK and Japan’s engagement with Southeast Asia, here. Full Article
end 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
end Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis By www.mcponline.org Published On :: 2012-06-01 Ludovic C. GilletJun 1, 2012; 11:O111.016717-O111.016717Research Full Article
end Cross-border conflict, evidence, policy and trends (XCEPT) By www.chathamhouse.org Published On :: Thu, 26 Aug 2021 08:03:34 +0000 Cross-border conflict, evidence, policy and trends (XCEPT) This five-year policy-focused research programme seeks to respond to the challenges of long-term cross-border conflicts by exploring the drivers behind them. dora.popova 26 August 2021 Protracted conflicts in the Middle East and North Africa, Horn of Africa and parts of Asia, although usually arising from intra-state disputes, rarely remain contained within national borders. Their effects reverberate outward and external actors are drawn in. The longer these wars last, the more difficult they are to resolve as the interests of international actors collide and the web of economic and political interactions which sustain violence and connect conflict across borders expand and deepen. The Cross-border conflict, evidence, policy and trends (XCEPT) research programme brings together world-leading experts to examine conflict-affected borderlands, how conflicts connect across borders, and the drivers of violent and peaceful behaviour. Chatham House provides research leadership to the programme, as part of the wider consortium, and our research explores: the intersection of conflict supply chains which sustain and embed violence coping supply chains for survival-based economic activity which occurs in the context of violence Three geographic case studies will be supported by cross-cutting workstreams on gender and social inclusion, livelihoods, and border security. Each will produce analysis and recommendations to inform international policy responses to conflict across borders. These case studies will focus on: armed actors and financial flows through Iraq and the Levant human smuggling across Libya, East and West Africa gold mining and weapons flows across Sudanese borderlands The consortium is made up of a range of other organizations, including the Asia Foundation, the Malcolm H. Kerr Carnegie Middle East Center, the Rift Valley Institute, Chemonics UK and King’s College London. XCEPT is funded by UK Aid from the UK government. Full Article
end Russia's end games and Putin's dilemmas By www.chathamhouse.org Published On :: Mon, 14 Feb 2022 16:16:00 +0000 Russia's end games and Putin's dilemmas Expert comment NCapeling 14 February 2022 As warnings from Washington and London intensify, the period of maximum danger in the Ukraine standoff has begun. Even if conflict is avoided, the status quo has gone. There are several reasons to believe conflict over the Ukraine is imminent. The military build-up is complete. Russia has added tactical support elements, including medical units, to its already large and comprehensive array of troops and equipment deployed to the east, north, and south of Ukraine. Additional naval units have entered the Black Sea, military exercises with Belarusian forces have begun and, along with those on Russian territory, these can all provide cover for an intervention of some sort. Far from being comforting, comments by Vladimir Putin and his entourage that it will not be Russia provoking a conflict are ominous. Russian media has ramped up domestic programming about the ‘imminent Ukrainian fascist threat’ to the motherland. And a recent US intelligence briefing alleges sophisticated preparations by Russian intelligence include releasing a video of a staged attack on Russian-speaking civilians in northern Ukraine. Reincorporating Ukraine into a ‘greater Russia’ would underpin his now constitutionally-mandated opportunity to reign until 2036, as well as being his biggest legacy. Should Russia attack, its ‘fortress economy’ could weather a new round of sanctions for several years, not least given the growth in Russia’s hard currency reserves to $630 billion, under 20 per cent of which are now held in US dollars, and the high demand for – and global price of – oil and gas. What does Putin really want? Diplomacy is in high gear but, as Putin and other senior Russian figures have made clear, the US and European offers of new security confidence-building measures do not address Russia’s two core, stated demands – namely to withdraw US and NATO forces close to its borders in former Soviet and Warsaw Pact states, and to end NATO’s ‘open door’ policy to future enlargement. For the Kremlin, enlargement to Ukraine would remove a critical buffer between Russia and the NATO alliance. If Putin’s objective, therefore, was simply to put down an unambiguous marker that Ukrainian membership of NATO is a red line, he has made progress. He has reminded the world and Ukraine’s leadership of that country’s strategic vulnerability. US president Joe Biden and his European counterparts have stated NATO will not commit forces to defend Ukraine if it is attacked. And although they remain resolute on the ‘open door’ policy, there have been reminders NATO does not accept new members who risk importing a pre-existing conflict into the alliance. If another Putin objective was to refocus US and, to a lesser extent, European attention away from China and back onto Russia and its security interests, he has succeeded. NATO has offered some new confidence-building measures around the conduct of military exercises and deployment of forces, while the US may be willing to enter negotiations for a new treaty with Russia to limit nuclear missiles deployed in Europe. This would mean setting aside the growing threat posed by Chinese missiles that had partly motivated the Donald Trump administration to withdraw unilaterally from the Intermediate-Range Nuclear Forces (INF) Treaty. But there is another scenario to consider – that although these two issues are both important, neither are Putin’s core objective, which instead is to right once and for all the historical ‘wrong’ of Ukraine’s separation from Russia in 1991. As Putin made clear in a lengthy essay in July 2021, he sees an independent, sovereign Ukraine as a historical aberration, and he blames the US for the deepening discord and animosity between ‘brotherly’ Ukraine and Russia. Not stated in the essay is that the emergence of a more democratic and functional Ukraine poses an existential threat to Putin’s own control over Russia. In contrast, reincorporating Ukraine into a ‘greater Russia’ would underpin his now constitutionally-mandated opportunity to reign until 2036, as well as being his biggest legacy. The problem is it seems impossible to bring Ukraine permanently back into Russia’s sphere of influence without some form of new military intervention. Putin’s options Putin’s strategy to date has been limited to ensuring the breakaway Ukrainian portions of Donetsk and Lugansk gain a legal right to block any future efforts by the central Ukrainian government to join either the European Union (EU) or NATO. If another Putin objective was to refocus US and, to a lesser extent, European attention away from China and back onto Russia and its security interests, he has succeeded. The Kremlin sees expansive interpretation and implementation of the 2014-15 Minsk protocols allowing self-governance for these areas currently under Russian military control as a potential route to this outcome. But for Volodomyr Zelensky or any future Ukrainian president to accept this would be political suicide, and Kyiv has already resisted French and German pressure to make this concession under the Normandy Format of meetings they share with Russia. If Putin has now decided to undermine Ukrainian sovereignty more explicitly, he can order a limited military intervention further into these occupied territories – and perhaps areas adjacent to them and Crimea – under the pretext of ‘protecting’ Russian-speaking communities there. This would be relatively easy to achieve and, combined with a blockade of Ukraine’s Black Sea ports, could successfully destabilize the government in Kyiv. But such steps would trigger international economic sanctions and drive Ukraine even further towards the West. A 21st century ‘blitzkrieg’ to take Ukrainian territory as far as the Dnipro River including Kyiv and all points east, would come closer to achieving Putin’s territorial and historic legacy. And this is now a feasible option given Russia’s military superiority. But how easily Russia could then hold the territory and consolidate its political control would be doubtful, and these moves also bring high-risk, long-term economic and diplomatic costs to Russia and to him personally. No return to the status quo On balance, Russian military intervention in the coming days or weeks is still less rather than more likely. Putin may yet accept a new, visible, bilateral accommodation with the US on the future of European security. Full Article
end Independent Thinking: War in Ukraine, Congress in China By www.chathamhouse.org Published On :: Fri, 21 Oct 2022 10:07:08 +0000 Independent Thinking: War in Ukraine, Congress in China Audio NCapeling 21 October 2022 The inaugural episode of our new podcast examines the latest developments surrounding Russia’s invasion of Ukraine, and Xi Jinping’s political report from the 20th National Congress of the Chinese Communist Party. Bronwen Maddox and her guests examine latest developments surrounding Russia’s invasion of Ukraine and Vladimir Putin’s nuclear threats, as well as Xi Jinping’s political report from the 20th National Congress of the Chinese Communist Party. Bronwen is joined by Gideon Rachman, chief foreign affairs columnist for the Financial Times, Orysia Lutsevych, head of the Ukraine Forum at Chatham House, and Dr Yu Jie, senior research fellow in Chatham House’s Asia-Pacific programme. Independent Thinking is a regular podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts to provide insight on the latest international issues. Full Article
end Independent Thinking: Rishi Sunak and the UK, John Kerry on COP27 By www.chathamhouse.org Published On :: Fri, 28 Oct 2022 08:47:31 +0000 Independent Thinking: Rishi Sunak and the UK, John Kerry on COP27 Audio NCapeling 28 October 2022 The second episode of our new podcast examines the changes in the UK government as Rishi Sunak become prime minister and looks ahead to COP27 with John Kerry. Bronwen Maddox and her guests discuss the arrival in Number 10 of Rishi Sunak, the UK’s youngest prime minister of modern times as well as its third of 2022, alongside analysing the Chatham House event with US Special Presidential Envoy on Climate John Kerry. Bronwen’s guests from Chatham House are John Kampfner, executive director of the UK in the World Initiative, Hans Kundani, associate fellow with the Europe programme, and Anna Åberg, research associate with the Environment and Society programme. They are joined by Sir Simon Fraser, formerly of the UK’s Foreign and Commonwealth Office, and Chatham House’s deputy chairman. Independent Thinking is a regular podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts to provide insight on the latest international issues. Full Article
end Independent Thinking: Lula wins in Brazil, US midterms By www.chathamhouse.org Published On :: Fri, 04 Nov 2022 10:39:59 +0000 Independent Thinking: Lula wins in Brazil, US midterms Audio NCapeling 4 November 2022 The third episode of our new podcast analyses the results from the Brazil presidential election, and looks ahead to the crucial midterm elections in the US next week. Bronwen Maddox and her guests examine the tight election result from Brazil and its impact on both the country and the region, and preview the US midterm elections being held on 8 November and the start of COP27. In Brazil, former president Luiz Inácio Lula da Silva beat incumbent Jair Bolsonaro by the narrowest of margins. Meanwhile in the US, the Democrats are fighting to retain the House and Senate from a resurgent Republican Party still enamoured with Donald Trump. Joining Bronwen Maddox this week are Leslie Vinjamuri, director of Chatham House’s US and Americas programme, Christopher Sabatini, senior fellow on Latin America in the same programme, and Ana Yang, executive director of Chatham House’s Sustainability Accelerator. Full Article