Những phim tham gia Viet Film Fest 2024 đã chạm vào rất nhiều vấn đề của cộng đồng người Việt khắp nơi trên thế giới: kí ức thời hậu chiến, sự xung đột giữa các thế hệ, hành trình hội nhập trên quê hương mới và cái nhìn về Việt Nam.

O Censo da Educação Superior aponta que a procura por cursos de psicologia disparou no Brasil. Entre 2010 e 2021, o aumento de matrículas nessa graduação foi de 112,4%.

"Customers must be able to reevaluate their willingness to have their genome data shared outside the original intent.”

The post Patronis Questions DNA Testing Companies’ User Confidentiality appeared first on Shark Tank.

Pakistan crush world champions Australia by nine wickets in Adelaide to set up a one-day international series decider.

Uncapped batter Nathan McSweeney will open for Australia in the first of five Tests against India.

Pakistan thrash Australia by eight wickets in Perth to claim their first one-day series win in the country for 22 years.

India travel to Australia for their five-Test series - here's everything you need to know including the schedule, squads and how to follow on the BBC.

President and CEO of Formula 1 Stefano Domenicali speaks to BBC Sport's Matt Warwick about his vision for the next decade.

Qualifying at the Sao Paulo Grand Prix is postponed until Sunday as a result of heavy rain.

Thousands of people have been evacuated from their homes in Ventura County, near Los Angeles.

The new president tells the BBC thousands of illegal Zimbabweans should be given temporary permits.

Eight teams are already assured of a place at the 2025 Africa Cup of Nations in Morocco - but who will fill the remaining 16 spots at the finals?

Dawit Isaak has been held without trial in an Eritrean prison for 23 years.

Daniel Khalife told jurors at his trial that he cannot remember the document in question.

James Barnor, who has photographed the likes of Muhammad Ali, is being honoured in Accra.

Watch the moment phone thieves were caught after stealing 35 phones in south-east London.

President Trump on Friday shared a pre-recorded video message on Twitter saying he is “doing very well” and thanked Americans for their overwhelming support following his early morning announcement of his COVID-19 diagnosis. pic.twitter.com/B4H105KVSs — Donald J. Trump (@realDonaldTrump) October 2, 2020 “I want to thank everybody for the tremendous support,” Trump said in the […]

The post Trump Tweets First Video Remarks Since Revealing COVID-19 Diagnosis appeared first on Hispolitica.

Australian airlines say it is unsafe to fly after Mount Lewotobi Laki-laki spewed ash.

Europe’s most powerful economy is left rudderless, when EU leaders are nervous about a new Trump presidency.

Over 2,100 forgeries, also targeting Warhol, Picasso, Monet and Dali, were recovered in the sting.

Parties agree 23 February vote after chancellor torpedoed the coalition government by sacking finance minister.

At the halfway stage of the revamped Champions League's new 36-team league phase, who is on track to progress and who could be in danger?

BBC Sport looks at what England, Scotland, Wales and Northern Ireland have to play for in the Nations League - and how it ties into the World Cup.

The CEO of a California gay charity has been charged with embezzling almost a million bucks of the organization’s money. The charity official, Jacob Joseph Aaron Rostovsky, has been charged with 53 felony counts including fraudulent claims, grand theft, misappropriation of public funds, insurance fraud, perjury and money laundering, according to KTLA-TV. The DA said […]

The post CEO of Gay Nonprofit Charged for Stealing Organization’s Money appeared first on The Lid.

Businessman Alix Didier Fils-Aime was sworn in as Haiti's new prime minister on Monday as a gun attack on a passenger jet at the capital's airport underscored the utter breakdown in law and order in the Caribbean country.

velocityconf: New #velocityconf CA program preview is up: http://t.co/rKjf91RXdD @ariyahidayat on End-to-End JS Quality Analysis.

Though not common, some Mac users are encountering a strange error message that says “Failed to personalize the software update. Please try again.” when attempting to update their Mac to MacOS Sequoia, and sometimes even with other MacOS software updates too. This is a frustrating error since it prevents the installation of a major system ... Read More

As a digital company, your business is not bound by conventional borders and has the freedom and opportunity to reach customers anywhere in the world. And just as you look outward for new markets, customers are also looking beyond their physical borders for their goods and services. As a study by KPMG shows, online buyers […]

Somalia insisted Saturday that Ethiopia will not be part of a new African Union peacekeeping mission, as the two nations remain locked in a dispute that has sent shivers through the Horn of Africa.

I met two debut authors at a summer conference and was taken with their warmth and earnestness. Their book, Black Boy, Black Boy, is an affirmation that celebrates both past accomplishments by Black men and the limitless possibilities for a child’s future. Their book is sure to encourage discussion with children and families, whether they are Black or not. Both authors graciously agreed to a blog interview.

Informational text — resources whose purpose is to inform — is essential to daily life and fundamental to literacy. Unfortunately, young children typically have limited exposure to informational text. Two 9-week randomized controlled trials with 263 first-grade children from low-income communities examined whether free educational videos and digital games from the PBS KIDS show “Molly of Denali” supported children’s ability to use informational text to answer real-world questions. Study 1 found significant positive intervention impacts on child outcomes; Study 2 replicated these findings.

The Central American nation of El Salvador currently holds nearly 5,932 Bitcoin (BTC), and sits on over $93 million of… Continue reading El Salvador’s Bitcoin adoption is paying off: $93M unrealized profit

The post El Salvador’s Bitcoin adoption is paying off: $93M unrealized profit appeared first on ReadWrite.

Bitcoin has been reaching new all-time highs almost daily, fueling a parabolic bull run that’s pushing various cryptocurrencies to surge… Continue reading Flockerz Capitalizes on Bitcoin Rally, Raising $1.6M in Presale

The post Flockerz Capitalizes on Bitcoin Rally, Raising $1.6M in Presale appeared first on ReadWrite.

The Cape South African Jewish Board of Deputies has asked the Equality Court in Cape Town to declare politician Mehmet Vefa Dag's social media posts about about Jewish people hate speech.

IDC released its Worldwide Quarterly Server Tracker on September 2, 2009, which reports that "factory revenue in the worldwide server market declined 30.1% year over year to $9.8 billion in the second quarter of 2009 (2Q09)."

According to IDC, this is the lowest quarterly server revenue since they began tracking this market in 1996.

The obvious implication is that the economy has been awful and companies have been avoiding / deferring IT spend. But beyond that it seems that virtualization has both benefited from and contributed to this decline.

With a single server now able to run multiple workloads, it seems inevitable that the server footprint is destined to continue getting smaller within the corporate data center. But the benefits of virtualization do not stop with simply running more apps on one machine; the whole datacenter becomes more agile, more flexible to deal with unexpected changes in workload.

The ability to get more from fewer boxes is certainly a contributing factor to less boxes being bought. And tight budgets in the 2009 economy have certainly contributed to IT managers seeking out less costly options.

It will be interesting to see how the server market rebounds.

Andy Patrizio in his InternetNews.com blog quotes Rahul Agarwal, co-founder of Infiniti Research. Within the dismal sales figures, Agarwal notes that both Gartner and IDC report that unit costs are going up for server sales. Agarwal believes that this is due to sellers trying to widen margins by selling more feature-rich machines:

Our view is that to offset this volume pressure, hardware vendors will be
forced to improve unit margins by building in virtualization capability, memory
and I/O interfaces in the hardware.

The server market of tomorrow will be a value game and not a volume game.

Interactive Media Strategies released data on July 14 showing that 62% of corporations that purchased video communications technology made the decision at the President/CEO level when there was no prior investment in this kind of technology.  That number dropped to 58% when the prior year's spend was as much as $10,000.

The same data shows that when an enterprise already spends $100,000 or more annually on video, the decision-making authority is almost evenly distributed between IT (35%), functional department heads (31%), and the President/CEO level (34%).

I think the clear implication of this data is that when corporations are already committing resources to video communications and the value of video has already been established, and this kind of technology is no longer considered exotic, then decision-making authority becomes more broadly distributed to IT and the business units.

This data is interesting when paired with data released in 2010 that shows 15% of executives surveyed that do not spend money on video and are thus not using video communications believe video communications are "very effective."  58% of executives surveyed that spend $100,000 or more annual on video technology indicated they believe video communications are "very effective."

I am sure this great difference is due to several factors, including: executives who are predisposed to see value in video are those most likely to invest in it, and those that have already made a six figure investment in video will likely not be motivated to feel as if the investment was wasted.  Nonetheless, video obviously wears well because executives who are heavily invested in video believe much more in its value than executives who do not employ the technology.

Financial Realities for Single Female Home Buyers

Republican primary opponents like Ron DeSantis said that every time they announced another indictment, his poll numbers got better. They should have known better. But they were blinded by hate.

The post BOOM: Trump Prosecutors React To New Post-Election Realities… Here’s Their Plan appeared first on Clash Daily.

Spend enough time talking with entrepreneurs, product people, designers, and anyone charged with proving something, and you’ll bump into questions about validation. “How do you validate if it’s going to work?”“How do you know if people will buy it to not?”“How do you validate product market fit?”“How do you validate if a feature is worth… keep reading

Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ.

China's Party Congress: a dose of foreign policy realism is needed The World Today mhiggins.drupal 11 October 2022

In the final article of three on the 20th Chinese Communist Party Congress, which opens on 16 October, Yu Jie argues that Beijing must show more pragmatism about Taiwan and the West.

How important is foreign policy at the congress?  

The political reports delivered to the delegates of the week-long 20th Chinese Communist Party Congress, which happens every five years, follow a Marxist-Leninist formula. Economics and the means of production form the base, while politics and society fill in the superstructure. 

We can expect sections on the work of the Chinese Communist Party (CCP), ideological discussion, economics, domestic politics, foreign affairs, cultural reform and social developments. Usually, the report prioritizes big domestic political issues.  

The political report typically sheds some light on the status of, and relationships between, senior party members. It can also provide insights into the political fortunes of various interest groups. The report acts as a summary of the party’s achievements and its plans – expressed as the lowest common denominator of consensus between competing factions. 

This year’s congress should be no different, and the political reshuffle that takes place is likely to signal how Beijing intends to rise to the many challenges at home and abroad. 

Given China’s growing power and its fraught relationship with the West, this year’s congress is expected to feature serious discussion on weighty foreign affairs issues affecting Beijing, and which will have long-lasting implications for the rest of the world.  

Which geopolitical issues will be priorities?  

When it comes to foreign affairs, China’s priorities rarely change. The CCP seeks to create a stable external environment to foster its domestic economic development. This conservative maxim was advocated in the 1980s by China’s then-paramount leader, Deng Xiaoping, and it will continue to guide Beijing’s relationships after this congress. 

While we don’t know the exact details of this year’s political report, we can expect discussion on relations with the US-led West, a possible shift in the relationship between Beijing and Moscow, and elaboration on China’s ties with the Global South.  

Notably, it’s likely that a separate chapter of the political report will see Taiwan treated alongside the special administrative regions of Hong Kong and Macau, signalling the party’s commitment to its claims over the contested island.  

Despite a chorus of nationalistic rhetoric surrounding the issue of Taiwan, Beijing will be careful not to stumble into an international conflict which risks causing colossal damage on all fronts. The choice of language on the so-called ‘Taiwan question’ in this political report will serve as a bellwether as to how, if at all, the party might fundamentally shift its views regarding Taiwan and deviate from the principle of ‘peaceful reunification’, the policy stated at every congress since 1979. 

How have China’s relations with the West worsened?  

President Richard Nixon’s visit to China in 1972, the first by an American president to the Communist nation, kicked off five decades of relative stability. However, as China’s global influence has grown, so have Washington’s fears.  

The relationship has transitioned from the cooperation and relative stability that existed under President George W. Bush and President Hu Jintao in the early 2000s, into one characterized by volatility and competition under Xi Jinping, Joe Biden and Donald Trump. These tensions are almost certain to continue in Xi’s likely third term. 

Elements of China’s relationship with the West, such as cooperation over military and aviation technology, are becoming far more competitive. At the same time, trade and investment, once viewed as strong ties, have been rapidly deteriorating – as seen, for example, by several major publicly listed Chinese state-owned enterprises and large private companies withdrawing from the New York Stock Exchange.  

Will Beijing stand by the Kremlin despite Russia’s invasion of Ukraine?  

At the same time, Beijing’s close relationship with Moscow and its lack of opposition to Russia’s war in Ukraine have put China in an awkward position. The CCP has realized that cooperation with its long-standing ally and neighbour must come with substantial limits to avoid undermining its own political priorities and interests.  

Russia’s recklessness may spur Xi and the CCP’s senior leadership to minimize the economic, financial and political risks associated with the Kremlin’s pursuit of war against a country aligned with, and supported by, the West.  

Will China continue to support its regional partners?  

On its ties with the Global South, Beijing began to rethink its Belt and Road Initiative (BRI) as the US-led Indo-Pacific strategy gained geopolitical momentum. Regions of Southeast Asia and South Asia received a lot of funding and resources for BRI projects, as seen with Chinese support for the China-Pakistan Economic Corridor.  

Xi also recently introduced the Global Development and Global Security initiatives, which the political report should flesh out. 

Beijing is fully aware that it can only prosper if its regional partners prosper, and it can only achieve resource security and border stability if its southern and western neighbours in Myanmar and Afghanistan cease to fight over land and resources. 

Chinese foreign policy over the last five years has been a strange combination of high-octane rhetoric and patient pragmatism. To respond to this contradiction, the congress could be used as an opportunity to inject a dose of realism.  

Read the two further articles in this series: the first is a guide to why the Chinese Communist Party Congress matters; the second discusses the key domestic policy themes that Xi Jinping is expected to outline at this year’s congress.

Xi Jinping prepares the Communist party for new reality Expert comment NCapeling 20 October 2022

Political report reflects a worsened economic and diplomatic position as Xi knows his unprecedented third term as leader will be judged on results.

In stark contrast to the aura of triumphant glory that greeted Xi Jinping at the last National Congress of the Chinese Communist Party in 2017, this week’s convocation opened with an air of sobriety.

Amid a domestic economic downturn and a return to enmity with Western liberal democracies, Xi offered his own recipe for party legitimacy and the country’s economic survival in the lengthy executive summary of his political report to the CCP congress. The prime keyword was security, with some 73 mentions, underscored with a message of self-reliance.

The periodic report acts as a summary of the party’s achievements and of its future plans, with both expressed as the lowest common denominator of consensus between competing voices in the CCP. It thus typically sheds some light on relationships among senior party members and insights into the political fortunes of important intraparty groups.

Most portions of the new report combined Xi’s personal preferences with concessions to the reality of what is necessary for China’s economic survival. Both ends point to an urgent prioritization of economic and political self-reliance for Xi’s third term as party general secretary.

Holistic concept of security

On the domestic front, much emphasis was given to enhancing national security and promoting equitable growth.

Since even before COVID-19, Xi has advocated a holistic conceptualization of security that includes food, the internet, energy and manpower. Reflecting Beijing’s deep anxieties about high-tech development and its frustrations with dependence on overseas suppliers vulnerable to the vagaries of geopolitical tensions, the political report noted the need for China’s supply chains to become more “self-determined and self-controlled.”

Xi, though, went further to stress the importance of improving scientific education and grooming and attracting the necessary talent to accelerate China’s quest to achieve breakthroughs in semiconductor production and overcome development choke points created by Western technological monopolies.

As China has traditionally relied on connectivity with the rest of the world to support innovation and attract talent, a turn toward autarky is not a viable option, given Xi’s technological priorities. Yet the renewed mention of his ‘dual circulation’ strategy in the report signals that Beijing is indeed turning to domestic consumption and homegrown technological prowess as the means to provide the rising wealth that the Chinese people have come to expect from the Communist Party.

Worsening Sino-US relations and tightening access to overseas markets for Chinese companies have prompted party leaders not only to reconsider the country’s sources of economic growth but have also forced them to reconfigure their approach to foreign affairs.

Judging by his report summary, Xi has completely abandoned the ‘new type of great power relations’ concept used repeatedly in the last two editions of his congressional update to refer to his preferred approach to relations with the US-led West.

The omission shows that Beijing has concluded that its fraught relationship with advanced developed nations is here to stay, with little prospect of improvement soon. To this end, China needs to prepare for the worst of decoupling and become more self-reliant in terms of markets and technologies.

In place of the discarded concept, Xi stressed that China should further develop its ties with the global South through the Global Development Initiative and the Global Security Initiative he announced earlier this year. These efforts aim to reshape the global governance agenda in multilateral forums and to project Beijing’s influence on the developing world.

Meanwhile, the party’s latest official rhetoric about the Belt and Road Initiative shows it is no longer a one-size-fits-all slogan but on its way to becoming a genuine tool of trade and investment promotion with China’s near neighbors but with provincial governments taking the lead rather than Beijing.

With the central government grappling with the country’s domestic economic woes, its spending spree on development assistance has had to come to an end. The new political report clearly signals this change.

A modern socialist society is still the aim

The current economic downturn and dangerous geopolitical tensions have not dented the CCP’s ambitions to build a modern socialist society by 2035 and thus join the world’s club of upper middle-income countries, but this is easier said than done.

Islamic radicalisation in Central Asia 18 September 2024 — 10:00AM TO 11:30AM Anonymous (not verified) 20 August 2024 Chatham House and Online

Experts analyse rising foreign recruitment, current counter-radicalisation efforts and challenge past Chatham House predictions made of the Central Asia region.

In 2014, Chatham House released a report titled The Myth of Post-Soviet Muslim Radicalisation in the Central Asian Republics. At that time, a significant, Western-funded counter-radicalisation industry was addressing what was believed to be a major issue of Islamic violent extremism in the region.

Over the past decade, two key developments have occurred. First, Western interest in the region has declined in favour of traditional geopolitical concerns. Second, while violent extremism incidents within Central Asia remain rare, there has been a notable recruitment of Central Asians by foreign groups, with several attacks carried out by Central Asians overseas.

In this event, the original report’s authors, John Heathershaw and David Montgomery, will discuss whether the report’s arguments are still valid and how we might answer these questions today.

This raises several questions:

• What did the report accurately predict, and where did it fall short?
• How can we explain the lack of violent extremist organisations (VEOs) within Central Asia but the presence of Central Asians in VEOs abroad?
• Could repression by Central Asian states both domestically and transnationally have contributed to this issue?
• What, if anything, can the counter-radicalisation industry do today to address this problem more effectively?

Please note that in-person places are limited. Please wait for confirmation before participating. 

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...

After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5).

Heterotrimeric G-proteins are signaling switches broadly divided into four families based on the sequence and functional similarity of their Gα subunits: Gs, Gi/o, Gq/11, and G12/13. Artificial mutations that activate Gα subunits of each of these families have long been known to induce oncogenic transformation in experimental systems. With the advent of next-generation sequencing, activating hotspot mutations in Gs, Gi/o, or Gq/11 proteins have also been identified in patient tumor samples. In contrast, patient tumor-associated G12/13 mutations characterized to date lead to inactivation rather than activation. By using bioinformatic pathway analysis and signaling assays, here we identified cancer-associated hotspot mutations in Arg-200 of Gα13 (encoded by GNA13) as potent activators of oncogenic signaling. First, we found that components of a G12/13-dependent signaling cascade that culminates in activation of the Hippo pathway effectors YAP and TAZ is frequently altered in bladder cancer. Up-regulation of this signaling cascade correlates with increased YAP/TAZ activation transcriptional signatures in this cancer type. Among the G12/13 pathway alterations were mutations in Arg-200 of Gα13, which we validated to promote YAP/TAZ-dependent (TEAD) and MRTF-A/B-dependent (SRE.L) transcriptional activity. We further showed that this mechanism relies on the same RhoGEF-RhoGTPase cascade components that are up-regulated in bladder cancers. Moreover, Gα13 Arg-200 mutants induced oncogenic transformation in vitro as determined by focus formation assays. In summary, our findings on Gα13 mutants establish that naturally occurring hotspot mutations in Gα subunits of any of the four families of heterotrimeric G-proteins are putative cancer drivers.

Ligand bias is the ability of ligands to differentially activate certain receptor signaling responses compared with others. It reflects differences in the responses of a receptor to specific ligands and has implications for the development of highly specific therapeutics. Whereas ligand bias has been studied primarily for G protein–coupled receptors (GPCRs), there are also reports of ligand bias for receptor tyrosine kinases (RTKs). However, the understanding of RTK ligand bias is lagging behind the knowledge of GPCR ligand bias. In this review, we highlight how protocols that were developed to study GPCR signaling can be used to identify and quantify RTK ligand bias. We also introduce an operational model that can provide insights into the biophysical basis of RTK activation and ligand bias. Finally, we discuss possible mechanisms underpinning RTK ligand bias. Thus, this review serves as a primer for researchers interested in investigating ligand bias in RTK signaling.

Network Power in the Asia-Pacific: Making Sense of the New Regionalism and Opportunities for Cooperation 7 February 2020 — 9:45AM TO 5:30PM Anonymous (not verified) 17 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

The Asia-Pacific region continues to increase in geopolitical and geoeconomic importance. The rise of China and tensions with the US are affecting bilateral relationships and traditional alliances in the region. Whether seen from the perspective of the Quad – Australia, India, Japan and the US – or the Indo-Pacific concept embraced by a wide range of countries but with no shared consensus on scope and objectives or with ASEAN who insists on the importance of its own centrality, the region is redefining and reconceptualising itself.

With a diverse range of initiatives – including the Regional Comprehensive Economic Partnership (RCEP) and Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) – there are a plethora of regional agreements and institutional groupings that add further complexity.

As the Bretton Woods architecture continues to be dominated by Western powers, China is also spearheading parallel governance initiatives such as the Asian Infrastructure Investment Bank (AIIB), the Belt and Road Initiative and the Shanghai Cooperation Organization (SCO) as a means of enhancing its geopolitical and geoeconomic influence.

This one-day conference will focus on how such networks and alliances have been built, and sustained, in the Asia-Pacific region. In order to understand how new regional initiatives might open up opportunities for new forms of international cooperation, the conference will focus on the themes of cyber-technology and innovation, sustainable development and mitigating the impacts of climate change and new infrastructure initiatives. It will assess whether there is a zero-sum conflict between competing networks and agendas or whether a common approach can be developed.

Webinar: Is It All Over For Globalization? 15 April 2020 — 1:00PM TO 2:00PM Anonymous (not verified) 8 April 2020

The coronavirus pandemic has led many to predict the end of globalization. Confronted with unprecedented social and economic challenges, countries are prioritizing their own citizens. Now, more than ever, international cooperation is necessary but, amidst the rise of nationalist-populist governments, global partnerships are absent or faltering. And as economies grind to a halt, so does international commerce — particularly in trade-dependent Asia, a region whose rise drove the period of ‘hyper-globalization’ which preceded the global financial crisis.

Yet there are other possible futures too. The level of scientific collaboration and information-sharing now underway in search of a vaccine is unprecedented, and after a hesitant beginning the major powers have woken up to the importance of concerted economic stimuli. The virus may in some ways have the paradoxical result of bringing countries together, not driving them apart. Rather than causing its demise, it could help begin a new period in which globalization is not as deep, but at least is better managed and more equitable? Could this be the catalyst for a new coming together at home and abroad?

In this webinar, speakers debate what impact the COVID-19 pandemic will have on the future of globalization, both in Asia and around the world.