Amid calls for ongoing protests after violent clashes on Thursday, South Africa's High Commissioner to Mozambique Siphiwe Nyanda has declared "Maputo is almost under siege".

It was business as usual at the Lebombo border post between SA and Mozambique on Saturday morning, with vehicles moving freely between both countries after a shutdown earlier this week.

Cape Town police have arrested two suspects in connection with the murder of Noem My Skollie actor David Manuel and his friend, Alfonso Fisher, in Gugulethu last month.

Earlier this year on April Fools' Day, the Empire State Building announced that they would be opening at a Rainforest Café on the iconic building's 86^th floor observatory. If you got your hopes up just to find out it was all an April Fools' joke, rejoice, because now the joke is about to become reality. — Read the rest

The post Rainforest Café fans: don't miss this Empire State Building pop-up appeared first on Boing Boing.

The other day my wife and I heard a report on our local public radio station that mentioned the Biden Administration’s American Climate Corps (ACC) initiative, a new program seeking to recruit 20,000 young people into jobs on the front line of the climate crisis. Modeled on Franklin Roosevelt’s Depression-Era Civilian Conservation Corps (CCC), the … Continue reading "Wrestling With The Gray Lady"

The attack on the US Capitol, and subsequent threats of violence surrounding the inauguration of the new US administration, has moved us to reflect and reacquaint ourselves with the reality that however good the maker’s intentions, technology can amplify the ability to cause great harm. This includes us and our products at Basecamp. Therefore, we… keep reading

G protein–coupled receptors (GPCRs) initiate signaling cascades via G-proteins and beta-arrestins (βarr). βarr-dependent actions begin with recruitment of βarr to the phosphorylated receptor tail and are followed by engagement with the receptor core. βarrs are known to act as adaptor proteins binding receptors and various effectors, but it is unclear whether in addition to the scaffolding role βarrs can allosterically activate their downstream targets. Here we demonstrate the direct allosteric activation of proto-oncogene kinase Src by GPCR–βarr complexes in vitro and establish the conformational basis of the activation. Whereas free βarr1 had no effect on Src activity, βarr1 in complex with M2 muscarinic or β2-adrenergic receptors reconstituted in lipid nanodiscs activate Src by reducing the lag phase in Src autophosphorylation. Interestingly, receptor–βarr1 complexes formed with a βarr1 mutant, in which the finger-loop, required to interact with the receptor core, has been deleted, fully retain the ability to activate Src. Similarly, βarr1 in complex with only a phosphorylated C-terminal tail of the vasopressin 2 receptor activates Src as efficiently as GPCR–βarr complexes. In contrast, βarr1 and chimeric M2 receptor with nonphosphorylated C-terminal tail failed to activate Src. Taken together, these data demonstrate that the phosphorylated GPCR tail interaction with βarr1 is necessary and sufficient to empower it to allosterically activate Src. Our findings may have implications for understanding more broadly the mechanisms of allosteric activation of downstream targets by βarrs.

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.

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.

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.

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? 

It sounds like an oxymoron: “How to keep blood-sports interesting?” You’ve got blood and you’ve got sports, the term does its own advertising! And yet, fighting promotions rise and fall, where Pride and Strikeforce once reigned, now stand One and Bellator, but one promotion stands above all its competitors. The world of MMA knows one promotion which has clawed its way to the international top and established itself as the gold standard upon whose hallowed surface skulls are crushed and blood is poured. I’m talking about none other than the UFC.

Having established itself over the years as a beacon of both quality matches and consistent drama, the UFC attracts the lion’s share of international talent in the MMA world, and with it the eyes and ears of MMA fans everywhere. Having well and truly stroked the ego of the promotion, you might be wondering what on earth any of this has to do with writing or fantasy?

Well, does your world happen to feature prizefighting, ritual combat, or the eternally popular fantasy fixture called the gladiatorial arena? If so, there are a lot of writing and worldbuilding lessons you can learn from observing the biggest promotion in the biggest modern blood-sport of the world.

Continue reading Lessons from the UFC: How to Keep Blood-Sports Interesting at Mythic Scribes.

JE Hixson
Mar 1, 1990; 31:545-548
Articles

Implications of post-COVID-19 Restructuring of Supply Chains for Global Investment Governance 14 July 2020 — 9:00AM TO 10:30AM Anonymous (not verified) 9 February 2021 Online

As companies rethink and diversify their supply chains in order to enhance resilience, what will this mean for current and future global investment governance?

What are the risks of negative effects on inclusivity and transparency? Does this shift create an opportunity to advance good governance of cross-border investment practices?

This event is part of the Inclusive Governance Initiative, which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world.

The regional and international implications of restrictions to online freedom of expression in Asia 25 March 2021 — 12:30PM TO 1:30PM Anonymous (not verified) 12 March 2021 Online

Panellists discuss the latest developments affecting online freedom of expression in the Asia region.

Please note this is an online event. Please register using the link below to finalize your registration.

In recent years, state-led clampdowns on online freedom of expression have become widespread in several countries across Asia, further intensified by the COVID-19 crisis.

The reasons for this are complex and diverse – drawing upon history, culture and politics, in addition to external influences. Across the region, governments have been accused of silencing online criticism and failing to uphold rights to free speech.

Individuals have been arrested, fined or attacked for the alleged spread of ‘fake news’, raising concern among human rights organizations. In some countries, this has culminated in the imposition of new social media rules, which could require social media companies to censor posts and share decrypted messages.

In China, the government’s restrictive online regime has relied on a combination of legal, technical and manipulation tactics to manage control of the internet, and now includes attempts at censorship beyond its borders.

Panellists will discuss the latest regional developments affecting online freedom of expression in the Asia region, and will consider the broader regional and international implications for technology governance.

This webinar launches the publication Restrictions on online freedom of expression in China: The domestic, regional and international implications of China’s policies and practices.

Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer's diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries.

Expert

Rhodopsin is a canonical class A photosensitive G protein–coupled receptor (GPCR), yet relatively few pharmaceutical agents targeting this visual receptor have been identified, in part due to the unique characteristics of its light-sensitive, covalently bound retinal ligands. Rhodopsin becomes activated when light isomerizes 11-cis-retinal into an agonist, all-trans-retinal (ATR), which enables the receptor to activate its G protein. We have previously demonstrated that, despite being covalently bound, ATR can display properties of equilibrium binding, yet how this is accomplished is unknown. Here, we describe a new approach for both identifying compounds that can activate and attenuate rhodopsin and testing the hypothesis that opsin binds retinal in equilibrium. Our method uses opsin-based fluorescent sensors, which directly report the formation of active receptor conformations by detecting the binding of G protein or arrestin fragments that have been fused onto the receptor's C terminus. We show that these biosensors can be used to monitor equilibrium binding of the agonist, ATR, as well as the noncovalent binding of β-ionone, an antagonist for G protein activation. Finally, we use these novel biosensors to observe ATR release from an activated, unlabeled receptor and its subsequent transfer to the sensor in real time. Taken together, these data support the retinal equilibrium binding hypothesis. The approach we describe should prove directly translatable to other GPCRs, providing a new tool for ligand discovery and mutant characterization.

Mining, Minerals and Metals Expert Roundtable: Forest-Smart Mining Report Launch 10 May 2019 — 5:30PM TO 6:30PM Anonymous (not verified) 12 April 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Rubén Medina and Andrés Quilis
Proc. Amer. Math. Soc. 152 (), 5137-5148.
Abstract, references and article information

The police have arrested an individual in the probe surrounding two bags of cash that allegedly fell from a Beryllium security vehicle en route to the Norman Manley International Airport in Kingston last week. 

24 July 2020

19 August 2020

27 August 2020

Environmental factors, such as viral infection, are proposed to play a role in the initiation of autoimmune diabetes. In response to encephalomyocarditis virus (EMCV) infection, resident islet macrophages release the pro-inflammatory cytokine IL-1β, to levels that are sufficient to stimulate inducible nitric oxide synthase (iNOS) expression and production of micromolar levels of the free radical nitric oxide in neighboring β-cells. We have recently shown that nitric oxide inhibits EMCV replication and EMCV-mediated β-cell lysis and that this protection is associated with an inhibition of mitochondrial oxidative metabolism. Here we show that the protective actions of nitric oxide against EMCV infection are selective for β-cells and associated with the metabolic coupling of glycolysis and mitochondrial oxidation that is necessary for insulin secretion. Inhibitors of mitochondrial respiration attenuate EMCV replication in β-cells, and this inhibition is associated with a decrease in ATP levels. In mouse embryonic fibroblasts (MEFs), inhibition of mitochondrial metabolism does not modify EMCV replication or decrease ATP levels. Like most cell types, MEFs have the capacity to uncouple the glycolytic utilization of glucose from mitochondrial respiration, allowing for the maintenance of ATP levels under conditions of impaired mitochondrial respiration. It is only when MEFs are forced to use mitochondrial oxidative metabolism for ATP generation that mitochondrial inhibitors attenuate viral replication. In a β-cell selective manner, these findings indicate that nitric oxide targets the same metabolic pathways necessary for glucose stimulated insulin secretion for protection from viral lysis.

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (Cltc), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of Cltc, similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency. Using atomic force microscopy (AFM), we demonstrate that mESCs lacking Cltc display higher Young's modulus, indicative of greater cellular stiffness, compared with WT mESCs. The increase in stiffness was accompanied by the presence of actin stress fibers and accumulation of the inactive, phosphorylated, actin-binding protein cofilin. Treatment of Cltc knockdown mESCs with actin polymerization inhibitors resulted in a decrease in the Young's modulus to values similar to those obtained with WT mESCs. However, a rescue in the expression profile of pluripotency factors was not obtained. Additionally, whereas WT mouse embryonic fibroblasts could be reprogrammed to a state of pluripotency, this was inhibited in the absence of Cltc. This indicates that the presence of active CME is essential for the pluripotency of embryonic stem cells. Additionally, whereas physical properties may serve as a simple readout of the cellular state, they may not always faithfully recapitulate the underlying molecular fate.

Consumers thinking of dining out for their next meal may want to consider one instruction for the server -- hold the salt.

A “moat” is a common term associated with Nvidia and its proprietary products that lock customers into their hardware and software. Another moat breakdown should have them concerned. The U.S. […]

The post Like Nvidia, Google’s Moat Draws Interest from DOJ appeared first on HPCwire.

NASA said on Tuesday that it will restart its Mentor-Protégé Program for contractors on Friday to expand commercial markets with eligible small businesses.

Democratic Gov. Gina Raimondo proposes to allow traditional public schools to be free of certain regulations, including opening up enrollment outside their neighborhoods.

Parents of a child with autism filed lawsuits against the Clark County, Nev. district, after video evidence showed him being restrained repeatedly.

A Nebraska senator introduced a bill that would give teachers legal cover to physically restraint disruptive students, prompting a strong positive response from members of the state teachers' union.

The Calgary Flames' fifth game in eight nights and three time zones was a tough one they need to learn from

Kyle E. Mathewson
Mar 4, 2009; 29:2725-2732
BehavioralSystemsCognitive

Estimating the direction of functional connectivity (FC) can help further elucidate complex brain function. However, the estimation of directed FC at the voxel level in fMRI data, and evaluating its performance, has yet to be done. We therefore developed a novel directed seed-based connectivity analysis (SCA) method based on normalized pairwise Granger causality that provides greater detail and accuracy over ROI-based methods. We evaluated its performance against 145 cortical retrograde tracer injections in male and female marmosets that were used as ground truth cellular connectivity on a voxel-by-voxel basis. The receiver operating characteristic (ROC) curve was calculated for each injection, and we achieved area under the ROC curve of 0.95 for undirected and 0.942 for directed SCA in the case of high cell count threshold. This indicates that SCA can reliably estimate the strong cellular connections between voxels in fMRI data. We then used our directed SCA method to analyze the human default mode network (DMN) and found that dlPFC (dorsolateral prefrontal cortex) and temporal lobe were separated from other DMN regions, forming part of the language-network that works together with the core DMN regions. We also found that the cerebellum (Crus I-II) was strongly targeted by the posterior parietal cortices and dlPFC, but reciprocal connections were not observed. Thus, the cerebellum may not be a part of, but instead a target of, the DMN and language-network. Summarily, our novel directed SCA method, visualized with a new functional flat mapping technique, opens a new paradigm for whole-brain functional analysis.

Prince Laurent of Belgium was today appointed FAO Special Ambassador for Forests and the Environment.

The announcement was made by FAO Director-General José Graziano da Silva at the Organization’s Committee on [...]

Cancun, Mexico. On [...]

Help shape FAO’s digital publishing programme by answering a 5-minute survey on the The State of the World’s Forests (SOFO) and Global Forest Resources Assessment (FRA).

The survey seeks to gather [...]

Rome - The experience of farmers who manage agricultural heritage can help achieve the UN Decade of Ecosystem Restoration's main goals: support and scale-up efforts [...]

The 2022 edition of The State of the World’s Forests explores the potential of three forest pathways for achieving green recovery and tackling environmental crises, including climate change and biodiversity [...]

In a conversation with architect David Rockwell, the philanthropic chef urges an invested effort to create technology that could collect water from the clouds

Learn how to stage a sit-in right next to the Greensboro lunch counter, the location of one of the civil rights movement's most famous protests (Video by: Katy June-Friesen). Read more at http://www.smithsonianmag.com/arts-culture/Courage-at-the-Greensboro-Lunch-Counter.html

As the dams begin to come down, the National Park Service looks back at the region’s history and prepares for the welcome changes to the ecosystem

African cuisine has always been well represented in the United States, particularly in dishes characterized as “Southern” in origin, like gumbo or hoppin’ john. But even before chef Serigne Mbaye’s New Orleans eatery Dakar NOLA was named (https://www.eater.com/24175309/james-beard-awards-2024-winners-restaurant-and-chef-awards) the Best New Restaurant of 2024 at the James Beard Awards this week, the contributions of the African diaspora to the American diet had at last begun to enjoy a long-overdue reappraisal via reality television, Netflix docuseries and, most important, a number of widely praised dining establishments: If you want to book a table at Tatiana (https://www.tatiananyc.com/story/) in Manhattan, Dept of Culture (https://www.deptofculturebk.com/) in Brooklyn or Kann (https://kannrestaurant.com/) in Portland, you’d better plan ahead, because their tables are often booked up well in advance. In this episode, Smithsonian contributor Rosalind Cummings-Yeates explains how the ascendancy of pan-African cuisine from “auntie” restaurants into the rarefied fine dining sphere is part of a larger and more meaningful campaign of cultural reclamation. And Mbaye tells us why it was so important to him to make Dakar NOLA (https://www.dakarnola.com/) a showcase of the distinctive flavors of Senegal, where he spent his formative years. Read Rosalind's Smithsonian story about the rise of West African fine dining in the U.S. here (https://www.smithsonianmag.com/arts-culture/these-chefs-are-elevating-african-and-caribbean-cuisines-from-carryouts-to-fine-dining-180984466/) . See the full list of 2024's James Beard Award winners here (https://www.jamesbeard.org/blog/the-2024-james-beard-award-winners) . Find prior episodes of our show here (https://www.smithsonianmag.com/podcast/) . There’s More to That is a production of Smithsonian magazine and PRX Productions. From the magazine, our team is Chris Klimek, Debra Rosenberg and Brian Wolly. From PRX, our team is Jessica Miller, Adriana Rosas Rivera, Genevieve Sponsler, Rye Dorsey, and Edwin Ochoa. The Executive Producer of PRX Productions is Jocelyn Gonzales. Fact-checking by Stephanie Abramson. Episode artwork by Emily Lankiewicz / photography by Katherine Kimball, Joshua Brasted, and Jeremy Tauriac Music by APM Music.

With an 80-acre scale model of the 1.6 million-acre Everglades wetland system, scientists study how to restore the flow of water that was interrupted years ago

Earth's highest peak has gained as much as an extra 165 feet in elevation as the planet's crust adjusts due to erosion from a river, according to a new study

In 1924, Andrew "Sandy" Irvine joined George Mallory’s expedition to the world’s highest peak. Now, Irvine’s recently found foot and boot hint at what might have happened on that ill-fated undertaking