Dogecoin has experienced a significant surge in value since last month, with impressive price gains continuing today as it trades… Continue reading Dogecoin at the Edge of a Major Breakout – Could $2 Be Possible with Bitcoin Dominance Holding Strong?

The post Dogecoin at the Edge of a Major Breakout – Could $2 Be Possible with Bitcoin Dominance Holding Strong? 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.

ByteDance founder Zhang Yiming is China's richest person, with personal wealth of $49.3 billion (R872 billion), an annual rich list showed on Tuesday, although counterparts in real estate and renewables have fared less well.

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.

The tales of New York City's rats are legendary. NY Rats are big and smart, and they have lots of babies. The city has a rat czar and recently held a rat summit to discuss the issue. Mayor Eric Adams was undoubtedly happy to talk about the rat problem rather than his own issues. — Read the rest

The post New York feeding rats tasty birth control appeared first on Boing Boing.

Forbes.com published an article by Dan Woods where he describes a battle between the traditional enterprise software providers (Microsoft, SAP, and Oracle) and Saas providers like Salesforce.com and NetSuite.

According to Woods, SaaS applications are easier to use because they offer streamlined interfaces that are modeled after successful web consumer sites like Amazon.com, Yahoo!, eBay, Google, etc. These SaaS interfaces were designed to be easily configurable.

Traditional enterprise software is not as easy to use because user interfaces are often created before it is known exactly how the software would be used. Customization to the user interface is often done at installation by systems integrators who do not have any actual user behavior on which to base their customizations.

The Big Three are well aware of the usability gap between their products and SaaS software, but it is unclear how to solve the problem. Oracle emphasizes Fusion as an integration platform. SAP recently announced an experiment called Blue Ruby that is attempting to adapt Ruby on Rails as a user interface and programming technology for its applications. But is it possible to affordably automate a business starting with a configurable application platform that must be adapted to the specific user interfaces and business processes in a company? The SaaS model starts with a usable interface and a working automation of common processes, and then has the configuration proceed from there. The hosted nature of SaaS removes the deployment barriers.

Interactive Media Strategies (IMS) is a market research firm that follows streaming media. They discuss the news of Microsoft’s $8.5 billion acquisition of Skype, and the prospects for Skype to emerge as a viable platform for business video communications. 

Their research compares usage levels for a range of social media and communications applications, including Skype, YouTube and Facebook. Here is a link to the video.

They report that personal use of Facebook and YouTube is relatively high but that has not yet translated into comparable levels of corporate use. They believe this raises the question of whether YouTube and Facebook will be able to outgrow their focus on the consumer side of the business to compete in the enterprise market.

Usage levels for Skype are significantly lower overall, but Skype’s penetration in business communications is higher than they see for other communications apps online among young users most likely to experiment with emerging technologies.

IMS puts forth the opinion that if Microsoft could make it easier for technology laggards to embrace Skype - i.e. integrate Skype with the Microsoft Office suite - then Skype could achieve significant enterprise adoption.

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.

Who Can Currently Afford to Buy a Home?

The following article, Biden’s Corrupt FEMA Told Workers Not to Help Hurricane Victims Who Had Trump Signs, was first published on Conservative Firing Line.

Joe Biden’s corrupt Federal Emergency Management Administration (FEMA) has been caught telling its on-the-ground operatives not to help anyone with a Donald Trump campaign sign in their yard. The news broke late last week when a whistleblower revealed agency messages that told workers to refuse to help Trump supporters in the wake of Hurricane Milton …

Continue reading Biden’s Corrupt FEMA Told Workers Not to Help Hurricane Victims Who Had Trump Signs ...

A quick note to point you toward this piece I wrote for P&G’s Signal publication. Since its inception, I’ve been co-editor of the monthly outlet, which covers innovation in large enterprise. This month I went in search of proof that the hype around generative AI – fueled in large part by both Google and Microsoft … Continue reading "Can GenAI Change Big Companies?"

We've all met some of those 'precious moments' type Christians who are far too 'holy' to involve themselves in such trivialities as politics.

The post This Biblical Passage is VERY Political (Eph.1:20-23) appeared first on Clash Daily.

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.

At the State of the Union, Joe Biden Joe Biden made a 'bold' announcement that America would be building a pier to deliver aid to Gaza. Four months later, he admitted it was a failure.

The post Soldier Succumbs To Injuries Sustained In Biden’s Doomed Gaza Pier Mission appeared first on Clash Daily.

There's a reason Hitler holds a special place of disgrace in public memory. He combined the ambition and destruction of Attila The Hun with the personal malice of a serial killer.

The post The REAL Harm Done By Calling Everyone You Don’t Like ‘Hitler’ Is BIGGER Than Lefties Think appeared first on Clash Daily.

Whichever candidate is sworn into office this January is the President who will be making decisions about how America and her legacy is remembered.

The post AMERICA’S BIG BIRTHDAY: An Election Argument Everyone Seems To Be Missing appeared first on Clash Daily.

While the rest of us were busy cheering (or crying) about the election results, the world kept turning and events continued to unfold at home and around the world.

The post Trump Scores Three Big Wins Less Than One Day After The Election appeared first on Clash Daily.

Team Biden thought it was a clever work-around to open up the border without looking like they were opening the border. Texas took the cheat to court.

The post AMNESTY: Texas & American First Legal Score BIG Win Against Open Border Policy appeared first on Clash Daily.

There appeared to be a definite frost between first lady Jill Biden and Vice President Kamala Harris during a Veterans Day event at Arlington National Cemetery on Monday. A close-up […]

The post Footage of Jill Biden and Kamala Harris Sitting Side-by-Side at Veterans Day Event Goes Viral appeared first on The Western Journal.

President-elect Donald Trump is expected to nominate Florida Sen. Marco Rubio as his secretary of state, reports late Monday indicate. According to The Wall Street Journal, while the nomination isn’t […]

The post Trump to Pick Senator Marco Rubio for Crucial Cabinet Position: Report appeared first on The Western Journal.

Melania Trump will not be traveling with her husband to Washington on Wednesday when President-elect Donald Trump and President Joe Biden have a formal transition meeting, according to multiple reports. […]

The post Melania Trump to Give Jill Biden the Cold Shoulder This Week: Report appeared first on The Western Journal.

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.

The race to succeed Bill Beaumont as chairman of World Rugby comes to a conclusion in a vote in Dublin at the governing body's headquarters on Thursday.

Wednesday's third T20 between South Africa and India at SuperSport Park in Centurion is shaping up to be a run-drenched one, especially if the weather holds and SA's bowling centre doesn't.

Mekka Newspaper, Mecca, Saudi Arabia: Oct. 28, 2022 It was my distinct honor to Arabic receive a wonderful review by Mecca Newspaper, one of the oldest newspapers in the Middle East. I am deeply grateful and humbled to be part of the historic reformation and renaissance taking place in the Middle East. When Mecca newspaper […]

Worldwide revenues will triple in 2022   April 11, 2022 (New York, NY) – TikTok’s worldwide ad revenues will triple this year and surpass that of two competitors combined, according […]

June 22, 2022 (New York, NY) – Will Apple’s entry into the buy now, pay later (BNPL) space upend the already competitive industry? That’s the question many are trying to […]

Marcelo Campos, Matthew Jenssen, Marcus Michelen and Julian Sahasrabudhe
J. Amer. Math. Soc. 38 (), 179-224.
Abstract, references and article information

Junyi Xie
J. Amer. Math. Soc. 38 (), 1-62.
Abstract, references and article information

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.

An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism.

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.

Sustainability Accelerator Summer Drinks 2024 6 September 2024 — 5:30PM TO 7:30PM Anonymous (not verified) 19 August 2024 Chatham House

Join us for the Sustainability Accelerator’s annual summer drinks reception.

This event brings together a diverse group of thinkers and changemakers from our network, as well as our collaboration partners, to reflect on our successes over the past year and give an opportunity to meet new people.

The reception will follow the Sustainability Accelerator’s annual UnConference, but is a separate event. Unless you have received confirmation of your place at UnConference, you must register for the summer drinks reception via this webpage to secure your place.

Fostering inclusive health systems amidst geopolitical instability 13 October 2024 — 9:00AM TO 10:00AM Anonymous (not verified) 11 September 2024 Sheraton Berlin Grand Hotel Esplanade

How can we build trust and inclusivity in the health sector in a fractured geopolitical environment?

Building trust in government, service provision and delivery are crucial considerations for policymakers who aim to make local, national and international health systems more inclusive. In the health space, trust can be a matter of life and death. Understanding and modulating policies that account for the trust factor, alongside the geopolitical determinants of health, can lead to more inclusive decision making and thus better health outcomes for larger proportions of a population.

International unity is key to addressing the challenges posed by geopolitical instability, which include disinformation campaigns, rising nationalism and growing divisions between states. If countries can find common ground through an inclusive approach to health, the effects could be transformative in achieving global health and equity targets.

This discussion, held in partnership with Haleon, will examine what it takes to foster trust and resilience in the health sector, achieve global inclusivity aims and chart a path for the public and private spheres to come together to navigate a fractured geopolitical environment.

• In what ways can localised health inclusivity data help policymakers to alleviate gaps in healthcare provision and why is this an essential element in instilling trust across the system?
• What role should multilateral organizations play in setting precedents for health inclusivity around the world?
• How do health inclusivity policies empower the service user and help reduce the burden placed on public healthcare systems?
• How can the health sector come together to ensure individuals are included within their own health decisions, are able to access services regardless of demographics and geography and trust their healthcare providers?

This event will be held at the Sheraton Hotel, Grand Esplanade, Berlin in the margins of the World Health Summit. You do not need a ticket for the World Health Summit to attend this event.

Numerous iron-sulfur (Fe-S) proteins with diverse functions are present in the matrix and respiratory chain complexes of mitochondria. Although [4Fe-4S] clusters are the most common type of Fe-S cluster in mitochondria, the molecular mechanism of [4Fe-4S] cluster assembly and insertion into target proteins by the mitochondrial iron-sulfur cluster (ISC) maturation system is not well-understood. Here we report a detailed characterization of two late-acting Fe-S cluster-carrier proteins from Arabidopsis thaliana, NFU4 and NFU5. Yeast two-hybrid and bimolecular fluorescence complementation studies demonstrated interaction of both the NFU4 and NFU5 proteins with the ISCA class of Fe-S carrier proteins. Recombinant NFU4 and NFU5 were purified as apo-proteins after expression in Escherichia coli. In vitro Fe-S cluster reconstitution led to the insertion of one [4Fe-4S]2+ cluster per homodimer as determined by UV-visible absorption/CD, resonance Raman and EPR spectroscopy, and analytical studies. Cluster transfer reactions, monitored by UV-visible absorption and CD spectroscopy, showed that a [4Fe-4S]2+ cluster-bound ISCA1a/2 heterodimer is effective in transferring [4Fe-4S]2+ clusters to both NFU4 and NFU5 with negligible back reaction. In addition, [4Fe-4S]2+ cluster-bound ISCA1a/2, NFU4, and NFU5 were all found to be effective [4Fe-4S]2+ cluster donors for maturation of the mitochondrial apo-aconitase 2 as assessed by enzyme activity measurements. The results demonstrate rapid, unidirectional, and quantitative [4Fe-4S]2+ cluster transfer from ISCA1a/2 to NFU4 or NFU5 that further delineates their respective positions in the plant ISC machinery and their contributions to the maturation of client [4Fe-4S] cluster-containing proteins.

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.

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.

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).

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.

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.

India Budget 2018: Who are the Biggest Winners and Losers? Expert comment sysadmin 2 February 2018

Any claims to boost farmers’ prospects will inevitably be seen as political, coming ahead of a series of key elections. But this budget recognises India’s most pressing concerns - and seeks to address them.

In 2016 India’s prime minister, Narendra Modi, pledged to double farmers’ incomes by 2022. While the pledge may have been aspirational, reliant on good weather as much as government policy, the 2018/19 budget demonstrates the depth of the government’s commitment to the agriculture sector.

There’s clearly a political edge to any moves to bolster agriculture: any solace to rural India will be described as political opportunism until most people in India are not engaged directly or indirectly in the agricultural sector.

And with a number of state elections coming up this year and a general election next – suggestions that it will be brought forward have increased in volume since the budget – a politically-astute budget is unsurprising. At the same time, there is a real sense of crisis in Indian agriculture which the budget is attempting to ameliorate.

Significant hike in infrastructure spending

The budget – which has Keynesian undertones – announces both direct and indirect support for rural India; it increases significantly the price at which the government purchases agricultural produce, and offers a range of further support through initiatives in areas such as irrigation. Furthermore, there is a significant hike in spending on infrastructure – roads, railways, ports and waterways – with a major allocation for rural infrastructure.

While government spending on infrastructure had been growing, the 2018/19 budget appears to accept that innovative funding models to fund rural projects are unlikely to work – instead, rural highways will have to be funded from overall taxation, as is generally the norm.

The other bold initiative focuses on healthcare. One hundred million poor families (so around half a billion Indians in total) will receive up to Rs500,000 for medical care under a health insurance programme. Given the correlation between ill health and poverty, this should have implications for the economy as well as healthcare itself. At the moment poverty effectively excludes many Indians from private healthcare.

Education too received a boost, with several proposals including teacher training. There have long been concerns over the quality of Indian education. In particular, even where schools exist physically, teachers themselves are absent.

As is often the case with India, the question will be in the implementation. While there are bound to be hiccups, the current Indian government does appear to realise the need for on-the-ground, visible change.

The recent state election in Gujarat demonstrated that while the ruling Bharatiya Janata Party (BJP) is clearly favourite to win another term, it is not invulnerable. If the changes do not reach the “last mile”, then they will accrue neither the economic nor the political benefits.

The downsides? Increased taxes will raise inflation, potentially exacerbated by sustained government borrowing; a 20% rise in customs duty will affect imports of mobile phones (though benefit domestic producers and encourage other foreign firms to set up manufacturing plants in India) and some of the revenue projections appear optimistic.

On balance though, this is a budget that recognises the most pressing challenges which India faces, and attempts to provide solutions to them.

This article was originally published in The Independent.

Mobile Ecosystems as a Driver of Innovation and Growth in the Asia-Pacific 19 September 2018 — 12:30PM TO 3:00PM Anonymous (not verified) 18 September 2018 Chatham House, London

International Arbitration: Exploring India’s Potential 15 November 2019 — 9:30AM TO 5:30PM Anonymous (not verified) 17 October 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

As India’s economic clout grows, so does its aspiration to become a favoured arbitration destination in a globalized world dominated by foreign investments flows and cross border transactions. India’s bid to enhance its status as an arbitration destination depends largely on the suitability of its legal environment in meeting the demands of an increasingly sophisticated approach to disputed resolution. This conference will assess these, and other related, issues.

To register your interest in attending this event, please contact Nisha Ramdas by phone +91 9650977833 or by e-mail nisha@globaldialoguereview.com.

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.

Why burning biomass is not zero-carbon Explainer Video NCapeling 17 October 2022

Short animation explaining why burning biomass produces more carbon dioxide per unit of energy generated than almost all fossil fuels.

The climate emergency requires countries to transition away from fossil fuels, but it is important to be careful about the alternative energy sources chosen.

In particular, concern is growing over the use of biomass for energy, which is generated when wood or other plant material is burnt to generate heat and electricity. Many governments treat biomass energy as zero-carbon at the point of combustion, and subsidize it in the same way as renewables such as solar or wind, resulting in a large increase in the use of biomass for energy in the UK and the European Union (EU) over the past 15 years.

The treatment of biomass as zero-carbon in policy frameworks rests on the argument that biomass emissions will be reabsorbed by forest growth, particularly from trees planted to replace those cut down to burn.

But growing trees to maturity takes many years and, depending on the feedstock used, biomass burning increases global warming for decades to centuries. This is called the ‘carbon payback period’ – the time it takes for carbon dioxide levels to return to what they would have been if biomass had not been used.

New research from Chatham House and the Woodwell Climate Research Center calculated the real climate impact of burning US wood pellets in the UK and EU. In 2019, according to this analysis, US-sourced pellets burned for energy in the UK were responsible for between 13 million and 16 million tonnes of carbon dioxide, equivalent to the annual greenhouse gas emissions from 6-7 million passenger vehicles.

But because biomass is treated as zero-carbon, almost none of these emissions were included in the UK’s national greenhouse gas reports. And the removal of forest carbon from US forests is not included accurately in US reports, either.

America’s vote shows a desire for stability and calm Expert comment NCapeling 11 November 2022

Joe Biden has presided over the best midterm election results by a party in power in two decades, but the future for the Republican Party leadership is now uncertain.

For a president continually struggling with low approval ratings, the midterms provided a stunning result as the widely anticipated Republican red wave failed to materialize.

Although Democrats look set to lose their majority in the House, it is by a much smaller margin than either history or today’s pollsters anticipated. Democrats have maintained their majority in the Senate, a result that was confirmed four days after election day when Senator Catherine Cortez Masto won reelection. The final Senate seat will be decided by a 6 December run-off in the state of Georgia. 

The midterm elections were not good for the Republican party but were especially bad for Donald Trump who has until now managed to defy expectations and maintain his grip on the party even after his 2020 defeat at the polls.

Trump managed to win the presidency once but he lost the popular vote twice and at no stage during his time in office did his approval ratings go above 40 per cent. Now, after six years of the most divisive and disruptive leadership the US has ever seen, he has presided over the worst midterm results a party out of power has suffered in two decades.

Trump’s influence is on the wane

Many of the candidates endorsed by the former president – including in battleground states such as Pennsylvania and Arizona – lost. In Georgia, the Republican governor and Trump GOP rival won, despite Trump’s opposition, and the candidate he endorsed for the US Senate has come up short of the 50 per cent needed to get over the line in the first round.

Trump’s nemesis, Ron DeSantis, the Republican governor of Florida, won a second four-year term in a landslide. Trump is suffering attacks from his own party and many loyal media supporters, such as Fox News, the New York Post, and the Wall Street Journal. None of this bodes well for the prospect of Trump leading the party through the 2024 presidential election.

After six years of chaos, this upset has been delivered with remarkably little chaos and, so far, no violence in a win for democracy and stability in the US which will reverberate beyond the US shores.

The system has worked, with multiple elections held across all 50 states. Hotly contested seats were decided peacefully even when the margins were thin. The midterm elections were also a win for democracy. In every battleground state, election deniers that were nominated to run for offices that would control state election systems, including in the 2024 presidential elections, have been defeated.

For a country with a polarized electorate and a radical Republican leader who has continued to spread disinformation and sought to rile his base, this election has been surprisingly normal.

This means the debate about the future of America’s international leadership is postponed. Biden is still in the saddle and, instead of a battle for control inside the Democratic party, it is the Republicans who look set to descend into internal conflict and recrimination.

The unofficial contest to win the Republican nomination for president has already begun. Donald Trump has signalled loudly that he plans to run. If he does, it could impact Republican prospects in the 6 December runoff for the final seat in the Senate. DeSantis may also run and could be followed by several aspiring Republican candidates. A disrupted party facing a period of significant change seems likely. 

Inflation and the economy proved key factors

As always, foreign policy barely featured in the elections but the result promises a period of continuity. Instead of facing dangerous sniping on Ukraine from an emboldened Republican House leadership, the Biden administration looks set to hold to its Ukraine policy.

Biden’s increasingly hard-line policy on China will continue to be qualified by a clear-headed determination – however hard – to cooperate on climate. Trade policy will remain stuck, as will US policy in the developing world.

Exit polls show Democrats were motivated to vote by the reversal of Roe vs Wade and the restrictions on abortion rights that followed, while Republicans voted against inflation.

But Democrats at the national level continually failed to effectively communicate the positive impacts of Biden’s legislative agenda for ordinary Americans, or to deliver a clear economic message.

The national leadership veered from abortion rights to the Inflation Reduction Act, to the future of democracy in the US – all of which proved too complicated to cut through.

The state level shows a more complex picture because inflation and the economy – which could have swept Republicans to victory – were blunted by dogged local campaigning from Democrats who knew their voters and spoke to the cost-of-living concerns which were top of their minds.

World in brief: Biden seeks to win over African leaders The World Today mhiggins.drupal 29 November 2022

At the US-Africa Leaders Summit, Washington will need to go beyond strategic geopolitical interest to compete with China’s offer, says James Orr.

African heads of state will join President Joe Biden in Washington in mid-December to take part in the second United States-Africa Leaders Summit. Some 50 African leaders will travel to the US capital for the two-day conference, which starts on December 13. 

Senior policymakers say  talks will focus on economic engagement, human rights, food security and climate, with an emphasis on partnerships that demonstrate an intention to go beyond strategic geo-political interest. President Biden has said he hopes to ‘reinforce the US-Africa commitment to democracy; mitigate the impact of Covid, respond to the climate crisis and amplify diaspora ties’. The White House will seek to offer reassurance to African governments concerned by a perceived cooling in relations with the US.

Africa’s cooling relations with the US 

‘As trite as it might sound, the key objective of this conference should really be to enhance trust between African leaders and the United States,’ said Gilbert Kaplan, a former under-secretary at the US Department of Commerce.  ‘I was in Africa in 2018 leading the President’s Advisory Council on Doing Business in Africa and the foreign minister of Ethiopia said to me: “Well you’re here but are you really here?” What he meant was: is the United States really committed to a long-term, strong relationship with the African continent or is it just a drive-through and a hello without making major commitments?’

The first summit was held by President Barack Obama in 2014. Addressing the inaugural conference, he spoke of the ‘blood of Africa’ that ran through his veins and how ‘the bonds between our countries are deeply personal’. Today, however, a succession of abstentions or no votes from African states over United Nations resolutions on Russia’s invasion of Ukraine points to a growing misalignment in the relationship. This is indicative of expanding Chinese and Russian influence on the continent, say analysts.

‘Africa is faced with some of the biggest governance challenges on the globe,’ said Kah Walla, president of the Cameroon People’s Party and the first woman in the nation’s history to run as a presidential candidate in 2011. ‘We need government that is functional, competent and innovative, and what we are getting instead is the US and a global international system that is supporting [via financial aid] autocratic and dysfunctional governments. We can’t continue in this way.’

Africa’s 54 nation states span six time zones and the continent’s population of 1.4 billion is on course to make up a quarter of the global population by 2050. It boasts the youngest demographic in the world, a potentially huge labour resource for private sector investors seeking to expand in manufacturing and processing, for example. The current median age in Africa is 18.8 years, compared with a global median age of 30.

In July this year, the US provided nearly $1.3 billion in humanitarian assistance to help stave off hunger due to drought in the Horn of Africa. Since June 2019, the US, under its Prosper Africa programme, has also helped close some 800 export and investment deals across 45 African nations with an estimated value of $50 billion.

The US is losing out to China in Africa

Meanwhile, China surpassed the US as Africa’s largest trade partner in 2009, with total bilateral trade reaching more than $254 billion in 2021, a 35 per cent rise on 2020.

‘Despite Africa’s tremendous economic potential, the US has lost substantial ground to traditional and emerging partners, especially China,’ Landry Signé, a member of the World Economic Forum’s Regional Action Group for Africa, told a Senate subcommittee on Africa last year. ‘While recent trends indicate that the US engagement with the region has fallen, it has not and should not cede its relationship with the region to other powers.’

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.

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.

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.