Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.

In quantitative proteomics work, the differences in expression of many separate proteins are routinely examined to test for significant differences between treatments. This leads to the multiple hypothesis testing problem: when many separate tests are performed many will be significant by chance and be false positive results. Statistical methods such as the false discovery rate (FDR) method that deal with this problem have been disseminated for more than one decade. However a survey of proteomics journals shows that such tests are not widely implemented in one commonly used technique, quantitative proteomics using two-dimensional electrophoresis (2-DE). We outline a selection of multiple hypothesis testing methods, including some that are well known and some lesser known, and present a simple strategy for their use by the experimental scientist in quantitative proteomics work generally. The strategy focuses on the desirability of simultaneous use of several different methods, the choice and emphasis dependent on research priorities and the results in hand. This approach is demonstrated using case scenarios with experimental and simulated model data.

Electrospray ionization is today the most widely used ionization technique in chemical and bio-chemical analysis. Interfaced with a mass spectrometer it allows to investigate the molecular composition of liquid samples. With electrospray a large variety of chemical substances can be ionized. There is no limitation in mass which enables even the investigation of large non-covalent protein complexes. Its high ionization efficiency profoundly changed bio-molecular sciences because proteins can be identified and quantified on trace amounts in a high throughput fashion. This review article focusses mainly on the exploration of the underlying ionization mechanism. Some ionization characteristics are discussed which are related to this mechanism. Typical spectra of peptides, proteins and non-covalent complexes are shown and the quantitative character of spectra is highlighted. Finally the possibilities and limitations in measuring the association constant of bivalent non-covalent complexes are described.

Protein tyrosine kinases (PTKs) play key roles in cellular signal transduction, cell cycle regulation, cell division, and cell differentiation. Dysregulation of PTK-activated pathways, often by receptor overexpression, gene amplification, or genetic mutation, is a causal factor underlying numerous cancers. In this study, we have developed a parallel reaction monitoring (PRM)-based assay for quantitative profiling of 83 PTKs. The assay detects 308 proteotypic peptides from 54 receptor tyrosine kinases and 29 nonreceptor tyrosine kinases in a single run. Quantitative comparisons were based on the labeled reference peptide method. We implemented the assay in four cell models: 1) a comparison of proliferating versus epidermal growth factor (EGF)-stimulated A431 cells, 2) a comparison of SW480Null (mutant APC) and SW480APC (APC restored) colon tumor cell lines, and 3) a comparison of 10 colorectal cancer cell lines with different genomic abnormalities, and 4) lung cancer cell lines with either susceptibility (11-18) or acquired resistance (11-18R) to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. We observed distinct PTK expression changes that were induced by stimuli, genomic features or drug resistance, which were consistent with previous reports. However, most of the measured expression differences were novel observations. For example, acquired resistance to erlotinib in the 11-18 cell model was associated not only with previously reported upregulation of MET, but also with upregulation of FLK2 and downregulation of LYN and PTK7. Immunoblot analyses and shotgun proteomics data were highly consistent with PRM data. Multiplexed PRM assays provide a targeted, systems-level profiling approach to evaluate cancer-related proteotypes and adaptations. Data are available through Proteome eXchange Accession PXD002706.

Paramphistomosis, caused by the rumen fluke, Calicophoron daubneyi, is a parasitic infection of ruminant livestock which has seen a rapid rise in prevalence throughout Western Europe in recent years. Following ingestion of metacercariae (parasite cysts) by the mammalian host, newly-excysted juveniles (NEJs) emerge and invade the duodenal submucosa which causes significant pathology in heavy infections. The immature larvae then migrate upwards, along the gastrointestinal tract, and enter the rumen where they mature and begin to produce eggs. Despite their emergence, and sporadic outbreaks of acute disease, we know little about the molecular mechanisms used by C. daubneyi to establish infection, acquire nutrients and to avoid the host immune response. Here, transcriptome analysis of four intra-mammalian life-cycle stages, integrated with secretome analysis of the NEJ and adult parasites (responsible for acute and chronic disease respectively), revealed how the expression and secretion of selected families of virulence factors and immunomodulators are regulated in accordance with fluke development and migration. Our data show that whilst a family of cathepsins B with varying S2 sub-site residues (indicating distinct substrate specificities) are differentially secreted by NEJs and adult flukes, cathepsins L and F are secreted in low abundance by NEJs only. We found that C. daubneyi has an expanded family of aspartic peptidases, which is up-regulated in adult worms, although they are underrepresented in the secretome. The most abundant proteins in adult fluke secretions were helminth defence molecules (HDMs) that likely establish an immune environment permissive to fluke survival and/or neutralise pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharide in the microbiome-rich rumen. The distinct collection of molecules secreted by C. daubneyi allowed the development of the first coproantigen-based ELISA for paramphistomosis which, importantly, did not recognise antigens from other helminths commonly found as co-infections with rumen fluke.

Malaria elimination is still pending on the development of novel tools that rely on a deep understanding of parasite biology. Proteins of all living cells undergo a myriad number of posttranslational modifications (PTMs) that are critical to multifarious life processes. An extensive proteome-wide dissection revealed a fine PTM map of most proteins in both Plasmodium falciparum, the causative agent of severe malaria, and the infected red blood cells. More than two-thirds of proteins of the parasite and its host cell underwent extensive and dynamic modification throughout the erythrocytic developmental stage. PTMs critically modulate the virulence factors involved in the host-parasite interaction and pathogenesis. Furthermore, P. falciparum stabilized the supporting proteins of erythrocyte origin by selective de-modification. Collectively, our multiple omic analyses, apart from having furthered a deep understanding of the systems biology of P. falciparum and malaria pathogenesis, provide a valuable resource for mining new antimalarial targets.

Gonadal soma-derived factor (gsdf) has been demonstrated to be essential for testicular differentiation in medaka (Oryzias latipes). To understand the protein dynamics of Gsdf in spermatogenesis regulation, we used a His-tag "pull-down" assay coupled with shotgun LC-MS/MS to identify a group of potential interacting partners for Gsdf, which included cytoplasmic dynein light chain 2, eukaryotic polypeptide elongation factor 1 alpha (eEF1α), and actin filaments in mature medaka testis. As for the interaction with TGFβ-dynein being critical for spermatogonial division in Drosophila melanogaster, the physical interactions of Gsdf-dynein and Gsdf-eEF1α were identified through a yeast 2-hybrid (Y2H) screening of an adult testis cDNA library using Gsdf as bait, which were verified by a paired Y2H assay. Co-immunoprecipitation of Gsdf and eEF1α was defined in adult testes as supporting the requirement of a Gsdf and eEF1α interaction in testis development. Proteomics analysis (data are available via ProteomeXchange with identifier PXD022153) and ultrastrutural observations showed that Gsdf deficiency activated eEF1α-mediated protein synthesis and ribosomal biogenesis, which in turn led to the differentiation of undifferentiated germ cells. Thus, our results provide a framework and new insight into the coordination of a Gsdf (TGFβ and eEF1α complex in the basic processes of germ cell proliferation, transcriptional and translational control of sexual RNA which may be fundamentally conserved across phyla during sexual differentiation.

Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol (GPI)-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology.

Recent advances in MS-based proteomics have vastly increased the quality and scope of biological information that can be derived from human samples. These advances have rendered current workflows increasingly applicable in biomedical and clinical contexts. As proteomics is poised to take an important role in the clinic, associated ethical responsibilities increase in tandem with the impact on the health, privacy, and well-being of individuals. Here we conducted and report a systematic literature review of ethical issues in clinical proteomics. We add our perspectives from a background of bioethics, the results of our accompanying paper extracting individual-sensitive results from patient samples, and the literature addressing similar issues in genomics. The spectrum of potential issues ranges from patient re-identification to incidental findings of clinical significance. The latter can be divided into actionable and unactionable findings. Some of these have the potential to be employed in discriminatory or privacy-infringing ways. However, incidental findings may also have great positive potential. A plasma proteome profile, for instance, could inform on the general health or disease status of an individual regardless of the narrow diagnostic question that prompted it. We suggest that early discussion of ethical issues in clinical proteomics is important to ensure that eventual regulations reflect the considered judgment of the community as well as to anticipate opportunities and problems that may arise as the technology matures further.

In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11–13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24–32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis. We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.

Jake Arrieta on Thursday offered an unexpected explanation for his second-half struggles in 2018: he pitched much of last season with an injured left knee.

VOLUME 289 (2014) PAGES 6604–6618In Fig. 4G, in the foxi1 panel, the images in Fig. 4G, i and l, corresponding to “smad1 MO” and “smad5 MO + samd1/9 mRNA” samples, respectively, were inadvertently reused during figure preparation. This error has now been corrected using images pertaining to each treatment and sample. This correction does not affect the results or conclusions of the work.jbc;295/52/18650/F4F1F4Figure 4G.

COVID-19 in South Africa: Leadership, Resilience and Inequality Expert comment sysadmin 7 May 2020

In a world looking for leadership, South Africa’s president Cyril Ramaphosa has been remarkable. One year after he carried the time-worn ANC through a national election, South Africans are crying out for more.

In the COVID-19 crisis so far, Cyril Ramaphosa has been widely praised for displaying the decisive leadership so many hoped for when they cast their ballot for him in May 2019. Buttressed by others such as health minister Dr Zweli Mkhize, and on a simple objective to prevent transmission, South Africa has been a lesson to the world. Act fast. Act hard.

Former president Thabo Mbeki’s disastrous response to the HIV crisis cast a long shadow over his legacy, and Ramaphosa has taken note. South Africa has had one of the tightest lockdowns in the world. No exercise. No cigarettes. No alcohol.

The lockdown was imposed when the country had only around 1,000 recorded cases and just two deaths. As a result, transmission from returning travellers has not yet led to an exponential infection rate within the community. The government’s swift reaction has bought much needed time with the peak now seemingly delayed to September or October.

Continental and national leadership

Ramaphosa has also emerged as a key focal point for Africa-wide responses. As current chair of the African Union (AU) he leads the continental engagement with the World Health Organization (WHO), and the various international finance institutions, while South African officials are working with the AU and the United Nations Economic Commission for Africa (UNECA) on a push for African debt restructuring.

He has also been active in trouble shooting to unlock external assistance to the continent, including from China and Russia. Appointing special envoys is typical of his boardroom-honed leadership style.

International and regional partnerships are vital for resilience and the arrival of 217 Cuban doctors to South Africa is strongly reminiscent of the liberationist solidarity of the Cold War era. And regional economies remain dependent on South Africa to protect their own vulnerable citizens. Following the 2008 financial crisis, it was South Africa’s regional trading relationships that remained robust, while trade with its main global partners in China and the US dropped.

Despite the plaudits, Ramaphosa remains vulnerable to challenge at home, notably around his failure to stimulate South Africa’s moribund economy. On the eve of lockdown, Moody’s joined its peers Standard and Poor’s and Fitch in giving South Africa a below investment grade credit rating. The move was a long time coming. Long mooted economic reforms were slow to materialise, and South Africa had fallen into recession.

Ramaphosa depends on a small core of close advisors and allies, initially united in apparent opposition to the kleptocratic rule of President Jacob Zuma and the deep patronage networks he created within both the party and the state. But this allegiance is being tested by economic reality. Support within the party was already drifting prior to the crisis.

Disagreements are not just technocratic – there are big ideological questions in play around the role of the state in the economy, the level of intervention, and its affordability, with key government figures sceptical of rapid market reforms. Energy minister and former union stalwart Gwede Mantashe is wary of job losses, and minister of public enterprises Pravin Gordhan protective of state-owned enterprises (SOEs). Before coronavirus hit, Ramaphosa seemed content to allow these policy disputes to play themselves out with little decisive intervention.

Slow progress on reform, against worsening economic performance, left Ramaphosa and his allies exposed. In January the president missed the UK’s African Investment Summit in order to assert control over a party meeting at which it was expected his detractors would seek to remove Gordhan.

COVID-19 has sharpened thinking

As the independently assertive - and eminently quotable - pro-market reformist finance minister Tito Mboweni stated, ‘you can’t eat ideology’. Accelerated reform and restructuring is required if the government turns to the International Monetary Fund (IMF) for assistance.

For the first time, Gordhan has been forced to deny a bailout to beleaguered state airline South African Airways (SAA), and the government’s lockdown bailout of R500 billion has been applauded by business. Much like the fiscal stimulus and recovery plan of 2018, it relies on smart spending, targeting sectors with high multiplier effects. It also includes significant reserve bank loans.

But it has been criticised for not doing enough to help the most vulnerable. There is considerable fear of what could happen when the virus takes hold in South Africa’s townships and informal settlements where social distancing is almost impossible, basic toilet facilities are shared, and HIV and TB rates high.

There are mounting concerns of the humanitarian cost of a prolonged lockdown, and the government has been faster than others in implementing a tiered lockdown system, trying to get people back to work and keep the economy afloat.

South Africa has been criticized by the UN for the use of lethal force by security forces in enforcing lockdown and, in a society plagued by corruption, there are fears legislation to stop the spread of false information could be used to restrict legitimate reporting on the virus response or other issues.

COVID-19 shines a spotlight on societies’ fault-lines worldwide. South Africa is often touted as having one of the highest levels of inequality in the world but, in a globalized economy, these divisions are international as much as they are local.

Resilience comes from within, but also depends on regional and global trading and financial systems. South Africans and international partners have long recognised Ramaphosa’s leadership qualities as an impressive voice for the global south.

But he must also be an advocate for South Africa’s poor. This crisis could accelerate implementation of his landmark pro-poor National Health Insurance and Universal Health Care programmes. Or the hit of COVID-19 on top of South Africa’s existing economic woes could see them derailed entirely. Ramaphosa must push through economic reforms at the same time as managing COVID-19 and rebuilding trust in his government.

A new transatlantic relationship? 4 October 2022 — 6:30PM TO 7:30PM Anonymous (not verified) 22 September 2022 Chatham House and Online

US senator Jeanne Shaheen examines the implications of new UK leadership, the war in Ukraine, and NATO expansion for the US–UK relationship.

In recent weeks, the UK has ushered in a new prime minister and a new monarch. The US will hold potentially power-shifting mid-term elections in November after nearly two years of the Biden presidency that promised to bring the US ‘back’ as a global leader in international affairs.

These leadership changes come at a time when Europe is at war, NATO is expanding and US–China competition is re-ordering long-held alliances. Old assumptions about foreign policy are in flux in the midst of huge international challenges.

Democratic senator Shaheen, a senior member of the Senate Foreign Relations Committee, explores how these changes might influence the US–UK ‘special’ relationship.

• How will the trajectory of Russia’s war on Ukraine influence the bilateral relationship? What leadership is needed now?

• What does Russia’s war on Ukraine mean for NATO in responding to other pressing security challenges?

• What domestic constraints might limit the US’s power to reinsert itself as a global leader?

As with all Chatham House member events, questions from the members drive the conversation.

Read the transcript. 

The future of the Russia-China relationship 9 February 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 26 January 2023 Chatham House and Online

What lies ahead for the ‘unlimited friendship’ between Moscow and Beijing?

Russia’s invasion of Ukraine has raised new questions about the nature of the relationship between Russia and China, with the war seen as having the potential to shift Russia from a close ally to a liability in the eyes of the Chinese government.

This event explores the latest developments in extent of the relationship and interactions between the two: new convergences and divergences, energy links and limitations, declared alliances and private disagreements.

Experts on the panel explore:

• How has the relationship changed since Russia’s 2022 invasion of Ukraine?
• What do the Russian and Chinese people make of the relationship?
• How could a war-weakened Russia be viewed by China?

As with all members events, questions from the audience drive the conversation.

Read the transcript.

Can diplomacy advance human rights? 25 April 2023 — 4:00PM TO 5:00PM Anonymous (not verified) 7 March 2023 Chatham House and Online

How is diplomacy contributing to advancing human rights through the multilateral system?

The international human rights system has come under significant pressure in recent years. Russia’s invasion of Ukraine and the US-China rivalry have created difficult political pressures, while major global challenges including climate change and global inequality demand answers. Effective diplomacy on human rights has become increasingly difficult, with incentives stacked against bold action.

The relationship between diplomacy and human rights is an uneasy one. Diplomacy is an art of negotiation, persuasion and compromise. Human rights are tightly defined and universal. The relationship between the two may seem paradoxical, but in the context of an unstable world order, it has never been more important.

In the 75th anniversary year of the Universal Declaration of Human Rights, this discussion will explore the critical role of diplomacy in advancing human rights in the future.

• What are the critical human rights challenges today? What is the role of diplomacy in addressing them?

• What is the impact of intensifying competition between the US and China on the human rights system?

• Is there an opening for more leadership emerging from the Global South?

• What is the future of the human rights system in the context of this polarized world?

As with all member events, questions from the audience drive the conversation.

Here we go again: Russia’s energy ‘diplomacy’ in Moldova Expert comment LJefferson 6 December 2021

The gas crisis shows that while the new Moldovan government may wish for geopolitics to go away, they are a weapon Russia will deploy at will.

In October, Moldova came under the spotlight when Russia, its primary provider of gas, slashed supplies by a third and refused to extend the existing contract.

The crisis was resolved at the end of October when Russia and Moldova signed a new contract, in which Moscow has used Moldova’s gas dependence to extract geopolitical concessions, weaken the new pro-western Chisinau government and drive a wedge between the EU and Moldova.

A chronic failure to reform

Moldova became a classic case of state capture when political elites – including nominally pro-European political elites – engaged in massive rent-extraction.

Up until 2020, when pro-reform forces came to power, Moldovan politics offered rapid route to riches for both the nominally pro-European parties and the pro-Russian Socialist Party; each was responsible for playing up ethnic and geopolitical cleavages in the country to mobilize votes and shore up legitimacy.

These predatory elites hollowed out Moldova economically and politically by a chronic failure to reform, in particular the energy sector which became a major source of rent.

However, this started to change when the pro-reform forces came to power as a result of the 2020 presidential and then 2021 parliament elections. The pro-reformist Maia Sandu defeated the incumbent president Igor Dodon (58 per cent to 42 per cent) in November of that year. And then her party got 58 per cent of the vote in the parliamentary elections which followed in July 2021.

Her Party of Action’s (PAS) winning formula was to focus on corruption and domestic reforms – rather than playing the ‘geopolitical’ card, a favourite strategy of their predecessors. As Sandu put it, the elections marked ‘the end of the reign of thieves in Moldova’.

A gas crisis is initiated  

Russia’s response to these results was to initiate a gas crisis. Up until the victory of the pro-reform forces, Russia had annually renewed a gas contract signed in 2007. However, in September 2021, Russia refused to renew the contract as it had done many times before and instead insisted on a new contract, which allowed Russia to create linkages between energy prices, debt settlement, a halt on energy market reforms and, it can be logically inferred, further integration with the EU.

Moldova’s national energy company, Moldovgaz, is 63.5 per cent de facto owned by Gazprom with the Moldovan government owning the remaining 35.5 per cent. (Moldova was forced to give Gazprom a controlling stake when faced with a cut in supplies in January 2006). It is therefore hardly surprising that no efforts were made to de-monopolise the sector and diversify energy supplies.

This lack of modernization can be explained by the somewhat surreal fact that in any negotiations and planning, Moldovagaz – majority owned by Gazprom – represents the Moldovan side in negotiations with Gazprom. So, when it came to signing of the new five-year contract in October 2021, Russia, through Gazprom, was able to institute a contract which made gas prices conditional on various geopolitical conditions.

It is noteworthy that Moldova’s original 2007 gas contract had been renewed annually despite the supposed accrual of debt. However, the very nature of this debt is suspect. While Moldova’s debt is said to be approximately $700 million, the debt of the much smaller breakaway Transnistria was around $7.3 billion.

The exact level and source of the debt remain murky. Russia appears to be making Moldova liable to repay at least some of Transnistria’s debt while only demanding the debt settlement with Moldova, but not with Transnistria.

High stakes for Moscow

Moreover, the contract is used to derail liberalisation of the energy market in line with EU’s energy market rules (through the so-called unbundling of supplies and distribution) which Moldova had committed itself to since the country joined the Energy Community in 2010.

Referring to ‘the non-application of forced reorganization and sanctions against Moldovagaz’, the new gas contract forces Moldova to postpone implementing the unbundling of supplies and distribution by making it conditional on resolving the energy debt.

Furthermore, Moldova ominously agreed to create an ‘intergovernmental commission on economic cooperation’ with Russia, which effectively blocks Moldova’s economic integration with the EU. (This demand is hardly new as Russia previously requested, and was granted, a seat at the negotiating table on a bilateral trade agreement between the EU and Ukraine. The trilateral EU-Ukraine-Russia negotiations have made it clear that Russia is seeking a veto over European integration of all neighbouring countries.)  

Targeting Moldova’s new reformist government reflects high personal stakes for Moscow. Moldova’s caretaker (kurator) in the Kremlin is Dimitrii Kozak, who in 2003 masterminded the so-called ‘Kozak Memorandum’. This sought to reintegrate breakaway Transnistria into a Moldova-Transnistria federation.

It was thwarted at the last minute but the Russian leadership has not given up on its plan. Now using his position as the deputy head of Presidential Administration, Kozak is masterminding Russia’s rehashed policy towards Moldova and has attempted to bring back his Memorandum as a political blueprint for a ‘settlement’.

Russia’s heavy-handed energy ‘diplomacy’

The new Moldovan government is caught in a crossfire of domestic expectations and Russian geopolitical demands. The gas crisis shows that while the new government may wish for geopolitics to go away, they are a weapon Russia will deploy at will.

The Moldovan government is brand new so it has relatively little experience of dealing with Russia’s heavy-handed ‘energy diplomacy’. But the EU has been on the receiving end of this before – this is a direct replica of Russia’s strategy toward Armenia and Ukraine – and neither ended well for the target countries or for the EU.

So, Russia’s plans for Moldova are likely to have similar consequences for the EU’s latest attempts to be a convincing foreign policy actor. 

Trump Media and Technology Group shares rose 15% in value on Tuesday as voters cast ballots on Election Day.

SpaceX has reportedly struck a deal with LG Energy Solution Ltd. to supply cylindrical lithium-ion batteries for Elon Musk's Starship rocket, expected to launch early next year, according to industry sources.

2025 Luis J. Alvarez and Admiral Grace M. Hopper Postdoc Fellowship in Computing Sciences - 102564 Division: AC-Computing Luis J. Alvarez Postdoctoral Fellowship and Admiral Grace M. Hopper Postdoctoral Fellowship in Computing Sciences The Computing Sciences Area (https://cs.lbl.gov/) at Lawrence Berkeley National Laboratory (https://www.lbl.gov) is now accepting applications for two distinguished postdoctoral fellowships in Computing Sciences: • Luis W. Alvarez Postdoctoral Fellowship, and • Admiral Grace M. Hopper Postdoctoral Fellowship. Researchers in computer science, mathematics, data science, or any computational science discipline who have received their Ph.D. no earlier than January 1, 2022 but no later than September 30, 2025 are encouraged to apply. Only one (1) application is needed and it will be considered for both postdoctoral fellowships. The successful candidates will participate in research activities in computer science, mathematics, data science, or any computational science discipline of interest to the Computing Sciences Area and Berkeley Lab. Alvarez Fellows apply advances in computer science, mathematics, computational science, data science, machine learning or AI to computational modeling, simulations, and advanced data analytics for scientific discovery in materials science, biology, astronomy, environmental science, energy, particle physics, genomics, and other scientific domains. Hopper Fellows concentrate on the development and optimization of scientific and engineering applications leveraging high-speed network capability provided by the Energy Sciences Network or run on next-generation high performance computing and data systems hosted by the National Energy Research Scientific Computing Center at Berkeley Lab. Since its founding in 2002, Berkeley Lab’s Luis W. Alvarez Postdoctoral Fellowship (go.lbl.gov/alvarez) has cultivated exceptional early career scientists who have gone on to make outstanding contributions to computer science, mathematics, data science, and computational sciences. The Admiral Grace Hopper Postdoctoral Fellowship (go.lbl.gov/hopper) was first awarded in 2015 with the goal of enabling early career scientists to make outstanding contributions in computer science and high performance computing (HPC) research. About Computing Sciences at Berkeley Lab: Whether running extreme-scale simulations on a supercomputer or applying machine-learning or data analysis to massive datasets, scientists today rely on advances in and integration across applied mathematics, computer science, and computational science, as well as large-scale computing and networking facilities, to increase our understanding of ourselves, our planet, and our universe. Berkeley Labs Computing Sciences Area researches, develops, and deploys new tools and technologies to meet these needs and to advance research in our core capabilities of applied mathematics, computer science, data science, and computational science. In addition to fundamental advances in our core capabilities, we impact such areas as astrophysics and cosmology, accelerator physics, chemical science and materials science, combustion, fusion energy, nuclear physics, biology, climate change, and HPC systems and network technology. Research areas in Computing Sciences include but are not limited to: • Developing scientific applications and software technologies for extreme-scale and energy-efficient • Developing mathematical modeling for complex scientific problems • Designing algorithms to improve the performance of scientific applications • Researching digital and post-digital computer architectures for science • Developing and advancing extreme-scale scientific data management, analysis, and visualization • Developing and advancing next-generation machine learning, AI, and data science approaches for science • Advancing quantum computing and networking technologies, software, algorithms and applications • Evaluating or developing new and promising HPC systems and networking technologies • Researching methods to control and manage next-generation networks • Managing scientific data and workflows in distributed environments Qualifications: • Requires a Ph.D. in computer science, mathematics, computational science, or related discipline. • Candidates must have no more than 3 years of Postdoctoral Researcher or similar experience. • Expertise with advanced algorithms, software techniques, HPC systems and/or networking in a related research field. • Demonstrated creativity and the ability to perform independent research. • Demonstrated excellence in a related research field. • Ability to develop new cross-disciplinary partnerships that use advanced computational and/or mathematical techniques to produce unique lab capabilities. • Excellent communication skills with the ability to facilitate communications and collaborations with internal and external stakeholders. Additional Desired Qualifications: • Knowledge of advanced computing and high-performance computing. Application Process: 1. As part of your application process, you must upload and submit the following materials with your online application. 1. Cover letter 2. CV, with publication list included 3. Research Statement (no more than five (5) pages in length when printed using standard letter-size (8.5 inch x 11 inch) paper with 1-inch margins (top, bottom, left, and right) and a font size not smaller than 11 point; figures and references cited, if included, must fit within the five-page limit) 4. Contact information (name, affiliation, and email address) of at least three (3) individuals who will be able to provide letters of reference. 2. Application deadline: October 31, 2024. * It is highly advisable that you have all the required application materials and information ready and available prior to completing and submitting your application. Your application will not be considered complete if any of the above information is missing. Tentative Application Timeline: The Computing Sciences Fellowship Selection Committee is made up of a diverse representation of scientists and engineers across Berkeley Lab’s Computing Sciences Area who will conduct a thorough review of all applications received. • Application deadline: October 31, 2024 • Review and Selection: October 2024 - December 2024 • Decisions made: January/February 2025 Want to learn more about working at Berkeley Lab? Please visit: careers.lbl.gov How To Apply Apply directly online at http://50.73.55.13/counter.php?id=290341 and follow the on-line instructions to complete the application process. Berkeley Lab is committed to inclusion, diversity, equity and accessibility and strives to continue building community with these shared values and commitments. Berkeley Lab is an Equal Opportunity and Affirmative Action Employer. We heartily welcome applications from women, minorities, veterans, and all who would contribute to the Labs mission of leading scientific discovery, inclusion, and professionalism. In support of our diverse global community, all qualified applicants will be considered for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, age, or protected veteran status. Equal Opportunity and IDEA Information Links: Know your rights, click here (http://www.dol.gov/ofccp/regs/compliance/posters/ofccpost.htm) for the supplement: Equal Employment Opportunity is the Law and the Pay Transparency Nondiscrimination Provision (https://www.dol.gov/sites/dolgov/files/ofccp/pdf/pay-transp_%20English_formattedESQA508c.pdf) under 41 CFR 60-1.4.

CHANDLER, Ariz., Oct. 23, 2024 — The global edge computing market is expected to grow by more than 30 percent in the next five years, serving mission-critical applications in the […]

The post Microchip Expands 64-Bit Portfolio with High-Performance PIC64HX Microprocessors for Edge Computing appeared first on HPCwire.

SANTA CLARA, Calif., Aug. 13, 2024 — Pure Storage today announced that it joined Ultra Ethernet Consortium (UEC), a Linux Foundation initiative dedicated to building a complete, open, and accessible Ethernet-based […]

The post Pure Storage Embraces Next-Gen Networking for AI with Ultra Ethernet Consortium Membership appeared first on HPCwire.

In AI, time is money. Top AI players are spending billions to create computing infrastructures to satisfy that need for speed. However, these companies are bottlenecked by computing constraints at […]

The post Ayar Labs CEO: Optical Chiplets Coming to SOCs Soon appeared first on HPCwire.

SANTA CLARA, Calif., Oct. 22, 2024 — Celestial AI today announced the acquisition of silicon photonics intellectual property from Rockley Photonics, including worldwide issued and pending patents. The combination of Celestial […]

The post Celestial AI Acquires Rockley Photonics Patent Portfolio, Strengthening Photonic Fabric IP appeared first on HPCwire.

BEAVERTON, Ore., Oct. 29, 2024 — Ultra Accelerator Link (UALink) Consortium, led by Board Members from AMD, Amazon Web Services (AWS), Astera Labs, Cisco, Google, Hewlett Packard Enterprise (HPE), Intel, Meta […]

The post Ultra Accelerator Link Consortium Launches with Industry Leaders, Opens Membership to Drive AI Connectivity Standards appeared first on HPCwire.

The USNS Choctaw County has arrived in Beirut, Lebanon, to participate in a first-of-its-kind mission intended to strengthen military ties between the countries, the U.S. Navy said Tuesday.

The Army has successfully tested the MK-22 Precision Sniper Rifle to clear it for fielding.

Nov. 8, 2024 — Across the United States, research shows that computer science (CS) courses teach a range of transferable skills that help students as they enter the workforce. But in […]

The post UT Austin-UTEP Partnership Supports Growth of Texas CS Education appeared first on HPCwire.

REDWOOD CITY, Calif., Nov. 4, 2024 — MinIO has announced compelling new optimizations and benchmarks for Arm-based chipsets powering on its object store. These optimizations underscore the relevance of low-power, […]

The post MinIO Optimizes Arm-Based Chipsets for High-Performance AI appeared first on HPCwire.

New cross-species research suggests a theory of mind is one thing that sets humans apart from apes

Studies of goal setting reveal why it’s so hard to keep resolutions—and how to make ones that actually stick

The wealthiest person on Earth has taken the next step toward a commercial brain interface

SAN ANTONIO, Nov. 1, 2024 — Rackspace Technology, a leading hybrid, multicloud, and AI technology services company, announced that it has signed a Strategic Collaboration Agreement (SCA) with Amazon Web […]

The post Rackspace and AWS Expand Partnership to Accelerate Generative AI and Cloud Solutions appeared first on HPCwire.

KAWASAKI, Japan and SANTA CLARA, Calif., Nov. 1, 2024 — Fujitsu and AMD have announced that they have signed a memorandum of understanding (MOU) to form a strategic partnership to […]

The post Fujitsu and AMD to Begin Strategic Partnership to Accelerate Open-source AI initiatives appeared first on HPCwire.

One of the most difficult problems with quantum computing relates to increasing the size of the quantum computer. Researchers globally are seeking to solve this “challenge of scale.” To bring […]

The post Recipe for Scaling: ARQUIN Framework for Simulating a Distributed Quantum Computing System appeared first on HPCwire.

The Biden administration is reportedly considering capping sales of advanced artificial intelligence (AI) chips from US-based manufacturers like AMD and Nvidia to certain countries, including those in the Middle East.  The […]

The post White House Mulls Expanding AI Chip Export Bans Beyond China appeared first on HPCwire.

SpaceX has reportedly struck a deal with LG Energy Solution Ltd. to supply cylindrical lithium-ion batteries for Elon Musk's Starship rocket, expected to launch early next year, according to industry sources.

PITTSBURGH, Feb. 22, 2024 — Ansys and Intel Foundry have collaborated to provide multiphysics signoff solutions for Intel’s innovative 2.5D chip assembly technology, which uses EMIB technology to connect the […]

The post Ansys, Intel Foundry Collaborate on Multiphysics Analysis Solution for EMIB 2.5D Assembly Tech appeared first on HPCwire.

PITTSBURGH, June 19, 2024 — Ansys today announced that it is adopting NVIDIA Omniverse application programming interfaces (APIs) to offer 3D-IC designers valuable insights from Ansys’ physics solver results through […]

The post Ansys Enables 3D Multiphysics Visualization of Next-Gen 3D-IC Designs with NVIDIA Omniverse appeared first on HPCwire.

Nov. 8. 2024 — High-performance computing (HPC) has been an indispensable research tool for accessing physical realms difficult, or impossible, to achieve with experiment alone. For several decades, the Department […]

The post ECP: ‘Forward’ Projects Boost US Leadership in Advanced Computing and AI appeared first on HPCwire.

Background: Faced with the limits of synthetic antipyretic substances, in particular their involvement in the occurrence of numerous and often serious adverse effects; the challenge is in search of new antipyretics especially from the African traditional pharmacopoeia. The objective of this study was to evaluate the antipyretic activity of an aqueous extract and a formulation of Ceiba pentandra, with a view to designing an herbal antipyretic drug. Methods: Trials of formulation of an antipyretic syrup with leaves extract of Ceiba pentandra were carried out. The antipyretic activity was investigated by the bewer's yeast induced pyrexia. Physicochemical and microbiological stability tests were carried out on the syrup. Results: It was found with the extract an antipyretic activity at doses of 125 mg/kg and 150 mg/kg. The effect was greater for the 125 mg/kg dose with inhibition percentages ranging from 27.58% to 71.25%. This antipyretic activity was early (from 30 minutes) and was preserved during the four hours of the experiment. The syrup dosed at 125 mg/kg gave an activity similar to that of the extract by significantly reducing the hyperthermia in the rats. Regarding the stability tests, the syrup remained stable both physico-chemically and microbiologically throughout the study period (28 days) both when exposed to low temperature (5 °±3 ° C) and at high temperature (40°±2° C). Conclusions: Ceiba pentandra leaves have antipyretic activity and could be used for the development of an herbal antipyretic drug.

You don’t have to be perfect to reach your goals -- why planning to cheat might actually help.

When negative feelings accumulate in a relationship, it can become a problem.

Around 3% of people are thought to hear voices when there is no one talking.

Animal behavior expert Philip Johns introduces us to the vibrant urban environments of Singapore, where city dwellers and skyscrapers coexist with a rich array of other species, including otters, hornbills and lizards — prompting the question: Can we design cities to be wildlife refuges?

In an astounding sonic experience, creative director Felipe Sánchez Luna takes you on a journey through the universe as told in sound. Take a deep breath, listen closely and discover the power of sound to provide you with a new emotional understanding of the world.

In his 2000 bestseller "The Tipping Point," Malcolm Gladwell told the story of why crime fell in New York City in the 1990s. Now, 25 years later, he's back with a confession and a mea culpa: "I was wrong," he says. He shares how his analysis contributed to the rise of the infamous "stop and frisk" policing policy in New York City — and shows why journalists should avoid the trap of imagining a story is ever really over. (Followed by a Q&A with TED's Monique Ruff-Bell)

We tend to consider romantic partners and family ties to be our most important relationships, but deep friendships can be just as meaningful. In a perspective-shifting talk, author Rhaina Cohen introduces us to the people unsettling norms by choosing a friend as a life partner — and shows why we're all better off recognizing there's more than one kind of significant other.

Nearly everyone in behavioral marketing and influence marketing was surprised when Dr. Robert Cialdini, the “godfather” of persuasion science and the creator of the celebrated Six Principles of Influence, introduced a seventh principle, Unity. In fact, in 2014 I asked Cialdini if, thirty years after completing his seminal book, Influence, he’d add on another one or […]

The post What is Unity, Cialdini’s 7th Principle? appeared first on Neuromarketing.