John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews

IJ Goldberg
Apr 1, 1996; 37:693-707
Reviews

Chatham House awarded major centenary grant to establish Stavros Niarchos Foundation Wing News Release sysadmin 16 April 2019

Chatham House has been awarded a transformational £10m grant ahead of its upcoming 2020 centenary.

Chatham House appoints Rob Yates as the new head of the Centre on Global Health Security News Release sysadmin 27 June 2019

Chatham House is pleased to announce that Rob Yates has been appointed as head of the Centre on Global Health Security.

Centenary Summer School Draws Over 500 Students News Release jon.wallace 4 December 2020

Our inaugural summer school took place in July, drawing 547 students from countries including Indonesia, the United States, Nigeria, India and Sri Lanka.

Rebuilding trust is central to the UN’s future Expert comment NCapeling 25 March 2021

António Guterres is under scrutiny as he prepares to report on the future of the United Nations, with a renewed focus on trust, resilience and prevention.

The United Nations Secretary-General’s inbox is full as his organization celebrates its 75th anniversary. Trust must be rebuilt amid increased geo-political rivalry, North-South divisions, and sceptical citizens left behind by globalization. The international community has manifestly underinvested in institutional resilience and prevention. Better partnerships are needed with the private sector, and innovative forms of cross-regional cooperation fostered.

There are positive signs UN member states want things to change. They unanimously agreed a Political Declaration last September strongly reaffirming multilateralism, and they gave António Guterres one year to present a roadmap on how to respond, ‘building back better’ in the face of climate change and COVID-19.

A key challenge is to steer mandates and resources towards prevention. The World Bank-WHO Global Preparedness Monitoring Board, which eerily predicted the pandemic in its inaugural report in September 2019, reminds us successful prevention rests not on warning alone, but on aligned incentives for early action.

Geopolitical tensions persist

China has invested significantly in the multilateral system over the last decade, both in formal organizations such as the UN and the African Union, and in fostering a set of China-centred ‘mini-lateral’ fora such as the SCO, BRICS and BRI. It has also deepened its ties with Russia in the UN Security Council. Western countries both begrudgingly admire and deeply distrust China’s nimbleness in advancing its interests and values in this way but are divided on how to respond.

The Biden administration has recommitted itself to multilateral processes but US bilateral relations are likely to remain the main foreign policy driver. The UK has sought to convert the G7 into an enlarged summit-level meeting for democracies but Europe is divided over the wisdom of formalizing a group which may increase divisions with China, and some major democracies – India for example – have divergent approaches on issues such as trade protection.

An increase in cross-regional informal caucusing within the UN system to advance norms and progress around specific common objectives is likely. Guterres can encourage smaller powers to become ‘bridge builders’ sitting in the middle of a ‘Venn diagram’ of such new member state constellations at the UN.

Guterres can also build on the recent Abraham Accords to encourage cross-regional cultural, political and security relationships on the back of trade and investment, and map practical opportunities for strategic cooperation between China and the West in health and food security, climate and biodiversity, and global macroeconomic management, while fostering new normative frameworks to manage strategic competition in artificial intelligence (AI), big data, cyber resilience, gene-editing, and automation.

North-South mistrust

Realizing the Sustainable Development Goals (SDGs) and climate objectives rests in part in mobilizing the expertise and resources of sub-state actors such as business and city and regional authorities. However, developing countries remain wary of granting the UN Secretary-General a greater role in fostering partnerships with the private sector and mobilizing private finance, out of fear this may overshadow the global North’s promises to provide aid and create fairer trade and debt conditions.

In addition, African governments are expressing growing frustration at their continued lack of ‘agency’ in UN decision-making, the reneging of promises on climate financing by the global North, and the slow rollout of the COVAX facility to developing countries.

Progress may lie in two areas. First, developing country leadership of initiatives – such as the Friends Group on SDG financing established by the Jamaican and Canadian ambassadors to the UN – can help build trust and allay concerns, which is vital to incentivise transformative investment by sovereign wealth, pension, and insurance funds in pro-poor low carbon infrastructure in developing countries.

The second area is curating multi-stakeholder initiatives outside the UN framework and then linking them back to the organization once they have proven to be beneficial to both developed and developing countries. Successful initiatives such as the Vaccine Alliance can be a model of how to do this while not detracting from state obligations.

Scepticism among citizens

Trust in governance also needs rebuilding at the level of the individual citizen. Mobilized by populist movements and ‘fake news’ online, individuals left behind by the uneven economic benefits of globalization view governments and international organizations as unaccountable and lacking their interests at heart.

Guterres has called for a new ‘social contract’ between governments and their citizens, and for ‘Multilateralism 2.0’ to demonstrate a practical ‘hard interest’ as well as a ‘values’ case for why international cooperation inclusively benefits individuals as well as states. And technological innovation can also help citizens hold governments to account. As the first Secretary-General with a science and engineering background, Guterres has championed how technology enhances UN delivery of its objectives.

The pairing of artificial intelligence (AI) with satellites and drones for geospatial insight has been pioneered by both the United Nations Environment Programme (UNEP) and the Food and Agriculture Organization (FAO) to help communities preserve ecosystems and agricultural productivity. The resultant data, accessible on smart phones and computers, enables civil society to measure governments’ promises against real-time progress, through monitoring greenhouse gas emissions from power stations.

Alongside trust and accountability, fostering inclusiveness is likely to be central to Guterres’ report as he navigates how the UN can legitimize multi-stakeholder partnerships, enhance transparency, and bring coherence to diverse ‘mini-lateral’ initiatives.

These themes are explored further in the forthcoming synthesis paper ‘Reflections on building more inclusive global governance: Ten insights into emerging practice’

Expert

Expert

Expert

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

Centrioles are key eukaryotic organelles that are responsible for the formation of cilia and flagella, and for organizing the microtubule network and the mitotic spindle in animals. Centriole assembly requires oligomerization of the essential protein spindle assembly abnormal 6 (SAS-6), which forms a structural scaffold templating the organization of further organelle components. A dimerization interaction between SAS-6 N-terminal “head” domains was previously shown to be essential for protein oligomerization in vitro and for function in centriole assembly. Here, we developed a pharmacophore model allowing us to assemble a library of low-molecular-weight ligands predicted to bind the SAS-6 head domain and inhibit protein oligomerization. We demonstrate using NMR spectroscopy that a ligand from this family binds at the head domain dimerization site of algae, nematode, and human SAS-6 variants, but also that another ligand specifically recognizes human SAS-6. Atomistic molecular dynamics simulations starting from SAS-6 head domain crystallographic structures, including that of the human head domain which we now resolve, suggest that ligand specificity derives from favorable Van der Waals interactions with a hydrophobic cavity at the dimerization site.

Bero Roos
Theor. Probability and Math. Statist. 111 (), 137-151.
Abstract, references and article information

VAR2CSA is the placental-malaria–specific member of the antigenically variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. It is expressed on the surface of Plasmodium falciparum-infected host red blood cells and binds to specific chondroitin-4-sulfate chains of the placental proteoglycan receptor. The functional ∼310 kDa ectodomain of VAR2CSA is a multidomain protein that requires a minimum 12-mer chondroitin-4-sulfate molecule for specific, high affinity receptor binding. However, it is not known how the individual domains are organized and interact to create the receptor-binding surface, limiting efforts to exploit its potential as an effective vaccine or drug target. Using small angle X-ray scattering and single particle reconstruction from negative-stained electron micrographs of the ectodomain and multidomain constructs, we have determined the structural architecture of VAR2CSA. The relative locations of the domains creates two distinct pores that can each accommodate the 12-mer of chondroitin-4-sulfate, suggesting a model for receptor binding. This model has important implications for understanding cytoadherence of infected red blood cells and potentially provides a starting point for developing novel strategies to prevent and/or treat placental malaria.

Visual Abstract

No abstract

Growing implications of glycosylation in physiological occurrences and human disease have prompted intensive focus on revealing glycomic perturbations through absolute and relative quantification. Empowered by seminal methodologies and increasing capacity for detection, identification, and characterization, the past decade has provided a significant increase in the number of suitable strategies for glycan and glycopeptide quantification. Mass spectrometry-based strategies for glycomic quantitation have grown to include metabolic incorporation of stable isotopes, deposition of mass difference and mass defect isotopic labels, and isobaric chemical labeling, providing researchers with ample tools for accurate and robust quantitation. Beyond this, workflows have been designed to harness instrument capability for label-free quantification and numerous software packages have been developed to facilitate reliable spectrum scoring. In this review, we present and highlight the most recent advances in chemical labeling and associated techniques for glycan and glycopeptide quantification.

Intact glycopeptide identification has long been known as a key and challenging barrier to the comprehensive and accurate understanding the role of glycosylation in an organism. Intact glycopeptide analysis is a blossoming field that has received increasing attention in recent years. Mass spectrometry (MS)-based strategies and relative software tools are major drivers that have greatly facilitated the analysis of intact glycopeptides, particularly intact N-glycopeptides. This manuscript provides a systematic review of the intact glycopeptide identification process using mass spectrometry data generated in shotgun proteomic experiments, which typically focus on N-glycopeptide analysis. Particular attention is paid to the software tools that have been recently developed in the last decade for the interpretation and quality control of glycopeptide spectra acquired using different MS strategies. The review also provides information about the characteristics and applications of these software tools, discusses their advantages and disadvantages, and concludes with a discussion of outstanding tools.

Tackling Illegal Wildlife Trade in Africa: Economic Incentives and Approaches Research paper sysadmin 5 October 2018

Combating illegal wildlife trade and further pursuing conservation-development models could help generate considerable economic benefits for African countries, while ensuring the long-term preservation of Africa’s wealth of natural capital.

Summary

• The illegal wildlife trade (IWT) significantly impacts African economies by destroying and corroding natural, human and social capital stocks. This hinders the achievement of the Sustainable Development Goals (SDGs) and has an impact on national budgets. Illicit financial flows from IWT deny revenue to governments where legal wildlife product trade exists and perpetuate cash externalization. IWT diverts national budgets away from social or development programmes, increases insecurity and threatens vulnerable populations.
• In expanding wildlife economies and pursuing conservation-driven development models, governments can protect their citizens, derive revenue from wildlife products, and establish world class tourism offerings. The illegal exploitation of wildlife is often due to a failure to enforce rights over those resources, where rights are unclearly defined or not fully exercised. Southern African countries have defined these rights in various ways, contributing to regional differences in conservation practices and the socio-economic benefits derived from wildlife resources. Combating IWT is an important step towards allowing legitimate business and communities to develop livelihoods that incentivize stewardship and connect people to conservation.
• The Southern African Development Community (SADC) has several framework policies for the establishment of transfrontier conservation areas (TFCAs). These promote local stewardship across multiple land-use areas to conserve biodiversity and increase the welfare and socioeconomic development of rural communities. Private-sector partnerships also increase skills transfer, improve access to investment finance, and expand economic opportunities, including through the promotion of local procurement. The economic benefits of TFCAs extend beyond tourism.
• The economic value of African ecosystems is often under-recognized because they remain unquantified, partly due to the lack of available data on the broader economic costs of IWT. Improved monitoring and evaluation with key performance indicators would help governments and citizens to appreciate the economic value of combating IWT.

Centenary Series: Exploring the International Affairs Archive dora.popova 14 September 2020

International Affairs has been a central part of the institute’s history, both as a record of speeches made by dignitaries such as Mahatma Gandhi and Henry Kissinger, and as a forum for policy-relevant academic research.

Delving into the International Affairs archive brings out stories behind some of the most significant players of the last century.

DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication.

New research on 21st-century conflict 25 April 2022 — 5:00PM TO 6:00PM Anonymous (not verified) 11 April 2022 Online

This International Affairs webinar shares research on US special operations, urban warfare, and digital activism in recent conflicts.

Given the ongoing Russian invasion of Ukraine, and continuing conflicts in Myanmar, Yemen, and other countries, it is important to understand the changing nature of conflict in the 21st century.

In this webinar, authors from the March 2022 issue of International Affairs share research on the transformation of Western special forces, the impact of army size in urban warfare, and the use of social media and online activism in war.

The speakers in this event drew on the following research:

• US Special Forces transformation: post-Fordism and the limits of networked warfare (https://doi.org/10.1093/ia/iiab213)
• Urban insurgency in the twenty-first century: smaller militaries and increased conflict in cities (https://doi.org/10.1093/ia/iiac007)
• Diasporas as cyberwarriors: infopolitics, participatory warfare and the 2020 Karabakh war (https://doi.org/10.1093/ia/iiac015)

International Affairs was started at Chatham House in 1922 to communicate research to members who could not attend in person. Over the past 100 years, it has transformed into a journal that publishes academically rigorous and policy-relevant research. It is published for Chatham House by Oxford University Press. Read the latest issue here.

Central and Eastern Europe become hawkish on China Expert comment LJefferson 16 September 2022

The recent withdrawal of the Baltic countries from the ‘17+1’ format displays changing perceptions of China due to its ambiguity towards the war in Ukraine.

While the Russian invasion of Ukraine only confirmed Central and Eastern Europe’s views of Russia, it is also affecting their relations with China. Although the relationship was already complicated due to unfulfilled Chinese economic promises to CEE countries and growing indications of efforts to influence their domestic politics, China’s support for Russia is pushing Central and Eastern Europeans even further away.

This shift was highlighted, and formalized, recently by several countries in the region leaving the ‘17+1’ format, through which China cooperates with a group of countries from the region. The shifting attitudes towards China will also influence the relationship between the European Union as a whole and China.

A Trojan Horse that never was

When the format was launched in 2012 between 16 CEE countries at the time and China, the countries jumping on board expected a wave of Chinese investment and an opportunity to diversify mostly west-bound trade.

These hopes never fully materialized as Chinese foreign direct investment (FDI) in CEE has been generally lower compared to the rest of Europe and China never became an important export destination for any of the countries. The growing disillusionment and concern about Chinese security threats has led to some of the countries speaking up about the perceived perils of closer cooperation.

The first to withdraw from what had become ‘17+1’ by 2021 was Lithuania, which also took an interest in strengthening ties with Taiwan and allowed it to open a Taiwanese representative office in Vilnius. This triggered a breakdown in the bilateral relations with China. As a retaliatory response, China blocked Lithuanian imports and imports from other EU states containing inputs from Lithuania, leading the EU to launch an official dispute at the WTO.

War in Ukraine

Since the invasion started, CEE countries have been dealing with large numbers of Ukrainian refugees, organizing shipments of military equipment to Ukraine, and at the same time worrying whether they could be next on Russia’s list.

However, the concerns and security environment that these countries face seems to be almost entirely disregarded by China. On the sidelines of the 2022 Winter Olympics in Beijing, Xi and Putin signed the joint communiqué in which China backed Moscow’s demands to reverse NATO borders to the pre-1997 situation, completely disregarding CEE’s security interests.

China’s implicit support for Russia after the invasion has sowed deep mistrust of its respect for the sovereignty of other nations. The Chinese diplomatic apparatus clearly noticed this changing mood among CEE governments and sent a special envoy to eight capitals in April-May tasked with ‘eliminating misunderstandings regarding Russia-Ukraine conflict’.

However, the trip was not particularly successful. The delegation failed to secure high-level meetings, with the most prominent case being the Polish minister of foreign affairs declining to meet Huo Yuzhen, the Chinese Special Councilor for CEEC cooperation. Given that Andrzej Duda, President of Poland, was the only head of an EU state who attended the Beijing Olympics opening ceremony just before the Russian invasion in February, the change in attitudes is clear.

Following the envoy’s visit to the Czech Republic, the Czech parliament’s foreign affairs committee unanimously approved a resolution calling for the country to quit the ‘16+1’ format and the government is expected to act upon it in the near future. Meanwhile, Latvia and Estonia recently jointly announced that they would no longer be participating in the cooperation framework, turning it into ‘14+1’.

This analysis aimed to identify clinical factors associated with positivity on repeat ⁶⁸Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 ⁶⁸Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann–Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2–1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9–3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative ⁶⁸Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat ⁶⁸Ga-PSMA-11 PET/CT.

COLLEGE PARK, Md., Nov. 8, 2024 — IonQ, a leader in the quantum computing industry, has announced a partnership with NKT Photonics, a subsidiary of Hamamatsu Photonics, to procure next-generation laser […]

The post IonQ and NKT Photonics Collaborate on Next-Gen Laser Tech for Quantum Data Centers appeared first on HPCwire.

Making the Most of Today’s Cloud-First Approach to Running HPC and AI Workloads With Penguin Scyld Cloud Central™ Bursting to cloud has long been used to complement on-premises HPC capacity […]

The post Penguin Computing Scyld Cloud Central™: A New Cloud-First Approach to HPC and AI Workloads appeared first on HPCwire.

Data centers are experiencing increasing power consumption, space constraints and cooling demands due to the unprecedented computing power required by today’s chips and servers. HVAC cooling systems consume approximately 40% […]

The post How Direct Liquid Cooling Improves Data Center Energy Efficiency appeared first on HPCwire.

NEW YORK, Nov. 1, 2024 — NANO Nuclear Energy Inc. has announced the October 29, 2024 closing of the sale of an additional 317,646 shares of its common stock at […]

The post NANO Nuclear Energy Raises Over $40M from Recent Underwritten Follow-On Offering appeared first on HPCwire.

A man drove a vehicle into a crowd at a sports center in Zhuhai, China, killing 35 people and injuring 43 others, police said.

The U.S. military conducted retaliatory airstrikes Tuesday in Syria, targeting facilities of Iran-backed militias following rockets launched at U.S. forces in the Middle Eastern country.

Is it possible to meet the world's seemingly infinite demand for data storage while also caring for the natural environment? Biomedical researcher Keolu Fox and professional surfer and scientist Cliff Kapono believe that Indigenous knowledge combined with the science of genetics may offer such a solution: using the DNA of plant cells (like those found in sugar cane) as mini data warehouses. Learn more about the incredible potential of this technology — and how it could help foster ecosystem resilience in a high-tech world.

The days are a technology overload, mixed with the joy of seeing her students' faces and worry about her own family's health and safety, New York City teacher Ariel Sacks writes.