Celebrating Black History Month at Chatham House 24 October 2024 — 6:00PM TO 8:00PM Anonymous (not verified) 2 October 2024 Chatham House

Join us for the ‘Beyond expectations: The impact and legacy of migration exhibition 2024’ exhibition and drinks reception.

About the Photographer  

Neil Kenlock, a photographer and media professional, has lived in London since arriving from Jamaica in 1963 to join his parents. He spent the early years of his career as a professional photographer, specialising in fashion, beauty, celebrities, and the cultural lifestyles of Black people in the UK. In the late 1960s and 1970s, he captured images of the UK Black Panther movement and documented demonstrations and anti-racism protests across the country.

“Neil Kenlock helps us to better understand the story of London’s Black communities and to appreciate the huge artistic and cultural impact they have had on all our lives. He is a significant photographer whose work documents a key chapter in London’s post-war history.” — Mike Seaborne, former curator of photographs at the Museum of London.

About the exhibition

This exhibition unveils a collection of photographs by Neil Kenlock, capturing Black British individuals who migrated from their homelands and settled in the UK. Curated by his daughter Emelia Kenlock, the series explores the theme of ‘expectations’ and its enduring legacy, featuring African and Caribbean subjects who brought their skills, passions, and dreams—contributions that have profoundly shaped British culture today.

Reflecting on the work, Kenlock stated: “Over 50 years since the concept of ‘black excellence’ first manifested, and more than 70 years since the Windrush, I truly hope this exhibition will add to the national cultural narrative and resonate with new audiences.” 

Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time

Amelia C. Peterson
Nov 1, 2012; 11:1475-1488
Technological Innovation and Resources

Leigh Anderson
Apr 1, 2006; 5:573-588
Research

Albrecht Gruhler
Mar 1, 2005; 4:310-327
Research

Redefine the Commonwealth now to safeguard its future Expert comment NCapeling 6 October 2022

Although seen as one of the Queen’s greatest legacies, the Commonwealth must provide tangible benefits to its citizens in an era of geopolitical competition.

The Commonwealth’s breadth allows a wide diversity of countries of different sizes, geographies, cultures, and values to be members – it is both rich and poor, north and south, and ethnically diverse. This makes it more interesting than many other multilateral institutions such as the G7, NATO, and the European Union (EU).

But it suffers from an unclear purpose. Since its inception, successive UK governments have grappled with its role – whether it is a preferential trading bloc or merely a source of most of Britain’s post-war immigration.

This lack of purpose – and structure – has left the Commonwealth impotent in dealing with a host of bilateral difficulties between the UK, its overseas territories, and Commonwealth partners in recent years.

Brexit could induce Britain to re-prioritize the Commonwealth, but so far the UK has only signed two new trade deals with Commonwealth members – Australia and New Zealand – while development aid, one of the most tangible ways the UK worked with many Commonwealth countries, has been cut and the UK’s defence focus has pivoted towards the Indo-Pacific and Europe’s Eastern front.

The UK also suffered embarrassing and overwhelming defeats in both the UN General Assembly (UNGA) and the International Court of Justice (ICJ) on the legality of its continued occupation of the Chagos Islands and has avoided directly challenging India’s tacit support for Russia’s invasion of Ukraine in the hope of securing a trade deal.

At the recent Commonwealth Heads of Government Meeting (CHOGM), Boris Johnson reportedly attempted to depose Baroness Scotland, the Commonwealth’s Secretary General, but suffered a humiliating defeat in a vote of Commonwealth members.

These challenges are likely to continue, especially in the wake of the death of HM The Queen which could be seen by republican movements as an opportune time to rally support. Australia and New Zealand’s leaders, both republicans, downplayed the idea of a poll on the monarchy immediately after the Queen’s death, but it would be a mistake to assume this has gone quiet forever. Antigua and Barbuda’s prime minister has already said there will be a referendum on becoming a republic within three years.

Defining a new vision for the future

A concrete vision for the Commonwealth is long overdue and there is no better time to cast one than now. HM The Queen was more than just a figurehead for the Commonwealth and it remains unknown exactly what role King Charles III will see for himself.

But, unlike his mother who was a young, modern Queen heralding a post-imperial future, Charles takes the throne at a later age and at a time when important questions need to be addressed in an increasingly fractured world.

Most importantly the UK should avoid the temptation to define the Commonwealth in terms of shared principles and values. India, Pakistan, and Bangladesh all abstained on the United Nations (UN) motion condemning Russia’s invasion of Ukraine, and Commonwealth members are likely to be similarly divided over China’s territorial claims, the US-China conflict, the net-zero agenda, and nuclear non-proliferation.

The Commonwealth’s breadth – its greatest strength – means consensus is often impossible, and so should not be the goal. Instead the Commonwealth should focus on tangible areas of cooperation where there is mutual interest such as trade, aid, and migration.

The UK and its allies may find that diplomatic efforts – such as condemning China or Russia for human rights abuses – are more successful if they have listened to and acted on fellow Commonwealth countries’ concerns, from post-COVID vaccine provision to climate financing. Boosting the aid budget and opening borders may prove more important in engaging developing country partners than traditional diplomatic avenues.

Liz Truss’s British International Investment project could be a valuable vehicle for financing, especially if it leverages private sector funding, but many Commonwealth countries are feeling the more immediate impact of the UK’s aid cuts. In these circumstances many have already turned to Chinese infrastructure financing.

This is where the Commonwealth could be valuable. In the Pacific, it links certain island nations to the UK, Australia, and New Zealand at a time of renewed geopolitical competition with China in the Pacific. The fact the Commonwealth is not explicitly about promoting a particular ideology or countering China is helpful.

Commonwealth should be less UK-centric

There is also no reason why all the Commonwealth operations need to be based in London, which is not only expensive but also reinforces an approach to governance that assumes everything must be decided by civil servants in London. As the world’s largest democracy, India is an obvious alternative candidate although its reluctance to condemn Russia’s invasion and its domestic political tensions may count against it.

It is also important the Commonwealth’s wealthier members – the UK, Canada, and Australia – provide financing for countries such as India to take on extra responsibilities. The Commonwealth Games is a good place to start – despite having 72 competing nations and territories, the games have only been held three times outside the UK, Canada, Australia, and New Zealand.

The Commonwealth also needs to be forward-looking and one of its most exciting assets is its demographic youthfulness. Europe, China, and the US have ageing populations whereas Nigeria, India, and Bangladesh have some of the world’s largest young populations.

UK is too tight on the money and too vague on China Expert comment NCapeling 13 March 2023

The new UK Integrated Review fills gaps left by the last one but is dominated by defence. It needs more clarity on Europe, trade, and development – and more money.

Following a long two years, the UK’s Integrated Review from March 2021 now looks prescient in calling Russia the main threat to UK interests. And Russia’s invasion of Ukraine is the main – but not the only – reason forcing an update of the review only 24 months later.

The UK’s commitment to Ukraine is now centre stage and so therefore is its cost, which immediately exposes a prime weakness of this review. An extra £5 billion on defence is more than nothing, as was originally rumoured, but far less than £11 billion which UK defence secretary Ben Wallace argues is needed.

UK military support for Ukraine cost £2.3 billion in the past year and a continuation will use up £2 billion of the new money. The report also notes £3 billion will go on infrastructure for building nuclear submarines at Barrow and nuclear training. That does not leave much for anything else.

There is a pledge to end the reduction of the armed forces which is essential if the UK contribution to Ukraine and European defence is to be credible. But an ambition to spend 2.5 per cent of GDP on defence by an unspecified date is all but meaningless – albeit prudent phrasing given fiscal uncertainties.

China challenge is one of balance

Ministers have been wrestling for months over their choice of language on China, and ‘epoch defining challenge’ is what has emerged, while also expressing concern over China’s links with Russia. But the review is careful to stop short of calling China a threat as Liz Truss intended.

The choice of vocabulary reflects a long desire to balance forging commercial ties with an increasing wariness of data and security threats under President Xi’s leadership of China. The UK wants to support the US in its concerns but not to presume conflict is inescapable.

The review does acknowledge the threat to Taiwan for the first time. Two years ago, it was fiercely criticized for not including any mention of that despite the potential disruption supposedly being ‘far more damaging than the renewed illegal invasion of Ukraine’ as MPs on the Foreign Affairs Select Committee put it.

But again the question of resources is inescapable. The ‘Indo-Pacific tilt’ which the UK declared two years ago is offered not just as a recognition of the region’s political and economic heft in any vision of the future, but as a favour to the US.

The UK lacks the resources to make that tilt credible in terms of substantial support to the US – nor, arguably, would it do the US any favours by neglecting the defence of Europe or the Middle East, which gets scant mention.

The AUKUS announcement on the same day appears to fill that gap. UK prime minister Rishi Sunak was in San Diego, California to greet the declaration that Australia will draw on British designs for its new nuclear submarines – a decision which brings more British jobs and underpins an alliance of both symbolic and practical weight in the region. But for the UK to play its part fully, it may need to divert resources from elsewhere, and this review sidesteps that hard choice.

More broadly, the UK would benefit from considering how to respond to the reality of China’s rise – analysing what happens to supply chains if tension disrupted them and how it might use membership of the Asia-Pacific CPTPP trading bloc, which appears likely to happen soon.

One of the biggest omissions in the 2021 review was relations with Europe and that is somewhat remedied but more is needed. The UK has been a leader for Europe in its clear response to Russia’s invasion of Ukraine – almost the only common thread of passionate agreement between the three UK prime ministers since the invasion – but it should now consider if it wants to take part in joint development of military assets. And a clear statement of cooperation with European Union (EU) governments would be a boost to NATO.

There is also now a Europe-shaped hole in the review’s discussion of trade. The 2021 version mentioned trade 79 times with the focus on new trade agreements outside Europe. It is now clear, if it was not before, these make little difference to GDP. The recent repairing of relations with the EU – and France in particular – may yield more practical results two years from now.

UK power in the world is changing

The review is also largely silent on another difficulty in the UK’s foreign policy which are the aims and size of its development aid – much changed from its original goal of poverty reduction to a focus on national interest with a reduced budget. This is sensitive political territory but must be better spelled out to count as a plan.

The FCDO intends to appoint a second permanent under-secretary to deliver the government’s development priorities and the minister for international development will join the National Security Council. This acknowledges the disruption caused by the merger of the FCO with DFID and the need for development staff to have clear leadership as well as, hopefully soon, a clear policy.

The pledge of a one-off payment of £20 million for the BBC World Service 42 foreign language channels for two years is welcome too as an acknowledgement of their ‘soft power’ value, especially in parts of the world where democracy is absent or in retreat.

Jorge H. Capdevila
Feb 1, 2000; 41:163-181
Reviews

Lord Hammond Joins Panel of Senior Advisers News Release NCapeling 10 December 2020

Chatham House is pleased to announce that Lord Hammond of Runnymede is joining our Panel of Senior Advisers.

Building trust in trade deals – is human rights monitoring the answer? 27 May 2021 — 4:00PM TO 5:15PM Anonymous (not verified) 14 May 2021 Online

Exploring the arguments in favour of more robust human rights monitoring systems and why effective monitoring mechanisms have proved so difficult to get up and running.

Please click on the below link to confirm your participation and receive your individual joining details from Zoom for this event. You will receive a confirmation email from Zoom, which contains the option to add the event to your calendar if you so wish.

The recent signing of the EU-China Investment Agreement has reignited arguments about trade and human rights. While many trade agreements envisage human rights monitoring in some shape or form, the monitoring systems that have emerged so far are not especially coherent, systematic or impactful. 

Are the human rights commitments in trade agreements more than just window-dressing?  If so, what kind of monitoring is needed to ensure they are lived up to? 

At this panel event, which marks the launch of a new Chatham House research paper, participants explore the arguments in favour of more robust human rights monitoring systems and why effective monitoring mechanisms have proved so difficult to get up and running in this context. 

• What factors are presently holding governments back, and where is innovation and investment most needed?
• What are the political, economic and structural conditions for fair and effective human rights monitoring of trade agreements? 
• Is human rights monitoring best done unilaterally – or should more effort be put into developing joint approaches? 
• What role might human rights monitoring have to play in governments’ strategies to ‘build back better’ from the COVID-19 pandemic?

Monitoring of trade deals needs a risk-based approach Expert comment NCapeling 24 May 2021

On human rights issues, trading partners must do more than trust to luck.

The recent row within the UK government about the treatment of agricultural products in a proposed new trade deal with Australia provides a reminder that changes to trading arrangements can have social and environmental costs, as well as benefits.

Although the UK government clearly feels political pressure to demonstrate its ‘Global Britain’ credentials with some speedily concluded new deals, rushing ahead without a full understanding of the social, environmental, and human rights implications risks storing up problems for later. In the meantime, calls for better evaluation and monitoring of trade agreements against sustainability-related commitments and goals – ideally with statutory backing – will only get stronger.

EU experiences with these kinds of processes are instructive. For more than 20 years the Directorate General for Trade of the European Commission (DG Trade) has been commissioning sustainability impact assessments (SIAs) from independent consultants in support of trade negotiations, and since 2012 these assessments have explicitly encompassed human rights impacts as a core part of the analysis.

These processes have since been augmented with a programme of periodic ‘ex post’ evaluations of trade agreements to ‘analyse the observed economic, social, human rights, and environmental impacts’ of live trade deals and to make recommendations about any mitigation action which may be needed.

For credibility and objectivity, the Commission outsources much of its sustainability assessment and ex post evaluation activities to independent consultants, who are encouraged to innovate and tailor their approaches subject to broad methodological parameters laid down by the Commission. Over time, experiences with specific assessment and monitoring assignments have enabled external SIA practitioners – and the Commission itself – to progressively strengthen these processes and underlying methodologies.

Yet despite the improvements there remains legitimate questions about whether the human rights aspects of these SIA processes – and subsequent evaluations – are having real policy impact. The difficulty of predicting human rights impacts of trade agreements in advance – as the COVID-19 crisis amply demonstrates – suggests a need for realism about the extent to which a ‘one off’ process, often carried out at a time when there is only ‘agreement in principle’ as to future trading terms, can produce a robust roadmap for heading off future human rights-related risks.

Human rights impact assessments have a potentially valuable role to play in laying down the substantive and structural foundations for future human rights monitoring as part of a broader, iterative, human rights risk management strategy. But the fragmented manner in which many trade agreements approach human rights issues, and the fact that outcomes are the product of negotiation rather than necessarily design, make it difficult to turn this vision into reality.

Controversies surrounding the SIA process for the EU-Mercosur agreement illustrate why striving for more coherence in the identification and subsequent management of human rights-related risks is important. In June 2019, the Commission decided to wrap up negotiations with the South America Mercosur bloc, even though the SIA process for the proposed agreement was still incomplete and the interim and final SIA reports yet to be delivered. Frustrated NGOs made their feelings clear in the form of a formal complaint – and a slap on the wrist from the EU Ombudsman duly followed.

However, when it eventually appeared in December 2020, the final SIA report for the EU-Mercosur deal did include a number of interesting recommendations for responding to specific areas of human rights-related risk identified through the pre-signing assessment process – such as flanking measures designed to address issues pertaining to health, equality, and protection of indigenous peoples, and stressing the need for ‘continuous monitoring’.

Hopefully these recommendations will be proactively followed up, but there are reasons not to be overly optimistic about that. To the extent that these recommendations might have required, or benefitted from, some tweaks to the terms of the trade agreement itself, it was clearly too late. And while there may be opportunities for EU institutions to follow up the recommendations through unilateral ex post evaluation processes, current legal, policy, and institutional arrangements provide few guarantees this will take place.

The credibility of the EU SIA programme has clearly taken a knock because of the problems with the EU-Mercosur process, and stakeholders could be forgiven for questioning whether expending time and effort on engaging in these processes is actually worthwhile. As a first step towards rectifying this, the Commission should be transparent about how it plans to respond to the EU-Mercosur SIA recommendations regarding flanking measures and follow up – ideally consulting with stakeholders about the various human rights monitoring options available.

Looking further ahead, the Commission should be urging SIA practitioners to deal more expansively with the options for follow up human rights monitoring in future SIA reports, setting out recommendations not just on the need for ongoing monitoring of human rights-related issues but on the detail of how this might be done, and how progress towards human rights-related goals could be tracked. And creativity should be encouraged because, as detailed in a newly-published Chatham House research paper, there may be more opportunities for human rights monitoring than first appear.

The SIA process could also provide a forum for exploring complementary measures needed to make future monitoring efforts as effective as possible – jointly and unilaterally; politically, structurally, and resources-wise; both within the framework of the trading relationship and extraneously. The credibility of the process – and hence stakeholder trust – would be further enhanced by commitments from the Commission to be more transparent in future about how different human rights monitoring recommendations laid out in SIAs have been taken into account in subsequent negotiations, in the supervisory arrangements developed for specific trading relationships, and in the implementation of EU trade policy more generally.

Expert

Erythromycin-resistance methyltransferases are SAM dependent Rossmann fold methyltransferases that convert A2058 of 23S rRNA to m6 2A2058. This modification sterically blocks binding of several classes of antibiotics to 23S rRNA, resulting in a multidrug-resistant phenotype in bacteria expressing the enzyme. ErmC is an erythromycin resistance methyltransferase found in many Gram-positive pathogens, whereas ErmE is found in the soil bacterium that biosynthesizes erythromycin. Whether ErmC and ErmE, which possess only 24% sequence identity, use similar structural elements for rRNA substrate recognition and positioning is not known. To investigate this question, we used structural data from related proteins to guide site-saturation mutagenesis of key residues and characterized selected variants by antibiotic susceptibility testing, single turnover kinetics, and RNA affinity–binding assays. We demonstrate that residues in α4, α5, and the α5-α6 linker are essential for methyltransferase function, including an aromatic residue on α4 that likely forms stacking interactions with the substrate adenosine and basic residues in α5 and the α5-α6 linker that likely mediate conformational rearrangements in the protein and cognate rRNA upon interaction. The functional studies led us to a new structural model for the ErmC or ErmE-rRNA complex.

The EU’s Un-Common Agricultural Policy 21 October 2019 — 8:30AM TO 10:00AM Anonymous (not verified) 27 September 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Sand: Monitoring and management for a sustainable future 2 March 2021 — 1:00PM TO 2:00PM Anonymous (not verified) 18 February 2021 Online

In partnership with the Global Sand Observatory Initiative, this event outlines the sand challenge, what actions are currently underway to address it, and what else needs to be done.

Please complete your registration on Zoom:

After water, sand is the raw material that the world consumes in the greatest quantity. It is no exaggeration to say that fine sand and coarser materials – the medium-to-coarse-grained pebbles, gravel and rock fragments used in construction – are the building blocks of the modern world.

When bound with cement, sand becomes concrete; when mixed with bitumen, it becomes asphalt; and when heated, it becomes glass. Without sand, we would have no highways, high-rises or high-speed trains. Yet sand – which is used here as shorthand for sand, gravel and crushed rock together – is a resource that is both abundant and finite.

In global terms, it is abundant, especially when compared with many other raw materials, albeit often not available close to where it is needed. It is finite in that the rate at which we are using it far exceeds the natural rate at which it is being replenished by the weathering of rocks by wind and water.

Industrialization, population growth and urbanization have fuelled explosive growth in the demand for sand. Precise data on sand extraction are hard to come by and the lack of data compounds the challenge of managing the resource sustainably.

However, the UN estimates that overall extraction could be in the region of 40 billion tonnes per year, driven primarily by construction sector demand. That equates to 18 kilograms of sand each day for every person on the planet and signals how strategically important these resources are for future sustainable development. Post-COVID-19 recovery investment in infrastructure, digital technologies, tourism and other economic activities are dependent on sand resources.

Current efforts to improve the management of sand resources at local, national and global levels are uneven. This is partly due to unique geological features and geography, but also differences in local manifestations of the ‘sand challenge’, national and regional demand for sand resources, as well as capacities to enforce or implement best practice assessment procedures, extractive practices, environmental management and restoration requirements.

We must put stronger conditions in place for a rapid, just and scaled transition to sustainable sand management. But where to focus our efforts for the greatest positive impact?

The 2020 Inner Mongolia Language Protests: Wider Meanings for China and the Region 24 November 2020 — 3:00PM TO 4:00PM Anonymous (not verified) 12 November 2020 Online

Speakers discuss the historical roots of the language issue, as well as the wider significance of the protests in China.

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

In September thousands of people protested in Inner Mongolia in opposition to a government move to replace Mongolian language with Standard Mandarin in three school subjects – history, politics and Chinese language.

Announced less than a week before the start of the new school year, the policy also requires schools to use new national textbooks in Chinese, instead of regional textbooks. The mass protests and classroom walk-outs reflect ethnic Mongolian’s anxiety that their native language may be eliminated. What has the government’s response to the protests been?

Gurmeet K. Bakshi, Jyoti Garg and Gabriela Olteanu
Math. Comp. 93 (), 3027-3058.
Abstract, references and article information

Torin Greenwood, Jonathan Kariv and Noah Williams
Math. Comp. 93 (), 2959-2983.
Abstract, references and article information

Yinji Li, Zhiwei Wang and Xiangyu Zhou
Trans. Amer. Math. Soc. 377 (), 5947-5992.
Abstract, references and article information

Forty-six mathematical scientists have been named recipients of AMS-Simons Research Enhancement Grants for Primarily Undergraduate Institution (PUI) Faculty. Each awardee will receive $3,000 per year for three years. 

The grants foster and support research collaboration by full-time mid-career mathematicians at US institutions that do not offer a mathematics doctoral degree.

This year’s grant recipients hail from 42 institutions across 21 US states. The grants will support their research in several different areas, from number theory to applied mathematics.

This is the grant program’s second cohort, said Sarah Bryant, associate vice president of programs. “Over the first two years, we’ve worked with faculty from 75 different institutions, including 19 minority-serving institutions, which shows just how much this program is expanding and making an impact,” Bryant said. She noted that “in the first year, the grants supported 87 trips, helped produce 70 publications and preprints, and gave awardees the resources needed to collaborate and advance their work.”

The grant allows for any activities that will further the awardee’s research program. Expenses include but are not limited to conference participation, institute visits, collaboration travel (awardee or collaborator), computer equipment or software, family-care expenses, and teaching assistants.

Administration of the award by the grantee’s institution is required; annual discretionary funds for a grantee’s department and administrative funds for a grantee's institution will be available at the end of each grant year.

The grants are made possible through funding from the Simons Foundation and the American Mathematical Society (AMS), as well as Eve, Kirsten, Lenore, and Ada of the Menger family.

Applications for the next cohort are anticipated to open on MathPrograms.org on January 9, 2025. Visit the AMS website to view an informational PowerPoint or sign up to receive email updates about the program. Faculty who applied for but did not receive the 2023 or 2024 awards are encouraged to reapply if they are still eligible for the grant. 

6 July 2020

Madison T Wright
Nov 18, 2020; 0:RA120.002168v1-mcp.RA120.002168
Research

Frank C. Nichols
Dec 1, 2020; 61:1645-1657
Research Articles

Lipoprotein (a) [Lp(a)] is a risk factor for CVD and a target of therapy, but Lp(a) measurements are not globally standardized. Commercially available assays generally use polyclonal antibodies that detect multiple sites within the kringle (K)IV₂ repeat region of Lp(a) and may lead to inaccurate assessments of plasma levels. With increasing awareness of Lp(a) as a cardiovascular risk factor and the active clinical development of new potential therapeutic approaches, the broad availability of reagents capable of providing isoform independence of Lp(a) measurements is paramount. To address this issue, we generated a murine monoclonal antibody that binds to only one site on apo(a). A BALB/C mouse was immunized with a truncated version of apo(a) that contained eight total KIV repeats, including only one copy of KIV₂. We generated hybridomas, screened them, and successfully produced a KIV₂-independent monoclonal antibody, named LPA-KIV9. Using a variety of truncated apo(a) constructs to map its binding site, we found that LPA-KIV9 binds to KIV₉ without binding to plasminogen. Fine peptide mapping revealed that LPA-KIV9 bound to the sequence ⁴⁰⁷⁶LETPTVV⁴⁰⁸² on KIV₉. In conclusion, the generation of monoclonal antibody LPA-KIV9 may be a useful reagent in basic research studies and in the clinical application of Lp(a) measurements.

For three decades, the LPL–specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that 5D2 binds with high affinity to a synthetic LPL peptide containing the Trp-rich loop of human (but not mouse) LPL. We also showed, by both fluorescence and UV resonance Raman spectroscopy, that the Trp-rich loop binds lipids. Finally, we used X-ray crystallography to solve the structure of the Trp-rich peptide bound to a 5D2 Fab fragment. The Trp-rich peptide contains a short α-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the α-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL.

Bile acids (BAs) have been established as ubiquitous regulatory molecules implicated in a large variety of healthy and pathological processes. However, the scope of BA heterogeneity is often underrepresented in current literature. This is due in part to inadequate detection methods, which fail to distinguish the individual constituents of the BA pool. Thus, the primary aim of this study was to develop a method that would allow the simultaneous analysis of specific C24 BA species, and to apply that method to biological systems of interest. Herein, we describe the generation and validation of an LC-MS/MS assay for quantification of numerous BAs in a variety of cell systems and relevant biofluids and tissue. These studies included the first baseline level assessment for planar BAs, including allocholic acid, in cell lines, biofluids, and tissue in a nonhuman primate (NHP) laboratory animal, Macaca mulatta, in healthy conditions. These results indicate that immortalized cell lines make poor models for the study of BA synthesis and metabolism, whereas human primary hepatocytes represent a promising alternative model system. We also characterized the BA pool of M. mulatta in detail. Our results support the use of NHP models for the study of BA metabolism and pathology in lieu of murine models. Moreover, the method developed here can be applied to the study of common and planar C24 BA species in other systems.

Oxylipins are potent lipid mediators involved in a variety of physiological processes. Their profiling has the potential to provide a wealth of information regarding human health and disease and is a promising technology for translation into clinical applications. However, results generated by independent groups are rarely comparable, which increases the need for the implementation of internationally agreed upon protocols. We performed an interlaboratory comparison for the MS-based quantitative analysis of total oxylipins. Five independent laboratories assessed the technical variability and comparability of 133 oxylipins using a harmonized and standardized protocol, common biological materials (i.e., seven quality control plasmas), standard calibration series, and analytical methods. The quantitative analysis was based on a standard calibration series with isotopically labeled internal standards. Using the standardized protocol, the technical variance was within ±15% for 73% of oxylipins; however, most epoxy fatty acids were identified as critical analytes due to high variabilities in concentrations. The comparability of concentrations determined by the laboratories was examined using consensus value estimates and unsupervised/supervised multivariate analysis (i.e., principal component analysis and partial least squares discriminant analysis). Interlaboratory variability was limited and did not interfere with our ability to distinguish the different plasmas. Moreover, all laboratories were able to identify similar differences between plasmas. In summary, we show that by using a standardized protocol for sample preparation, low technical variability can be achieved. Harmonization of all oxylipin extraction and analysis steps led to reliable, reproducible, and comparable oxylipin concentrations in independent laboratories, allowing the generation of biologically meaningful oxylipin patterns.

Porphyromonas gingivalis is a Gram-negative anaerobic periodontal microorganism strongly associated with tissue-destructive processes in human periodontitis. Following oral infection with P. gingivalis, the periodontal bone loss in mice is reported to require the engagement of Toll-like receptor 2 (TLR2). Serine-glycine lipodipeptide or glycine aminolipid classes of P. gingivalis engage human and mouse TLR2, but a novel lipid class reported here is considerably more potent in engaging TLR2 and the heterodimer receptor TLR2/TLR6. The novel lipid class, termed Lipid 1256, consists of a diacylated phosphoglycerol moiety linked to a serine-glycine lipodipeptide previously termed Lipid 654. Lipid 1256 is approximately 50-fold more potent in engaging TLR2 than the previously reported serine-glycine lipid classes. Lipid 1256 also stimulates cytokine secretory responses from peripheral blood monocytes and is recovered in selected oral and intestinal Bacteroidetes organisms. Therefore, these findings suggest that Lipid 1256 may be a microbial TLR2 ligand relevant to chronic periodontitis in humans.

Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection, leading to high morbidity and mortality. Currently, bronchoalveolar lavage (BAL) is used in hospitals for VAP diagnosis and guiding treatment options. Although BAL collection procedures are invasive, alternatives such as endotracheal aspirates (ETA) may be of diagnostic value, however, their use has not been thoroughly explored. Longitudinal ETA and BAL were collected from 16 intubated patients up to 15 days, of which 11 developed VAP. We conducted a comprehensive LC–MS/MS based proteome and metabolome characterization of longitudinal ETA and BAL to detect host and pathogen responses to VAP infection. We discovered a diverse ETA proteome of the upper airways reflective of a rich and dynamic host-microbe interface. Prior to VAP diagnosis by microbial cultures from BAL, patient ETA presented characteristic signatures of reactive oxygen species and neutrophil degranulation, indicative of neutrophil mediated pathogen processing as a key host response to the VAP infection. Along with an increase in amino acids, this is suggestive of extracellular membrane degradation resulting from proteolytic activity of neutrophil proteases. The metaproteome approach successfully allowed simultaneous detection of pathogen peptides in patients' ETA, which may have potential use in diagnosis. Our findings suggest that ETA may facilitate early mechanistic insights into host-pathogen interactions associated with VAP infection and therefore provide its diagnosis and treatment.

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.

The histidine kinase Hik33 plays important roles in mediating cyanobacterial response to divergent types of abiotic stresses including cold, salt, high light (HL), and osmotic stresses. However, how these functions are regulated by Hik33 remains to be addressed. Using a hik33-deficient strain (hik33) of Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found that Hik33 depletion induces differential protein expression highly similar to that induced by divergent types of stresses. This typically includes downregulation of proteins in photosynthesis and carbon assimilation that are necessary for cell propagation, and upregulation of heat shock proteins, chaperons, and proteases that are important for cell survival. This observation indicates that depletion of Hik33 alone mimics divergent types of abiotic stresses, and that Hik33 could be important for preventing abnormal stress response in the normal condition. Moreover, we found the majority of proteins of plasmid origin were significantly upregulated in hik33, though their biological significance remains to be addressed. Together, the systematically characterized Hik33-regulated cyanobacterial proteome, which is largely involved in stress responses, builds the molecular basis for Hik33 as a general regulator of stress responses.

Thyroglobulin (Tg) is a secreted iodoglycoprotein serving as the precursor for T3 and T4 hormones. Many characterized Tg gene mutations produce secretion-defective variants resulting in congenital hypothyroidism (CH). Tg processing and secretion is controlled by extensive interactions with chaperone, trafficking, and degradation factors comprising the secretory proteostasis network. While dependencies on individual proteostasis network components are known, the integration of proteostasis pathways mediating Tg protein quality control and the molecular basis of mutant Tg misprocessing remain poorly understood. We employ a multiplexed quantitative affinity purification–mass spectrometry approach to define the Tg proteostasis interactome and changes between WT and several CH-variants. Mutant Tg processing is associated with common imbalances in proteostasis engagement including increased chaperoning, oxidative folding, and engagement by targeting factors for ER-associated degradation (ERAD). Furthermore, we reveal mutation-specific changes in engagement with N-glycosylation components, suggesting distinct requirements for one Tg variant on dual engagement of both oligosaccharyltransferase complex isoforms for degradation. Modulating dysregulated proteostasis components and pathways may serve as a therapeutic strategy to restore Tg secretion and thyroid hormone biosynthesis.

Drones and the European Union: Prospects for a Common Future Research paper sysadmin 30 January 2018

The debate over the use of drones is an opportunity for states to identify elements of military practice that their publics find uncomfortable or troubling, and to explain these areas of military operations in context.

Summary

• The debate over the use of drones is an opportunity for states to identify elements of military practice that their publics find uncomfortable or troubling, and to explain these areas of military operations in context.
• Countries would benefit from working together to identify accountability gaps arising from fundamental elements of military cooperation, including the role of intelligence transfers in joint operations, and the distribution of responsibility for lethal actions in the context of coalition operations.
• Transparency in investigation procedures, as well as devoting sufficient resources towards ensuring that mistakes are identified, will improve the perception of drone use among domestic audiences.
• Identifying and communicating common standards and practices of mitigating complicity should be a priority for countries to ensure that they do not unwittingly become complicit in unlawful lethal operations.
• Although operational safety may hinder the ability of states to be completely transparent, understanding among the general public could be improved through the communication of policies and procedures regarding non-lethal assistance to partner states conducting lethal operations, both inside and outside the context of an armed conflict.

The Phillies acquired All-Star catcher J.T. Realmuto from the Marlins on Thursday for catcher Jorge Alfaro, right-hander Sixto Sanchez, left-hander Will Stewart and $250,000 in international bonus slot money, the latest move in a busy and ambitious offseason for a team eager to return to the postseason.

General Manager Matt Klentak discussed the Phillies' offseason in a press conference on Thursday in Clearwater, Fla. The Phillies remain in contact with the agents for Bryce Harper and Manny Machado. The belief is that the front office still prefers Machado over Harper because of Machado's combination of offense and defense.

MLB Network's countdown of baseball's best players at each position continued with the third installment of the "Top 10 Right Now!" series, featuring the game's top left and center fielders.

The Commonwealth reimagined 8 November 2022 — 6:00PM TO 7:00PM Anonymous (not verified) 18 October 2022 Chatham House and Online

Ghana’s minister of foreign Affairs, the Hon. Shirley Ayorkor Botchwey, discusses her vision for a modern Commonwealth and how it can evolve and match demands from its members.

The death of HM Queen Elizabeth II has focused attention on the future of the Commonwealth. The Commonwealth is an expanding voluntary organization of 56 independent countries in Africa, Asia, the Americas, Europe, and the Pacific.

Its appeal is increasingly beyond the circle of former British colonies – ex-French colonies Togo and Gabon officially joined in October 2022 and the ex-Portuguese colony, Angola, has applied. The Commonwealth Secretariat, established in 1965, is its main intergovernmental agency, which coordinates and carries out much of the Commonwealth’s work, supported by a network of more than 80 organizations.

King Charles III now heads the Commonwealth, which is focused on shared goals of prosperity, democracy and peace. However, the future of the Commonwealth and its purpose are unclear, and the organization needs to develop a sharper agenda on what its international contribution can be across its 56 state members and their peoples.

The minister discusses key questions including:

• What should a modern Commonwealth look like and how can it best operate?

• How can the organization impact policies and actions at a country level?

• What role will young people play in the future of the Commonwealth?

• How can the organization harness collective resources and technology to tackle major global issues such as climate change?

• Can the issue of mobility and immigration among member states be managed?

What’s next in UK monetary policy? 4 November 2022 — 4:00PM TO 5:30PM Anonymous (not verified) 19 October 2022 Chatham House and Online

A panel of leading experts discuss the future direction of UK monetary policy.

The UK’s so-called ‘mini-budget’ on 23 September led to a severe market reaction and a wave of criticism at home and abroad that ultimately forced the sacking of UK chancellor Kwasi Kwarteng and contributed to the downfall of Liz Truss’s government.

The new chancellor Jeremy Hunt is due to deliver what will essentially be an entirely new budget in mid-November, with a full assessment from the Office of Budget Responsibility. This will follow the meeting of the Bank of England’s interest rate setting Monetary Policy Committee (MPC) on Thursday 3 November.

Given rising inflationary pressures worldwide, it seems highly likely that the MPC will increase interest rates once again, but by how much and how far there will have to be an additional premium linked to the government’s fiscal strategy is far from clear.

Chatham House’s Global Economy and Finance programme is pleased to partner with Fathom Consulting to host a special session of Fathom’s Monetary Policy Forum.

A presentation of Fathom’s latest economic outlook, fully updated to take account of the previous day’s MPC decision, will be followed by a discussion among four of the MPC’s original former external members. Key questions will include:

• How far has the government been able to restore its fiscal credibility?
• Did the MPC make the right decision on 3 November?
• What is the likely pace and extent of monetary tightening in the UK going forward?
• What will be the long-term consequences for the UK economy of the past month’s policy experiment?
• What are the international implications?

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

This event is in partnership with Fathom Consulting.

How do Eurasian kleptocracies earn and use their money? 9 November 2021 — 1:00PM TO 2:30PM Anonymous (not verified) 22 October 2021 Chatham House and Online

This event explores the presence of corrupt funds from Eurasia in Western democracies, what they are used for, and how they can be constrained.

The Pandora Papers once again shone the spotlight on the UK being home to corrupt funds from kleptocracies, where the ruling elite abuse their political power for private gain.

In recent years much focus has been placed on this term, and the possible effects such money could have on Western democracies.

• How do such states create this wealth in the first place?
• How do these funds make their way to the UK?
• Is the term kleptocracy appropriate for the majority of countries in Eurasia?
• What evidence is there that such funds are ‘weaponized’ to achieve foreign policy goals?

This event discusses the term, how it can be applied, and the differences between how ’grey’ funds are used by various countries. It also highlights how the UK and the wider international community can counteract these flows, both from a legal point of view, and via other methods.

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post–myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with ¹⁸F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with ¹⁸F a quinazolinone derivative ([¹⁸F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [¹⁸F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [¹⁸F]LCE470 was determined by time–activity curve and SUV analysis in 3 regions of the left ventricle—area of infarct, territory served by the left circumflex coronary artery, and remote myocardium—over a period of 1.5 y. Changes in cardiac perfusion were tracked by [¹³N]NH₃ PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [¹⁸F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [¹⁸F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [¹⁸F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [¹⁸F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.

Unspecific bone uptake (UBU) related to [¹⁸F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [¹⁸F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [¹⁸F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUV_max, SUV_mean, PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HU_mean) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less (n = 2) or more (n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake (n = 178) as PCa metastases or not. Results: In total, 448 bone [¹⁸F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT (P < 0.001) with determination of SUV_max (P < 0.001) and HU_mean (P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation (n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score’s AUC was significantly higher than that of HU_mean (AUC, 0.62) and remained high among lesions with HU_mean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [¹⁸F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging.

The U.S. Food and Drug Administration has determined commonly used oral phenylephrine is "not effective" and has proposed its removal from over-the-counter nasal decongestants.