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Britain should treat Europe as its ‘inner circle’ or risk losing international influence

13 October 2015

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British Prime Minister David Cameron sits with other world leaders at the G20 summit in Brisbane, Australia on 15 November 2014. Photo by Getty Images.

Given the international context, it is in Britain’s best interests to treat Europe as the ‘inner circle’ of its foreign, security and international economic policy, argues Dr Robin Niblett, director of Chatham House, in a new paper.

The British government’s approach since 2010 of seeking to enhance the UK's relations with the world’s emerging powers while balancing these with relationships with the United States and Europe has had only limited success. With constrained resources, and in the face of intense global economic competition, mounting security challenges and decaying international institutions, trying to commit the UK equally on all three fronts will not succeed in the future.

Britain, Europe and the World: Rethinking the UK’s Circles of Influence calls for a different mindset and strategy towards the UK’s place in the world – one in which Britain is surrounded by three concentric circles of influence:

  • The first or ‘inner circle’ is the EU, the region with which the UK’s relationships need to be strongest and most active.
  • The ‘second circle’ consists of the protective and enabling set of economic and security relationships with the US.
  • Finally, an ‘outer circle’ comprises the UK’s other key bilateral and institutional relationships.

Should the UK vote to remain in the EU, policy-makers should commit to placing the EU at the centre of Britain's foreign policy, using the country’s economic weight, diplomatic skills and networks to play a leading role in leveraging more effective EU-wide policies.
 
Should the country vote to leave, the UK and the EU would enter an extended period of dislocation before arriving at a new, mutually diminished settlement. British policy-makers would be forced to deal and negotiate with the EU on critical policy issues from the outside. It is hard to see, argues Dr Niblett, how that could lead to EU policies or an international context more in line with British interests.                          

Despite its structural flaws and competing national interests, the EU offers the best prospects for managing the rapidly changing global context, for three main reasons:

First, it allows the UK to leverage the EU’s global economic weight to enhance the UK’s economic interests internationally, including securing beneficial trade agreements and contributing to EU and global standard-setting and rule-writing. Conversely, leaving would require the UK to renegotiate over 100 trade agreements, and would disadvantage UK interests in EU markets, including making EU governments less likely to liberalize services.                          

Second, it gives the UK a say in designing new EU initiatives to strengthen both British and European security in the face of diverse threats, whether managing the flow of refugees and other emigrants; combatting terrorism; or managing a more assertive Russia and the fallout from a disintegrating Middle East.                          

Third, cooperating with other EU members offers a way of maximizing opportunities to find joint solutions to shared problems, whether in terms of responding to climate change; managing growing cyber insecurity; reversing the decay of governance in failing states; or combating the rise of dangerous non-state actors.

Dr Robin Niblett said:

‘Britain is likely to be richer, safer and more influential in the coming decades if it treats Europe as the ‘inner circle’ of its foreign policy. For a mid-sized country like the UK, being a major player in a strong regional institution can offer a critical lever for international influence. In the UK’s case, this means choosing to be a leading player in the world’s principal civilian power, the European Union.’

                          

Editor's notes

Read Britain, Europe and the World: Rethinking the UK's Circles of Influence

Chatham House will host a press briefing with Dr Robin Niblett on Monday 19 October at 11:00-11:45 BST. To register, or for interview requests, please contact the press office.

The views expressed in this paper are those of the author. Chatham House experts will publish a series of papers and commentaries in the run up to the UK’s referendum on its membership of the EU. The institute will also offer a platform for debate on the referendum and Britain’s role in Europe via a series of events and meetings.

Read more about the EU referendum.

Contacts

Press Office

+44 (0)20 7957 5739




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Stavros Niarchos Foundation makes £3m grant for expansion at Chatham House

18 December 2015

The Royal Institute of International Affairs is pleased to announce a Cornerstone Contribution of £3m by the Stavros Niarchos Foundation (SNF) towards the Chatham House Second Century Initiative to support the expansion and renovation of the institute’s ground floor.

Following the institute’s purchase of the ground floor of the adjoining building (Ames House) in 2013, this generous grant from SNF will enable Chatham House to occupy this space and undertake a significant renovation project to create the ‘Stavros Niarchos Foundation Floor’ at Chatham House.

This will help the institute meet the growing demand for its research and analysis and take full advantage of its location in central London, given the city’s exceptional international connectivity and status as a global hub.

The SNF Floor will contain state-of-the-art meeting facilities for the institute’s research staff and fellows of the Queen Elizabeth II Academy for Leadership in International Affairs, and will significantly enhance the institute’s convening and communication capacities. To this end, the renovated space will include a ‘simulation room’, the Asfari Centre and a media room, as well as new breakout and meeting areas. The SNF Floor will be directly accessible from the ground floor of 10 St James’s Square, the institute’s main building.

The SNF grant is an important step forward for the institute’s Second Century Initiative which aims to ensure the institute’s long-term financial independence. The initiative has three principal targets:

● to endow a number of Research Fellowships and interdisciplinary Research Centres;

● to secure endowments to support the Queen Elizabeth II Academy for Leadership in International Affairs in order to nurture independent thinking on international policy among a new generation from around the world; and

● to secure the necessary physical space and infrastructure here in London to meet the growing demand for and scope of the institute’s work.

Dr Robin Niblett, director of Chatham House said: ‘We are enormously grateful to the Stavros Niarchos Foundation for this transformational grant which will significantly enhance Chatham House’s capacity to serve as a trusted and creative space for addressing the most important challenges in international affairs.’

Andreas Dracopoulos, co-president of SNF’s board of directors, said: ‘We are delighted to support the growth of Chatham House, one of Europe’s leading independent, non partisan policy institutes, at a time when the risks to global prosperity and stability are expanding. Chatham House’s reputation for providing world-leading analysis needs to remain as strong as ever and I am confident that this grant will help the institute take its research and convening activities in new interactive and interdisciplinary directions.

Editor's notes

Chatham House launched its Second Century Initiative in November 2014 as part of its preparations for its centenary in 2020. The Initiative aims to help secure the institute’s financial base and independence by strengthening its capacity to innovate in an increasingly competitive field of thought leadership and policy ideas. Renovation work on the ground floor of Ames House is expected to begin in the spring of 2016.

The Stavros Niarchos Foundation is one of the world’s leading international philanthropic organizations, making grants in the areas of arts and culture, education, health, medicine and sports, and social welfare. The Foundation funds organizations and projects that exhibit strong leadership and sound management and are expected to achieve a broad, lasting and positive impact for society at large. The Foundation also seeks actively to support projects that facilitate the formation of public-private partnerships as an effective means for serving public welfare.




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Prince Harry Opens the Stavros Niarchos Foundation Floor

16 June 2017

Prince Harry visited Chatham House on 15 June to open the Stavros Niarchos Foundation Floor.

His Royal Highness met with young fellows from the Queen Elizabeth II Academy for Leadership in International Affairs and discussed the important role that the next generation of leaders must play in bringing about positive change in their communities. 

The Academy was formally launched by Her Majesty The Queen at Chatham House in 2014.

Prince Harry also contributed to the first scenario exercise held in the institute’s new simulation centre, which explored how to respond to a humanitarian emergency that required landmine clearance, drawing on the prince’s work in the field of landmine eradication.

The opening of the Stavros Niarchos Foundation Floor marks a significant moment in the modern history of the institute and is a core component of the Chatham House Second Century Initiative, which aims to strengthen the institute’s capacity to innovate and meet the growing demand for its research in the lead-up to its centenary in 2020.

The extension includes a series of new facilities, including the Asfari Centre for Academy Fellows, the simulation centre, new meeting spaces and a media studio, which will ensure that Chatham House can continue to contribute to building a sustainably secure, prosperous and just world over the coming decades.

Mine Action in Angola: Landmine-Free by 2025

HM The Queen Launches Academy for Leadership




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Chatham House awarded major centenary grant to establish Stavros Niarchos Foundation Wing

17 April 2019

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

The gift will create the Stavros Niarchos Foundation (SNF) Wing, enabling a permanent expansion of the institute’s research and providing a home to its Queen Elizabeth II Academy for Leadership in International Affairs. The wing will also house the ‘Chatham House SNF CoLab’, an initiative to open Chatham House’s policy research to wider public audiences.

The funds from the Stavros Niarchos Foundation (SNF) will be used to integrate a three-storey wing with the institute’s renowned building at 10 St James’s Square. The SNF Wing will support research collaboration and provide a stimulating environment to explore ways to engage people in the institute’s research, using interactive multimedia and other digital tools. Inauguration of the Chatham House SNF CoLab and the SNF Wing is anticipated in fall of 2019.

The gift from SNF is one of the largest in the institute’s history and is a major milestone in the foundation’s long-standing support of Chatham House, which dates back to 2007 and includes grants for research, infrastructure and student outreach totalling over £4.5m in the past 5 years.

Chairman of Chatham House, Lord Jim O’Neill said, 'This exceptional gift from SNF is a vote of confidence in the independence, quality and impact of the institute’s work. It will guarantee that the institute can innovate for the future, especially by engaging younger generations into its research and ideas, which is essential.'

Director of Chatham House Dr Robin Niblett said the gift will encourage informed public debate at a time of unprecedented global uncertainty and deepening political polarisation.

'The SNF Wing and Chatham House SNF CoLab will ensure Chatham House can continue to serve as a trusted hub for dialogue and a source of credible information, analysis and ideas on international affairs. It is an enormous boost to our staff and their work as we begin our second century, and of special value in such turbulent times.'

SNF Co-President Andreas Dracopoulos said, 'Chatham House is one of our key partners, and this grant marks an important new stage in our collaboration. At a time of uncertainty in international affairs, supporting the world-class independent analysis that can help citizens around the world engage in informed decisions about their future is essential. We are proud to help Chatham House maintain its independent voice while deepening its engagement with the public.'

The Stavros Niarchos Foundation’s past support has enabled Chatham House to establish an ‘SNF Floor’ with a broadcast media studio, a purpose-built simulation centre and training facilities, which will now be incorporated into the larger SNF Wing. The floor was officially opened by His Royal Highness the Duke of Sussex in 2017, when he took part in a scenario exercise exploring how to respond to a humanitarian emergency that required landmine clearance, drawing on the Duke’s ongoing work in this field.

For more information please contact:

pressoffice@chathamhouse.org
Phone: +44 (0)207 957 5739

Editor's notes

Chatham House, the Royal Institute of International Affairs, is a world-leading policy institute based in London. Our mission is to help governments and societies build a sustainably secure, prosperous and just world.

We engage governments, the private sector, civil society and our members in open debate and private discussions about the most significant developments in international affairs.  Our research and policy ideas involve rigorous analysis of critical global, regional and country-specific challenges and opportunities.

The Stavros Niarchos Foundation (SNF) is one of the world’s leading private, international philanthropic organizations, making grants to non-profit organizations in the areas of arts and culture, education, health and sports, and social welfare. Since 1996, the Foundation has committed more than $2.8 billion, through more than 4,400 grants to non-profit organizations in 124 nations around the world.

The SNF funds organizations and projects worldwide that aim to achieve a broad, lasting and positive impact for society at large and exhibit strong leadership and sound management. The Foundation also supports projects that facilitate the formation of public-private partnerships as an effective means for serving public welfare.




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Chatham House appoints Tim Benton as Research Director for Energy, Environment and Resources

30 May 2019

Chatham House is pleased to announce that Professor Tim Benton has been appointed as research director of the Energy, Environment and Resources Department.

He brings substantial expertise on food systems and environmental change to the role and will focus on establishing new initiatives at the intersection of research and policymaking.

Tim was appointed as a distinguished visiting fellow of Chatham House in the Energy, Environment and Resources Department in 2016. He has since contributed to the institute in a number of ways, not least through leading the GCRF-AFRICAP project which aims to enhance policy making in Sub-Saharan Africa, through building climate-smart food systems.

Tim’s research focuses on food security and building food systems that are resilient and sustainable, working within the broader areas of ecology, natural resources and climate change impacts. He has published over 150 academic papers, most tackling the core themes of agriculture’s environmental impact and more generally how systems respond to environmental change. He is a lead author of the upcoming Intergovernmental Panel on Climate Change (IPCC) special report on climate change and land. He is also coordinating lead author on international risks for the UK’s Climate Change Risk Assessment, which draws on his broader interests in sustainable finance, trade and energy. He has advised other governments as well as global companies on related issues.

Tim joins Chatham House in his new capacity from the University of Leeds where he is dean of strategic research initiatives. Prior to this, from 2011 to 2016, Tim was the champion of the UK’s Global Food Security programme, a large multi-agency partnership of the UK’s public bodies involved in addressing challenges around food. He has also been research dean in the Faculty of Biological Sciences, and head of department, at Leeds.

Dr Robin Niblett, director of Chatham House, said: 'Tim’s wealth of experience will be especially valuable as we build up our interdisciplinary Chatham House research theme of promoting sustainable growth. We look forward to welcoming Tim to his new role in early July.'

Tim Benton said: 'I am honoured to be joining Chatham House as Research Director for Energy, Environment and Resources. Chatham House has a global reputation in these areas, on which we can build. Informed analysis, combined with effective action to transition towards sustainable economies, is needed now, more than ever.'

About the Energy, Environment and Resources Department

The Energy, Environment and Resources department at Chatham House seeks to advance the international debate on energy, environment and development policy and to influence and enable decision-makers – governments, NGOs and business – to take well-informed decisions that contribute to achieving sustainable development. Independent of any actor or ideology, we do this by carrying out innovative research on major policy challenges, bringing together diverse perspectives and constituencies and injecting new ideas into the international arena.

Tim Benton takes over the role from Rob Bailey who has joined Marsh & McLennan Insights as Director, Climate Resilience.




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In Search of the American State

6 April 2020

Dr Leslie Vinjamuri

Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme
The urgent need for US leadership to drive forward a coordinated international response to coronavirus is developing rapidly alongside snowballing demands for Washington to step up its efforts at home.

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Exercising in front of a deserted Lincoln Memorial in Washington, DC. Photo by Win McNamee/Getty Images.

As the US surgeon general warns Americans to brace for ‘our Pearl Harbor moment’, the US faces a week in which it may see the worst of the global pandemic. The absence of US leadership at the global level has enabled the Security Council’s inaction. And at the G7, President Trump actively obstructed efforts to agree a joint statement.

US efforts to increase its support of international aid to the tune of $274million are minimal, not least in light of a 50% reduction in its support for the World Health Organization (WHO) and radically diminished support for other global health programmes as well. International coordination is essential to mitigate unregulated competition for critical medical supplies, manage border closures, and guarantee international economic stability.

True, it won’t be possible to control the epidemic at home if the global effort to defeat the pandemic fails. But the absence of leadership from Washington at home is palpable. And what happens at home sets a natural limit on America’s internationalism.

Both solution and problem

In response to the coronavirus crisis, the US state is proving to be a solution - and a problem. The dramatic response to the economic crisis is evident with the $2.3trillion stimulus package signed into law by President Trump boldly supported by both Democrats and Republicans in the most significant piece of bipartisan legislation passed in decades.

America’s political economy is unrecognisable, moving left and looking increasingly more European each week as Congress and the executive branch agree a series of stimulus packages designed to protect citizens and businesses. Some elements of this legislation were more familiar to Americans, notably $200bn in corporate tax breaks.

But Congress also agreed unemployment insurance, and cheques - one in April, one in May – to be sent directly to those Americans most directly hit by the economic impact of COVID-19. In effect, this is adopting a temporary universal basic income.

The stimulus plan also dedicated $367bn to keep small businesses afloat for as long as the economy is shuttered. Already the government is negotiating a fourth stimulus package, but the paradox is that without rigorous steps to halt the health crisis, no level of state intervention designed to solve the economic response will be sufficient.

The scale of the state’s economic intervention is unprecedented, but it stands in stark contrast to Washington’s failure to coordinate a national response to America’s health crisis. An unregulated market for personal protective equipment and ventilators is driving up competition between cities, states, and even the federal government.

In some cases, cities and states are reaching out directly beyond national borders to international organisations, foreign firms and even America’s geopolitical competitors as they search for suppliers. In late March, the city of New York secured a commitment from the United Nations to donate 250,000 protective face masks.

Now Governor Cuomo has announced New York has secured a shipment of 140 ventilators from the state of Oregon, and 1,000 ventilators from China. The Patriots even sent their team plane to China to pick up medical supplies for the state of Massachusetts. And following a phone call between President Putin and President Trump, Russia sent a plane with masks and medical equipment to JFK airport in New York.

Networks of Chinese-Americans in the United States are rapidly mobilising their networks to access supplies and send them to doctors and nurses in need. And innovative and decisive action by governors, corporates, universities and mayors drove America’s early response to coronavirus.

This was critical to slowing the spread of COVID-19 by implementing policies that rapidly drove social distancing. But the limits of decentralized and uncoordinated action are now coming into sharp focus. President Trump has so far refused to require stay-at-home orders across all states, leaving this authority to individual governors. Unregulated competition has driven up prices with the consequence that critical supplies are going to the highest bidder, not those most in need.

Governor Cuomo’s call for a nationwide buying consortium has so far gone unheeded and, although the Federal Emergency Management Agency has attempted to deliver supplies to states most in need, the Strategic National Stockpile is depleting fast. Without critical action, the federal government risks hindering the ability of cities and states to get the supplies they need.

But President Trump is reluctant to fully deploy his powers under the Defense Production Act (DPA). In March, he did invoke the DPA to require certain domestic manufacturers to produce ventilators. But calls for it to be used to require manufacturers to produce PPE (personal protective equipment), control costs, and manage allocations has so far gone unheeded by a president generally opposed to state interventions for managing the economy.

It is true that federalism and a deep belief in competition are critical to the fabric of US history and politics, and innovations made possible by market values of entrepreneurism and competition cannot be underestimated. In the search for a vaccine, this could still prove to be key.

But with current estimates that more Americans will die from coronavirus than were killed in the Korean and Vietnam wars combined, it is clear now is the time to reimagine and reinvent the role of the American state.

In the absence of a coordinated effort driven by the White House, governors are working together to identify the areas of greatest need. Whether this will lead to a recasting of the American state and greater demand for a deeper and more permanent social safety net is a key question in the months ahead.

In the short-term the need for coordinated state action at the national level is self-evident. US leadership globally, to manage the health crisis and its economic impacts, is also vital. But this is unlikely to be forthcoming until America gets its own house in order.




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Why an Inclusive Circular Economy is Needed to Prepare for Future Global Crises

15 April 2020

Patrick Schröder

Senior Research Fellow, Energy, Environment and Resources Programme
The risks associated with existing production and consumption systems have been harshly exposed amid the current global health crisis but an inclusive circular economy could ensure both short-term and long-term resilience for future challenges.

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Lima city employees picking up garbage during lockdown measures in Peru amid the COVID-19 crisis. Photo: Getty Images.

The world is currently witnessing how vulnerable existing production and consumption systems are, with the current global health crisis harshly exposing the magnitude of the risks associated with the global economy in its current form, grounded, as it is, in a linear system that uses a ‘take–make–throw away’ approach.

These ‘linear risks’ associated with the existing global supply chain system are extremely high for national economies overly dependent on natural resource extraction and exports of commodities like minerals and metals. Equally vulnerable are countries with large manufacturing sectors of ready-made garments and non-repairable consumer goods for western markets. Furthermore, workers and communities working in these sectors are vulnerable to these changes as a result of disruptive technologies and reduced demand.

In a recently published Chatham House research paper, ‘Promoting a Just Transition to an Inclusive Circular Economy’, we highlight why a circular economy approach presents the world with a solution to old and new global risks – from marine plastic pollution to climate change and resource scarcity.

Taking the long view

So far, action to transition to a circular economy has been slow compared to the current crisis which has mobilized rapid global action. For proponents of transitioning to a circular economy, this requires taking the long view. The pandemic has shown us that global emergencies can fast-forward processes that otherwise might take years, even decades, to play out or reverse achievements which have taken years to accomplish.

In this vein, there are three striking points of convergence between the COVID-19 pandemic and the need to transition to an inclusive circular economy.

Firstly, the current crisis is a stark reminder that the circular economy is not only necessary to ensure long-term resource security but also short-term supplies of important materials. In many cities across the US, the UK and Europe, councils have suspended recycling to focus on essential waste collection services. The UK Recycling Association, for example, has warned about carboard shortages due to disrupted recycling operations with possible shortages for food and medicine packaging on the horizon.

Similarly, in China, most recycling sites were shut during the country’s lockdown presenting implications for global recycling markets with additional concerns that there will be a fibre shortage across Europe and possibly around the world.

Furthermore, worldwide COVID-19 lockdowns are resulting in a resurgence in the use of single-use packaging creating a new wave of plastic waste especially from food deliveries – already seen in China – with illegal waste fly-tipping dramatically increasing in the UK since the lockdown.

In this vein, concerns over the current global health crisis is reversing previous positive trends where many cities had established recycling schemes and companies and consumers had switched to reusable alternatives.

Secondly, the need to improve the working conditions of the people working in the informal circular economy, such as waste pickers and recyclers, is imperative. Many waste materials and recyclables that are being handled and collected may be contaminated as a result of being mixed with medical waste.

Now, more than ever, key workers in waste management, collection and recycling require personal protective equipment and social protection to ensure their safety as well as the continuation of essential waste collection so as not to increase the potential for new risks associated with additional infectious diseases.

In India, almost 450 million workers including construction workers, street vendors and landless agricultural labourers, work in the informal sector. In the current climate, the poorest who are unable to work pose a great risk to the Indian economy which could find itself having to shut down.

Moreover, many informal workers live in make-shift settlements areas such as Asia’s largest slum, Dharavi in Mumbai, where health authorities are now facing serious challenges to contain the spread of the disease. Lack of access to handwashing and sanitation facilities, however, further increase these risks but circular, decentralized solutions could make important contributions to sustainable sanitation, health and improved community resilience.

Thirdly, it is anticipated that in the long term several global supply chains will be radically changed as a result of transformed demand patterns and the increase in circular practices such as urban mining for the recovery and recycling of metals or the reuse and recycling of textile fibres and localized additive manufacturing (e.g. 3D printing).

Many of these supply chains and trade flows have now been already severely disrupted due to the COVID-19 pandemic. For example, the global garment industry has been particularly hard-hit due to the closure of outlets amid falling demand for apparel.

It is important to note, workers at the bottom of these garment supply chains are among the most vulnerable and most affected by the crisis as global fashion brands, for example, have been cancelling orders – in the order of $6 billion in the case of Bangladesh alone. Only after intense negotiations are some brands assuming financial responsibility in the form of compensation wage funds to help suppliers in Myanmar, Cambodia and Bangladesh to pay workers during the ongoing crisis.

In addition, the current pandemic is damaging demand for raw materials thereby affecting mining countries. Demand for Africa’s commodities in China, for example, has declined significantly, with the impact on African economies expected to be serious, with 15 per cent of the world’s copper and 20 per cent of the world’s zinc mines currently going offline

A further threat is expected to come from falling commodity prices as a result of the curtailment of manufacturing activity in China particularly for crude oil, copper, iron ore and other industrial commodities which, in these cases, will have direct impacts on the Australian and Canadian mining sectors.

This is all being compounded by an associated decline in consumer demand worldwide. For example, many South African mining companies – leading producers of metals and minerals – have started closing their mining operations following the government’s announcement of a lockdown in order to prevent the transmission of the virus among miners who often work in confined spaces and in close proximity with one another. As workers are laid off due to COVID-19, there are indications that the mining industry will see fast-tracking towards automated mining operations

All of these linear risks that have been exposed through the COVID-19 pandemic reinforce the need for a just transition to a circular economy. But while the reduction in the consumption of resources is necessary to achieve sustainability, the social impacts on low- and middle- income countries and their workers requires international support mechanisms.

In addition, the current situation also highlights the need to find a new approach to globalized retail chains and a balance between local and global trade based on international cooperation across global value chains rather than implementation of trade protectionist measures.

In this vein, all of the recovery plans from the global COVID-19 pandemic need to be aligned with the principles of an inclusive circular economy in order to ensure both short-term and long-term resilience and preparedness for future challenges and disruptions.  




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The Human Plasma Proteome: A Nonredundant List Developed by Combination of Four Separate Sources

N. Leigh Anderson
Apr 1, 2004; 3:311-326
Research




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Discordant Protein and mRNA Expression in Lung Adenocarcinomas

Guoan Chen
Apr 1, 2002; 1:304-313
Research




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GPS 2.0, a Tool to Predict Kinase-specific Phosphorylation Sites in Hierarchy

Yu Xue
Sep 1, 2008; 7:1598-1608
Research




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The Paragon Algorithm, a Next Generation Search Engine That Uses Sequence Temperature Values and Feature Probabilities to Identify Peptides from Tandem Mass Spectra

Ignat V. Shilov
Sep 1, 2007; 6:1638-1655
Technology




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The cytochrome P450 enzyme CYP24A1 increases proliferation of mutant KRAS-dependent lung adenocarcinoma independent of its catalytic activity [Cell Biology]

We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high.




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Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations [Enzymology]

3-Mercaptopyruvate sulfur transferase (MPST) catalyzes the desulfuration of 3-mercaptopyruvate (3-MP) and transfers sulfane sulfur from an enzyme-bound persulfide intermediate to thiophilic acceptors such as thioredoxin and cysteine. Hydrogen sulfide (H2S), a signaling molecule implicated in many physiological processes, can be released from the persulfide product of the MPST reaction. Two splice variants of MPST, differing by 20 amino acids at the N terminus, give rise to the cytosolic MPST1 and mitochondrial MPST2 isoforms. Here, we characterized the poorly-studied MPST1 variant and demonstrated that substitutions in its Ser–His–Asp triad, proposed to serve a general acid–base role, minimally affect catalytic activity. We estimated the 3-MP concentration in murine liver, kidney, and brain tissues, finding that it ranges from 0.4 μmol·kg−1 in brain to 1.4 μmol·kg−1 in kidney. We also show that N-acetylcysteine, a widely-used antioxidant, is a poor substrate for MPST and is unlikely to function as a thiophilic acceptor. Thioredoxin exhibits substrate inhibition, increasing the KM for 3-MP ∼15-fold compared with other sulfur acceptors. Kinetic simulations at physiologically-relevant substrate concentrations predicted that the proportion of sulfur transfer to thioredoxin increases ∼3.5-fold as its concentration decreases from 10 to 1 μm, whereas the total MPST reaction rate increases ∼7-fold. The simulations also predicted that cysteine is a quantitatively-significant sulfane sulfur acceptor, revealing MPST's potential to generate low-molecular-weight persulfides. We conclude that the MPST1 and MPST2 isoforms are kinetically indistinguishable and that thioredoxin modulates the MPST-catalyzed reaction in a physiologically-relevant concentration range.




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A single amino acid substitution uncouples catalysis and allostery in an essential biosynthetic enzyme in Mycobacterium tuberculosis [Enzymology]

Allostery exploits the conformational dynamics of enzymes by triggering a shift in population ensembles toward functionally distinct conformational or dynamic states. Allostery extensively regulates the activities of key enzymes within biosynthetic pathways to meet metabolic demand for their end products. Here, we have examined a critical enzyme, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS), at the gateway to aromatic amino acid biosynthesis in Mycobacterium tuberculosis, which shows extremely complex dynamic allostery: three distinct aromatic amino acids jointly communicate occupancy to the active site via subtle changes in dynamics, enabling exquisite fine-tuning of delivery of these essential metabolites. Furthermore, this allosteric mechanism is co-opted by pathway branchpoint enzyme chorismate mutase upon complex formation. In this study, using statistical coupling analysis, site-directed mutagenesis, isothermal calorimetry, small-angle X-ray scattering, and X-ray crystallography analyses, we have pinpointed a critical node within the complex dynamic communication network responsible for this sophisticated allosteric machinery. Through a facile Gly to Pro substitution, we have altered backbone dynamics, completely severing the allosteric signal yet remarkably, generating a nonallosteric enzyme that retains full catalytic activity. We also identified a second residue of prime importance to the inter-enzyme communication with chorismate mutase. Our results reveal that highly complex dynamic allostery is surprisingly vulnerable and provide further insights into the intimate link between catalysis and allostery.




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Building LGBTIQ+ Inclusivity in the Armed Forces, 20 Years After the Ban Was Lifted

16 January 2020

Will Davies

Army Chief of General Staff Research Fellow, International Security Programme
Change was slow to come but progress has since been swift. Not only can a continuing focus on inclusivity benefit service people and the organization, it is also an essential element of a values-based foreign policy.

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Crew members from HMS Westminster march through Admiralty Arch as they exercise their freedom of the city in August 2019 in London. Photo: Getty Images.

The new UK government will conduct a review of foreign, security and defence policy in 2020. If the UK decides to use values as a framework for foreign policy this needs to be reflected in its armed forces. One area where this is essential is continuing to deepen inclusivity for LGBTIQ+ personnel, building on the progress made since the ban on their service was lifted in 2000.

I witnessed the ban first-hand as a young officer in the British Army in 1998. As the duty officer I visited soldiers being held in the regimental detention cells to check all was well. One day a corporal, who I knew, was there awaiting discharge from the army having been convicted of being gay. On the one hand, here was service law in action, which was officially protecting the army’s operational effectiveness and an authority not to be questioned at my level. On the other, here was an excellent soldier in a state of turmoil and public humiliation. How extreme this seems now.

On 12 January 2000 Tony Blair’s Labour government announced an immediate lifting of the ban for lesbian, gay and bisexual personnel (LGB) and introduced a new code of conduct for personal relationships. (LGB is the term used by the armed forces to describe those personnel who had been banned prior to 2000.) This followed a landmark ruling in a case taken to the European Court of Human Rights in 1999 by four LGB ex-service personnel – supported by Stonewall – who had been dismissed from service for their sexuality.

Up to that point the Ministry of Defence's long-held position had been that LGB personnel had a negative impact on the morale and cohesion of a unit and damaged operational effectiveness. Service personnel were automatically dismissed if it was discovered they were LGB, even though homosexuality had been decriminalized in the UK by 1967.

Proof that the armed forces had been lagging behind the rest of society was confirmed by the positive response to the change among service personnel, despite a handful of vocal political and military leaders who foresaw negative impacts. The noteworthy service of LGBTIQ+ people in Iraq and Afghanistan only served to debunk any residual myths.

Twenty years on, considerable progress has been made and my memories from 1998 now seem alien. This is a story to celebrate – however in the quest for greater inclusivity there is always room for improvement.

Defence Minister Johnny Mercer last week apologized following recent calls from campaign group Liberty for a fuller apology. In December 2019, the Ministry of Defence announced it was putting in place a scheme to return medals stripped from veterans upon their discharge.

The armed forces today have a range of inclusivity measures to improve workplace culture including assessments of workplace climate and diversity networks supported by champions drawn from senior leadership.

But assessing the actual lived experience for LGBTIQ+ people is challenging due to its subjectivity. This has not been helped by low participation in the 2015 initiative to encourage people to declare confidentially their sexual orientation, designed to facilitate more focused and relevant policies. As of 1 October 2019, only 20.3 per cent of regular service people had declared a sexual orientation.

A measure of positive progress is the annual Stonewall Workplace Equality Index, the definitive benchmarking tool for employers to measure their progress on LGBTIQ+ inclusion in the workplace; 2015 marked the first year in which all three services were placed in the top 100 employers in the UK and in 2019 the Royal Navy, British Army and Royal Air Force were placed 15th=, 51st= and 68th respectively.

Nevertheless, LGBTIQ+ service people and those in other protected groups still face challenges. The 2019 Ministry of Defence review of inappropriate behaviour in the armed forces, the Wigston Report, concluded there is an unacceptable level of sexual harassment, bullying and discrimination. It found that 26-36% of LGBTIQ+ service people have experienced negative comments or conduct at work because of their sexual orientation.

The Secretary of State for Defence accepted the report’s 36 recommendations on culture, incident reporting, training and a more effective complaints system. Pivotal to successful implementation will be a coherent strategy driven by fully engaged leaders.

Society is also expecting ever higher standards, particularly in public bodies. The armed forces emphasise their values and standards, including ‘respect for others’, as defining organisational characteristics; individuals are expected to live by them. Only in a genuinely inclusive environment can an individual thrive and operate confidently within a team.

The armed forces also recognize as a priority the need to connect to and reflect society more closely in order to attract and retain talent from across all of society. The armed forces’ active participation in UK Pride is helping to break down barriers in this area.

In a post-Brexit world, the UK’s values, support for human rights and reputation for fairness are distinctive strengths that can have an impact on the world stage and offer a framework for future policy. The armed forces must continue to push and promote greater inclusivity in support. When operating overseas with less liberal regimes, this will be sensitive and require careful handling; however it will be an overt manifestation of a broader policy and a way to communicate strong and consistent values over time.

The armed forces were damagingly behind the times 20 years ago. But good progress has been made since. Inclusion initiatives must continue to be pushed to bring benefits to the individual and the organization as well as demonstrate a values-based foreign policy.




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Civil society perspectives on sexual violence in conflict: patriarchy and war strategy in Colombia

4 March 2020 , Volume 96, Number 2

Anne-Kathrin Kreft

In international policy circles, conflict-related sexual violence (CRSV) is commonly viewed as a weapon of war, a framing that researchers have criticized as overly simplistic. Feminist scholars in particular caution that the ‘weapon of war’ framing decontextualizes sexual violence in conflict from the structural factors of gender inequality that underpin its perpetration. In light of these tensions, how do politically relevant local actors perceive the nature and the origins of conflict-related sexual violence? Civil society organizations often actively confront conflict-related sexual violence on the ground. A better understanding of how their perceptions of this violence align or clash with the globally dominant ‘weapon of war’ narratives therefore has important policy implications. Interviews with representatives of Colombian women's organizations and victims' associations reveal that these civil society activists predominantly view conflict-related sexual violence as the result of patriarchal structures. The mobilized women perceive sexual violence as a very gendered violence that exists on a continuum extending through peace, the everyday and war, and which the presence of arms exacerbates. Strategic sexual violence, too, is understood to ultimately have its basis in patriarchal structures. The findings expose a disconnect between the globally dominant ‘weapon of war’ understanding that is decontextualized from structural factors and a local approach to CRSV that establishes clear linkages to societal gender inequality.




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Virtual Roundtable: Evaluating Outcomes in Fragile Contexts: Adapting Research Methods in the Time of COVID-19

Invitation Only Research Event

5 May 2020 - 12:00pm to 1:00pm

Event participants

Rebecca Wolfe, Lecturer, Harris School for Public Policy and Associate, Pearson Institute for the Study and Resolution of Global Conflicts, University of Chicago
Tom Gillhespy, Principal Consultant, Itad
Shodmon Hojibekov, Chief Executive Officer, Aga Khan Agency for Habitat (Afghanistan)
Chair: Champa Patel, Director, Asia-Pacific Programme, Chatham House

This virtual roundtable has been co-convened by Chatham House and the Aga Khan Foundation.  

While conducting research in fragile and conflict-affected contexts has always presented challenges, the outbreak of COVID-19 creates additional challenges including travel restrictions, ethical challenges, and disruptions to usual modes of working. This virtual roundtable will explore how organizations can adapt their research and monitoring and evaluation models in response to the coronavirus pandemic. This event aims to discuss the research methods being used to mitigate the impact of the COVID-19 crisis; the important role of technology; and ways to engage policy and decision-makers during this time.

 

Event attributes

Chatham House Rule

Lucy Ridout

Programme Administrator, Asia-Pacific Programme
+44 (0) 207 314 2761




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Marked reduction in bile acid synthesis in cholesterol 7{alpha}-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia

Margrit Schwarz
Sep 1, 1998; 39:1833-1843
Articles




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A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent

M el-Saadani
Apr 1, 1989; 30:627-630
Articles




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Civil society perspectives on sexual violence in conflict: patriarchy and war strategy in Colombia

4 March 2020 , Volume 96, Number 2

Anne-Kathrin Kreft

In international policy circles, conflict-related sexual violence (CRSV) is commonly viewed as a weapon of war, a framing that researchers have criticized as overly simplistic. Feminist scholars in particular caution that the ‘weapon of war’ framing decontextualizes sexual violence in conflict from the structural factors of gender inequality that underpin its perpetration. In light of these tensions, how do politically relevant local actors perceive the nature and the origins of conflict-related sexual violence? Civil society organizations often actively confront conflict-related sexual violence on the ground. A better understanding of how their perceptions of this violence align or clash with the globally dominant ‘weapon of war’ narratives therefore has important policy implications. Interviews with representatives of Colombian women's organizations and victims' associations reveal that these civil society activists predominantly view conflict-related sexual violence as the result of patriarchal structures. The mobilized women perceive sexual violence as a very gendered violence that exists on a continuum extending through peace, the everyday and war, and which the presence of arms exacerbates. Strategic sexual violence, too, is understood to ultimately have its basis in patriarchal structures. The findings expose a disconnect between the globally dominant ‘weapon of war’ understanding that is decontextualized from structural factors and a local approach to CRSV that establishes clear linkages to societal gender inequality.




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Virtual Roundtable: The End of Globalism? Remaining Interconnected While Under Increased Pressure to Isolate

Invitation Only Research Event

30 March 2020 - 1:00pm to 2:00pm

Zoom Audio Call

Event participants

Fred Hochberg, Chairman and President, Export-Import Bank of the United States, 2009 -17
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House

This event is part of the Chatham House Global Trade Policy Forum. We would like to take this opportunity to to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc and EY for their generous support of the forum. 

US and Americas Programme




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In Search of the American State

6 April 2020

Dr Leslie Vinjamuri

Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme
The urgent need for US leadership to drive forward a coordinated international response to coronavirus is developing rapidly alongside snowballing demands for Washington to step up its efforts at home.

2020-04-06-US-covid-washington

Exercising in front of a deserted Lincoln Memorial in Washington, DC. Photo by Win McNamee/Getty Images.

As the US surgeon general warns Americans to brace for ‘our Pearl Harbor moment’, the US faces a week in which it may see the worst of the global pandemic. The absence of US leadership at the global level has enabled the Security Council’s inaction. And at the G7, President Trump actively obstructed efforts to agree a joint statement.

US efforts to increase its support of international aid to the tune of $274million are minimal, not least in light of a 50% reduction in its support for the World Health Organization (WHO) and radically diminished support for other global health programmes as well. International coordination is essential to mitigate unregulated competition for critical medical supplies, manage border closures, and guarantee international economic stability.

True, it won’t be possible to control the epidemic at home if the global effort to defeat the pandemic fails. But the absence of leadership from Washington at home is palpable. And what happens at home sets a natural limit on America’s internationalism.

Both solution and problem

In response to the coronavirus crisis, the US state is proving to be a solution - and a problem. The dramatic response to the economic crisis is evident with the $2.3trillion stimulus package signed into law by President Trump boldly supported by both Democrats and Republicans in the most significant piece of bipartisan legislation passed in decades.

America’s political economy is unrecognisable, moving left and looking increasingly more European each week as Congress and the executive branch agree a series of stimulus packages designed to protect citizens and businesses. Some elements of this legislation were more familiar to Americans, notably $200bn in corporate tax breaks.

But Congress also agreed unemployment insurance, and cheques - one in April, one in May – to be sent directly to those Americans most directly hit by the economic impact of COVID-19. In effect, this is adopting a temporary universal basic income.

The stimulus plan also dedicated $367bn to keep small businesses afloat for as long as the economy is shuttered. Already the government is negotiating a fourth stimulus package, but the paradox is that without rigorous steps to halt the health crisis, no level of state intervention designed to solve the economic response will be sufficient.

The scale of the state’s economic intervention is unprecedented, but it stands in stark contrast to Washington’s failure to coordinate a national response to America’s health crisis. An unregulated market for personal protective equipment and ventilators is driving up competition between cities, states, and even the federal government.

In some cases, cities and states are reaching out directly beyond national borders to international organisations, foreign firms and even America’s geopolitical competitors as they search for suppliers. In late March, the city of New York secured a commitment from the United Nations to donate 250,000 protective face masks.

Now Governor Cuomo has announced New York has secured a shipment of 140 ventilators from the state of Oregon, and 1,000 ventilators from China. The Patriots even sent their team plane to China to pick up medical supplies for the state of Massachusetts. And following a phone call between President Putin and President Trump, Russia sent a plane with masks and medical equipment to JFK airport in New York.

Networks of Chinese-Americans in the United States are rapidly mobilising their networks to access supplies and send them to doctors and nurses in need. And innovative and decisive action by governors, corporates, universities and mayors drove America’s early response to coronavirus.

This was critical to slowing the spread of COVID-19 by implementing policies that rapidly drove social distancing. But the limits of decentralized and uncoordinated action are now coming into sharp focus. President Trump has so far refused to require stay-at-home orders across all states, leaving this authority to individual governors. Unregulated competition has driven up prices with the consequence that critical supplies are going to the highest bidder, not those most in need.

Governor Cuomo’s call for a nationwide buying consortium has so far gone unheeded and, although the Federal Emergency Management Agency has attempted to deliver supplies to states most in need, the Strategic National Stockpile is depleting fast. Without critical action, the federal government risks hindering the ability of cities and states to get the supplies they need.

But President Trump is reluctant to fully deploy his powers under the Defense Production Act (DPA). In March, he did invoke the DPA to require certain domestic manufacturers to produce ventilators. But calls for it to be used to require manufacturers to produce PPE (personal protective equipment), control costs, and manage allocations has so far gone unheeded by a president generally opposed to state interventions for managing the economy.

It is true that federalism and a deep belief in competition are critical to the fabric of US history and politics, and innovations made possible by market values of entrepreneurism and competition cannot be underestimated. In the search for a vaccine, this could still prove to be key.

But with current estimates that more Americans will die from coronavirus than were killed in the Korean and Vietnam wars combined, it is clear now is the time to reimagine and reinvent the role of the American state.

In the absence of a coordinated effort driven by the White House, governors are working together to identify the areas of greatest need. Whether this will lead to a recasting of the American state and greater demand for a deeper and more permanent social safety net is a key question in the months ahead.

In the short-term the need for coordinated state action at the national level is self-evident. US leadership globally, to manage the health crisis and its economic impacts, is also vital. But this is unlikely to be forthcoming until America gets its own house in order.




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Virtual Roundtable: Evaluating Outcomes in Fragile Contexts: Adapting Research Methods in the Time of COVID-19

Invitation Only Research Event

5 May 2020 - 12:00pm to 1:00pm

Event participants

Rebecca Wolfe, Lecturer, Harris School for Public Policy and Associate, Pearson Institute for the Study and Resolution of Global Conflicts, University of Chicago
Tom Gillhespy, Principal Consultant, Itad
Shodmon Hojibekov, Chief Executive Officer, Aga Khan Agency for Habitat (Afghanistan)
Chair: Champa Patel, Director, Asia-Pacific Programme, Chatham House

This virtual roundtable has been co-convened by Chatham House and the Aga Khan Foundation.  

While conducting research in fragile and conflict-affected contexts has always presented challenges, the outbreak of COVID-19 creates additional challenges including travel restrictions, ethical challenges, and disruptions to usual modes of working. This virtual roundtable will explore how organizations can adapt their research and monitoring and evaluation models in response to the coronavirus pandemic. This event aims to discuss the research methods being used to mitigate the impact of the COVID-19 crisis; the important role of technology; and ways to engage policy and decision-makers during this time.

 

Event attributes

Chatham House Rule

Lucy Ridout

Programme Administrator, Asia-Pacific Programme
+44 (0) 207 314 2761




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Undercurrents: Episode 2 – The Calabrian Mafia and Transatlantic Relations




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Undercurrents: Episode 3 – Duterte’s War on Drugs, and European Security




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Undercurrents: Episode 4 – Illegal Hospital Detentions in Africa, and LGBTQ+ Rights in Lebanon




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Undercurrents: Episode 5 - Chokepoints in Global Food Trade, and How the Internet is Changing Language




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Undercurrents: Episode 6 - Tribes of Europe, and the International Women's Rights Agenda at the UN




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Undercurrents: Episode 7 - Libya's War Economy, and Is the United Nations Still Relevant?




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Undercurrents: Episode 8 - Ronan Farrow on Diplomacy




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Undercurrents: Episode 9 - Digital Subversion in Cyberspace, and Oleg Sentsov's Hunger Strike




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Undercurrents: Episode 10 - Artificial Intelligence in International Affairs, and Women Drivers in Saudi Arabia




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Undercurrents: Bonus Episode - How Can Political Elites Reconnect With Voters?




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Undercurrents: Episode 11 - New Approaches to Peacebuilding, and Gender-Inclusive Growth at the G20




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How to Fix Finance by Reinforcing Human Rights




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Undercurrents: Episode 12 - Trump's Visit to the UK, and Japanese Foreign Policy in Asia




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Undercurrents: Episode 13 - India's Billionaires, and Sexual Exploitation in the UN




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Undercurrents: Episode 14 - Sustainable Energy for Refugees and Australian Foreign Policy




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Undercurrents: Episode 15 - Brexit Update, and Corruption in the World of the Global Super-Rich




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Undercurrents - Episode 16: Cybercrime in the GCC States, and Fiction from Refugee Camps




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Undercurrents: Episode 17 - Alastair Campbell on New Labour and Brexit, Alistair Darling on the Financial Crisis




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Managing the Real and Perceived Challenges Facing the World




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Undercurrents: Episode 18 - The American Dream vs America First, and Uganda's Illegal Ivory Trade




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Undercurrents: Episode 19 - Green Building Projects in Jordan, and Qatar's Football World Cup




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Undercurrents: Episode 20 - #MeToo and the Power of Women's Anger




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Undercurrents: Episode 21 - EU-US Relations after the Midterms, and Tackling the Illegal Wildlife Trade in Africa




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Women in the Armed Forces: Improving Integration




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Undercurrents: Episode 22 - China's Belt and Road Initiative, and the Rise of National Populism




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Undercurrents: Episode 23 - Robin Niblett on the Future of Think-Tanks




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Dark Commerce: Technology’s Contribution to the Illegal Economy