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Shaping modern Britain: the role of African and Caribbean communities

Shaping modern Britain: the role of African and Caribbean communities 24 October 2024 — 5:00PM TO 6:00PM Anonymous (not verified) Chatham House and Online

As part of Black History Month, this event celebrates the enduring contributions of African and Caribbean communities to the UK.

When British colonial rule ended, newly independent countries in Africa and the Caribbean retained influences such as the English language and governance systems modelled on that of the UK. Initially, these post-independence relations were largely marked by the UK’s soft power, shaping the nation-building processes in these regions.

Over time, however, this influence has become a two-way exchange. African and Caribbean cultures have profoundly shaped modern Britain – from music and food to sports, arts, literature and beyond. These evolving dynamics have not only enriched the UK’s cultural landscape but also provided significant benefits for diaspora communities, fostering a sense of belonging and promoting cultural exchange. Diaspora groups and civil society organizations have adeptly utilised these connections to advocate for their communities and advance their interests.

At this event, speakers will explore how African and Caribbean influences rose to prominence in the UK and how this cultural momentum can be harnessed to build stronger, forward-looking partnerships. By highlighting the shared histories and more vibrant present-day exchanges, this event will explore how these ties can be used to break down stereotypes, promote social cohesion, and contribute to a more inclusive future.

This event forms part of our series of events celebrating Black History Month, including a photo exhibition and drinks reception.




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Is the world ready for the next pandemic?

Is the world ready for the next pandemic? 29 October 2024 — 6:00PM TO 7:00PM Anonymous (not verified) Chatham House and Online

In a joint event with The Elders, Helen Clark, Ban Ki-moon and other experts discuss the policies needed to prevent the next health catastrophe. A drinks reception will follow this event.

The world faces multiple interlinked existential threats such as pandemics and the climate crisis, exacerbated by conflict and extreme poverty. However, the multilateral system is failing to respond with sufficient urgency or impact. As the fifth anniversary of the COVID-19 pandemic approaches, Chatham House and The Elders will discuss the risk of a general slide into complacency. 

Amid the expanding outbreak of mpox in Africa, rich countries continue to withhold stockpiled mpox vaccines. The failure to release the required amount is contributing to the diseases spread across the continent. 

Meanwhile, the Pandemic Accord negotiations are in overtime, with nations unable to reach agreement over concerns around sovereignty and resource distribution in any future pandemic. Similarly, a proposal to include a UN Emergency Platform in the recent Summit of the Future to strengthen the multilateral response to complex global shocks was shelved due to political deadlock.

Can the world learn from past mistakes and break the cycle of panic and neglect? In today’s fractious and polarized geopolitical context, what would it take for leaders to do what’s necessary? And why is it so critical to have equity at the heart of any sustainable global response?

Join Chatham House for this event in which the panel discuss key questions including:

  • Five years on from COVID-19, who is showing global leadership today in preparing for future pandemics?
  • Are international organizations and institutions fit for purpose to respond to pandemics in a multipolar geopolitical environment? How can they best adapt?
  • What can be done to clarify and detoxify current debates around sovereignty to improve global pandemic prevention, preparedness and response?

A post-event reception will follow this event. This is open to members only.

Individual membership provides you with the complete Chatham House experience, connecting you with a unique global policy community. Find out more about membership.




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Reply to Sysel et al.: Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor]

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...




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Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor]

After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5).




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Hdac3 regulates bone modeling by suppressing osteoclast responsiveness to RANKL [Signal Transduction]

Hdac3 is a lysine deacetylase that removes acetyl groups from histones and additional proteins. Although Hdac3 functions within mesenchymal lineage skeletal cells are defined, little is known about Hdac3 activities in bone-resorbing osteoclasts. In this study we conditionally deleted Hdac3 within Ctsk-expressing cells and examined the effects on bone modeling and osteoclast differentiation in mice. Hdac3 deficiency reduced femur and tibia periosteal circumference and increased cortical periosteal osteoclast number. Trabecular bone was likewise reduced and was accompanied by increased osteoclast number per trabecular bone surface. We previously showed that Hdac3 deacetylates the p65 subunit of the NF-κB transcriptional complex to decrease DNA-binding and transcriptional activity. Hdac3-deficient osteoclasts demonstrate increased K310 NF-κB acetylation and NF-κB transcriptional activity. Hdac3-deficient osteoclast lineage cells were hyper-responsive to RANKL and showed elevated ex vivo osteoclast number and size and enhanced bone resorption in pit formation assays. Osteoclast-directed Hdac3 deficiency decreased cortical and trabecular bone mass parameters, suggesting that Hdac3 regulates coupling of bone resorption and bone formation. We surveyed a panel of osteoclast-derived coupling factors and found that Hdac3 suppression diminished sphingosine-1-phosphate production. Osteoclast-derived sphingosine-1-phosphate acts in paracrine to promote bone mineralization. Mineralization of WT bone marrow stromal cells cultured with conditioned medium from Hdac3-deficient osteoclasts was markedly reduced. Expression of alkaline phosphatase, type 1a1 collagen, and osteocalcin was also suppressed, but no change in Runx2 expression was observed. Our results demonstrate that Hdac3 controls bone modeling by suppressing osteoclast lineage cell responsiveness to RANKL and coupling to bone formation.




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FUS contributes to mTOR-dependent inhibition of translation [Signal Transduction]

The amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)–linked RNA-binding protein called FUS (fused in sarcoma) has been implicated in several aspects of RNA regulation, including mRNA translation. The mechanism by which FUS affects the translation of polyribosomes has not been established. Here we show that FUS can associate with stalled polyribosomes and that this association is sensitive to mTOR (mammalian target of rapamycin) kinase activity. Specifically, we show that FUS association with polyribosomes is increased by Torin1 treatment or when cells are cultured in nutrient-deficient media, but not when cells are treated with rapamycin, the allosteric inhibitor of mTORC1. Moreover, we report that FUS is necessary for efficient stalling of translation because deficient cells are refractory to the inhibition of mTOR-dependent signaling by Torin1. We also show that ALS-linked FUS mutants R521G and P525L associate abundantly with polyribosomes and decrease global protein synthesis. Importantly, the inhibitory effect on translation by FUS is impaired by mutations that reduce its RNA-binding affinity. These findings demonstrate that FUS is an important RNA-binding protein that mediates translational repression through mTOR-dependent signaling and that ALS-linked FUS mutants can cause a toxic gain of function in the cytoplasm by repressing the translation of mRNA at polyribosomes.




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Water, Ecosystems and Energy in South Asia: Making Cross-Border Collaboration Work

Water, Ecosystems and Energy in South Asia: Making Cross-Border Collaboration Work Research paper sysadmin 29 June 2016

A new paper sets out the factors that have made previous cross-border projects in South Asia successful, arguing that cooperation around water is feasible despite the region’s political differences and economic assymetries.

Indian people walk in the Ganga riverbed in Allahabad on 1 September 2015. Photo: Getty images.

  • The countries of South Asia share some of the world’s major river basins – the Ganga (or Ganges), the Brahmaputra and the Indus. These rivers and their tributaries flow through seven countries, support more than 1 billion people, irrigate millions of hectares of land and are of cultural importance to many of those who rely on them.
  • River management presents common challenges across the region. These include physical factors such as droughts, flooding, cyclones and climate change, as well political and institutional factors impeding the development of solutions and policies to improve resource management and reduce vulnerability. Water is increasingly seen as a source of competition, with population growth, industrialization and urbanization exacerbating the pressures on supply.
  • Although South Asian examples of regional cooperation in general are limited, there is a clear positive trend. In areas such as disaster response and cross-border power trading, regional and bilateral engagement is beginning to take place. Multilateral official arrangements exist for trade and other economic issues, but there is none on water or ecosystems. However, as the benefits from cooperation become proven, its desirability is likely to gradually enter mainstream policy thinking on water issues.
  • This research paper sets out the factors that have enabled cooperation, and the processes adopted, in previous successful cross-border projects. It focuses on four categories of cooperation: development of early-warning systems for natural disasters, in particular floods; protection of cross-border ecosystems; sharing of learning, through the showcasing of innovative approaches in one country that can be adopted by others; and power trading, in particular the development of hydropower in Bhutan and its export to India.
  • The paper argues that cooperation around water in South Asia is feasible despite political differences and economic asymmetries. Different forms of collective action, and common understanding of both the threats and the shared benefits from cooperation, are required to foster more partnerships within the river basin states.




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Development Prospects in the Asia-Pacific: The Role of the Asian Development Bank

Development Prospects in the Asia-Pacific: The Role of the Asian Development Bank 25 September 2019 — 12:30PM TO 1:30PM Anonymous (not verified) 4 September 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

The speaker will discuss development prospects in the Asia-Pacific and their implications for Europe and the UK. He will outline prospects for the region’s growth, the impact of the current US-China trade conflict as well as other challenges faced by the region. He will also discuss the future role of the Asian Development Bank and how it plans to support the further development of the region.




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International relations: The ‘how not to’ guide

International relations: The ‘how not to’ guide Expert comment NCapeling 11 October 2022

A centenary special issue of International Affairs explores past foreign policy failures to help policymakers avoid future catastrophes.

Policy decisions in international relations frequently have a long-lasting effect on the world order, shaping the lives of millions. Often acting under pressure and severe time constraints, decision-makers must rely on their own experience and the best expertise available. And so, despite many striving for a more peaceful and prosperous world, policy failures are all too common.

The second of International Affairs’ centenary special issues – devised and guest-edited by Amrita Narlikar and Daniel W. Drezner – is a ‘how not to guide’ for international relations. Focusing on historic failures, 14 experts examine what went wrong, and how policy practitioners and researchers can get it right together.

Between theory and outcome fall two ‘shadows’: one of decision-makers not taking advantage of sound academic policy advice – in some cases ignoring it because they think they already know best – and a second of bias in academic analyses and researchers simply erring, or erring on the side of their own self-importance. Between these two, there lies a joint path toward better policies.

The special issue provides policymakers with cautionary lessons, transforming well-known cases into a guide of what not to do in international politics. Building on that, the collection also suggests ways forward, including borrowing the medical Hippocratic Oath of ‘do no harm’, which in international relations serves as a cautionary warning against action merely for action’s sake, and then going decidedly beyond this minimum requirement.

A series of comics also accompanies the articles, produced in collaboration with Sequential Potential comics.

In their introduction, Drezner and Narlikar draw out four overarching factors which increase the likelihood of foreign policy failure – these are a focus on short-term successes, underestimating the power of narratives, hubris, and technocratic bubbles. If academics and policymakers can work together with these careful considerations, perhaps mistakes can avoid being repeated.

Richard Toye examines three pivotal moments in the UK’s history – the Munich crisis of 1938, the Suez crisis and war of 1956, and the Iraq war of 2003. He finds that in these cases the failures were over-determined, a consequence of Britain’s relative decline rather than its cause.

Daniel W. Drezner reviews two high profile failures of sanction use – United Nations (UN) sanctions on Iraq during the two Gulf wars, and the US re-imposition of sanctions on Iran in 2018. In both cases the main goals were not achieved and the costs were great. Drezner highlights ten ‘do’s and don’ts’ for sanctions as a result.

Amrita Narlikar shows how the World Trade Organization (WTO) has become an almost perfect example of how not to negotiate, even when taking into account recent limited successes. She identifies three broad categories of bargaining failures and explores the impact of narratives on the course of events, giving a clear list of do’s and don’ts for international negotiation.

Harold James also looks at three historic moments, the financial crises in 1931, 1997, and 2008. While responses to the crises initially looked successful, ironically in each case the drive to avoid past mistakes opened the door for the next crisis.

Cecilia Emma Sottilotta considers recent disasters in the European Union (EU) – the eurozone crisis and COVID-19 pandemic – and recommends for policymakers to find a middle ground between supranationalism and intergovernmentalism in crisis situations.

The growth of Chinese influence is a key issue in international relations today. Various articles in the special issue explain how not to deal with a rising China, coming from different angles. Exploring the US-China relationship, Janice Gross Stein is critical of the narrative around US decline and Chinese growth. The world should look beyond GDP as an indicator of a country’s growth and pay attention to strategic choices made by leaders in both states.

Joseph S. Nye Jr also provides a US perspective, arguing that while some historic analogies are misleading, the US should contemplate the cautionary narrative of sleepwalking into World War One when thinking about its relationship with China.

Amitabh Mattoo gives a south Asian view, asserting there is a need to understand Chinese policies in the region. Through examining China’s relations with India, Pakistan, and Sri Lanka he concludes that because China is adopting aggressive policies in the region, states must start cooperating with like-minded allies.

Yuen Foong Khong answers two questions in his paper tackling which ‘how not to’s’ are relevant when learning from history, and whether policymakers are aware of them. His research points to four things to avoid, which he then applies to how the Cold War analogy is used to understand contemporary US-China relations.

On the theme of foreign interference, Igor Istomin looks at the Soviet support for Mao Zedong’s Communist Party in the 1920s to 1940s. He argues strongly against interfering with major powers, as short-term gains cannot last.

From Iraq and Afghanistan to Somalia and the Balkans, there have been many failed interventions by the West since the end of the Cold War. Stephanie Carvin asserts the overreliance on automated weaponry has allowed supposedly ‘easy wars’ to turn into ‘forever wars’ – and this is not likely to stop.




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America’s vote shows a desire for stability and calm

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

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

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

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

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

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

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

Trump’s influence is on the wane

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

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

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

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

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

Biden is still in the saddle and, instead of a battle for control inside the Democratic party, it is the Republicans who look set to descend into internal conflict and recrimination

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

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

Inflation and the economy proved key factors

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

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

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

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

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

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




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Next steps for EU-US cooperation on trade and technology

Next steps for EU-US cooperation on trade and technology 8 December 2022 — 3:00PM TO 4:00PM Anonymous (not verified) 21 November 2022 Online

How can the EU and US increase cooperation on AI, semi-conductors and funding information communication technology services?

On trade and technology policy, the EU and the US are making meaningful progress towards cooperation while at the same time navigating tensions. As senior officials meet on 5 December for the third meeting of the Trade and Technology Council (TTC), both sides have vowed to move towards concrete results. But can the US and EU increase cooperation on artificial intelligence, semiconductors, and funding information communication technology services? 

This event draws on insights from a forthcoming Briefing Paper by Marianne Schneider-Petsinger that explores next steps for US-EU cooperation on trade and technology, which is part of a project supported by the Hanns Seidel Foundation. 




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World in brief: Biden seeks to win over African leaders

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

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

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

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

Africa’s cooling relations with the US 

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

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

The US and an international system supports autocratic and dysfunctional governments – we can’t continue this way

Kah Walla, president of the Cameroon People’s Party

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

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

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

The US is losing out to China in Africa

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

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




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The near death and uncertain future of the US National Security Council

The near death and uncertain future of the US National Security Council 27 January 2023 — 9:00AM TO 10:00AM Anonymous (not verified) 9 January 2023 Chatham House

What role should the US National Security Council play in an era of great power competition?

Please plan to arrive at Chatham House from 08:45 GMT as the event will begin promptly at 09:00 GMT

Over the last three years, the US National Security Council (NSC) has gone from being neglected to necessary again, in Washington.

After former US President Donald Trump ignored and then tried to dismantle the NSC, current US President Joe Biden has restored the body but chosen not to reform it.

Born in the days before the Cold War and empowered during the War on Terror, what role should the NSC play in an era of great power competition?

Plus, how must it, and the rest of Washington, evolve to meet the challenges and opportunities that remain in the 21st century?




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Digital politics threatens democracy and must change

Digital politics threatens democracy and must change Expert comment NCapeling 13 January 2023

Violence in Brazil has again brought into focus the need for technology platforms to prioritize social responsibility to help prevent anti-democratic action.

Immediately following the violent storming of Brazil’s congressional building, supreme court, and presidential palace, comparisons to the infamous events of 6 January 2021 in the US came quickly and easily – and with good reason.

Both Donald Trump and Jair Bolsonaro built a fervent – albeit inchoate – political base of grievance which included Christian evangelicals, gun enthusiasts, and the disenfranchised. Both cynically spread doubts about the election victories of their successors without evidence. And it has been claimed both incited their supporters to overturn these results.

But this list of similarities extend beyond mere politics. The attack on democracy in Brazil was recorded, amplified, coordinated, and funded by exactly the same technologies used by the protesters in the US on 6 January.

In Brazil, the main engines of misinformation and insurrection planning were Telegram, Facebook, and WhatsApp, although some election-denying diehards also shifted to Twitter.

Tactical use of social media to mobilize and fundraise

When Bolsonaro was originally elected in 2018, these platforms were already a medium for promoting disinformation, conspiracy, and fear. But in the lead-up to the violence of 8 January, they became a means by which ‘Bolsonaristas’ raised funding for an attack and mobilized supporters to come to Brasilia – advertising the availability of buses and even free food for marchers – using the Festa da Selma hashtag.

Well-intentioned regulation will fall short so long as it is narrowly focused on a never-ending game of ‘content whack-a-mole’ and is hamstrung by powerful voices

To avoid detection by authorities, organizers used a simple switch of the letter ‘v’ to ‘m’ so that Selva, meaning ‘jungle’, became Selma – which means ‘party in the jungle’ to those in the know. But the authorities in the Brasilia state of Distrito Federal appeared to care little about preventing the attack anyway.

Civil society organizations have warned for decades that policies made in a Silicon Valley boardroom fit poorly to the realities of countries such as Brazil, Somalia, or Myanmar. Content moderation is a near-impossible task at the scale demanded by platforms as vast as those operated by big tech, and automated solutions are far from being a silver bullet as they create as many problems as they solve.

Extremism has found an unfettered enabler on mainstream platforms, and an increasingly sprawling network of alternative tech has made such voices resilient to challenge. Platforms such as Gettr, Gab, and Telegram have become go-to platforms for extremist networks when fringe voices find themselves blocked by mainstream platforms.

Telegram has come under significant scrutiny for the role it played in the storming of Congress in Brasilia but any number of tools and platforms – each with millions of users – could have achieved similar results.

The sordid events in Brasilia are just the latest chapter in digital extremism and conspiracy- mongering which often erupts into anti-democratic violence, and should serve as a reminder of the urgent risks of disinformation and the role digital technology plays in inciting, coordinating, fundraising, and amplifying such events.

But the checks on the power of private social media companies are still few and splintered. In Brazil, Supreme Court Justice Alexandre de Moraes, head of the elections tribunal, attempted to crack down on social media, banning users for spreading misinformation in a move which sparked complaints of censorship from Bolsonaro supporters.

Following the elections, Moraes has advocated for greater judicial authority to regulate social media – but the justice is only one person and his impartiality is already being challenged given his aggressive pursuit of Bolsonaro supporters posting inflammatory messages.

And one justice doing it alone only inflames an already volatile situation. Effective regulation of social media requires an independent body vested with multiparty support and operating under clearly-defined rules and authority.

A global movement to find solutions

Brazil is not alone in an increasingly frantic search for checks on digital power as dozens of regulatory regimes are springing up around the world. All are premised on platforms being responsible for their own fiefdoms, but few tackle the threat posed to democracy by unchecked corporate power over digital commons.

Telegram has come under significant scrutiny for the role it played in the storming of Congress in Brasilia but any number of tools and platforms – each with millions of users – could have achieved similar results

Well-intentioned regulation will fall short so long as it is narrowly focused on a never-ending game of ‘content whack-a-mole’ and is hamstrung by powerful voices who see any rules as an attack on freedoms of expression or corporate decision-making.

Democracies are traditionally cautious in managing speech, in separating good information from bad information, or in defining acceptable politics. The steady watering down of the UK’s Online Safety Bill, now so thin on disinformation as to be essentially homeopathic, shows that democratic regulation is willing to go only so far in tackling challenges posed by digital politics.




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National security and transatlantic unity top Biden’s agenda

National security and transatlantic unity top Biden’s agenda Expert comment NCapeling 1 February 2023

The timing of the State of the Union address is significant as Joe Biden tries to maintain focus on Ukraine and China while navigating partisanship at home.

Although primarily a domestic affair, the president’s remarks in the annual State of the Union (SOTU) telegraph the US’s foreign policy priorities to the rest of the world. They reveal the prism through which the US understands its national security and its role in the world.

The 2023 address comes as the first anniversary of the Ukraine invasion rapidly approaches, and the US is also trying to build international support for tough economic measures towards China. Domestically, Republican control of the House of Representatives will exert new pressure on US foreign policy choices. Electoral pressures are also around the corner and Joe Biden should announce soon whether he plans to run for president in 2024.

Alliances and partnerships are a driving force for Biden. As pressure to end the war in Ukraine intensifies, maintaining transatlantic unity on Ukraine will be a key priority for the president. And as US electoral politics rise to the fore, ensuring the visibility of Europe’s role as a security provider in its own backyard will be essential.

For a US president who sees China and the Indo-Pacific as America’s most significant long-term geopolitical challenge – and the only peer competitor to the US – transatlantic unity on China will also come under pressure.

Ukraine, China, and controlling domestic division

Republican leaders who now chair key committees in the House of Representatives continue to signal support for Ukraine, and polling shows a majority of US public opinion (54 per cent) favours sending either weapons or air defence systems.

But recent polls also reveal a growing gap between Democrat and Republican supporters with a slight majority of Republicans (52 per cent) now opposing further support for Ukraine.

Biden’s ability to demonstrate that America and its European partners remain unified in their policy towards Ukraine and Russia will help him ward off partisanship at home. Congressional approval of $45 billion for Ukraine in its end of year spending budget will help the president remain above the fray of partisan politics for now. But if there is an absence of clear signs Ukraine is succeeding in its war aims, the challenge of maintaining domestic support could become more difficult.

Bipartisanship is strong on China, Republicans are more singular and hawkish in their approach to China than the US president, and the public support tough measures

A greater US focus on China, India, and on the Indo-Pacific in 2023 is also likely. Bipartisanship is strong on China, Republicans are more singular and hawkish in their approach to China than the US president, and the public support tough measures. At a time of war in Europe, the president will place great emphasis on the need to maintain transatlantic unity and to work with a broader coalition of partners in the Indo-Pacific.

The groundwork for focus on China has already been laid. Throughout 2022, the Biden administration worked steadily, but quietly, to set out its China policy. Just before Russia’s invasion of Ukraine in February 2022, the US released its new US-Indo Pacific Strategy stressing regional partnerships – especially the Quad and ASEAN – and it’s determination to shape essential norms for the region.

It stated boldly – albeit in a document which was largely unnoticed – that the objective is not to change China but to ‘shape the strategic environment in which it operates’, a policy which signifies a clear departure from the more ideological approach pursued by the US during Donald Trump’s final year in office. And in May, the US announced its economic strategy for the region, the Indo-Pacific Economic Framework.

Now the terrain for competition with China and alignment with US partners and allies is heavily focused on technology and the daylight between national security and economic strategy in US China policy is rapidly disappearing. Biden’s policy focus of ‘invest (at home), align (with allies and partners), and compete (with China)’ has overshadowed earlier talk of cooperation between the US and China.

Those listening carefully to the State of the Union and who have followed US policy will also note the unchallenged hegemony of neoliberalism is rapidly vanishing

But as China opens its doors and Europe looks to bolster its economies, the US will have to work far harder to maintain transatlantic unity. Japan and the Netherlands embracing the US adoption of export controls on semiconductor chips is a positive sign, but the US’s economic strategy towards China may present harder choices to come for Europe. If China leans into its diplomacy, the pressure on transatlantic unity will also grow.

The new US Congress will only sharpen the president’s tough stance on China. Some Republican leaders still deny climate change and have demonstrated little interest in cooperating with China on debt relief for developing countries. The prospects for addressing critical global challenges appear dim without China’s collaboration, and the UK and Europe should work with the US president and Congress to correct this.

President Biden has clearly recognized that diplomacy will be critical in the months ahead. At a time of growing tensions, the potential for misperceptions or misunderstandings to create conflict will also increase, and so a US – and also European – commitment to broadening and deepening diplomacy with China is urgent but it also needs to be patient and sustained.

A new American industrial policy?

Those listening carefully to the State of the Union and who have followed US policy will also note the unchallenged hegemony of neoliberalism is rapidly vanishing. The American state appeared to be disturbingly absent in the early months of the US pandemic response – but now it is back and, in a surprising turn of events, is being cast as a solution not a problem.




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World economy is fracturing, not deglobalizing

World economy is fracturing, not deglobalizing Expert comment LJefferson 8 February 2023

Geopolitics are creating a more uncertain economic environment as the global economy splinters into competing blocs.

There is now broad agreement among economists and commentators that the world has reached peak globalization, but there is little consensus about what comes next. One view is that we are entering a period of ‘deglobalization’, in which global trade volumes decline and cross-border capital flows recede. An alternative and more likely outcome is that the global economy starts to splinter into competing blocs.

This would result in an altogether more volatile macroeconomic and market environment which would pose a formidable challenge to some countries and companies operating in vulnerable sectors. But this process needn’t involve any significant shrinkage of international flows of goods, services and capital, nor a broad reversal of other gains of globalization.

Whereas the period of globalization was driven by governments and companies working in unison, fracturing is being driven by governments alone. 

This most recent era of globalization was underpinned by a belief that economic integration would lead to China and the former Eastern Bloc countries becoming what former World Bank Chief Robert Zoellick termed ‘responsible stakeholders’ within the global system.

But China has instead emerged as a strategic rival to the US. This strategic rivalry is already forcing others to pick sides as the world splinters into two blocs: one that aligns primarily with the US and another that aligns primarily with China.

Increasingly, policy choices within these blocs will be shaped by geopolitical considerations. This process can be thought of as ‘global fracturing’. Whereas the period of globalization was driven by governments and companies working in unison, fracturing is being driven by governments alone. 

The effects of fracturing

Viewed this way, ‘deglobalization’ is by no means inevitable. There are few compelling geopolitical reasons why the US or Europe should stop importing the majority of consumer goods from China. Roll the clock forward ten years and it is likely that the West will still be buying toys and furniture from China. Instead, fracturing between the blocs will take place along fault lines that are geopolitically important.

In some aspects, the effects of fracturing will be profound. But in other areas, warnings of a seismic reordering of the global economy and financial system will prove wide of the mark.

For example, the politically-driven nature of fracturing will have a significant impact on the operating environment for US and European firms in those sectors that are most exposed to restrictions on trade, such as technology and pharmaceuticals. And all firms and investors will be operating in a different environment in which geopolitical considerations play a greater role in decisions over the allocation of resources.

In cases where production does shift location, it is likely to be to other low-cost centres that align more clearly with the US. There will be no great ‘reshoring’ of manufacturing jobs.

But where production is moved to alternative locations, this is likely to only involve the manufacture of goods that are deemed to be strategically significant. This may include those with substantial technological and/or intellectual property components: think iPhones, pharmaceuticals, or high-end engineering products.

What’s more, in cases where production does shift location, it is likely to be to other low-cost centres that align more clearly with the US. There will be no great ‘reshoring’ of manufacturing jobs.

Within this process, trade linkages will be reordered, rather than severed. This will result in trade’s share of global GDP flatlining in the coming years, rather than shrinking outright, as is being forecast under many attempts to quantify deglobalization’s potential impact.

Finances of global fracturing

There will be a substantial financial component to global fracturing, but once again the implications are likely to be more nuanced than the current debate suggests. Cross-border financial links are likely to grow more slowly, and the overall stock of cross-border claims will plateau relative to global GDP. But whereas the first era of globalization in the 1870s was followed by a broad retreat in global capital flows during the interwar years, the same is unlikely to happen today.

Beijing will increasingly push its partners to settle trade in renminbi but this is unlikely to seriously challenge the dollar’s position.

Similarly, while financial fracturing will fuel growing speculation about the dollar’s role as the world’s reserve currency, reports of its impending demise are exaggerated. Beijing will increasingly push its partners to settle trade in renminbi but three factors suggest that this is unlikely to seriously challenge the dollar’s position.

First, while trade between China and its partners is growing, it still accounts for only six per cent of global trade. Most trade still happens between US-aligned countries, and will continue to be denominated in US dollars (see chart).

Second, China runs a large current account surplus, which will make it harder for the renminbi to supplant the dollar. High demand for reserve assets means that reserve countries tend to run current account deficits. 

Share of global goods and services trade (%) Source: Capital Economics

Finally, the dollar still has several things working in its favour. For a currency to be widely used as an international medium of exchange, it must be readily and cheaply available around the world. In turn, that depends on foreigners being willing to hold it in large volumes: in other words, it must function as a store of value. 




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Divided US support shows time is not on Ukraine’s side

Divided US support shows time is not on Ukraine’s side Expert comment LJefferson 17 February 2023

Growing public opinion evidence and uncertainty about the future of the war suggests that continued American support for aiding Ukraine should not be assumed.

One year into Russia’s war on Ukraine, fears that American support for Kyiv would rapidly wane have proven demonstrably wrong. Western financial and military backing has been robust thanks to allied unity and an unexpectedly mild winter. But, as financial analysts constantly remind us, past performance is no guarantee of future results.

People like to back winners. If the anticipated Russian spring offensive looks successful or the counterpart Ukrainian offensive is uninspiring, expect louder US voices calling for a negotiated settlement. The warning signs are already here.

American officials privately express growing apprehension that there will be an early resolution of the conflict. As one White House official recently observed to me, by the end of the year the war could well be about where it is today. And a plurality of Americans intuitively grasp this: 46 per cent believe neither Russia nor Ukraine currently has the advantage in the conflict.

Momentum matters  

In public opinion, perception of momentum matters. Americans’ support for the Vietnam War waned as the conflict persisted, falling from six-in-ten Americans in 1965 to four-in-ten in 1973.

Similarly, backing for the Iraq war fell from more than seven-in-ten in 2003 to barely four-in-ten in 2008. And with Afghanistan, as the war dragged on, support for US involvement fell from more than nine-in-ten in 2002 to less than five-in-ten in 2021. Notably, once the American public turned on these wars, support never returned.

Of course, Americans were fighting and dying in those wars, which is not the case in the Ukraine conflict. But initially the Vietnam, Iraq, and Afghanistan war support was buoyed by the belief that continued US engagement was justified, otherwise American sons and daughters had died in vain. With no American lives at stake in Ukraine, only financial and military resources, there is a growing wariness of throwing good money after bad.

In the last year, the share of Americans who say the United States is doing too much for Ukraine has nearly quadrupled, from seven to 26 per cent. And the portion that believe Washington has not done enough has halved, from 49 per cent to 17 per cent.

Sentiment about Ukraine support has become increasingly partisan. In March 2022, nine per cent of Republicans and five per cent of Democrats said the US was doing too much for Ukraine. By January 2023, 40 per cent of Republicans but just 15 per cent of Democrats complained Washington was doing too much.

In the last year, the share of Americans who say the United States is doing too much for Ukraine has nearly quadrupled, from 7% to 26%.

This erosion of Americans’ support for Ukraine does not bode well for the future. Less than half (48 per cent) of the public in November, compared to 58 per cent in July, believed Washington should support Ukraine for as long as it takes, even if it means American households have to pay higher gas and food prices as a consequence.

A similar share, 47 per cent – up from 38 per cent in July – said the United States should urge Ukraine to settle for peace as soon as possible so the costs aren’t so great for American households, even if that means Ukraine will lose some territory.

A partisan divide

The partisan divide over Ukraine is largely driven by Republican political rhetoric during and after the 2022 midterm elections. Current Republican Speaker of the House Kevin McCarthy observed last October: ‘I think people are going to be sitting in a recession and they’re not going to write a blank cheque to Ukraine.’

More recently, in the wake of Ukrainian president Zelenskyy’s December speech to Congress, Florida Republican Representative Matt Gaetz, whose vote was pivotal in making McCarthy Speaker, tweeted: ‘Hemorrhaging billions in taxpayer dollars for Ukraine while our country is in crisis is the definition of America last.’

In January, newly-elected Ohio Republican Senator J.D. Vance told a Cleveland radio station that it was ‘ultimately not in our national security interest’ to send M1 Abrams tanks to Ukraine, despite the fact that they will be built by his constituents in Ohio.

In addition, ten Republican members of the House of Representatives have introduced legislation asserting ‘that the United States must end its military and financial aid to Ukraine, and urges all combatants to reach a peace agreement.’ 

And this month former President Donald Trump said: ‘That war has to stop, and it has to stop now, and it’s easy to do’ and it ‘can be negotiated within 24 hours’. Why worry about continued support for the war if it’s about to be over?

The road to 2024

With the 2024 US presidential election already revving up, Americans’ appetite for continued backing for Ukraine may hinge on how voters judge the Biden administration’s handling of the conflict.

Democrats are more than twice as likely as Republicans (61 per cent versus 27 per cent) to approve of the Biden administration’s response to the Russia invasion, suggesting Ukraine will be yet another partisan talking point as the campaign heats up. Notably, men are much more likely than women to approve of Biden’s efforts, as are older Americans compared with younger Americans.




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Japan’s G7 leadership: Defending the liberal order amid crisis

Japan’s G7 leadership: Defending the liberal order amid crisis 28 February 2023 — 9:00AM TO 10:00AM Anonymous (not verified) 20 February 2023 Online

How G7 countries should best respond to global economic and security challenges in order to defend the liberal international order.

In May 2023 Japan hosts the G7 summit in Hiroshima, where leaders of the US, UK, Canada, France, Germany and Italy come to discuss the most urgent challenges facing the world.

This year’s summit takes place against a backdrop of continued global economic and political instability from the war in Ukraine to intensifying competition between China and the West.

The speakers discuss Japanese Prime Minister Fumio Kishida’s priorities at the summit and consider how G7 countries should best respond to global economic and security challenges in order to defend the liberal international order.

This event is the third of a three-part series held in partnership with Japan House London.

Watch the first event which looked at Africa-Japan relations here, and the second event, on the UK and Japan’s engagement with Southeast Asia, here.




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Ethics of dealing with authoritarians

Ethics of dealing with authoritarians 28 March 2023 — 12:00PM TO 1:00PM Anonymous (not verified) 20 March 2023 Chatham House

How can democracies simultaneously defend human rights and promote open societies while still engaging with leaders from non-democratic states as strategic allies?

In 2022, the Biden administration called upon the world’s democracies to unite against a rising tide of autocracy. Through its messaging, conferences, and op-eds, the US and its allies presented the public with a binary choice: democracy or autocracy.

But in today’s world, and in the practice of international relations, the choice is rarely this simple.  

Joel Rosenthal, president of Carnegie Council, joins Chatham House to discuss how democracies and multilateral institutions can leverage ethics as a tool to assess concerns and trade-offs when engaging with illiberal actors.

Can democracies afford to be adversarial with certain countries or overly selective in cooperation when facing global-scale challenges such as climate change and the emergence of AI?

How can democracies simultaneously defend human rights and promote open societies while still engaging with leaders from non-democratic states as strategic allies?




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Relative and Absolute Quantification of Postsynaptic Density Proteome Isolated from Rat Forebrain and Cerebellum

Dongmei Cheng
Jun 1, 2006; 5:1158-1170
Datasets




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Targeted Peptide Measurements in Biology and Medicine: Best Practices for Mass Spectrometry-based Assay Development Using a Fit-for-Purpose Approach

Steven A. Carr
Mar 1, 2014; 13:907-917
Technological Innovation and Resources




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In Vivo Identification of Human Small Ubiquitin-like Modifier Polymerization Sites by High Accuracy Mass Spectrometry and an in Vitro to in Vivo Strategy

Ivan Matic
Jan 1, 2008; 7:132-144
Research




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Global Identification and Characterization of Both O-GlcNAcylation and Phosphorylation at the Murine Synapse

Jonathan C. Trinidad
Aug 1, 2012; 11:215-229
Research




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Time-resolved Mass Spectrometry of Tyrosine Phosphorylation Sites in the Epidermal Growth Factor Receptor Signaling Network Reveals Dynamic Modules

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research




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A Proteomic Analysis of Human Cilia: Identification of Novel Components

Lawrence E. Ostrowski
Jun 1, 2002; 1:451-465
Research




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Extending the Limits of Quantitative Proteome Profiling with Data-Independent Acquisition and Application to Acetaminophen-Treated Three-Dimensional Liver Microtissues

Roland Bruderer
May 1, 2015; 14:1400-1410
Research




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A Proteome-wide, Quantitative Survey of In Vivo Ubiquitylation Sites Reveals Widespread Regulatory Roles

Sebastian A. Wagner
Oct 1, 2011; 10:M111.013284-M111.013284
Research




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A Tandem Affinity Tag for Two-step Purification under Fully Denaturing Conditions: Application in Ubiquitin Profiling and Protein Complex Identification Combined with in vivoCross-Linking

Christian Tagwerker
Apr 1, 2006; 5:737-748
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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A Multidimensional Chromatography Technology for In-depth Phosphoproteome Analysis

Claudio P. Albuquerque
Jul 1, 2008; 7:1389-1396
Research




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Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis

Ludovic C. Gillet
Jun 1, 2012; 11:O111.016717-O111.016717
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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Highly Selective Enrichment of Phosphorylated Peptides from Peptide Mixtures Using Titanium Dioxide Microcolumns

Martin R. Larsen
Jul 1, 2005; 4:873-886
Technology




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Exponentially Modified Protein Abundance Index (emPAI) for Estimation of Absolute Protein Amount in Proteomics by the Number of Sequenced Peptides per Protein

Yasushi Ishihama
Sep 1, 2005; 4:1265-1272
Research




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Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics

Linn Fagerberg
Feb 1, 2014; 13:397-406
Research




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Accurate Proteome-wide Label-free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ

Jürgen Cox
Sep 1, 2014; 13:2513-2526
Technological Innovation and Resources




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Development and validation of a high-throughput whole cell assay to investigate Staphylococcus aureus adhesion to host ligands [Microbiology]

Staphylococcus aureus adhesion to the host's skin and mucosae enables asymptomatic colonization and the establishment of infection. This process is facilitated by cell wall-anchored adhesins that bind to host ligands. Therapeutics targeting this process could provide significant clinical benefits; however, the development of anti-adhesives requires an in-depth knowledge of adhesion-associated factors and an assay amenable to high-throughput applications. Here, we describe the development of a sensitive and robust whole cell assay to enable the large-scale profiling of S. aureus adhesion to host ligands. To validate the assay, and to gain insight into cellular factors contributing to adhesion, we profiled a sequence-defined S. aureus transposon mutant library, identifying mutants with attenuated adhesion to human-derived fibronectin, keratin, and fibrinogen. Our screening approach was validated by the identification of known adhesion-related proteins, such as the housekeeping sortase responsible for covalently linking adhesins to the cell wall. In addition, we also identified genetic loci that could represent undescribed anti-adhesive targets. To compare and contrast the genetic requirements of adhesion to each host ligand, we generated a S. aureus Genetic Adhesion Network, which identified a core gene set involved in adhesion to all three host ligands, and unique genetic signatures. In summary, this assay will enable high-throughput chemical screens to identify anti-adhesives and our findings provide insight into the target space of such an approach.




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Biosynthesis of the sactipeptide Ruminococcin C by the human microbiome: Mechanistic insights into thioether bond formation by radical SAM enzymes [Microbiology]

Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and posttranslationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether–containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of nonnatural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC–MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element, present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the peptide recognition element and the core peptide for the installation of posttranslational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation.




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Identification of a domain critical for Staphylococcus aureus LukED receptor targeting and lysis of erythrocytes [Molecular Bases of Disease]

Leukocidin ED (LukED) is a pore-forming toxin produced by Staphylococcus aureus, which lyses host cells and promotes virulence of the bacteria. LukED enables S. aureus to acquire iron by lysing erythrocytes, which depends on targeting the host receptor Duffy antigen receptor for chemokines (DARC). The toxin also targets DARC on the endothelium, contributing to the lethality observed during bloodstream infection in mice. LukED is comprised of two monomers: LukE and LukD. LukE binds to DARC and facilitates hemolysis, but the closely related Panton–Valentine leukocidin S (LukS-PV) does not bind to DARC and is not hemolytic. The interaction of LukE with DARC and the role this plays in hemolysis are incompletely characterized. To determine the domain(s) of LukE that are critical for DARC binding, we studied the hemolytic function of LukE–LukS-PV chimeras, in which areas of sequence divergence (divergence regions, or DRs) were swapped between the toxins. We found that two regions of LukE's rim domain contribute to hemolysis, namely residues 57–75 (DR1) and residues 182–196 (DR4). Interestingly, LukE DR1 is sufficient to render LukS-PV capable of DARC binding and hemolysis. Further, LukE, by binding DARC through DR1, promotes the recruitment of LukD to erythrocytes, likely by facilitating LukED oligomer formation. Finally, we show that LukE targets murine Darc through DR1 in vivo to cause host lethality. These findings expand our biochemical understanding of the LukE–DARC interaction and the role that this toxin-receptor pair plays in S. aureus pathophysiology.




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Can I? When Doubt Kills Your Ideas

Alright! The Muses sing, drawing you to the desk, pump your veins with hot blood and fill your mind with combustible imagination. You’re on fire and ready to write. The idea once tumbling in your mind is bucking with life and wants to breath words on your screen. It’s awesome. You’re awesome. All is good.

Then the passions temper under the cool, steady light of your computer screen. The process of fleshing out your idea with words demands time. So much so, you feel the vibrant energy of your story suffocate under the process. Now you’re using the logical, analytical side of your brain. Each scene or circumstance demands continuity and must fit into the internal logic of your world. Everything must make sense; else the reader will dismiss this pile of junk for amateur hubris.

With logic comes the questions. A train of them, each rumbling down the tracks uncaring of the idea which once bucked in the stables of your mind, eager for freedom, now tied to the rails. All of the doubts can easily be summarized into “Can I?”

Of course, this isn’t the real question haunting the halls of your mind.

Continue reading Can I? When Doubt Kills Your Ideas at Mythic Scribes.




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New essay anthology examines the future of the international order

New essay anthology examines the future of the international order News release jon.wallace 7 May 2021

Featuring a new essay by Robin Niblett, Chief Executive of Chatham House, and Leslie Vinjamuri, Director of the US and Americas programme.

Anchoring the World”, a new anthology, features an important new essay by Robin Niblett, Chief Executive of Chatham House, and Leslie Vinjamuri, Director of the US and Americas programme. The essay, “The Liberal Order Begins At Home”, argues powerfully for the revival of a liberal international order.

The essay collection has been produced by the Lloyd George Study Group on World Order, and celebrates the centennial years of Chatham House, Georgetown University’s School of Foreign Service, and the Council on Foreign Relations.

Robin Niblett said:

“In this excellent collection, some authors argue that the United Nations should continue to anchor the international system, while others argue for the creation of a new Concert of Powers.

“Our essay argues that it is both necessary and possible to revive the idea of a liberal international order: necessary (and urgent) because of heightened global competition with China, and possible only if western democracies repair their deep social and economic problems at home.

“We hope this volume carries forward the fortitude and creative spirit that the School of Foreign Service, Chatham House, and the Council on Foreign Relations have brought to the study and practice of international affairs over the past century.”

The Lloyd George Study Group and book were made possible by the generosity of the family of Robert Lloyd George, the great-grandson of British Prime Minister, David Lloyd George.

Anchoring the World is published by Foreign Affairs magazine.




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Helen Clark elected president of Chatham House

Helen Clark elected president of Chatham House News release jon.wallace 23 July 2021

The former New Zealand prime minister and Head of UN Development Programme has been elected president of Chatham House.

Former New Zealand prime minister and Head of the United Nations Development Programme, Helen Clark, has been elected president of Chatham House.

Ms Clark will replace former United Kingdom Prime Minister, Sir John Major, who is retiring from the role. She will join Baroness Eliza Manningham-Buller and Lord Darling as one of the institute’s three serving presidents.

Helen Clark was prime minister of New Zealand from 1999-2008. She then became the 8th and first female administrator of the UN Development Programme, completing two terms from 2009-2017.  

She is actively engaged in important international issues that are central to the institute’s priorities. She is currently chairing the Independent Panel for Pandemic Preparedness and Response with former president of Liberia, Ellen Johnson Sirleaf, which was convened by the World Health Organization last year and has just completed its main report. Her expertise extends to sustainable development, tackling climate change and developments in the Asia-Pacific.

Chatham House Director Robin Niblett welcomed the appointment:

‘We are excited to have found someone with the high-level political experience and who shares the strong reputation for integrity that Sir John enjoys. Helen Clark is highly regarded around the world for her past and current endeavours. Her election also underscores the institute’s global outlook and priorities, which she is so well qualified to help guide.’

Ms Clark was elected at the Annual General Meeting of Chatham House on 20 July which also marked the last official engagement for Lord O’Neill, who has now handed over to Sir Nigel Sheinwald as Chair of the institute.

Chatham House is delighted that Sir John Major will remain affiliated with the institute as president emeritus, and that Lord O’Neill will become a member of the institute’s panel of senior advisers.

 




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Cross-border conflict, evidence, policy and trends (XCEPT)

Cross-border conflict, evidence, policy and trends (XCEPT)

This five-year policy-focused research programme seeks to respond to the challenges of long-term cross-border conflicts by exploring the drivers behind them.

dora.popova 26 August 2021

Protracted conflicts in the Middle East and North Africa, Horn of Africa and parts of Asia, although usually arising from intra-state disputes, rarely remain contained within national borders. Their effects reverberate outward and external actors are drawn in.

The longer these wars last, the more difficult they are to resolve as the interests of international actors collide and the web of economic and political interactions which sustain violence and connect conflict across borders expand and deepen.

The Cross-border conflict, evidence, policy and trends (XCEPT) research programme brings together world-leading experts to examine conflict-affected borderlands, how conflicts connect across borders, and the drivers of violent and peaceful behaviour.

Chatham House provides research leadership to the programme, as part of the wider consortium, and our research explores:

  • the intersection of conflict supply chains which sustain and embed violence
  • coping supply chains for survival-based economic activity which occurs in the context of violence

Three geographic case studies will be supported by cross-cutting workstreams on gender and social inclusion, livelihoods, and border security. Each will produce analysis and recommendations to inform international policy responses to conflict across borders.

These case studies will focus on:

  • armed actors and financial flows through Iraq and the Levant
  • human smuggling across Libya, East and West Africa
  • gold mining and weapons flows across Sudanese borderlands

The consortium is made up of a range of other organizations, including the Asia Foundation, the Malcolm H. Kerr Carnegie Middle East Center, the Rift Valley Institute, Chemonics UK and King’s College London.

XCEPT is funded by UK Aid from the UK government.




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Robin Niblett awarded knighthood in Queen's Birthday Honours

Robin Niblett awarded knighthood in Queen's Birthday Honours News release NCapeling 1 June 2022

Chatham House director Dr Robin Niblett CMG receives a knighthood for services to international relations and to British foreign policy.

Chatham House Council and staff congratulate the institute’s director Robin Niblett, who has been appointed as a Knight Commander of the Order of St Michael and St George (KCMG) by HM The Queen in her Birthday Honours list.

The citation for the KCMG, awarded at the recommendation of the UK foreign secretary, recognizes Dr Niblett’s ‘outstanding personal contribution to British soft power and influence in his role as director of Chatham House over the last 15 years’.

The citation also states: ‘With exceptional energy and talent, he has greatly enhanced the research reputation of the Institute, strengthened its international convening power, finances and staffing, and modernised its premises, image and diverse outreach’.

Dr Niblett is standing down in the summer and will be replaced by Bronwen Maddox, who joins from the Institute for Government.

Dr Niblett says: ‘I am deeply honoured by this award, which is as much a recognition of the tireless and selfless work of my colleagues at Chatham House throughout my tenure as director.

‘Together, and through challenging times, we have offered a vital source of independent debate and analysis. And, with the engagement of our supporters and a new generation of thinkers and actors, I know the institute will continue to provide creative ideas for a better future.’




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Redefine the Commonwealth now to safeguard its future

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 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

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.

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

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.




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Independent Thinking: War in Ukraine, Congress in China

Independent Thinking: War in Ukraine, Congress in China Audio NCapeling 21 October 2022

The inaugural episode of our new podcast examines the latest developments surrounding Russia’s invasion of Ukraine, and Xi Jinping’s political report from the 20th National Congress of the Chinese Communist Party.

Bronwen Maddox and her guests examine latest developments surrounding Russia’s invasion of Ukraine and Vladimir Putin’s nuclear threats, as well as Xi Jinping’s political report from the 20th National Congress of the Chinese Communist Party.  

Bronwen is joined by Gideon Rachman, chief foreign affairs columnist for the Financial Times, Orysia Lutsevych, head of the Ukraine Forum at Chatham House, and Dr Yu Jie, senior research fellow in Chatham House’s Asia-Pacific programme.

Independent Thinking is a regular podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts to provide insight on the latest international issues.




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Independent Thinking: Rishi Sunak and the UK, John Kerry on COP27

Independent Thinking: Rishi Sunak and the UK, John Kerry on COP27 Audio NCapeling 28 October 2022

The second episode of our new podcast examines the changes in the UK government as Rishi Sunak become prime minister and looks ahead to COP27 with John Kerry.

Bronwen Maddox and her guests discuss the arrival in Number 10 of Rishi Sunak, the UK’s youngest prime minister of modern times as well as its third of 2022, alongside analysing the Chatham House event with US Special Presidential Envoy on Climate John Kerry. 

Bronwen’s guests from Chatham House are John Kampfner, executive director of the UK in the World Initiative, Hans Kundani, associate fellow with the Europe programme, and Anna Åberg, research associate with the Environment and Society programme.

They are joined by Sir Simon Fraser, formerly of the UK’s Foreign and Commonwealth Office, and Chatham House’s deputy chairman. 

Independent Thinking is a regular podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts to provide insight on the latest international issues.




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Independent Thinking: Lula wins in Brazil, US midterms

Independent Thinking: Lula wins in Brazil, US midterms Audio NCapeling 4 November 2022

The third episode of our new podcast analyses the results from the Brazil presidential election, and looks ahead to the crucial midterm elections in the US next week.

Bronwen Maddox and her guests examine the tight election result from Brazil and its impact on both the country and the region, and preview the US midterm elections being held on 8 November and the start of COP27.

In Brazil, former president Luiz Inácio Lula da Silva beat incumbent Jair Bolsonaro by the narrowest of margins. Meanwhile in the US, the Democrats are fighting to retain the House and Senate from a resurgent Republican Party still enamoured with Donald Trump.

Joining Bronwen Maddox this week are Leslie Vinjamuri, director of Chatham House’s US and Americas programme, Christopher Sabatini, senior fellow on Latin America in the same programme, and Ana Yang, executive director of Chatham House’s Sustainability Accelerator.




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Independent Thinking: US midterms surprise, COP27 begins

Independent Thinking: US midterms surprise, COP27 begins Audio NCapeling 11 November 2022

The fourth episode of our new podcast analyses early results from the US midterm elections and brings the latest insights from a crucial COP27.

The US midterm elections threw up some surprising results with the anticipated Republican ‘red wave’ failing to materialize. Meanwhile at COP27 in Egypt, world leaders met in the first week of the summit. What did their presence achieve?

To find out, returning to the podcast this week with Bronwen Maddox are Leslie Vinjamuri, director of the Chatham House US and Americas programme who was in Atlanta Georgia for the midterms, and Anna Aberg, research associate in the Environment and Society programme who is on the ground at COP27.

Joining them are Peter Trubowitz, professor of international relations and director of the Phelan US Centre at the London School of Economics and Antony Froggart, deputy director and senior research fellow in the Environment and Society programme.




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Independent Thinking: Iran protests, Iraq's invasion legacy

Independent Thinking: Iran protests, Iraq's invasion legacy Audio NCapeling 17 November 2022

Episode five of our new weekly podcast has a Middle East focus with insights into what is driving the ongoing protests in Iran, and the progress of Iraq in the years since the fall of Saddam Hussein.

Since September, Iran has been swept by thousands of women-led protests, demanding an end to the morality police and the even calling for the fall of the Islamic Republic.

Meanwhile at Chatham House this week saw our Iraq Initiative conference 2022, which delved heavily into the multiple challenges facing Iraq two decades on from the invasion which toppled Saddam Hussein.

Joining Bronwen Maddox on the podcast this week are the Chatham House Middle East and North Africa programme deputy director Dr Sanam Vakil and senior research fellow Dr Renad Mansour, who is also project director of the Iraq Initiative. They are joined by Sanya Burgess, digital investigations journalist with Sky News.