Platform engineering is the latest buzzword in IT operations. And like all other buzzwords, it’s in danger of becoming meaningless—in danger of meaning whatever some company with a “platform engineering” product wants to sell. We’ve seen that happen to too many useful concepts: Edge computing meant everything from caches at a cloud provider’s data center […]

The first battle cry has sounded ahead of the showdown at Twickenham on Saturday, with English winger Tommy Freeman reckoning that the Springboks are 'still human' and 'still playing the same game'.

Dilated cardiomyopathy (DCM) is associated with mutations in cardiomyocyte sarcomeric proteins, including α-tropomyosin. In conjunction with troponin, tropomyosin shifts to regulate actomyosin interactions. Tropomyosin molecules overlap via tropomyosin–tropomyosin head-to-tail associations, forming a continuous strand along the thin filament. These associations are critical for propagation of tropomyosin's reconfiguration along the thin filament and key for the cooperative switching between heart muscle contraction and relaxation. Here, we tested perturbations in tropomyosin structure, biochemistry, and function caused by the DCM-linked mutation, M8R, which is located at the overlap junction. Localized and nonlocalized structural effects of the mutation were found in tropomyosin that ultimately perturb its thin filament regulatory function. Comparison of mutant and WT α-tropomyosin was carried out using in vitro motility assays, CD, actin co-sedimentation, and molecular dynamics simulations. Regulated thin filament velocity measurements showed that the presence of M8R tropomyosin decreased calcium sensitivity and thin filament cooperativity. The co-sedimentation of actin and tropomyosin showed weakening of actin-mutant tropomyosin binding. The binding of troponin T's N terminus to the actin-mutant tropomyosin complex was also weakened. CD and molecular dynamics indicate that the M8R mutation disrupts the four-helix bundle at the head-to-tail junction, leading to weaker tropomyosin–tropomyosin binding and weaker tropomyosin–actin binding. Molecular dynamics revealed that altered end-to-end bond formation has effects extending toward the central region of the tropomyosin molecule, which alter the azimuthal position of tropomyosin, likely disrupting the mutant thin filament response to calcium. These results demonstrate that mutation-induced alterations in tropomyosin–thin filament interactions underlie the altered regulatory phenotype and ultimately the pathogenesis of DCM.

Managing Risks Along the Belt and Road 27 March 2018 — 8:30AM TO 11:30AM Anonymous (not verified) 5 March 2018 Chatham House, London

China’s ‘Belt and Road Initiative’ offers potential benefits in connectivity, infrastructure and trade, through significantly increased Chinese engagement across many different countries. However, many of these countries face internal tensions and have relatively underdeveloped market structures, legal systems and governance frameworks. While Belt and Road investments can make positive contributions in host countries, there is also the potential for these investments to exacerbate tensions and risks.

This roundtable, held in partnership with the Security & Crisis Management International Centre (Shanghai Academy of Social Sciences-UNITO), will seek to examine risk management along the Belt and Road, differentiating between roles that can be played by public sector and private sector actors.

Attendance at this event is by invitation only.

Managing Risk to Build a Better Belt and Road Expert comment sysadmin 4 July 2018

Risk management is a key part of economic development. China could use some simple principles for managing risk to improve the prospects of its flagship infrastructure initiative.

One of the original motivating forces for China’s Belt and Road Initiative is risk management: the aim being to use infrastructure to drive economic development, so improving political stability and creating a favorable impression of China in countries bordering China and beyond.

Yet these investments themselves are inherently risky: large-scale, debt-financed, long-term infrastructure projects in countries that often have weak governance, undefined or poorly-executed rule of law and corruption. China has experience managing infrastructure risks within its borders in its own ways, but it has much less experience overseas.

And, while well-executed investments can enhance stability, the same investments, executed poorly, can create their own backlash in countries that see costs exceed benefits. This increases rather than reduces risks – not just the risks of defaulting on loans, but also the risk of damage to physical assets, loss of life and deteriorating relations with China.

Moreover, China states its desire for greater private sector and non-Chinese involvement in Belt and Road. This will be needed if China is to realize some of its larger ambitions for the initiative. But companies seek attractive returns – adjusted for risk. It is the perceived and actual riskiness of projects that makes commercial involvement a challenge. Focusing on the risk rather than return may be the better place to start to attract partners alongside Chinese institutions.

The risks on the Belt and Road

Overall, these risks fall into four categories.

The first and most critical issues are when projects cannot even get initial funding. Concerns about compliance, corruption and project governance combined with high costs and low revenues mean that the numbers simply do not add up. Working on any of these dimensions to improve them means more projects will get off the ground.

Secondly, there are the familiar risks during construction – budget overruns, unforeseen design issues and work delays, all commonplace in such challenging operating environments. Alongside these are risks to personnel caused by internal tensions and security challenges.

Thirdly, once completed, financial and non-financial risks remain. At its simplest, revenues may fall short and the project debt cannot be repaid. A series of other factors may reduce willingness to pay: difficulties in enforcing penalties against non-repayment; fiscal pressures elsewhere in the budget; popular resistance to sending money to overseas financiers. And the completed projects and individuals operating them often remain at risk to local political tensions and security challenges.

Finally, throughout the whole process, projects risk stirring up resentment and hostility rather building stability through economic growth. Incumbent governments may make project commitments that fit their own interests rather than those of the country – or at least are perceived to do so. Sri Lanka and Malaysia offer current examples. The way in which projects are implemented can compound the problem – for example, if promised job creation among local contractors does not happen or local ethnic rivalries are not taken into account.

Approaches to risk

How then to address these risks? Some simple principles about risk management highlight avenues to explore and institutions to get involved.

First, what can actions be taken to mitigate or reduce the risks and who is best-placed to do this?

Secondly, who is best-placed to bear and accept risks that cannot be reduced at an economical cost? Should the risk be diversified across many different parties so that each bears only a portion of the risk or rather concentrated and held by those who are knowledgeable on the specifics of the risk?

Thirdly, for those who end up bearing the remaining risk, how large is it and what actions are needed now to protect against future loss?

The myriad of risks along the Belt and Road suggests a myriad of risk solutions and participants. Putting that all together is in itself a skill and will not happen of its own accord. It requires active planning and structuring of which partners to involve where in a way that makes sense for all involved. Three areas stand out.

Successful construction is more than an engineering exercise. It requires positive engagement with local communities; credible, active communication of the benefits that the project brings; and protection of the people and equipment involved in the work. Doing this well means understanding the specific situation on the ground in often remote regions and acting accordingly.

Donor agencies, NGOs, other multinationals and provincial and national governments all have experience to bring to the table. Chinese contractors have demonstrated success in rapid, low-cost implementation and are learning about how to work in a wide range of countries. This is, though, an opportunity to draw on the experience of contractors from other countries, local subcontractors and the experience of multilateral organizations.

Financing is at core about the risk/return-based allocation of capital. The raison d’etre of the insurance sector is risk management. Multilateral institutions have a complementary role to play alongside private sector financial institutions. Drawing on this experience can play an important role in making investment projects economically attractive and bankable.

The opportunity to match the investment portfolios of long-term institutional investors with the long-term financing needs of infrastructure has long been a topic of discussion: the Belt and Road provides a new menu of projects. These approaches all thrive on verifiable data, standardization and transparency clarity and standardization.

Not all projects will fit these requirements, but some will. And in all cases, drawing on sector- and country-specific risk management experience from banks and insurers can reduce risks.

Government can be thought of as the ultimate back-stop, a risk manager for its people across the entire risk spectrum. Actions that strengthen the capacity of all governments involved to assess and address risk mean more effective risk management, greater success and the avoidance of ‘debt traps’.

Examples include sharing experience between countries; multilateral or bilateral support with the assessment of financial burden and debt terms; support to strengthen governance and oversight of project implementation; and approaches that ensure the involvement of affected local populations. Making use of dispute resolution procedures that are accepted by the key participants reduces risk all round.

Countries, businesses and individuals grow through the judicious taking of risks. But unnecessary risk-taking is wasted effort. Belt and Road projects will be most effective when those best-placed to tackle risks and opportunities are encouraged to do so.

Jesper V. Olsen
Jun 1, 2004; 3:608-614
Technology

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

Philip L. Ross
Dec 1, 2004; 3:1154-1169
Research

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.

Moldova and Georgia face crucial elections – and diverging paths Expert comment LToremark 16 October 2024

The two countries face unusually consequential elections where their populations must choose between moving unambiguously towards the West – or towards closer ties with Russia.

Moldova and Georgia both go to the polls at the end of October; Moldova for presidential elections on the 20^th and Georgia for parliamentary elections on the 26^th. The two countries share a number of similarities – beyond their justified reputation as world-class wine producers. They are both small, low- to middle-income countries that have struggled to consolidate their democracies and have experienced oligarchic political influence. Both are candidate countries for EU membership, with Moldova a step ahead having been invited to start negotiations. 

For both countries these elections represent a fork in the road: either move unambiguously into the Western world, or step back from it and become more closely tied to Russia again and its way of governance. However, the second option has caused yet-to-be-resolved territorial conflicts in both countries – Transnistria for Moldova, and Abkhazia and South Ossetia for Georgia.

Some would say it should not be such a ‘zero sum’ choice. Why must a nation choose between Russia and the West? While that may be a fair statement for countries like India or South Africa, it does not work for Russia’s former colonies, which Moscow wishes to control. 

Moldova and Georgia’s final similarity is that they face Russian interference and attempts to manipulate votes in their elections. In Moldova this has been especially brazen with the uncovering in September of a $15 million vote-buying scheme, including instructions on who to vote for distributed to over 130,000 citizens. Russian interference in Georgia’s election is less overt but at the same time more endemic considering its government has in effect been captured by pro-Russia forces.

Diverging paths

But this is where the similarities end and the contrasts become clear.

Moldova has a young, pro-Western and equality-conscious government, and 44 of the 100 MPs in its parliament are women. In this election, Maia Sandu is seeking her second and final term as president. The election is combined with a referendum asking the people if they wish to embed Moldova’s EU aspirations into the country’s constitution. The results of both the presidential election and the EU referendum will be close, reflecting a genuine split in attitudes (and debate) in the country. 

Georgia’s EU aspirations, meanwhile, are already embedded in its constitution – but that has not prevented Tbilisi from pivoting away from the West. Polls show   that around 80 per cent of Georgia’s population desires EU (and NATO) membership – rising to 90 per cent among the under 30s – but its government seems determined to deny them that future. 

Its new ‘foreign agents’ law is seemingly copy-pasted from Russia – and incompatible with EU membership. The election can be seen as a de facto referendum on the EU too. Georgia’s accession is suspended until its political crisis is resolved. 

Georgia faces other challenges to its democracy. Due to the country’s limited presidential powers, Georgia is in effect run by the unelected Bidzina Ivanishvili – founder of the ruling Georgian Dream (GD) party – whose relationship with Russia is murky at best. Judging by his recent speeches, Ivanishvili now blames the Western world not just for igniting the war in Ukraine, but also for the war in Georgia 16 years ago which resulted in the loss of 20 per cent of its territory at the hands of Russia. This extraordinary position is both factually incorrect and out of step with the Georgian people.

Both countries are now at a critical point. Whatever the outcome in Moldova, the election will pass off peacefully and competently. Its problems (Russia aside) are demographic and economic, and the country’s pro-Russian opposition is relatively weak.

Georgia’s election looks like it is going to be messy. Ivanishvili’s party will likely manipulate the election to a win. There is still a chance that Georgia’s pro-Western but also weak opposition will regain power and return the country to its European path. But if the manipulation by the incumbency is heavy, people will likely take to the streets in protest, as in April this year – and in the 2003 Rose Revolution.

Regime change via popular revolution shows political immaturity but the Georgian people may feel it is the only way they can have their views represented and their ambitions realised. 

Linda J. Pike
Apr 1, 2003; 44:655-667
Thematic Reviews

RK Tangirala
Nov 1, 1995; 36:2320-2328
Articles

Insights from Climate Policy: Engaging Subnational Governments in Global Platforms 10 June 2020 — 2:45PM TO 6:00PM Anonymous (not verified) 9 February 2021 Online

How have subnational governments shaped the global agenda and created momentum on climate change where national and international governance processes could not?

Can these advances be converted into meaningful collaboration channels for policy development? What works, or does not, when it comes to engagement with multilateral negotiation processes? What ingredients are necessary for success? What are the broader implications of these trends for inclusivity and innovation in international governance?

This event is part of the Inclusive Governance Initiative, which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world.

Imagine a World Without Fake News Explainer Video NCapeling 25 February 2021

Harriet Moynihan and Mathieu Boulegue explain how we can avoid drowning in an ocean of fake news and information manipulation.

The flow of fake news is vast and unlikely to go away. What’s more, imagining a world where fake news is eradicated completely has implications for freedom of expression.

But what if, instead of wishing fake news away, we can adapt and become immune to it? 

Chatham House is built on big ideas. Help us imagine a better world.

Our researchers develop positive solutions to global challenges, working with governments, charities, businesses and society to build a better future.

SNF CoLab is our project supported by the Stavros Niarchos Foundation (SNF) to share our ideas in experimental, collaborative ways – and to learn about designing a better future, overcoming challenges such as fake news, COVID-19, food security, and conflict.

Digital governance must not marginalize smaller states Expert comment LToremark 19 May 2021

For effective and inclusive digital governance, multi-stakeholderism must raise its game.

Last month, the G7 announced it is to work towards a trusted, values-driven digital ecosystem. While this is commendable, the G7 must recognize that key international digital governance decisions should involve all states whose populations will be affected. Not doing so is to deny the legitimate interests of those populations and may cause a lack of trust in international digital governance that embeds longer-term instability.

While a multi-stakeholder approach to digital governance is important, it must be structured in a way that allows for meaningful representation of states’ interests and ensures their representatives have the opportunity and capacity to take part. As the internet becomes fundamental to life in every country of the world, international digital governance is increasingly important to all governments and excluding some states’ perspectives may engender wider risks to international security and governance.

The ‘glitter ball’ of digital governance

International digital governance is playing catch-up with the digital sphere it needs to govern. Its starting point is a ‘glitter ball’ of governance initiatives: a large number of complex facets with overlapping impacts – and an almost impenetrable core. Governance initiatives (see infographic) include governance of the internet itself and its uses, international cybersecurity, international human rights, data management, as well as the impact of digital developments in areas such as armed conflict, trade and health.

Many of the bodies involved – such as the Internet Governance Forum, the Internet Corporation for Assigned Names and Numbers (ICANN) and technical standards bodies – include a wide range of stakeholders, yet there is no one accessible, central body. Furthermore, certain key issues, such as the role and responsibilities of tech platforms, are barely touched upon by international governance mechanisms. There is also currently only a limited role for traditional UN multilateral decision-making, a process which builds in a role for smaller states.

The sheer number of forums involved, each with a different set of working methods and rules on participation, makes it difficult to fully grasp what digital governance looks like as a whole. The UN secretary-general’s High-level Panel on Digital Cooperation recognized the complexity of digital cooperation arrangements and the barriers to inclusion facing small and developing countries as well as under-represented groups. In response, the June 2020 UN Roadmap on Digital Cooperation accepts the need to streamline digital governance while ensuring marginalized voices are heard.

The UN is considering potential models for future governance, each of which would – reassuringly – involve multi-stakeholder participation, dedicated funds to boost participation, consolidation of discussions currently split between different forums and a minor coordinating role for the UN.  

Building in roles for smaller states

As the UN designs new digital governance architecture, it is particularly important to build in roles for small and medium states. Core constituencies affected by decisions should be at the centre and governments – as guardians of public interest – should have a key say in the decision-making process. The distrust generated by built-in power imbalances needs to be addressed, as does the dominance of voices from the Global North in bodies such as ICANN.   

There has been some progress made to increase participation. For example, the Freedom Online Coalition includes a number of developing countries and the 2020 Internet Governance Forum included input from 175 states.

However, participation is not only a matter of having a seat at the table. As discussed at the March 2021 UN Open-ended Working Group on ICTs in the context of international security, capacity-building is vital. The group’s conclusions include the suggested development of a global cyber capacity-building agenda with information sharing and norms guidance under the auspices of the UN. Representatives of small and medium states need a roadmap to understand in which forums they can defend and pursue their interests, and the financial help to do so if necessary.

Managing multi-stakeholder participation

A multi-stakeholder approach has been fundamental to digital governance from the start and has played a vital role in helping to secure the openness and universality of the internet. This approach is rightly seen as essential to effective governance because it introduces diverse expertise, allows the interests of all impacted sectors to be taken into account and helps ensure decisions are accepted by those affected.

However, as identified in a Chatham House report on inclusive global governance, multi-stakeholderism needs to raise its game. One of its downsides is that in the cacophony some important voices may not be heard because they lack resource or capacity to speak up. There is a perennial risk of debate and decision-making being captured by the wealthiest companies or the most powerful states. At present, small and medium states are under-represented in multi-stakeholder forums and it is important that those managing such forums seek to identify and include previously excluded voices.

Multi-stakeholderism should not come at the expense of efficiency. While it does not have to mean huge, inefficient meetings or endless discussion, it should also not mean that smaller, less well-funded voices are not heard. Instead, such processes should enable representation of appropriate interest groups, complemented by wider meetings (such as regional meetings, or sector-specific meetings) as needed. While inclusivity and transparency are key, synergies between regional and global forums can work well –  for example, some countries have adopted national versions of the Internet Governance Forum –  and so too can hybrid models such as the Freedom Online Coalition, which meets both as government members and for regular multi-stakeholder dialogue.

A multi-stakeholder approach should also not lose sight of the key role of states – and where mandated, sub-state entities – in making public policy decisions.

An important role for the UN

For 75 years, the UN has acted as a bulwark of international security and shared values, and a promoter of economic and social development. If misused, technology has the potential to undermine this bulwark, to facilitate conflict, erode rights and undermine development. The UN must encourage the harnessing of technology for society’s benefit, while leading a collective effort to guard against the risks through the retention and growth of a universal, open internet – particularly in the face of growing digital authoritarianism exacerbated by COVID-19.

The UN can also help protect against a commercial culture that threatens to trample fundamental freedoms of privacy and autonomy in its pursuit of wealth and to widen economic and social gulfs by leaving large swathes of the world behind. If the UN is to play this role effectively – and for the benefit of all its members ­– it requires the active participation of all states, large and small.

Protecting universal human rights: Imagine a better world Explainer Video NCapeling 19 November 2021

Short animation examining why protecting and defending human rights ensures an equitable response to humanitarian crises and addresses economic inequality.

Human rights are not policies that can be overturned, they are not granted by governments. They belong to everyone as human beings.

For the most part, states are meeting their commitments to defend and protect universal human rights. But increasingly some governments are beginning to shy away from their obligations, and some are even actively seeking to subvert human rights.

And the regional and international bodies created and charged with defending these rights are being challenged by the rise of new powers and political movements.

Chatham House is built on big ideas. Help us imagine a better world.

Our researchers develop positive solutions to global challenges, working with governments, charities, businesses and society to build a better future.

SNF CoLab is our project supported by the Stavros Niarchos Foundation (SNF) to share our ideas in experimental, collaborative ways – and to learn about designing a better future.

Re-imagining trade for domestic and foreign policy Expert comment NCapeling 7 December 2021

Exploring future trade policy through issues such as the green transition, labour standards, human rights, the role of the WTO, and non-trade policy objectives.

Balancing trade and non-trade policy objectives

Marianne Schneider-Petsinger

The supply chain disruptions stemming from the COVID-19 pandemic highlight trade cannot be taken for granted, and economic interdependencies have both benefits and costs. As international commerce rebounds and trade policy is increasingly seen through the prism of enhancing resilience, the moment is ripe to redefine and reimagine trade.

The goal of trade policy has never been to increase trade for trade’s sake, so a new narrative and framework for global trade requires striking a careful balance between pursuing trade and non-trade policy objectives.

Protecting the environment, strengthening labour standards, and upholding human rights have long been goals for which trade policy is used as a lever, and the interaction of trade and national security interests as well as the links between trade and competition policy are not new issues either.

All these non-trade policy aspects have come to the forefront as the geopolitical context has shifted and the transition to green and digital economies has gathered force – and, at times, these different non-trade policy goals clash.

The US and European Union (EU) are promoting solar energy to fight climate change but supply chains for solar panels are heavily reliant on forced labour from Xinjiang, and hence it is not yet certain whether environmental or human rights concerns will prevail. However, it is clear trade policy tools can be part of a comprehensive solution which manages inherent tensions while still advancing both objectives.

Trade policy is also not just a foreign policy instrument but links closely to domestic policy – the populist backlash against globalization in much of the developed world, especially the US and Europe, was in part driven by anti-trade sentiment.

While American attitudes towards trade improved after the 2016 election of Donald Trump, positive views towards trade dropped sharply in 2021. The Biden administration’s worker-centred trade policy aims to address distributional effects of international economic integration which is a long-standing challenge. Thus, tackling non-trade policy issues without losing sight of this unresolved core issue requires careful calibration.

Trade policy is being pulled in many different directions at the same time as the core institution governing global trade – the World Trade Organization (WTO) – is in crisis, and it is uncertain how much of the non-trade policy agenda the WTO can handle. If the linkage to non-trade policy becomes too strong, this could be the straw that breaks the WTO’s back, but if it is too weak, the WTO risks becoming irrelevant in efforts to tackle key global challenges.

But if its 164 members can generate trade-oriented solutions to non-trade issues, they can revive the organization and mobilize domestic support for global trade at the same time. This balancing act in managing the tensions between trade and non-trade policy objectives lies at the centre of future-proofing trade policy and global trade governance.

Developing countries must be part of green trade revolution

Carolyn Deere Birkbeck

The biggest challenge in taking environmental efforts forward within the multilateral context is to successfully combine environmental ambition with an approach which engages developing countries as partners, reflects their environment-related trade priorities, and addresses their sustainable development interests.

The importance of engaging developing countries must not be underestimated because it is vital a global green economy does not leave the poorest behind, or becomes two-tier where green trade happens only between certain countries and the essential task of incentivizing and supporting sustainable production and consumption patterns in all countries is neglected.

The new member-led initiatives at the WTO do signal that, while the rulemaking and negotiating functions remain central to the global trade body, governments recognize the need for enhanced, transparent, and inclusive policy dialogue as well as problem-solving on sectoral issues and specific trade-related challenges.

Given the well-documented challenges of achieving multilateral consensus at the WTO, governments are exploring new ways to work within multilateral frameworks and to redefine what progress and successful outcomes should look like.

Therefore, there is a need for best practices, voluntary action, pledges, and guidelines to both sustain the relevance of the multilateral trading system and support policy action at the national level for trade which underpins environmental and wider sustainable goals.

Making progress on an environmental agenda which reflects sustainable development concerns requires stronger leadership, engagement, and advocacy from business, civil society, and research communities in both developing and developed countries, as well as economies in transition.

Meaningful, inclusive dialogue and action at the WTO also requires deeper efforts to build policy coherence among environment, development, and trade policymaking at home, with environmental ministries having a key role to play in bringing expertise to bear and ensuring strong regulatory environments and institutions for the implementation of national, regional, and international environmental commitments.

But at the domestic level, many countries still have to overcome complex politics and diverse interests as they work to transform their economies toward greater sustainability and tackle the costs of transition.

Social preparation holds the key to trade transitions

Bernice Lee 

Trade being often depicted as the mother of all ills should not come as a surprise, as politicians are only too happy to put the blame on trade when all sorts of exogenous shocks, such as technological change, could actually be the trigger which fires the bullet into local industries or jobs.

Admittedly trade does have a way of breaking the seams in the social fabric but the fact politicians often ignore negative impacts of trade means its benefits can be likened to Schrodinger’s cat, both real and illusive. But trade being mainly depicted as a ‘zero-sum’ pursuit and trade deals as the result of swashbuckling duels belie the reality that the real business of trade is often boring, bureaucratic, but necessary.

This is particularly true when trade provides access to a much larger variety of necessary products, such as medicine, food, and minerals, which can be expensive to make domestically. Selling products and services abroad also brings in the hard currency needed to buy these goods or to spend on trips abroad.

This does not take away the fact trade is extremely disruptive but, as a result of all the theorizing and understandable rants about trade, large swathes of the international community have effectively foregone it as a force for good or as an instrument which – while not the answer to all problems – can help smooth the path to well-being through efficiency gains and income growth, as well as putting to work the theory of comparative advantage as promised by the textbooks.

Alas, what the textbooks do not clearly spell out – until recently – is that trade brings positive benefits only if a society is ready for trade, which often means having the cushion for social protection such as healthcare, unemployment benefits, and opportunities for training and reskilling.

The ‘China shock’ literature vividly depicts how workers rarely seamlessly move from one job or sector to another and so, without adequate social protection, trade not only magnifies existing fractures, it also exacerbates inequality. As the aftershock lingers for decades, the lesson learned is the importance of social readiness for trade, especially the role played by governments in providing support for workers as part of the adjustment to trade and globalization.

Authors of this China shock literature recently suggested the next shock will be the transition from fossil fuel production, but the good news is this so-called ‘just transition’ challenge is one which proponents of green energy are well aware of.

But ultimately the China shock could be the dry run for the advent of machine intelligence, meaning better preparation is needed with solid social policies, investment in institutional readiness, and social preparedness to ensure the machines only take on monotonous and unsafe work – not our livelihoods and communities.

Trading partners must move to creating human rights impact

Dr Jennifer Zerk

The question of whether, and how, trade policy should be used as a way of addressing human rights concerns remains controversial and attempts to link the two still attract accusations of ‘protectionism’ and ‘neo-colonialism’.

Momentum appears to be behind those arguing for greater alignment between trade policy and human rights objectives – a trend which is most noticeable in the increasing willingness of trade partners to reference human rights standards in their trade agreements and in the growth of complementary activities such as human rights impact assessment and monitoring.

Evidence that these are having an impact ‘on the ground’ remains elusive. Nevertheless, efforts to enhance scrutiny of trade agreements from a human rights perspective, and to signal the importance of respect for human rights to a trading relationship, can still have value.

Even if causal relationships between trading arrangements and human rights impacts are difficult to establish conclusively, human rights impact assessment and subsequent monitoring activities provide valuable opportunities for stakeholders to weigh in on aspects of trade policy which are of concern.

Such processes not only help governments to realize rights of public participation, they also contribute to good governance by making it more likely that potential human rights problems will be recognized and addressed.

Turning to the agreements themselves, various ideas have been put forward on how to make these more responsive to human rights concerns.

Options mooted by EU institutions in recent years include an enhanced monitoring and enforcement role for consultative bodies established under specialized ‘trade and sustainable development’ chapters, and better mainstreaming of human rights commitments in sector-specific chapters.

However, given the political and resource-related difficulties in developing credible monitoring systems for human rights-related issues, and the unlikelihood of actual enforcement, many view this as little more than window-dressing.

For governments wanting to see real impact, ‘supply chain due diligence’ regimes pioneered by the EU in relation to timber and conflict minerals present a promising regulatory model.

These regimes seek to curb trade in products derived from, or which aggravate, human rights abuses as well as aiming to promote more responsible sourcing of products by EU importers. They create powerful incentives within partner countries to crack down on harmful practices by producers, which are bolstered further by regulations that demand more proactive human rights risk management by EU operators throughout their supply chains. Capacity-building and aid packages have been deployed to help speed up the necessary reforms.

New regulatory measures imposing mandatory human rights due diligence obligations on companies operating in a much broader range of sectors are now under consideration by the European Commission. While the role of trade-related measures in the enforcement of this new regime is still unclear, trading partners should be sure to preserve the regulatory space for sector-level and company-level initiatives such as these in future agreements.

Understanding the impact of NTPOs on investment

Professor Michael Gasiorek

Increasingly, trade policy is not just all about achieving trade-related outcomes as international trade, by definition, involves interaction with partner countries and therefore trade policy with regard to those partner countries can be used as a means to achieve ‘non-trade policy objectives’ (NTPOs).

In turn this means trade policy is also no longer just about the domestic economy but also about policies and economies in other countries – such as poorer countries achieving sustainable development goals (SDGs), concerns about practices in other countries in areas such as governance or corruption, or a desire to address broader challenges such as climate change.

But the inclusion of NTPOs in trade policy arrangements between countries also creates possible impacts on investment flows between countries. Stronger NTPO commitments could have a negative impact both on foreign direct investment (FDI) and domestic investment because the commitments increase costs for the companies involved which makes the investment less attractive.

However, NTPOs bringing progress on governance, or strengthening institutions, or giving more clarity on environmental regulations could signal a more stable and safe business environment, with production standards which create increased market access for exports – all of which may lead to increased incentives to invest.

A third possibility is that NTPOs do not have much effect either way because, although trade agreement increasingly include provisions on economic and social rights, or civil and political rights, or environmental protection – these are typically ‘best endeavour’ clauses which are frequently not binding or subject to dispute settlement, making them less likely to be implemented.

CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss. We thus performed a screen of type I PRMTs, which revealed that PRMT6 can also deposit the H3R17me2a mark in vitro. CARM1 knockout mice are perinatally lethal and display a reduced fetal size, whereas PRMT6 null mice are viable, which permits the generation of double knockouts. Embryos that are null for both CARM1 and PRMT6 are noticeably smaller than CARM1 null embryos, providing in vivo evidence of redundancy. Mouse embryonic fibroblasts (MEFs) from the double knockout embryos display an absence of the H3R17me2a mark during mitosis and increased signs of DNA damage. Moreover, using the combination of CARM1 and PRMT6 inhibitors suppresses the cell proliferation of WT MEFs, suggesting a synergistic effect between CARM1 and PRMT6 inhibitions. These studies provide direct evidence that PRMT6 also deposits the H3R17me2a mark and acts redundantly with CARM1.

Expert

DNA polymerases are today used throughout scientific research, biotechnology, and medicine, in part for their ability to interact with unnatural forms of DNA created by synthetic biologists. Here especially, natural DNA polymerases often do not have the “performance specifications” needed for transformative technologies. This creates a need for science-guided rational (or semi-rational) engineering to identify variants that replicate unnatural base pairs (UBPs), unnatural backbones, tags, or other evolutionarily novel features of unnatural DNA. In this review, we provide a brief overview of the chemistry and properties of replicative DNA polymerases and their evolved variants, focusing on the Klenow fragment of Taq DNA polymerase (Klentaq). We describe comparative structural, enzymatic, and molecular dynamics studies of WT and Klentaq variants, complexed with natural or noncanonical substrates. Combining these methods provides insight into how specific amino acid substitutions distant from the active site in a Klentaq DNA polymerase variant (ZP Klentaq) contribute to its ability to replicate UBPs with improved efficiency compared with Klentaq. This approach can therefore serve to guide any future rational engineering of replicative DNA polymerases.

RNA-protein interfaces control key replication events during the HIV-1 life cycle. The viral trans-activator of transcription (Tat) protein uses an archetypal arginine-rich motif (ARM) to recruit the host positive transcription elongation factor b (pTEFb) complex onto the viral trans-activation response (TAR) RNA, leading to activation of HIV transcription. Efforts to block this interaction have stimulated production of biologics designed to disrupt this essential RNA-protein interface. Here, we present four co-crystal structures of lab-evolved TAR-binding proteins (TBPs) in complex with HIV-1 TAR. Our results reveal that high-affinity binding requires a distinct sequence and spacing of arginines within a specific β2-β3 hairpin loop that arose during selection. Although loops with as many as five arginines were analyzed, only three arginines could bind simultaneously with major-groove guanines. Amino acids that promote backbone interactions within the β2-β3 loop were also observed to be important for high-affinity interactions. Based on structural and affinity analyses, we designed two cyclic peptide mimics of the TAR-binding β2-β3 loop sequences present in two high-affinity TBPs (KD values of 4.2 ± 0.3 and 3.0 ± 0.3 nm). Our efforts yielded low-molecular weight compounds that bind TAR with low micromolar affinity (KD values ranging from 3.6 to 22 μm). Significantly, one cyclic compound within this series blocked binding of the Tat-ARM peptide to TAR in solution assays, whereas its linear counterpart did not. Overall, this work provides insight into protein-mediated TAR recognition and lays the ground for the development of cyclic peptide inhibitors of a vital HIV-1 RNA-protein interaction.

Environmental Change and Emerging Diseases 28 October 2020 — 3:00PM TO 4:00PM Anonymous (not verified) 13 October 2020 Online

Understanding how environmental changes are directly and indirectly affecting the emergence and spread of disease has assumed global importance.

There is growing awareness that deforestation and land-use conversion, urbanization, human migration, international commerce, and climate change are having significant impacts on human health, but their impact on increasing infectious disease risks has only become more evident with the coronavirus pandemic.

With climate change, and environmental change more generally, disrupting ecologies, and people interacting with wildlife in new ways, it creates the conditions for new diseases to emerge: a better understanding of the health dimensions of environmental change will be critical to managing pandemic risks in future. 

Our event will examine the relationship between environmental change and disease, how these linkages have manifested in historical outbreaks and in the coronavirus pandemic, and the role of environmental policies in minimizing the risk of future emerging diseases.  What can be done to ensure equitable action? What can we learn from our responses to previous pandemics? And will the growing recognition of the diverse risks arising from climate change motivate more climate action?

This event will launch the Energy, Environment and Resources (EER) Programme’s Environment and Society Discussion Series. This series aims to provide a platform to promote interdisciplinary knowledge sharing and policy dialogue to mitigate and adapt to the impacts that climate change, biodiversity loss and natural resource depletion are having on people and communities globally, and on geopolitics, security and international development.

Sign up to find out about more events in this series here. 

Dr. Rekha Thomas from the University of Washington discusses three-dimensional image reconstructions from two-dimensional photos. The mathematics of image reconstruction is both simpler and more abstract than it seems. To reconstruct a 3D model based on photographic data, researchers and algorithms must solve a set of polynomial equations. Some solutions to these equations work mathematically, but correspond to an unrealistic scenario — for instance, a camera that took a photo backwards. Additional constraints help ensure this doesn't happen. Researchers are now investigating the mathematical structures underlying image reconstruction, and stumbling over unexpected links with geometry and algebra.

Carnosine (β-alanyl-l-histidine) and anserine (β-alanyl-3-methyl-l-histidine) are abundant peptides in the nervous system and skeletal muscle of many vertebrates. Many in vitro and in vivo studies demonstrated that exogenously added carnosine can improve muscle contraction, has antioxidant activity, and can quench various reactive aldehydes. Some of these functions likely contribute to the proposed anti-aging activity of carnosine. However, the physiological role of carnosine and related histidine-containing dipeptides (HCDs) is not clear. In this study, we generated a mouse line deficient in carnosine synthase (Carns1). HCDs were undetectable in the primary olfactory system and skeletal muscle of Carns1-deficient mice. Skeletal muscle contraction in these mice, however, was unaltered, and there was no evidence for reduced pH-buffering capacity in the skeletal muscle. Olfactory tests did not reveal any deterioration in 8-month-old mice lacking carnosine. In contrast, aging (18–24-month-old) Carns1-deficient mice exhibited olfactory sensitivity impairments that correlated with an age-dependent reduction in the number of olfactory receptor neurons. Whereas we found no evidence for elevated levels of lipoxidation and glycation end products in the primary olfactory system, protein carbonylation was increased in the olfactory bulb of aged Carns1-deficient mice. Taken together, these results suggest that carnosine in the olfactory system is not essential for information processing in the olfactory signaling pathway but does have a role in the long-term protection of olfactory receptor neurons, possibly through its antioxidant activity.

Managing natural resources

Research analyzing options for the sustainable management of natural resources and how to use them in a way that enhances the resilience of ecosystems.

Areas of focus include examining what is the future for fossil fuels and other extractive industries (especially coal, oil and natural gas), forest governance in light of continued illegal logging and deforestation, and ocean governance.

Natural resources are vital for the future sustainability of major industries such as agriculture, mining, tourism, fisheries and forestry. Research is carried out in areas such as land use planning, water management, biodiversity conservation, and the scientific and technical understanding of resources governance.

Connexin (Cx) protein forms hemichannels and gap junctional channels, which play diverse and profound roles in human physiology and diseases. Gap junctions are arrays of intercellular channels formed by the docking of two hemichannels from adjacent cells. Each hexameric hemichannel contains the same or different Cx isoform. Although homomeric Cxs forms have been largely described functionally and structurally, the stoichiometry and arrangement of heteromeric Cx channels remain unknown. The latter, however, are widely expressed in human tissues and variation might have important implications on channel function. Investigating properties of heteromeric Cx channels is challenging considering the high number of potential subunit arrangements and stoichiometries, even when only combining two Cx isoforms. To tackle this problem, we engineered an HA tag onto Cx26 or Cx30 subunits and imaged hemichannels that were liganded by Fab-epitope antibody fragments via atomic force microscopy. For Cx26-HA/Cx30 or Cx30-HA/Cx26 heteromeric channels, the Fab-HA binding distribution was binomial with a maximum of three Fab-HA bound. Furthermore, imaged Cx26/Cx30-HA triple liganded by Fab-HA showed multiple arrangements that can be derived from the law of total probabilities. Atomic force microscopy imaging of ringlike structures of Cx26/Cx30-HA hemichannels confirmed these findings and also detected a polydisperse distribution of stoichiometries. Our results indicate a dominant subunit stoichiometry of 3Cx26:3Cx30 with the most abundant subunit arrangement of Cx26-Cx26-Cx30-Cx26-Cx30-Cx30. To our knowledge, this is the first time that the molecular architecture of heteromeric Cx channels has been revealed, thus providing the basis to explore the functional effect of these channels in biology.

16 July 2020

2 September 2020

Cancer cachexia is characterized by reductions in peripheral lean muscle mass. Prior studies have primarily focused on increased protein breakdown as the driver of cancer-associated muscle wasting. Therapeutic interventions targeting catabolic pathways have, however, largely failed to preserve muscle mass in cachexia, suggesting that other mechanisms might be involved. In pursuit of novel pathways, we used untargeted metabolomics to search for metabolite signatures that may be linked with muscle atrophy. We injected 7-week–old C57/BL6 mice with LLC1 tumor cells or vehicle. After 21 days, tumor-bearing mice exhibited reduced body and muscle mass and impaired grip strength compared with controls, which was accompanied by lower synthesis rates of mixed muscle protein and the myofibrillar and sarcoplasmic muscle fractions. Reductions in protein synthesis were accompanied by mitochondrial enlargement and reduced coupling efficiency in tumor-bearing mice. To generate mechanistic insights into impaired protein synthesis, we performed untargeted metabolomic analyses of plasma and muscle and found increased concentrations of two methylarginines, asymmetric dimethylarginine (ADMA) and NG-monomethyl-l-arginine, in tumor-bearing mice compared with control mice. Compared with healthy controls, human cancer patients were also found to have higher levels of ADMA in the skeletal muscle. Treatment of C2C12 myotubes with ADMA impaired protein synthesis and reduced mitochondrial protein quality. These results suggest that increased levels of ADMA and mitochondrial changes may contribute to impaired muscle protein synthesis in cancer cachexia and could point to novel therapeutic targets by which to mitigate cancer cachexia.

The online media changing African news The World Today mhiggins.drupal 2 August 2022

Africa’s news sites are gripping audiences with digital innovation and bold directions. Helen Fitzwilliam talks to editors at three platforms.

Lydia Namubiru
News editor of ‘The Continent’ (South Africa)

At the start of the pandemic, we realized a lot of fake news was being shared on WhatsApp. So, The Continent chose to launch on that platform to insert some real journalism in a way that could easily be shared. We now have about 100,000 readers across Africa and the rest of the world, but we had to dramatically change the way we write and edit stories: to compete with the likes of Twitter and Instagram, we try to keep stories tight at 300 words. 

There’s a real variety. We can run an investigation into corruption in the Democratic Republic of the Congo a week after a front page on the fashion designer who dresses Africa’s ‘big men’ [powerful leaders]. We cover feminist issues, the backlash against LGBT people in Ghana; we’ve had the Namibian first lady talking to us about misogyny. These are not the sort of topics a typical African newspaper is going to lead with.

With a story such as Ukraine, the war’s impact on the cost of living has been the most obvious angle for us. It has driven countries such as Malawi into crisis, forcing a devaluation of the currency.
 
As for the future, we see two issues looming. Workers’ economic rights and their treatment by multinationals will be a big story. There are refugees in camps in Kenya working in data operations and being paid a pittance to help create huge, potentially multimillion-dollar systems for US companies. 

Second, Africa has the world’s youngest population and the oldest leaders, so this will likely lead to activism and protests. The young are exposed to the global village, so they want different things and have different values. They speak a completely different language their leaders do not understand. It will be an interesting conflict, but could lead to real violence. 

John Githongo
Editor of ‘The Elephant’ (Kenya)

We set up this platform four years ago. Due to political and commercial pressures, mainstream media wasn’t doing much critical reporting. We have between 30,000 and 80,000 readers a week, the majority of them in Africa. 

The digital space reaches a completely different demographic. When The Elephant started, it was 80 per cent male and over 40, but we have gained more younger people and more women. Now it is 60 per cent men, 40 per cent women and that is something we have been working at. 

Our editorial approach is that as long as a piece has a strong argument and fits into our pan-African brief, we will publish it – even if we don’t agree with it.

The conflicts in Ethiopia and parts of the Sahel make the war in Ukraine pale in comparison. So many people have died in Ethiopia or been displaced and now we have the onset of a famine after four years of failed rain. During the 1960s and 1970s, when the Cold War found its way on to African soil, millions of people died – so there is caution about getting involved in a European fight.

There is always a lot of fake news around during elections. But people are beginning to be more sceptical. We go after those who attempt to change the level of debate with reputation-laundering and try to expose their actions. 
 
The future of democracy is going to be a big issue. When Africans were watching the attack on the US Capitol last year, they were hoping it was not a Black Lives Matter protest, which could have resulted in a ‘blackbath’. As soon as they saw the white guys wearing horns, people laughed with relief. 

There is an ongoing recalibration of Africa’s geopolitical relations with the rest of the world. A poll released in June showed China has overtaken the United States as the foreign power having the biggest positive influence in Africa in the eyes of young people across the continent. The younger generation is writing its own narrative. 

Wale Lawal
Editor of ‘The Republic’ (Nigeria)

Nigerian audiences are increasingly online and tend to read both local and international publications. They also know that the issues they care about are either under-reported or reported at lower quality levels. 

At The Republic, we provide political journalism that tends to require high levels of expertise. Yet online audiences also prioritize engagement: it is not enough for an issue to be important, it also needs to be interesting.

Some topics we have covered that Western media tend not to include how people experience blackness in different parts of the world; the waves of mostly female-led and youth-led movements rising up against autocratic governments across Africa; and relationships between countries within Africa itself. In the early days of the pandemic, we launched a Covid-19 and Africa series, having noticed a glaring lack of African expert voices in global media.
 
We also cover Africa’s evolving relations with Russia. Whenever we encounter a story like Russia’s invasion of Ukraine, the first thing we always ask ourselves is what missing voice can we add to the current discussion? All we were reading about after the invasion was how neighbouring countries were opening their borders and their homes to Ukrainians. Most people saw only that. 

But we knew that around 15,000 Africans were studying in Ukraine, that Africans routinely face harsh treatment at international borders, and that clearly their voices were missing from the discussion.

With fake news and information gaps on social media, our usual approach is to develop expert-led columns and circulate these as widely as possible.

Our next mission is to think about the role that independent media can play in supporting democracies, such as by increasing voter turnout. During the last election in Nigeria, less than 35 per cent of those who registered to vote eventually did so.

PREAMBLE

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The EANM was founded in 1985. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine.

The SNMMI and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated.

Each practice guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized.

These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, both the SNMMI and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question.

The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines.

The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment.

Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Visual Abstract

Visual Abstract

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Visual Abstract

Decades of obsolete and unpatched hardware and software endanger us all

Colin T. McDowell
Nov 24, 2020; 0:RA120.002256v1-mcp.RA120.002256
Research