Mary G. McCoy
Jun 1, 2002; 43:921-929
Research Articles

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

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

Nica M. Borradaile
Dec 1, 2006; 47:2726-2737
Research Articles

Oswald Quehenberger
Nov 1, 2010; 51:3299-3305
Research Articles

Vitali Matyash
May 1, 2008; 49:1137-1146
Methods

The regional and international implications of restrictions to online freedom of expression in Asia 25 March 2021 — 12:30PM TO 1:30PM Anonymous (not verified) 12 March 2021 Online

Panellists discuss the latest developments affecting online freedom of expression in the Asia region.

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

In recent years, state-led clampdowns on online freedom of expression have become widespread in several countries across Asia, further intensified by the COVID-19 crisis.

The reasons for this are complex and diverse – drawing upon history, culture and politics, in addition to external influences. Across the region, governments have been accused of silencing online criticism and failing to uphold rights to free speech.

Individuals have been arrested, fined or attacked for the alleged spread of ‘fake news’, raising concern among human rights organizations. In some countries, this has culminated in the imposition of new social media rules, which could require social media companies to censor posts and share decrypted messages.

In China, the government’s restrictive online regime has relied on a combination of legal, technical and manipulation tactics to manage control of the internet, and now includes attempts at censorship beyond its borders.

Panellists will discuss the latest regional developments affecting online freedom of expression in the Asia region, and will consider the broader regional and international implications for technology governance.

This webinar launches the publication Restrictions on online freedom of expression in China: The domestic, regional and international implications of China’s policies and practices.

Battle lines being drawn over online freedoms in Asia Expert comment NCapeling 22 March 2021

Social media giants are increasingly clashing with Asian governments over free expression and censorship as the region lurches towards digital authoritarianism.

Freedom of expression was subject to significant restrictions in Asia even before the pandemic, with several governments having enacted laws that stifle online debate. But since COVID-19, restrictions have increased even further due to a rash of so-called ‘emergency measures’ introduced by governments across the region.

Bangladesh, India, Indonesia, Malaysia, Myanmar, Nepal, Pakistan, the Philippines, Sri Lanka, Thailand, and Vietnam have all put new laws into place, and many restrictions are already being applied in a draconian fashion, such as in the Philippines and Bangladesh.

As outlined in a new Chatham House research paper, one inspiration behind this trend is China, home to the world’s most sophisticated and restrictive system of internet control. The Chinese government’s restrictive online regime, which has tightened further under COVID-19, relies on a combination of legal regulations, technical controls, and proactive manipulation of online debates.

This model was an inspiration for Vietnam’s cybersecurity law, as well as Myanmar’s new draft cybersecurity bill, proposed by the Military-run State Administration Council in the wake of the military coup last month, which would give the military there extensive powers to access individuals’ data, restrict, or suspend access to the internet.

This ‘sovereignty and control’ model of internet governance is also gaining impetus through China’s ‘Digital Silk Road’ initiative, under which the Chinese government is exporting both its technology – such as through the establishment of smart cities, the installation of AI, and surveillance technology – and its vision of how the internet should be governed.

In November 2020, Xi Jinping pledged to further deepen cooperation with ASEAN through the Digital Silk Road, and the pandemic has expanded the appeal of Chinese surveillance technologies and data collection platforms to governments both in Asia and beyond. China’s Health Silk Road, which aims to promote global health cooperation, is centered on the Chinese government’s high-tech model under which civic freedoms are sacrificed in the name of public health.

An alternative model

This ‘sovereignty and control’ model is increasingly at odds with the more ‘human-centric’ model of tech governance favoured by many democratic states, Western social media companies, and international institutions, especially the United Nations (UN) and European Union (EU).

Although this emerging model also involves regulation, it is regulation which aims to be inclusive, risk-based, and proportionate – balancing the need for protection against online harms with the need to preserve freedom of expression. It is a multi-stakeholder, rights-based approach which brings together not just governments but also representatives of the private sector, civil society, and academia. The EU’s draft Digital Services Act and the UK’s proposals for an Online Safety Bill are both reflective of this approach.

Western social media giants such as Facebook and Twitter have recently introduced new policies which seek to identify and mitigate online harms, such as hate speech and disinformation. Industry bodies such as the Global Network Initiative, independent oversight bodies such as the Oversight Board established by Facebook, and civil society advocacy and initiatives such as the Santa Clara Principles on Transparency and Accountability in Content Moderation are also an important part of the picture.

Admittedly, these various digital governance initiatives are in some cases embryonic, and are by no means a silver bullet solution to the complex problem of online content moderation, which continues to be hotly debated in democratic societies. But they are at least underpinned by the same philosophy – that international human rights law standards must continue to apply even during emergencies such as COVID-19. With the Biden administration in the US prioritizing tech governance in its policy agenda, there is added momentum to the international leadership behind this model.

A clash of ideology

These conflicting philosophies are playing out in debates on technology governance at the UN, with one group of countries led by China and Russia advocating for greater government control of the internet, and many Western democracies emphasizing the need for an open, global internet that protects human rights.

These differing ideologies are also creating tensions between Western social media companies operating in Asia and the various governments in that region which have increased restrictions on online expression. And the gulf between the two appears to be widening.

In 2017, the Thailand government threatened Facebook with legal action unless it agreed to remove content critical of Thailand’s royal family and, in 2020, Facebook announced it had been ‘forced to block’ such material. Also in 2020, the Vietnam government pressured state-owned telecom companies to throttle internet traffic to Facebook, effectively restricting access to the platform, until Facebook agreed to take down content the government deemed to be anti-state.

Platforms refuse to silence legitimate criticism

However, Silicon Valley’s social media companies have also been pushing back. Facebook restricted the accounts of Myanmar’s military on the basis of ‘spreading misinformation’ in the wake of the military’s imposition of an internet shutdown that blocked access to Facebook, Twitter, and Instagram. And Twitter resisted requests by the Indian government to block accounts involved in protests by farmers.

Twitter stated that while it would block any accounts which it felt incited violence, it would not take action on accounts belonging to news media entities, journalists, activists, and politicians because it believed that would ‘violate the fundamental right to free expression under the Indian law’. The Indian government responded by fast-tracking stringent new social media regulations heavily criticized by rights groups for increasing government power over content on social media platforms, including online news.

So how can social media companies find avenues for operating in Asia and beyond without being co-opted into the lurch towards digital authoritarianism? There are no easy answers here, but collaboration is key. Cooperation between tech companies and local civil society partners can help companies better understand risks to human rights in the country concerned and how they might be mitigated. And tech companies are more effective in alliance with each other than acting on their own, such as the refusal by Facebook, Google, Telegram, and Twitter to hand over data on protestors to the Hong Kong police.

The fact that in many countries in Asia there are no alternatives to Western social media companies – unlike China, where platforms such as WeChat are part of the government’s internet control apparatus – gives the companies concerned some leverage. In February 2020, Facebook, Google, and Twitter together – through the Asia Internet Coalition – threatened to leave Pakistan in response to the government’s draconian proposals to regulate social media. Along with pressure and lawsuits from civil society, this forced the government into retreat, although the tussle over the new rules, introduced in November, continues.

At a time when illiberalism was already on the rise in Asia (including in democracies – Freedom House has just downgraded India’s status from ‘free’ to ‘partly free’), COVID-19 has made tighter state control of online freedom of expression even more attractive to many governments. As it seems increasingly unlikely that restrictions enacted under the guise of pandemic-related emergency measures will be repealed once the COVID-19 crisis ends, it is even more important that tech companies work with civil society on the ground to minimize the censorship of citizen voices.

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.

Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3' UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3' UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through–deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential.

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Histone recognition by “reader” modules serves as a fundamental mechanism in epigenetic regulation. Previous studies have shown that Spindlin1 is a reader of histone H3K4me3 as well as “K4me3-R8me2a” and promotes transcription of rDNA or Wnt/TCF4 target genes. Here we show that Spindlin1 also acts as a potent reader of histone H3 “K4me3-K9me3/2” bivalent methylation pattern. Calorimetric titration revealed a binding affinity of 16 nm between Spindlin1 and H3 “K4me3-K9me3” peptide, which is one to three orders of magnitude stronger than most other histone readout events at peptide level. Structural studies revealed concurrent recognition of H3K4me3 and H3K9me3/2 by aromatic pockets 2 and 1 of Spindlin1, respectively. Epigenomic profiling studies showed that Spindlin1 colocalizes with both H3K4me3 and H3K9me3 peaks in a subset of genes enriched in biological processes of transcription and its regulation. Moreover, the distribution of Spindlin1 peaks is primarily associated with H3K4me3 but not H3K9me3, which suggests that Spindlin1 is a downstream effector of H3K4me3 generated in heterochromatic regions. Collectively, our work calls attention to an intriguing function of Spindlin1 as a potent H3 “K4me3-K9me3/2” bivalent mark reader, thereby balancing gene expression and silencing in H3K9me3/2-enriched regions.

The functional mechanisms of multidomain proteins often exploit interdomain interactions, or “cross-talk.” An example is human Pin1, an essential mitotic regulator consisting of a Trp–Trp (WW) domain flexibly tethered to a peptidyl-prolyl isomerase (PPIase) domain, resulting in interdomain interactions important for Pin1 function. Substrate binding to the WW domain alters its transient contacts with the PPIase domain via means that are only partially understood. Accordingly, we have investigated Pin1 interdomain interactions using NMR paramagnetic relaxation enhancement (PRE) and molecular dynamics (MD) simulations. The PREs show that apo-Pin1 samples interdomain contacts beyond the range suggested by previous structural studies. They further show that substrate binding to the WW domain simultaneously alters interdomain separation and the internal conformation of the WW domain. A 4.5-μs all-atom MD simulation of apo-Pin1 suggests that the fluctuations of interdomain distances are correlated with fluctuations of WW domain interresidue contacts involved in substrate binding. Thus, the interdomain/WW domain conformations sampled by apo-Pin1 may already include a range of conformations appropriate for binding Pin1's numerous substrates. The proposed coupling between intra-/interdomain conformational fluctuations is a consequence of the dynamic modular architecture of Pin1. Such modular architecture is common among cell-cycle proteins; thus, the WW–PPIase domain cross-talk mechanisms of Pin1 may be relevant for their mechanisms as well.

RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RecQ C-terminal domain, and an auxiliary element helicase and RNaseD C-terminal (HRDC) domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3'-partial duplex and fork DNA with a moderate processivity and periodically patrols on the ssDNA in the 5'-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA-binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms.

What does sustainable agriculture mean? 24 May 2022 — 5:30PM TO 6:30PM Anonymous (not verified) 11 May 2022 Chatham House and Online

Experts compare and contrast visions of ‘sustainable’ agriculture.

There is growing and unprecedented recognition of the adverse effects of food systems on global warming, air and water pollution, biodiversity, soil, and managing the emergence and spread of infectious diseases. At the same time, concern is rising over the role of climate change itself in compromising food security, supply-chain resilience and food price spikes.

Against this backdrop, the need for agriculture to become more ‘sustainable’ is clear. However, there is little consensus over what that means in practice. To address this, Chatham House is launching a new research paper comparing and contrasting the two most commonly articulated versions of ‘sustainable agriculture’.

The first focuses on sparing land for nature and increasing the productivity of agricultural land while minimizing environmental impacts. The second involves scaling up nature-friendly farming while emphasizing demand-side changes to reduce the overall pressure on land.

• How can we understand the arguments in support of either version and the assumptions and ideologies which underpin them?

• What are the implications of promoting one version of agriculture over the other

• How can policy transform agriculture and food systems?

• What should civil society support as ‘sustainable’ choices?

Twenty Years After Hong Kong Handover, Does ‘One Country, Two Systems’ Still Work? Expert comment sysadmin 28 June 2017

This unique constitutional framework can endure – if Hong Kong society can reconcile its different visions of the future.

Twenty years after the handover of Hong Kong from British to Chinese sovereignty, the ‘one country, two systems’ arrangement – the main aim of which was to guarantee the continuity of Hong Kong’s open society and way of life – can be said to have worked well. Street protests remain a regular feature of Hong Kong’s political culture. Freedom of information and expression are alive and well. Hong Kong retains its ‘capitalist way of life’, its legal system based on common law and independent judiciary, and its status as an international financial centre. As a result the city remains one of the most open economies across Asia, with robust institutions and transparency which are hard to find anywhere else in the region.

Yet the 79-day ‘occupy’ protests of autumn 2014 showed that something is not quite right in the city of Hong Kong.

The protests themselves had a number of causes. Partly they reflected socioeconomic concerns, especially the rise in income inequality and lack of affordable housing. These might have been dealt with to some extent by better governance over the years, but they are also a feature of many societies in the current phase of globalization – a case, perhaps, of too much ‘capitalist way of life’.

Politically, the desire expressed by many in 2014 was for a form of ‘genuine universal suffrage’ for the selection of Hong Kong’s chief executive which went beyond a provision of Hong Kong’s mini constitution, the Basic Law, that candidates should be put forward by a ‘nominating committee’. It was on this point that the possibility of constitutional reform foundered in 2015, leaving Hong Kong no further ahead in its ‘gradual progress’ towards democracy.

But this episode also brought to the surface the tension between different visions for Hong Kong’s future. In particular, many in Hong Kong are still uncomfortable with the ‘one country’ part of the deal, rejected by some (especially young people) in the ways that they conceptualize Hong Kong identity – according to one recent survey, as little as 3.1% of Hong Kong youths identify themselves as ‘Chinese’. These issues are likely to constrain political development for some time to come.

At their sharpest, some of these visions are for some form of self-determination, or even independence, for Hong Kong. This is not just anathema to the national authorities in Beijing, but contradicts a basic tenet of Hong Kong’s handover in 1997, the return to Chinese sovereignty. This is not just something on which Beijing will never compromise, but will seek to challenge.

It is this which explains the sense in Hong Kong that the central government has been looking to become politically more involved since 2014. But the challenge of influencing Hong Kong society is great, and other than strengthening relations with the establishment camp, Beijing has not been able to tighten its grip. If anything, the centre of gravity of Hong Kong politics has continued to drift away from Beijing, not towards it.

How this will play out remains to be seen. Some amelioration of social tensions could help. But the fundamental divergence in visions of Hong Kong’s future will not be resolved so easily.

Looking forward therefore, the key to the continued success of ‘one country, two systems’ lies in Hong Kong society. If mainstream acceptance of the compromises involved can return, then this unique constitutional framework can still work for years to come.

Ran Gu and Bing Gao
Math. Comp. 93 (), 2837-2860.
Abstract, references and article information

Math may sometimes seem as if it's comprised of countless meaningless unconnected exercises, but in reality, it's much more. It's figuring out how to do something, and, even better, why something works the way it does. The math you're doing now can open doors for you so that you can answer deep questions yourself about a subject or idea that you're interested in. Give those questions a shot and perhaps someday also help others solve their problems. Five mathematicians (Alexander Diaz-Lopez, Trachette Jackson, Francis Su, Erika Tatiana Camacho, and Deanna Haunsperger) talk about what mathematics means to them.

Imelda Flores Vazquez from Econometrica, Inc. explains how economists use mathematics to evaluate the efficacy of health care policies. When a hospital or government wants to adjust their health policies — for instance, by encouraging more frequent screenings for certain diseases — how do they know whether their program will work or not? If the service has already been implemented elsewhere, researchers can use that data to estimate its effects. But if the idea is brand-new, or has only been used in very different settings, then it's harder to predict how well the new program will work. Luckily, a tool called a microsimulation can help researchers make an educated guess.

Daniel López Neumann
Trans. Amer. Math. Soc. 377 (), 5361-5387.
Abstract, references and article information

Christoforos Neofytidis
Trans. Amer. Math. Soc. 377 (), 5289-5321.
Abstract, references and article information

Marko Voutilainen, Lauri Viitasaari and Pauliina Ilmonen
Theor. Probability and Math. Statist. 111 (), 181-197.
Abstract, references and article information

Ta Cong Son, Tran Manh Cuong, Le Quang Dung and Le Van Dung
Theor. Probability and Math. Statist. 111 (), 153-165.
Abstract, references and article information

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

Abdessamad Dehaj and Mohamed Guessous
Theor. Probability and Math. Statist. 111 (), 1-8.
Abstract, references and article information

Yongqiang Liu, Laurentiu Maxim and Botong Wang
Proc. Amer. Math. Soc. 152 (), 5279-5288.
Abstract, references and article information

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In a touching display of compassion and solidarity, a group of St Thomas residents has come together to organise the funeral of a a well-known and beloved man with intellectual challenges. For years, Donovan Sinclair was a familiar face in the...

Distinct cell types emerge from embryonic stem cells through a precise and coordinated execution of gene expression programs during lineage commitment. This is established by the action of lineage specific transcription factors along with chromatin complexes. Numerous studies have focused on epigenetic factors that affect embryonic stem cells (ESC) self-renewal and pluripotency. However, the contribution of chromatin to lineage decisions at the exit from pluripotency has not been as extensively studied. Using a pooled epigenetic shRNA screen strategy, we identified chromatin-related factors critical for differentiation toward mesodermal and endodermal lineages. Here we reveal a critical role for the chromatin protein, ARID4B. Arid4b-deficient mESCs are similar to WT mESCs in the expression of pluripotency factors and their self-renewal. However, ARID4B loss results in defects in up-regulation of the meso/endodermal gene expression program. It was previously shown that Arid4b resides in a complex with SIN3A and HDACS 1 and 2. We identified a physical and functional interaction of ARID4B with HDAC1 rather than HDAC2, suggesting functionally distinct Sin3a subcomplexes might regulate cell fate decisions Finally, we observed that ARID4B deficiency leads to increased H3K27me3 and a reduced H3K27Ac level in key developmental gene loci, whereas a subset of genomic regions gain H3K27Ac marks. Our results demonstrate that epigenetic control through ARID4B plays a key role in the execution of lineage-specific gene expression programs at pluripotency exit.

Thoracic great vessels such as the aorta and subclavian arteries are formed through dynamic remodeling of embryonic pharyngeal arch arteries (PAAs). Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. However, how Hey1 mediates vascular formation remains unclear. In this study, we revealed that Hey1 in vascular endothelial cells, but not in smooth muscle cells, played essential roles for PAA development and great vessel morphogenesis in mouse embryos. Tek-Cre–mediated Hey1 deletion in endothelial cells affected endothelial tube formation and smooth muscle differentiation in embryonic fourth PAAs and resulted in interruption of the aortic arch and other great vessel malformations. Cell specificity and signal responsiveness of Hey1 expression were controlled through multiple cis-regulatory regions. We found two distal genomic regions that had enhancer activity in endothelial cells and in the pharyngeal epithelium and somites, respectively. The novel endothelial enhancer was conserved across species and was specific to large-caliber arteries. Its transcriptional activity was regulated by Notch signaling in vitro and in vivo, but not by ALK1 signaling and other transcription factors implicated in endothelial cell specificity. The distal endothelial enhancer was not essential for basal Hey1 expression in mouse embryos but may likely serve for Notch-dependent transcriptional control in endothelial cells together with the proximal regulatory region. These findings help in understanding the significance and regulation of endothelial Hey1 as a mediator of multiple signaling pathways in embryonic vascular formation.

Clostridium difficile is an anaerobic and spore-forming bacterium responsible for 15–25% of postantibiotic diarrhea and 95% of pseudomembranous colitis. Peptidoglycan is a crucial element of the bacterial cell wall that is exposed to the host, making it an important target for the innate immune system. The C. difficile peptidoglycan is largely N-deacetylated on its glucosamine (93% of muropeptides) through the activity of enzymes known as N-deacetylases, and this N-deacetylation modulates host–pathogen interactions, such as resistance to the bacteriolytic activity of lysozyme, virulence, and host innate immune responses. C. difficile genome analysis showed that 12 genes potentially encode N-deacetylases; however, which of these N-deacetylases are involved in peptidoglycan N-deacetylation remains unknown. Here, we report the enzymes responsible for peptidoglycan N-deacetylation and their respective regulation. Through peptidoglycan analysis of several mutants, we found that the N-deacetylases PdaV and PgdA act in synergy. Together they are responsible for the high level of peptidoglycan N-deacetylation in C. difficile and the consequent resistance to lysozyme. We also characterized a third enzyme, PgdB, as a glucosamine N-deacetylase. However, its impact on N-deacetylation and lysozyme resistance is limited, and its physiological role remains to be dissected. Finally, given the influence of peptidoglycan N-deacetylation on host defense against pathogens, we investigated the virulence and colonization ability of the mutants. Unlike what has been shown in other pathogenic bacteria, a lack of N-deacetylation in C. difficile is not linked to a decrease in virulence.