Islamic radicalisation in Central Asia 18 September 2024 — 10:00AM TO 11:30AM Anonymous (not verified) 20 August 2024 Chatham House and Online

Experts analyse rising foreign recruitment, current counter-radicalisation efforts and challenge past Chatham House predictions made of the Central Asia region.

In 2014, Chatham House released a report titled The Myth of Post-Soviet Muslim Radicalisation in the Central Asian Republics. At that time, a significant, Western-funded counter-radicalisation industry was addressing what was believed to be a major issue of Islamic violent extremism in the region.

Over the past decade, two key developments have occurred. First, Western interest in the region has declined in favour of traditional geopolitical concerns. Second, while violent extremism incidents within Central Asia remain rare, there has been a notable recruitment of Central Asians by foreign groups, with several attacks carried out by Central Asians overseas.

In this event, the original report’s authors, John Heathershaw and David Montgomery, will discuss whether the report’s arguments are still valid and how we might answer these questions today.

This raises several questions:

• What did the report accurately predict, and where did it fall short?
• How can we explain the lack of violent extremist organisations (VEOs) within Central Asia but the presence of Central Asians in VEOs abroad?
• Could repression by Central Asian states both domestically and transnationally have contributed to this issue?
• What, if anything, can the counter-radicalisation industry do today to address this problem more effectively?

Please note that in-person places are limited. Please wait for confirmation before participating. 

What are MENA countries’ priorities for climate action and COP? 24 October 2024 — 1:00PM TO 2:00PM Anonymous (not verified) 2 October 2024 Online

Experts discuss the impacts of COP27 and 28 on the region and priorities for COP29.

In November this year, all eyes will be on Azerbaijan as Baku hosts the 29th UN Climate Conference (COP). Hosting COP offers an opportunity to push for climate action that reflects the host country’s unique circumstances, as well as regional interests. COP28 in the United Arab Emirates and COP27 in Egypt highlighted the climate priorities for the Middle East and North Africa (MENA), one of the world’s most vulnerable regions to the impacts of climate change.

From rising temperatures and deadly heatwaves, to extreme weather events such as heavy rainstorms, sandstorms, and cyclones, climate change exacerbates existing vulnerabilities. These vulnerabilities include water scarcity, food security, and the preservation of livelihoods increasingly threatening the region’s social and economic stability.

While there has been some progress in advancing formal negotiations on key issues, the gap between COP agreements and tangible actions to address the increasingly severe effects of climate change in the MENA region remains vast. 

This webinar aims to assess:

• What are the key tangible impacts of COP27 and COP28 in Egypt and the UAE respectively on driving climate action in the region?
• How do MENA countries balance COP28’s landmark agreement to transition away from fossil fuels with their unique national circumstances?
• How will the region benefit from COP28 breakthrough in integrating the issues of climate, peace and security in climate action through the ‘Declaration of Climate, Relief, Recovery and Peace’?
• What are the priorities for COP29 and how do they align with the climate agenda in the MENA region?

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

Jacek R. Wiśniewski
Dec 1, 2014; 13:3497-3506
Research

Saturday Club introduces young people to international affairs News release jon.wallace 24 February 2022

Clubs will help 13-16 year-olds learn more about the forces that are shaping the world and discover how young people can influence the future.

National Saturday Club and Chatham House are delighted to announce the launch of the Society&Change Saturday Club. This new programme creates opportunities for UK 13–16-year-olds to develop a global mindset and build awareness of trends that will shape the world in the coming decades.

Three pilot Society&Change Clubs will be hosted by the University of Sussex, Manchester Metropolitan University, and the University of Huddersfield. Chatham House will provide speakers and generate ideas for the clubs.

National Saturday Club gives 13–16-year-olds across the country the opportunity to study subjects they love at their local university, college or cultural institution, for free.

Society&Change Club members will be introduced to a wide range of careers including policy making and diplomacy, advocacy, media and journalism, international trade and business, and the international development and humanitarian sector.

Weekly classes will be led by led by professional tutors from the host institutions. Club members will also take part in masterclasses with industry professionals, as well as an end of year summer show and graduation ceremonies.

Lucy Kennedy, Chief Executive of the Saturday Club Trust said:

‘We are delighted to be partnering with Chatham House to launch the Society&Change Saturday Club, the sixth subject within the National Saturday Club programme. Over the past 12 years, working nationally with 13–16-year-olds, we have seen that young people are eager to share their hopes and ideas for the future and address the issues the world faces.

‘We hope this new Saturday Club will empower them to shape their own futures and will bring the urgent voice of young people to international debate.’

Rose Abdollahzadeh, Managing Director for Research Partnerships at Chatham House said:

‘We are really excited about the potential for this partnership to encourage young people across the UK to explore their role in the world. The National Saturday Club network will also give Chatham House opportunities to harness the energy, ideas and passion of young people towards positive change.

‘By introducing Club members to contemporary debates on global issues and a range of professions in foreign policy and international relations, our hope is that some Club members will choose to follow a career path into this sector.’

Learn more about the Society&Change Saturday Club.

Is there an end to the Central Bank of Libya crisis? 14 November 2024 — 3:00PM TO 4:00PM Anonymous (not verified) 6 November 2024 Online

Experts discuss implications for Libya’s economic governance.

In August this year, the Libyan Presidency Council moved to replace Libya’s longtime central bank governor, Sadiq al-Kabir. Kabir had been in position since September 2011, and in the period following the administrative division of Libya, he rose to prominence as one of the most influential figures on the Libyan political scene.

In the absence of a functioning relationship between executive and legislature, the Central Bank of Libya (CBL) took on many of the competencies of the ministry of finance and became an arbiter of which payments were made and when. In October, following UN-led and parallel back-channel negotiations, a new governor was selected and the CBL board of directors reconstituted.

In this webinar, experts will examine:

• What challenges will the new CBL leadership face?
• Can we expect significant changes for Libya’s economic governance?
• What are the implications for the balance of power between Libya’s rival power centres?

This webinar is organized in partnership with the North Africa Initiative (NAI) at the Foreign Policy Institute (FPI) of the Johns Hopkins Paul H. Nitze School of Advanced International Studies.

MS Brown
Jul 1, 1980; 21:505-517
Reviews

CJ Fielding
Aug 1, 1997; 38:1503-1521
Reviews

John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews

EJ Blanchette-Mackie
Jun 1, 1995; 36:1211-1226
Articles

Dawn L. Brasaemle
Dec 1, 2007; 48:2547-2559
Thematic Reviews

IJ Goldberg
Apr 1, 1996; 37:693-707
Reviews

Chatham House appoints Rob Yates as the new head of the Centre on Global Health Security News Release sysadmin 27 June 2019

Chatham House is pleased to announce that Rob Yates has been appointed as head of the Centre on Global Health Security.

Rebuilding trust is central to the UN’s future Expert comment NCapeling 25 March 2021

António Guterres is under scrutiny as he prepares to report on the future of the United Nations, with a renewed focus on trust, resilience and prevention.

The United Nations Secretary-General’s inbox is full as his organization celebrates its 75th anniversary. Trust must be rebuilt amid increased geo-political rivalry, North-South divisions, and sceptical citizens left behind by globalization. The international community has manifestly underinvested in institutional resilience and prevention. Better partnerships are needed with the private sector, and innovative forms of cross-regional cooperation fostered.

There are positive signs UN member states want things to change. They unanimously agreed a Political Declaration last September strongly reaffirming multilateralism, and they gave António Guterres one year to present a roadmap on how to respond, ‘building back better’ in the face of climate change and COVID-19.

A key challenge is to steer mandates and resources towards prevention. The World Bank-WHO Global Preparedness Monitoring Board, which eerily predicted the pandemic in its inaugural report in September 2019, reminds us successful prevention rests not on warning alone, but on aligned incentives for early action.

Geopolitical tensions persist

China has invested significantly in the multilateral system over the last decade, both in formal organizations such as the UN and the African Union, and in fostering a set of China-centred ‘mini-lateral’ fora such as the SCO, BRICS and BRI. It has also deepened its ties with Russia in the UN Security Council. Western countries both begrudgingly admire and deeply distrust China’s nimbleness in advancing its interests and values in this way but are divided on how to respond.

The Biden administration has recommitted itself to multilateral processes but US bilateral relations are likely to remain the main foreign policy driver. The UK has sought to convert the G7 into an enlarged summit-level meeting for democracies but Europe is divided over the wisdom of formalizing a group which may increase divisions with China, and some major democracies – India for example – have divergent approaches on issues such as trade protection.

An increase in cross-regional informal caucusing within the UN system to advance norms and progress around specific common objectives is likely. Guterres can encourage smaller powers to become ‘bridge builders’ sitting in the middle of a ‘Venn diagram’ of such new member state constellations at the UN.

Guterres can also build on the recent Abraham Accords to encourage cross-regional cultural, political and security relationships on the back of trade and investment, and map practical opportunities for strategic cooperation between China and the West in health and food security, climate and biodiversity, and global macroeconomic management, while fostering new normative frameworks to manage strategic competition in artificial intelligence (AI), big data, cyber resilience, gene-editing, and automation.

North-South mistrust

Realizing the Sustainable Development Goals (SDGs) and climate objectives rests in part in mobilizing the expertise and resources of sub-state actors such as business and city and regional authorities. However, developing countries remain wary of granting the UN Secretary-General a greater role in fostering partnerships with the private sector and mobilizing private finance, out of fear this may overshadow the global North’s promises to provide aid and create fairer trade and debt conditions.

In addition, African governments are expressing growing frustration at their continued lack of ‘agency’ in UN decision-making, the reneging of promises on climate financing by the global North, and the slow rollout of the COVAX facility to developing countries.

Progress may lie in two areas. First, developing country leadership of initiatives – such as the Friends Group on SDG financing established by the Jamaican and Canadian ambassadors to the UN – can help build trust and allay concerns, which is vital to incentivise transformative investment by sovereign wealth, pension, and insurance funds in pro-poor low carbon infrastructure in developing countries.

The second area is curating multi-stakeholder initiatives outside the UN framework and then linking them back to the organization once they have proven to be beneficial to both developed and developing countries. Successful initiatives such as the Vaccine Alliance can be a model of how to do this while not detracting from state obligations.

Scepticism among citizens

Trust in governance also needs rebuilding at the level of the individual citizen. Mobilized by populist movements and ‘fake news’ online, individuals left behind by the uneven economic benefits of globalization view governments and international organizations as unaccountable and lacking their interests at heart.

Guterres has called for a new ‘social contract’ between governments and their citizens, and for ‘Multilateralism 2.0’ to demonstrate a practical ‘hard interest’ as well as a ‘values’ case for why international cooperation inclusively benefits individuals as well as states. And technological innovation can also help citizens hold governments to account. As the first Secretary-General with a science and engineering background, Guterres has championed how technology enhances UN delivery of its objectives.

The pairing of artificial intelligence (AI) with satellites and drones for geospatial insight has been pioneered by both the United Nations Environment Programme (UNEP) and the Food and Agriculture Organization (FAO) to help communities preserve ecosystems and agricultural productivity. The resultant data, accessible on smart phones and computers, enables civil society to measure governments’ promises against real-time progress, through monitoring greenhouse gas emissions from power stations.

Alongside trust and accountability, fostering inclusiveness is likely to be central to Guterres’ report as he navigates how the UN can legitimize multi-stakeholder partnerships, enhance transparency, and bring coherence to diverse ‘mini-lateral’ initiatives.

These themes are explored further in the forthcoming synthesis paper ‘Reflections on building more inclusive global governance: Ten insights into emerging practice’

Expert

Expert

Expert

Expert

Expert

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.

Centrioles are key eukaryotic organelles that are responsible for the formation of cilia and flagella, and for organizing the microtubule network and the mitotic spindle in animals. Centriole assembly requires oligomerization of the essential protein spindle assembly abnormal 6 (SAS-6), which forms a structural scaffold templating the organization of further organelle components. A dimerization interaction between SAS-6 N-terminal “head” domains was previously shown to be essential for protein oligomerization in vitro and for function in centriole assembly. Here, we developed a pharmacophore model allowing us to assemble a library of low-molecular-weight ligands predicted to bind the SAS-6 head domain and inhibit protein oligomerization. We demonstrate using NMR spectroscopy that a ligand from this family binds at the head domain dimerization site of algae, nematode, and human SAS-6 variants, but also that another ligand specifically recognizes human SAS-6. Atomistic molecular dynamics simulations starting from SAS-6 head domain crystallographic structures, including that of the human head domain which we now resolve, suggest that ligand specificity derives from favorable Van der Waals interactions with a hydrophobic cavity at the dimerization site.

Minerals and Metals for a Low-Carbon Future: Implications for Developing Countries 30 October 2017 — 5:00PM TO 8:00PM Anonymous (not verified) 13 October 2017 Chatham House, London

This roundtable will explore two sides of minerals and metals for a low-carbon future - the growing demand for metals required for low-carbon technology and the technological and policy innovations that will be required to manage the carbon footprint of the mining sector and its wider energy and industrial linkages. Based around a presentation and scenarios developed by the World Bank, this roundtable discussion will assess which strategic metals will likely rise in demand in order to deliver a low-carbon future, before exploring the possible implications for resource-rich developing countries. In particular, what does a growing demand of minerals for a clean energy future mean for governments and industry, and how might developing countries benefit from this trend? What impact might growth of the mining sector have on a sustainable and climate-smart development? Can renewable energy and other clean tech innovations in the mining industry help reduce the carbon footprint of the sector and related industries, and under what circumstances? And how fit-for-purpose are current donor approaches to the mining sector in an increasingly carbon-constrained world?

Attendance at this event is by invitation only.

An Attack on the ‘One Country, Two Systems’ Principle in Hong Kong Expert comment sysadmin 11 January 2016

The disappearance of publisher Lee Bo may mark the beginning of the end of Beijing’s commitment to uphold the framework that provides the territory with a high degree of autonomy.

The disappearance of a publisher in Hong Kong, Lee Bo, who owns a well-known bookshop that sells books critical of Chinese leaders, is a landmark event and potentially a historical turning point for Hong Kong. It is not clear if this happened at the behest of the senior Chinese leadership. But if those responsible for the disappearing of Lee are not punished, it will be clear that their acts are condoned by the authorities.

This is deeply worrying as it gravely undermines the ‘one country, two systems’ framework, which provides Hong Kong with high degree of autonomy from Beijing. Under the Sino-British Agreement of 1984 and Hong Kong’s Basic Law, which govern relations between Hong Kong and China, the rights of Hong Kong citizens are meant to be protected within the territory. Mainland Chinese authorities do not have the legal power to arrest or detain an individual in, or remove anyone from, Hong Kong.

The Chinese know the limit of their legal authority in Hong Kong. Hence, Lee was quietly disappeared, rather than openly arrested. But that it happened at all may mark the beginning of the end of Beijing’s commitment to uphold the ‘one country, two systems’ framework – a relationship that requires Beijing to tolerate, if not respect, the judicial integrity and the way of life in Hong Kong.

Do we know for sure that Lee was ‘disappeared’ by China’s security apparatus? Before he disappeared, Lee said in an interview that he knew he had been watched and that his emails were accessed by Chinese agents, and that he would not travel to the mainland as a result. And we know that Lee’s travel documents are all in his home; yet he is now supposedly in China ‘assisting the authorities in an investigation’ into something unspecified. This explanation comes from a fax sent to Lee’s wife, probably intended by the Chinese authorities to put an end to speculation. But why would Chinese authorities work with Lee, a British citizen who carries no travel documents and would thus have broken the law by entering China? The circumstantial evidence is strong enough to show that whether he was taken by Chinese officers or someone else, his removal from Hong Kong to China must have received official endorsement.

Should the rest of the world be concerned about this? Hong Kong is a major financial center that services the world economy, and it can do so largely because it enjoys judicial independence and the high degree of autonomy under the ‘one country, two systems’ framework. It is also a shining example of how the rights and scope of development for individuals can be respected in a Chinese community. Should the ‘one country, two systems’ framework be undermined, Hong Kong as we know it will be no more.

Beijing’s quick response in requiring Lee to fax his family may come across as ham-fisted and callous, but it also demonstrates that it had not expected the strong backlash to Lee’s disappearance. A strong and well-articulated international response that brings the matter to Xi’s attention may persuade him that it is in China’s best interest to put a stop to this process of undermining the ‘one country, two systems’ framework. Given Hong Kong’s importance to the global economy, this should be a priority for the international community.

This article was originally published in the Diplomat.

To comment on this article, please contact Chatham House Feedback

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.

Artificial Intelligence Apps Risk Entrenching India’s Socio-economic Inequities Expert comment sysadmin 14 March 2018

Artificial intelligence applications will not be a panacea for addressing India’s grand challenges. Data bias and unequal access to technology gains will entrench existing socio-economic fissures.

Artificial intelligence (AI) is high on the Indian government’s agenda. Some days ago, Prime Minister Narendra Modi inaugurated the Wadhwani Institute for Artificial Intelligence, reportedly India’s first research institute focused on AI solutions for social good. In the same week, Niti Aayog CEO Amitabh Kant argued that AI could potentially add $957 billion to the economy and outlined ways in which AI could be a ‘game changer’.

During his budget speech, Finance Minister Arun Jaitley announced that Niti Aayog would spearhead a national programme on AI; with the near doubling of the Digital India budget, the IT ministry also announced the setting up of four committees for AI-related research. An industrial policy for AI is also in the pipeline, expected to provide incentives to businesses for creating a globally competitive Indian AI industry.

Narratives on the emerging digital economy often suffer from technological determinism — assuming that the march of technological transformation has an inner logic, independent of social choice and capable of automatically delivering positive social change. However, technological trajectories can and must be steered by social choice and aligned with societal objectives. Modi’s address hit all the right notes, as he argued that the ‘road ahead for AI depends on and will be driven by human intentions’. Emphasising the need to direct AI technologies towards solutions for the poor, he called upon students and teachers to identify ‘the grand challenges facing India’ – to ‘Make AI in India and for India’.

To do so, will undoubtedly require substantial investments in R&D, digital infrastructure and education and re-skilling. But, two other critical issues must be simultaneously addressed: data bias and access to technology gains.

While computers have been mimicking human intelligence for some decades now, a massive increase in computational power and the quantity of available data are enabling a process of ‘machine learning.’ Instead of coding software with specific instructions to accomplish a set task, machine learning involves training an algorithm on large quantities of data to enable it to self-learn; refining and improving its results through multiple iterations of the same task. The quality of data sets used to train machines is thus a critical concern in building AI applications.

Much recent research shows that applications based on machine learning reflect existing social biases and prejudice. Such bias can occur if the data set the algorithm is trained on is unrepresentative of the reality it seeks to represent. If for example, a system is trained on photos of people that are predominantly white, it will have a harder time recognizing non-white people. This is what led a recent Google application to tag black people as gorillas.

Alternatively, bias can also occur if the data set itself reflects existing discriminatory or exclusionary practices. A recent study by ProPublica found for example that software that was being used to assess the risk of recidivism in criminals in the United States was twice as likely to mistakenly flag black defendants as being at higher risk of committing future crimes.

The impact of such data bias can be seriously damaging in India, particularly at a time of growing social fragmentation. It can contribute to the entrenchment of social bias and discriminatory practices, while rendering both invisible and pervasive the processes through which discrimination occurs. Women are 34 per cent less likely to own a mobile phone than men – manifested in only 14 per cent of women in rural India owning a mobile phone, while only 30 per cent of India’s internet users are women.

Women’s participation in the labour force, currently at around 27 per cent, is also declining, and is one of the lowest in South Asia. Data sets used for machine learning are thus likely to have a marked gender bias. The same observations are likely to hold true for other marginalized groups as well.

Accorded to a 2014 report, Muslims, Dalits and tribals make up 53 per cent of all prisoners in India; National Crime Records Bureau data from 2016 shows in some states, the percentage of Muslims in the incarcerated population was almost three times the percentage of Muslims in the overall population. If AI applications for law and order are built on this data, it is not unlikely that it will be prejudiced against these groups.

(It is worth pointing out that the recently set-up national AI task force is comprised of mostly Hindu men – only two women are on the task force, and no Muslims or Christians. A recent article in the New York Times talked about AI’s ‘white guy problem’; will India suffer from a ‘Hindu male bias’?)

Yet, improving the quality, or diversity, of data sets may not be able to solve the problem. The processes of machine learning and reasoning involve a quagmire of mathematical functions, variables and permutations, the logic of which are not readily traceable or predictable. The dazzle of AI-enabled efficiency gains must not blind us to the fact that while AI systems are being integrated into key socio-economic systems, their accuracy and logic of reasoning have not been fully understood or studied.

The other big challenge stems from the distribution of AI-led technology gains. Even if estimates of AI contribution to GDP are correct, the adoption of these technologies is likely to be in niches within the organized sector. These industries are likely to be capital- rather than labour-intensive, and thus unlikely to contribute to large-scale job creation.

At the same time, AI applications can most readily replace low- to medium-skilled jobs within the organized sector. This is already being witnessed in the outsourcing sector – where basic call and chat tasks are now automated. Re-skilling will be important, but it is unlikely that those who lose their jobs will also be those who are being re-skilled – the long arch of technological change and societal adaptation is longer than that of people’s lives. The contractualization of work, already on the rise, is likely to further increase as large industries prefer to have a flexible workforce to adapt to technological change. A shift from formal employment to contractual work can imply a loss of access to formal social protection mechanisms, increasing the precariousness of work for workers.

The adoption of AI technologies is also unlikely in the short- to medium-term in the unorganized sector, which engages more than 80 per cent of India’s labor force. The cost of developing and deploying AI applications, particularly in relation to the cost of labour, will inhibit adoption. Moreover, most enterprises within the unorganized sector still have limited access to basic, older technologies – two-thirds of the workforce are employed in enterprises without electricity. Eco-system upgrades will be important but incremental. Given the high costs of developing AI-based applications, most start-ups are unlikely to be working towards creating bottom-of-the-pyramid solutions.

Access to AI-led technology gains is thus likely to be heavily differentiated – a few high-growth industries can be expected, but these will not necessarily result in the welfare of labour. Studies show that labour share of national income, especially routine labour, has been declining steadily across developing countries.

We should be clear that new technological applications themselves are not going to transform or disrupt this trend – rather, without adequate policy steering, these trends will be exacerbated.

Policy debates about AI applications in India need to take these two issues seriously. AI applications will not be a panacea for addressing ‘India’s grand challenges’. Data bias and unequal access to technology gains will entrench existing socio-economic fissures, even making them technologically binding.

In addition to developing AI applications and creating a skilled workforce, the government needs to prioritize research that examines the complex social, ethical and governance challenges associated with the spread of AI-driven technologies. Blind technological optimism might entrench rather than alleviate the grand Indian challenge of inequity and growth.

This article was originally published in the Indian Express.

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

Sudip Ranjan Bhuia
Proc. Amer. Math. Soc. 152 (), 5249-5263.
Abstract, references and article information

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E-mail: clarasouzin@gmail.com

E-mail: clarasouzin@gmail.com...

Stromal interaction molecule 1 (STIM1) plays a pivotal role in store-operated Ca2+ entry (SOCE), an essential mechanism in cellular calcium signaling and in maintaining cellular calcium balance. Because O-GlcNAcylation plays pivotal roles in various cellular function, we examined the effect of fluctuation in STIM1 O-GlcNAcylation on SOCE activity. We found that both increase and decrease in STIM1 O-GlcNAcylation impaired SOCE activity. To determine the molecular basis, we established STIM1-knockout HEK293 (STIM1-KO-HEK) cells using the CRISPR/Cas9 system and transfected STIM1 WT (STIM1-KO-WT-HEK), S621A (STIM1-KO-S621A-HEK), or T626A (STIM1-KO-T626A-HEK) cells. Using these cells, we examined the possible O-GlcNAcylation sites of STIM1 to determine whether the sites were O-GlcNAcylated. Co-immunoprecipitation analysis revealed that Ser621 and Thr626 were O-GlcNAcylated and that Thr626 was O-GlcNAcylated in the steady state but Ser621 was not. The SOCE activity in STIM1-KO-S621A-HEK and STIM1-KO-T626A-HEK cells was lower than that in STIM1-KO-WT-HEK cells because of reduced phosphorylation at Ser621. Treatment with the O-GlcNAcase inhibitor Thiamet G or O-GlcNAc transferase (OGT) transfection, which increases O-GlcNAcylation, reduced SOCE activity, whereas treatment with the OGT inhibitor ST045849 or siOGT transfection, which decreases O-GlcNAcylation, also reduced SOCE activity. Decrease in SOCE activity due to increase and decrease in O-GlcNAcylation was attributable to reduced phosphorylation at Ser621. These data suggest that both decrease in O-GlcNAcylation at Thr626 and increase in O-GlcNAcylation at Ser621 in STIM1 lead to impairment of SOCE activity through decrease in Ser621 phosphorylation. Targeting STIM1 O-GlcNAcylation could provide a promising treatment option for the related diseases, such as neurodegenerative diseases.

CD81 plays a central role in a variety of physiological and pathological processes. Recent structural analysis of CD81 indicates that it contains an intramembrane cholesterol-binding pocket and that interaction with cholesterol may regulate a conformational switch in the large extracellular domain of CD81. Therefore, CD81 possesses a potential cholesterol-sensing mechanism; however, its relevance for protein function is thus far unknown. In this study we investigate CD81 cholesterol sensing in the context of its activity as a receptor for hepatitis C virus (HCV). Structure-led mutagenesis of the cholesterol-binding pocket reduced CD81–cholesterol association but had disparate effects on HCV entry, both reducing and enhancing CD81 receptor activity. We reasoned that this could be explained by alterations in the consequences of cholesterol binding. To investigate this further we performed molecular dynamic simulations of CD81 with and without cholesterol; this identified a potential allosteric mechanism by which cholesterol binding regulates the conformation of CD81. To test this, we designed further mutations to force CD81 into either the open (cholesterol-unbound) or closed (cholesterol-bound) conformation. The open mutant of CD81 exhibited reduced HCV receptor activity, whereas the closed mutant enhanced activity. These data are consistent with cholesterol sensing switching CD81 between a receptor active and inactive state. CD81 interactome analysis also suggests that conformational switching may modulate the assembly of CD81–partner protein networks. This work furthers our understanding of the molecular mechanism of CD81 cholesterol sensing, how this relates to HCV entry, and CD81's function as a molecular scaffold; these insights are relevant to CD81's varied roles in both health and disease.

Intrinsically disordered protein domains often have multiple binding partners. It is plausible that the strength of pairing with specific partners evolves from an initial low affinity to a higher affinity. However, little is known about the molecular changes in the binding mechanism that would facilitate such a transition. We previously showed that the interaction between two intrinsically disordered domains, NCBD and CID, likely emerged in an ancestral deuterostome organism as a low-affinity interaction that subsequently evolved into a higher-affinity interaction before the radiation of modern vertebrate groups. Here we map native contacts in the transition states of the low-affinity ancestral and high-affinity human NCBD/CID interactions. We show that the coupled binding and folding mechanism is overall similar but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex and more heterogeneous transient interactions, including electrostatic pairings, and an increased disorder for the human complex. Adaptation to new binding partners may be facilitated by this ability to exploit multiple alternative transient interactions while retaining the overall binding and folding pathway.

Abnormal changes of neuronal Tau protein, such as phosphorylation and aggregation, are considered hallmarks of cognitive deficits in Alzheimer's disease. Abnormal phosphorylation is thought to precede aggregation and therefore to promote aggregation, but the nature and extent of phosphorylation remain ill-defined. Tau contains ∼85 potential phosphorylation sites, which can be phosphorylated by various kinases because the unfolded structure of Tau makes them accessible. However, methodological limitations (e.g. in MS of phosphopeptides, or antibodies against phosphoepitopes) led to conflicting results regarding the extent of Tau phosphorylation in cells. Here we present results from a new approach based on native MS of intact Tau expressed in eukaryotic cells (Sf9). The extent of phosphorylation is heterogeneous, up to ∼20 phosphates per molecule distributed over 51 sites. The medium phosphorylated fraction Pm showed overall occupancies of ∼8 Pi (± 5) with a bell-shaped distribution; the highly phosphorylated fraction Ph had 14 Pi (± 6). The distribution of sites was highly asymmetric (with 71% of all P-sites in the C-terminal half of Tau). All sites were on Ser or Thr residues, but none were on Tyr. Other known posttranslational modifications were near or below our detection limit (e.g. acetylation, ubiquitination). These findings suggest that normal cellular Tau shows a remarkably high extent of phosphorylation, whereas other modifications are nearly absent. This implies that abnormal phosphorylations at certain sites may not affect the extent of phosphorylation significantly and do not represent hyperphosphorylation. By implication, the pathological aggregation of Tau is not likely a consequence of high phosphorylation.

11 July 2020

The synthesis of cholesterol requires more than 20 enzymes, many of which are intricately regulated. Post-translational control of these enzymes provides a rapid means for modifying flux through the pathway. So far, several enzymes have been shown to be rapidly degraded through the ubiquitin–proteasome pathway in response to cholesterol and other sterol intermediates. Additionally, several enzymes have their activity altered through phosphorylation mechanisms. Most work has focused on the two rate-limiting enzymes: 3-hydroxy-3-methylglutaryl CoA reductase and squalene monooxygenase. Here, we review current literature in the area to define some common themes in the regulation of the entire cholesterol synthesis pathway. We highlight the rich variety of inputs controlling each enzyme, discuss the interplay that exists between regulatory mechanisms, and summarize findings that reveal an intricately coordinated network of regulation along the cholesterol synthesis pathway. We provide a roadmap for future research into the post-translational control of cholesterol synthesis, and no doubt the road ahead will reveal further twists and turns for this fascinating pathway crucial for human health and disease.

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