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Screening Room: This is Congo




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Rethinking the Governance of Solar Geoengineering




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Negotiating With Terrorists




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Weak States: Rebel Governance and War Economies




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Our Shared Humanity: Governance, Youth and Leadership




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Angola's Business Promise: Evaluating the Progress of Privatization and Other Economic Reforms




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Implications of post-COVID-19 Restructuring of Supply Chains for Global Investment Governance

Implications of post-COVID-19 Restructuring of Supply Chains for Global Investment Governance 14 July 2020 — 9:00AM TO 10:30AM Anonymous (not verified) 9 February 2021 Online

As companies rethink and diversify their supply chains in order to enhance resilience, what will this mean for current and future global investment governance?

What are the risks of negative effects on inclusivity and transparency? Does this shift create an opportunity to advance good governance of cross-border investment practices?

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.




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Insights from Climate Policy: Engaging Subnational Governments in Global Platforms

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.




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Innovating Governance: Examples from the Digital Arena

Innovating Governance: Examples from the Digital Arena 25 February 2020 TO 26 February 2020 — 10:00AM TO 11:30AM Anonymous (not verified) 9 February 2021 Chatham House

The Inclusive Governance Initiative is launched with this roundtable on digital governance.

The Inclusive Governance Initiative, a centenary project which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world, is launched with this roundtable on digital governance.

The event brings together a diverse and multidisciplinary group of leading experts to consider where and how early initiatives around governance of the digital sphere have succeeded – or not – and how they are evolving today.

The conversation will include the debate between multilateral and multi-stakeholder approaches, the opportunities and challenges of collective non-binding commitments, and converting civil society collaboration into policy contribution.




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A seat at the table – why inclusivity matters in global governance

A seat at the table – why inclusivity matters in global governance 10 May 2021 — 1:30PM TO 3:00PM Anonymous (not verified) 22 April 2021 Online

Exploring the changing dynamics of global cooperation and the role inclusivity can play in building collaborative action.

Please click on the below link to confirm your participation and receive your individual joining details from Zoom for this event. You will receive a confirmation email from Zoom, which contains the option to add the event to your calendar if you so wish.

The scale of today’s global challenges demand collaborative and coordinated action. But deepening geopolitical competition is threatening multilateralism while growing inequality and social tensions continue to undermine public confidence in the ability of international institutions to deliver.

Into this challenging environment, add the complexity and sheer pace of many global challenges such as the climate crisis and the proliferation of new technologies – issues that cannot be addressed effectively by governments alone.

  • How do global institutions and mechanisms need to adapt to address the demands for a fairer distribution of power between states and to engage the diverse set of actors essential today for effective solutions?
  • What can be learnt from existing initiatives that bring together governments, civil society, private sector, cities, next generation leaders and other stakeholders?
  • And what are the political obstacles to greater inclusivity?

This event supports the launch of a synthesis paper from Chatham House’s Inclusive Governance Initiative.




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Can global technology governance anticipate the future?

Can global technology governance anticipate the future? Expert comment NCapeling 27 April 2021

Trying to govern disruption is perilous as complex technology is increasingly embedded in societies and omnipresent in economic, social, and political activity.

Technology governance is beset by the challenges of how regulation can keep pace with rapid digital transformation, how governments can regulate in a context of deep knowledge asymmetry, and how policymakers can address the transnational nature of technology.

Keeping pace with, much less understanding, the implications of digital platforms and artificial intelligence for societies is increasingly challenging as technology becomes more sophisticated and yet more ubiquitous.

To overcome these obstacles, there is an urgent need to move towards a more anticipatory and inclusive model of technology governance. There are some signs of this in recent proposals by the European Union (EU) and the UK on the regulation of online harms.

Regulation failing to keep up

The speed of the digital revolution, further accelerated by the pandemic, has largely outstripped policymakers’ ability to provide appropriate frameworks to regulate and direct technology transformations.

Governments around the world face a ‘pacing problem’, a phenomenon described by Gary Marchant in 2011 as ‘the growing gap between the pace of science and technology and the lagging responsiveness of legal and ethical oversight that society relies on to govern emerging technologies’.

The speed of the digital revolution, further accelerated by the pandemic, has largely outstripped policymakers’ ability to provide appropriate frameworks to regulate and direct technology transformations

This ever-growing rift, Marchant argues, has been exacerbated by the increasing public appetite for and adoption of new technologies, as well as political inertia. As a result, legislation on emerging technologies risks being ineffective or out-of-date by the time it is implemented.

Effective regulation requires a thorough understanding of both the underlying technology design, processes and business model, and how current or new policy tools can be used to promote principles of good governance.

Artificial intelligence, for example, is penetrating all sectors of society and spanning multiple regulatory regimes without any regard for jurisdictional boundaries. As technology is increasingly developed and applied by the private sector rather than the state, officials often lack the technical expertise to adequately comprehend and act on emerging issues. This increases the risk of superficial regulation which fails to address the underlying structural causes of societal harms.

The significant lack of knowledge from those who aim to regulate compared to those who design, develop and market technology is prevalent in most technology-related domains, including powerful online platforms and providers such as Facebook, Twitter, Google and YouTube.

For example, the ability for governments and researchers to access the algorithms used in the business model of social media companies to promote online content – harmful or otherwise – remains opaque so, to a crucial extent, the regulator is operating in the dark.

The transnational nature of technology also poses additional problems for effective governance. Digital technologies intensify the gathering, harvesting, and transfer of data across borders, challenging administrative boundaries both domestically and internationally.

While there have been some efforts at the international level to coordinate approaches to the regulation of – for example – artificial intelligence (AI) and online content governance, more work is needed to promote global regulatory alignment, including on cross-border data flows and antitrust.

Reactive national legislative approaches are often based on targeted interventions in specific policy areas, and so risk failing to address the scale, complexity, and transnational nature of socio-technological challenges. Greater attention needs to be placed on how regulatory functions and policy tools should evolve to effectively govern technology, requiring a shift from a reactionary and rigid framework to a more anticipatory and adaptive model of governance.

Holistic and systemic versus mechanistic and linear

Some recent proposals for technology governance may offer potential solutions. The EU publication of a series of interlinked regulatory proposals – the Digital Services Act, Digital Markets Act and European Democracy Action Plan – integrates several novel and anticipatory features.

The EU package recognizes that the solutions to online harms such as disinformation, hate speech, and extremism lie in a holistic approach which draws on a range of disciplines, such as international human rights law, competition law, e-commerce, and behavioural science.

By tackling the complexity and unpredictability of technology governance through holistic and systemic approaches rather than mechanistic and linear ones, the UK and EU proposals represent an important pivot from reactive to anticipatory digital governance

It consists of a combination of light touch regulation – such as codes of conduct – and hard law requirements such as transparency obligations. Codes of conduct provide flexibility as to how requirements are achieved by digital platforms, and can be updated and tweaked relatively easily enabling regulations to keep pace as technology evolves.

As with the EU Digital Services Act, the UK’s recent proposals for an online safety bill are innovative in adopting a ‘systems-based’ approach which broadly focuses on the procedures and policies of technology companies rather than the substance of online content.

This means the proposals can be adapted to different types of content, and differentiated according to the size and reach of the technology company concerned. This ‘co-regulatory’ model recognizes the evolving nature of digital ecosystems and the ongoing responsibilities of the companies concerned. The forthcoming UK draft legislation will also be complemented by a ‘Safety by Design’ framework, which is forward-looking in focusing on responsible product design.

By tackling the complexity and unpredictability of technology governance through holistic and systemic approaches rather than mechanistic and linear ones, the UK and EU proposals represent an important pivot from reactive to anticipatory digital governance.

Both sets of proposals were also the result of extensive multistakeholder engagement, including between policy officials and technology actors. This engagement broke down silos within the technical and policy/legal communities and helped bridge the knowledge gap between dominant technology companies and policymakers, facilitating a more agile, inclusive, and pragmatic regulatory approach.

Coherence rather than fragmentation

Anticipatory governance also recognizes the need for new coalitions to promote regulatory coherence rather than fragmentation at the international level. The EU has been pushing for greater transatlantic engagement on regulation of the digital space, and the UK – as chair of the G7 presidency in 2021 – aims to work with democratic allies to forge a coherent response to online harms.

Meanwhile the OECD’s AI Policy Observatory enables member states to share best practice on the regulation of AI, and an increasing number of states such as France, Norway, and the UK are using ‘regulatory sandboxes’ to test and build AI or personal data systems that meet privacy standards.

Not all states currently have the organizational capacity and institutional depth to design and deliver regulatory schemes of this nature, as well as the resource-intensive consultation processes which often accompany them.

So, as an increasing number of states ponder how to ‘futureproof’ their regulation of tomorrow’s technology – whether 6G, quantum computing or biotechnology – there is a need for capacity building in governments both on the theory of anticipatory governance and on how it can be applied in practice to global technology regulation.




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Digital governance must not marginalize smaller states

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.

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 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 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.

Multi-stakeholderism needs to raise its game.

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.

There is a perennial risk of debate and decision-making being captured by the wealthiest companies or the most powerful states.

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.




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Influence of soft law grows in international governance

Influence of soft law grows in international governance Expert comment NCapeling 17 June 2021

Soft law is increasingly being used by policymakers to enable greater cooperation and inclusivity, and its role is here to stay in creating effective regimes.

As the UK government’s recent Integrated Review points out, international law-making in a fragmented international order is becoming increasingly difficult.

Geopolitical tensions, and the length of time required to agree multilateral treaties – typically decades – make it challenging to reach binding agreements in complex and fast-evolving policy areas such as climate change and technology governance.

As a result, the regulation of international behaviour through soft law – meaning non-binding instruments such as principles, codes of conduct or declarations – is starting to assume greater significance. And states increasingly find soft law-making attractive because there are relatively fewer decision costs involved.

Soft law also lays the ground for the possibility of transforming into hard law if, over time, its principles become widely accepted and it is evident states are treating them as legal obligations. And the emergence of a hybrid of both soft and hard law components in treaties has started to develop in recent years, such as the Paris Agreement on Climate Change.

Opening access to global governance

A major attraction of soft law-making is that it provides for non-traditional, non-state actors to take part in the process of global governance. Non-governmental organizations (NGOs), social movements, corporate sector, and individuals are more easily drawn into soft law-making compared to treaties, to which only states can be party.

States increasingly find soft law-making attractive because there are relatively fewer decision costs involved

This holds out the promise for greater inclusiveness in global rulemaking and governance, but soft law processes also pose many challenges. Soft law provides an avenue for states to avoid legal obligations on important subjects and developing rules in such an informal manner can lead to fragmentation and a lack of coherence in the international system.

As noted in dialogues held under Chatham House’s Inclusive Governance Initiative, some areas of international interaction require hard law, such as economic competition, certain international security issues, and aspects of the global commons. In these areas, soft law is just not appropriate or enough.

Soft law measures such as codes of conduct may be useful in rapidly developing areas such as technology, as they are more flexible and adaptable than hard law. And they may be particularly effective if used in conjunction with binding regulation, and subject to monitoring and enforcement by a regulator, as in recent proposals by the European Union (EU) for a Digital Services Act.

The Chatham House Inclusive Governance Initiative report highlights that the proliferation of soft law does not necessarily have to compete with the existing system of hard law, so long as soft law solutions do not conflict with, or undermine, hard law such as existing treaty provisions.

Case study: Business and human rights

The UN Guiding Principles on Business and Human Rights (UNGPs) are an interesting example of both the promise of soft law-making, and its challenges. Officially adopted by the UN General Assembly in 2011, the UNGPs set out the global standard of what is expected of companies as regards human rights due diligence (HRDD) to prevent and address business-related human rights harms.

The sections on HRDD in the UNGPs have been constructed as a non-binding ‘social’ standard of conduct, though with the expectation that this would eventually be reinforced through a “smart mix” of both soft law and hard law initiatives. Arguments in favour of the predominantly soft law approach at the time – subsequently borne out in practice – were that this would encourage a higher level of participation, by states and businesses in particular, and better foster creativity and innovation in a still-developing field.

The UNGPs recognize and reinforce the importance of meaningful and inclusive stakeholder engagement for both the credibility and legitimacy of processes, and for the quality of substantive outcomes. The Ruggie process which led to the UNGPs, drew extensively from a wide range of stakeholder engagement processes covering many different jurisdictions and all UN regional groupings. The importance of deep and inclusive stakeholder engagement is also recognized in the mandate of the UN Working Group on Business and Human Rights.

The annual UN Forum on Business and Human Rights is one of the largest and most vibrant multi-stakeholder events in the UN calendar. Now in its tenth year, the forum provides an opportunity for an annual review by stakeholders – government, business and civil society – of past achievements in implementing the UNGPs and knowledge sharing on ways to address more persistent, underlying challenges.

The sluggish responses of many companies, coupled with revulsion at reports of serious abuses in the value chains of many well-known brands, have prompted some governments to seek ways of translating some aspects of HRDD methodologies into binding legal standards

Its relatively informal approach to agenda setting has, year on year, enabled an increasingly diverse array of stakeholder-organized sessions, supporting a ‘bottom up’ approach which raises awareness of under-reported issues and undervalued solutions.

In addition, while the UNGPs provide the substantive framework for discussion, flexible governance arrangements allow for rapid reorientation to respond to present and emerging crises, such as COVID-19 pandemic and climate change.

However, the sluggish responses of many companies, coupled with revulsion at reports of serious abuses in the value chains of many well-known brands, have prompted some governments to seek ways of translating some aspects of HRDD methodologies into binding legal standards. France passed a Corporate Duty of Vigilance Law in 2017 and Germany adopted a new law on supply chain due diligence in June 2021 which is to enter into effect on 1 January 2023. The European Commission is also working up proposals for an EU-wide regime to be unveiled in mid-2021.

Soft law versus hard law

At the international level, there are signs of divergence between those states which see value in persevering with the soft law route towards better regulation and corporate standards, and those which want to move as rapidly as possible to a hard law framework for business and human rights, enshrined in treaty, to improve domestic-level regulation and access to effective remedies.

Ultimately, the most effective domestic regimes are likely to be a mix of hard law standards supported by more flexible standards and guidance

Those supporting the hard law route – largely less industrialized states – received a boost in 2016 when the UN Human Rights Council mandated an Intergovernmental Working Group to explore options for a new treaty on business and human rights.

This initiative, known as the ‘treaty process’, has completed six rounds of negotiations. Despite the necessarily greater formality, these treaty negotiation sessions continue to emphasize the importance of stakeholder consultation. NGOs with ECOSOC status are invited to contribute views on the framing and content of draft treaty provisions immediately following the interventions by states, intergovernmental organizations and national human rights institutions, in that order.

The key question is whether this dynamism and inclusivity can be preserved as the transition is made from soft law to more binding approaches. Translating soft law standards into binding regimes inevitably means making hard choices, and different stakeholder groups have different views as to where legal lines should be drawn, how key concepts should be defined, and where the balance between legal certainty and flexibility should be struck.

The negotiations needed to strike an effective balance between competing objectives and needs can be challenging and time-consuming, as experiences with the treaty process have shown. But stakeholder demand for inclusive processes to help shape the law remains strong. Stakeholder groups clearly want a say in how the new EU-wide regime for ‘mandatory human rights due diligence’ will work in practice. A recent online ‘stakeholder survey’ garnered more than 400,000 responses.

Ultimately, the most effective domestic regimes are likely to be a mix of hard law standards supported by more flexible standards and guidance. Civil society organizations and trade unions will continue to have a multi-faceted role to play. Not only are they vital sources of expertise on human rights challenges connected to business activities, at home and abroad, they can also act as private enforcers of standards and advocates for affected people and communities.




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How can governance be more inclusive?

How can governance be more inclusive? Explainer Video NCapeling 28 June 2021

Short animation exploring how global governance can be reshaped to meet the challenges of today’s world.

The COVID-19 pandemic has illustrated the urgent need for change in the structures and mechanisms of international cooperation.

This animation supports the release of a major synthesis paper as part of the Inclusive Governance Initiative, which was launched in 2020 to mark Chatham House’s centenary.

Read the synthesis paper Reflections on building more inclusive global governance.




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Cyberspace governance at the United Nations

Cyberspace governance at the United Nations 18 January 2023 — 3:00PM TO 4:00PM Anonymous (not verified) 30 November 2022 Online

How can member states achieve lasting, adaptable, and meaningful success in cyberspace governance at the United Nations?

Now in its second iteration, the Open-ended Working Group on Information and Communications Technologies (OEWG) has been a space for United Nations member states to discuss the use, regulation and governance of cyberspace since 2019.

The progress of this forum in shaping cyberspace and its governance is evidenced by two consensus reports including a framework for responsible state behaviour in cyberspace and, more recently, plans for a Programme of Action. 
 
However, the true impact of these UN processes in limiting the threats of ICTs to international peace and security is contingent upon operationalizing the consensus at the international level and reflecting it in national policies and practices.

Pervasive challenges continue to hamper operationalization efforts, including differences in national capacities and capabilities, and divergences in national perspectives regarding the application of international law to cyberspace.

So, how can member states overcome these challenges and set this vital forum up for lasting, adaptable and meaningful success? What role does ‘multi-stakeholderism’ play in realizing responsible state behaviour in cyberspace?

With a dual focus on cyber capacity building and international law, this event considers how these two elements interact and intersect, how discussions on them could progress in the UN space and outside it and how the two contribute to a safer and more secure cyberspace for all. 
 
This event is organized jointly by the International Security and International Law Programmes at Chatham House to launch Phase 2 of the project ‘Cyberspace4All: Towards an inclusive approach to cyber governance’ which is funded by the Ministry of Foreign Affairs of the Netherlands.









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Biochemical and biophysical analyses of hypoxia sensing prolyl hydroxylases from Dictyostelium discoideum and Toxoplasma gondii [Molecular Biophysics]

In animals, the response to chronic hypoxia is mediated by prolyl hydroxylases (PHDs) that regulate the levels of hypoxia-inducible transcription factor α (HIFα). PHD homologues exist in other types of eukaryotes and prokaryotes where they act on non HIF substrates. To gain insight into the factors underlying different PHD substrates and properties, we carried out biochemical and biophysical studies on PHD homologues from the cellular slime mold, Dictyostelium discoideum, and the protozoan parasite, Toxoplasma gondii, both lacking HIF. The respective prolyl-hydroxylases (DdPhyA and TgPhyA) catalyze prolyl-hydroxylation of S-phase kinase-associated protein 1 (Skp1), a reaction enabling adaptation to different dioxygen availability. Assays with full-length Skp1 substrates reveal substantial differences in the kinetic properties of DdPhyA and TgPhyA, both with respect to each other and compared with human PHD2; consistent with cellular studies, TgPhyA is more active at low dioxygen concentrations than DdPhyA. TgSkp1 is a DdPhyA substrate and DdSkp1 is a TgPhyA substrate. No cross-reactivity was detected between DdPhyA/TgPhyA substrates and human PHD2. The human Skp1 E147P variant is a DdPhyA and TgPhyA substrate, suggesting some retention of ancestral interactions. Crystallographic analysis of DdPhyA enables comparisons with homologues from humans, Trichoplax adhaerens, and prokaryotes, informing on differences in mobile elements involved in substrate binding and catalysis. In DdPhyA, two mobile loops that enclose substrates in the PHDs are conserved, but the C-terminal helix of the PHDs is strikingly absent. The combined results support the proposal that PHD homologues have evolved kinetic and structural features suited to their specific sensing roles.




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Identification of compounds that bind the centriolar protein SAS-6 and inhibit its oligomerization [Computational Biology]

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.




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The Gonchar–Chudnovskies conjecture and a functional analogue of the Thue–Siegel–Roth theorem

A. I. Aptekarev and M. L. Yattselev
Trans. Moscow Math. Soc. 83 (), 251-268.
Abstract, references and article information




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The Hard Truth Is Rohingya Refugees Are Not Going Home

The Hard Truth Is Rohingya Refugees Are Not Going Home Expert comment sysadmin 6 October 2017

The only likely outcome of the crisis is the near-permanent presence of hundreds of thousands of Rohingya along the Bangladesh border.

A Rohingya refugee camp in Bangladesh. Photo: Getty Images.

The harrowing scenes of human suffering on the Myanmar–Bangladesh border have provoked outpourings of sympathy and some firm statements by international politicians. At least half a million people have been brutally expelled from their homes and are now living in miserable conditions in muddy refugee camps and storm-drenched shanty towns. As the international community debates how to respond, it needs to take a clear-eyed view of the situation and recognise a brutal truth: the refugees are almost certainly not going home.

Consequently, policymakers must not hide behind the fiction that Bangladesh is only temporarily hosting the refugees in preparation for their rapid return home. Over-optimistic assumptions now will lead to worse misery in the long term. Instead, the world needs to plan on the basis that Bangladesh will be hosting a very large and permanent refugee population.

The expulsion of the Rohingya Muslims from Rakhine State in northwestern Myanmar is the culmination of decades of discriminatory policies enacted by the country’s military rulers since 1962. In 1978, the Burmese military’s ‘Operation Dragon King’ pushed 200,000 Muslims into Bangladesh. International pressure forced the military to allow most of them to return. Then, in 1991–92, the military again expelled a quarter of a million people. Bangladesh forced some of them back over the border and eventually the military agreed to allow the United Nations High Commissioner for Refugees to manage the repatriation of most of the remainder.

State-sponsored abuses of the Rohingya and ethnic violence perpetrated against them by chauvinists among the ethnic Rakhine population have continued. The abuse became dramatically worse in 2012 when tens of thousands of Rohingya were forced to flee their homes, although most remained inside the country. This year, armed attacks by self-proclaimed defenders of the Rohingya, the Arakan Rohingya Salvation Army, gave the military an excuse to mount what the UN High Commissioner for Human Rights called ‘a textbook example of ethnic cleansing’.

It is tempting to believe that, as before, the Myanmar government will allow the expelled Rohingya to return after international pressure. However, recent geopolitical developments in southeast Asia and the election of a democratic government in Myanmar in 2015 make this much less likely.

Southeast Asia is now an arena of geopolitical competition between China and its rivals: mainly the United States, India and Japan. All are battling for influence. Both China and India have made public statements of support for Myanmar’s government in the current crisis. In that context, diplomatic pressure or economic sanctions imposed by Europe or the United States will only have one effect – to push Myanmar towards China.

Moreover, those in the EU and US who want to see democracy survive in Myanmar will be unwilling to push the elected government led by Aung San Suu Kyi too far. There is an extraordinary degree of hostility towards the Rohingya among the majority Bamar population. This has broken out into street violence on occasions but even where the situation is calm, anti-Muslim prejudice is easily awoken. The current government is very unlikely to challenge such sentiments at a time when it is trying to preserve its position against the military’s continuing domination of political and economic life.

Myanmar is one of the 10 members of the Association of Southeast Asian Nations but ASEAN is unlikely to impose any meaningful pressure. Only Malaysia has been publicly critical of Myanmar’s government. Indonesia has attempted to mediate – its foreign minister Retno Marsudi has held face-to-face meetings with Aung San Suu Kyi – but without apparent effect. Both countries have sent aid and volunteers to the Rohingya refugee camps but there is absolutely no talk of sanctions or other overt pressure.

The question then is: what will happen to the refugees? One option could be resettlement, but neither Bangladesh nor any of the other states in the region are willing to take them in. Malaysia already hosts 60,000 registered Rohingya refugees and probably another 150,000 unregistered ones. Unknown thousands of Rohingya have fled to Thailand and Indonesia by boat but have often fallen victim to unscrupulous human traffickers in cahoots with local officials. Thailand has already said it will refuse to allow new ‘boat people’ to land.

The only likely outcome therefore is the near-permanent presence of hundreds of thousands of Rohingya along the Bangladesh border. Delaying preparations for a permanent refugee population in the hope that they will be allowed to re-cross the border back into Myanmar will only make the situation worse. Seventy years ago, another ‘temporary’ movement of people into refugee camps created decades of instability around the Middle East. The world must remember the Palestinians as it plans for the future of the Rohingya.




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The 2020 Inner Mongolia Language Protests: Wider Meanings for China and the Region

The 2020 Inner Mongolia Language Protests: Wider Meanings for China and the Region 24 November 2020 — 3:00PM TO 4:00PM Anonymous (not verified) 12 November 2020 Online

Speakers discuss the historical roots of the language issue, as well as the wider significance of the protests in China.

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

In September thousands of people protested in Inner Mongolia in opposition to a government move to replace Mongolian language with Standard Mandarin in three school subjects – history, politics and Chinese language.

Announced less than a week before the start of the new school year, the policy also requires schools to use new national textbooks in Chinese, instead of regional textbooks. The mass protests and classroom walk-outs reflect ethnic Mongolian’s anxiety that their native language may be eliminated. What has the government’s response to the protests been?






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LEGO Taken 2008

bradders1999 posted a photo:

Each item refers to a scene from the iconic movie, progressing from left to right.

Minifigures made, photographed and edited by me.




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LEGO The Batman 2004 D.A.V.E. Rooftop Scene GRADED

bradders1999 posted a photo:

The MATRIX-Style colour grading version.

Minifigures made, photographed and edited by me.




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LEGO Classic Space: the robot final rebellion on the capital planet ousts the federation rule and replace with a techno republic and dictatorship (the final episode (for a while)) (AFOL toy hobby photography with droids, police and minifigures city MOC

dannyhennesy posted a photo:

On the Capital planet the rebellious droids had followed maily the Bat-Bot, but as time progressed his circuits had gone all mushy at 780 years or so without maintenance…

Several splinter groups all with their local bot leaders emerged such as the Che-bot, the traffic-light-robot and the Butt-bot, but none of these collected enough sentient circuits to call themselves a popular (or Animata) mass movement!

That was until a cyborg came along, one known as Jones, a long time prisoner and terrorist, his easy solutions to every problem rang well in the masses' auditory circuits!!!

His slogans and simple rhetoric were simple enough for the simple traffic-light to comprehend and cheer!

His language was full of hate towards the organics and especially the humans who were the most common races among the ruling class of the federation!!!

Despite being a “Fleshie” himself his message collected the angry enslaved
bot community by only weeks all rebellious robots except for a few fringe loonies had forgotten the old leaders…

One morning at Jones gave the signal…

All over the capital planet hordes and swarms of any form of mechanical sentient beings attacked first the police stations, then the Company boards running the planet and the federation as well as their starfleet…

Many died, especially the low level police and army! Many mechanicals died too, but their ranks were soon filled by Mutant fleshie allies of the lower levels who hated the Federation feudal society and upper classes as much as their technological allies…

The Federation state apparatus and ruling class, most of their fleet army fled when they knew the game was up, they activated the emergency escape plan and whole city blocks with important factories, administrational units, valuable assets and so on separated from the capital by hidden rocket engines and homed in their course to Mars…

On Mars the federation regrouped and formed their new society…

On the Capital planet, the robots proclaimed the first Techno-republic of the advanced inorganic civilization, the low level fleshies left behind, became slaves and their mutant allies got to rule their own minute chiefdoms as protectorates under the Techno-republic…

Jones was now the undisputed ruler of the capital planet, but the victory was a pyrros one since, all important buildings, all of value was now one Mars!

But as Jones put it:

Our proud race the Techno-species didn’t need the Fleshies administration, their infrastructure, their spaceships…

We shall start from scratch, with a new administration, a new order, every droid shall work at 4x speed than they did during human oppression since now we are free and the fleshies shall work twice as hard than the Techno-Race, until we have breed enough new fleshies so they can do all work!

Our future is bright and shiny like glistering shiny metal!

The snapshot seen here is from the first police station attacked in sector 45-34v-ss-g the first one to fall according to official techno-history!

———————————————/
Designers note:

I am sad to say that this is the last episode in this years-spanning space series… At least for a while, I will still post LEGO hobby stuff here but without a storyline, perhaps small designs and builds… and occasionally a story when I feel like it!!!

I would like to thank all who had been in this journey of our heros, but it has taken far to much time and effort and since the state of the world is as it is, I am spiraling down in another depression, I must stop it before I reach the abyss, so I have remove some stress out of my equation… I ended it in a cliffhanger so I can easily restart it when my mental health improves… I hope that won’t be forever???

I would love if someone used my characters or ideas, please send me a link if you do, I would love to read it or look at it!!!

But there will be more Lego, just in different format without long stories, I need to focus more on my art and to be honest that is the only time the mental pain eases, when I create!!!


Peace and Noise!

MushroomBrain a FOL




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Tekno - The Irish Collection - Ref. 258 - Scania Articulated Truck - Glynns, Galway - Miniature Diecast Metal Scale Model Heavy Goods Vehicle

firehouse.ie posted a photo:




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Tekno - The Irish Collection - Ref. 258 - Scania Articulated Truck - Glynns, Galway - Miniature Diecast Metal Scale Model Heavy Goods Vehicle

firehouse.ie posted a photo:




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Kennedy (My Scene, Let's Go Disco!)

AO-Koun posted a photo:




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Smoothness and Lévy concentration function inequalities for distributions of random diagonal sums

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







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Jon Stewart Blows Up Key Theory on Why Dems Got ‘Shellacked’




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China reveals reusable cargo shuttle design for Tiangong space station (video)




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King tides, 28-foot waves to swamp the Oregon Coast this week




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Northern California man goes missing after Uber ride from Bay Area to Placer County




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N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation [Molecular Bases of Disease]

Myelination plays an important role in cognitive development and in demyelinating diseases like multiple sclerosis (MS), where failure of remyelination promotes permanent neuro-axonal damage. Modification of cell surface receptors with branched N-glycans coordinates cell growth and differentiation by controlling glycoprotein clustering, signaling, and endocytosis. GlcNAc is a rate-limiting metabolite for N-glycan branching. Here we report that GlcNAc and N-glycan branching trigger oligodendrogenesis from precursor cells by inhibiting platelet-derived growth factor receptor-α cell endocytosis. Supplying oral GlcNAc to lactating mice drives primary myelination in newborn pups via secretion in breast milk, whereas genetically blocking N-glycan branching markedly inhibits primary myelination. In adult mice with toxin (cuprizone)-induced demyelination, oral GlcNAc prevents neuro-axonal damage by driving myelin repair. In MS patients, endogenous serum GlcNAc levels inversely correlated with imaging measures of demyelination and microstructural damage. Our data identify N-glycan branching and GlcNAc as critical regulators of primary myelination and myelin repair and suggest that oral GlcNAc may be neuroprotective in demyelinating diseases like MS.




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Rage Against the Algorithm: the Risks of Overestimating Military Artificial Intelligence

27 August 2020

Yasmin Afina

Research Assistant, International Security Programme
Increasing dependency on artificial intelligence (AI) for military technologies is inevitable and efforts to develop these technologies to use in the battlefield is proceeding apace, however, developers and end-users must ensure the reliability of these technologies, writes Yasmin Afina.

GettyImages-112897149.jpg

F-16 SimuSphere HD flight simulator at Link Simulation in Arlington, Texas, US. Photo: Getty Images.

AI holds the potential to replace humans for tactical tasks in military operations beyond current applications such as navigation assistance. For example, in the US, the Defense Advanced Research Projects Agency (DARPA) recently held the final round of its AlphaDogfight Trials where an algorithm controlling a simulated F-16 fighter was pitted against an Air Force pilot in virtual aerial combat. The algorithm won by 5-0. So what does this mean for the future of military operations?

The agency’s deputy director remarked that these tools are now ‘ready for weapons systems designers to be in the toolbox’. At first glance, the dogfight shows that an AI-enabled air combat would provide tremendous military advantage including the lack of survival instincts inherent to humans, the ability to consistently operate with high acceleration stress beyond the limitations of the human body and high targeting precision.

The outcome of these trials, however, does not mean that this technology is ready for deployment in the battlefield. In fact, an array of considerations must be taken into account prior to their deployment and use – namely the ability to adapt in real-life combat situations, physical limitations and legal compliance.

Testing environment versus real-life applications

First, as with all technologies, the performance of an algorithm in its testing environment is bound to differ from real-life applications such as in the case of cluster munitions. For instance, Google Health developed an algorithm to help with diabetic retinopathy screening. While the algorithm’s accuracy rate in the lab was over 90 per cent, it did not perform well out of the lab because the algorithm was used to high-quality scans in its training, it rejected more than a fifth of the real-life scans which were deemed as being below the quality threshold required. As a result, the process ended up being as time-consuming and costly – if not more so – than traditional screening.

Similarly, virtual environments akin to the AlphaDogfight Trials do not reflect the extent of risks, hazards and unpredictability of real-life combat. In the dogfight exercise, for example, the algorithm had full situational awareness and was repeatedly trained to the rules, parameters and limitations of its operating environment. But, in a real-life dynamic and battlefield, the list of variables is long and will inevitably fluctuate: visibility may be poor, extreme weather could affect operations and the performance of aircraft and the behaviour and actions of adversaries will be unpredictable.

Every single eventuality would need to be programmed in line with the commander’s intent in an ever-changing situation or it would drastically affect the performance of algorithms including in target identification and firing precision.

Hardware limitations

Another consideration relates to the limitations of the hardware that AI systems depend on. Algorithms depend on hardware to operate equipment such as sensors and computer systems – each of which are constrained by physical limitations. These can be targeted by an adversary, for example, through electronic interference to disrupt the functioning of the computer systems which the algorithms are operating from.

Hardware may also be affected involuntarily. For instance, a ‘pilotless’ aircraft controlled by an algorithm can indeed undergo higher accelerations, and thus, higher g-force than the human body can endure. However, the aircraft in itself is also subject to physical limitations such as acceleration limits beyond which parts of the aircraft, such as its sensors, may be severely damaged which in turn affects the algorithm’s performance and, ultimately, mission success. It is critical that these physical limitations are factored into the equation when deploying these machines especially when they so heavily rely on sensors.

Legal compliance

Another major, and perhaps the greatest, consideration relates to the ability to rely on machines for legal compliance. The DARPA dogfight exclusively focused on the algorithm’s ability to successfully control the aircraft and counter the adversary, however, nothing indicates its ability to ensure that strikes remain within the boundaries of the law.

In an armed conflict, the deployment and use of such systems in the battlefield are not exempt from international humanitarian law (IHL) and most notably its customary principles of distinction, proportionality and precautions in attack. It would need to be able to differentiate between civilians, combatants and military objectives, calculate whether its attacks will be proportionate against the set military objective and live collateral damage estimates and take the necessary precautions to ensure the attacks remain within the boundaries of the law – including the ability to abort if necessary. This would also require the machine to have the ability to stay within the rules of engagement for that particular operation.

It is therefore critical to incorporate IHL considerations from the conception and throughout the development and testing phases of algorithms to ensure the machines are sufficiently reliable for legal compliance purposes.

It is also important that developers address the 'black box' issue whereby the algorithm’s calculations are so complex that it is impossible for humans to understand how it came to its results. It is not only necessary to address the algorithm’s opacity to improve the algorithm’s performance over time, it is also key for accountability and investigation purposes in cases of incidents and suspected violations of applicable laws.

Reliability, testing and experimentation

Algorithms are becoming increasingly powerful and there is no doubt that they will confer tremendous advantages to the military. Over-hype, however, must be avoided at the expense of the machine’s reliability on the technical front as well as for legal compliance purposes.

The testing and experimentation phases are key during which developers will have the ability to fine-tune the algorithms. Developers must, therefore, be held accountable for ensuring the reliability of machines by incorporating considerations pertaining to performance and accuracy, hardware limitations as well as legal compliance. This could help prevent incidents in real life that result from overestimating of the capabilities of AI in military operations. 




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Sudan’s gold boom: Connections to conflict and transnational impacts

Sudan’s gold boom: Connections to conflict and transnational impacts 7 December 2022 — 2:00PM TO 3:30PM Anonymous (not verified) 24 November 2022 Online

At this event, experts will discuss Sudan’s gold sector, its connections to conflict, and transnational impacts. 

At this webinar panellists will discuss Sudan’s gold sector, its connections to conflict, and transnational impacts.

Sudan is one of the largest gold producers on the continent, with the industry constituting Sudan’s foremost source of hard currency since the secession of South Sudan in 2011 and resulting loss of oilfields.

The gold rush that has ensued has had important implications for domestic and transnational conflict dynamics. Military actors and armed groups have sought control of gold-producing areas in the peripheries and to capitalize on the flow of labour migrants, against a wider backdrop of conflict partly stemming from contestation for control between central and local actors.

International interests are prominent, including increased Russian involvement in the sector, while gold smuggling has also interlaced with mercenary activity in neighbouring CAR, Chad and Libya.
 
At this event, panellists will discuss Sudan’s gold trade, its connections to conflict, and transnational impacts, including the international politics of Sudan’s gold extraction and role of armed groups. It will also explore the environmental and socio-economic dimensions of gold in Sudan’s border areas. 
 
This roundtable is an output of the Cross-Border Conflict: Evidence, Policy and Trends (XCEPT) research programme, funded by UK Aid from the UK government.
 




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Fighting over ‘white gold’: Sesame in Ethiopia and Sudan

Fighting over ‘white gold’: Sesame in Ethiopia and Sudan Expert comment LJefferson 3 April 2023

The supply chain of a seemingly innocuous cash crop – sesame – has intersected with transnational conflict dynamics, exacerbating tensions between Ethiopia and Sudan.

Late 2020 saw the beginning of the devastating war in Tigray and the occupation of a disputed region on the Ethiopia–Sudan border – Al Fashaga – by the Sudanese army. These shocks disrupted settled patterns of land ownership and control in both Ethiopia’s volatile north and Sudan’s borderlands, historically the heart of the sesame and oilseed production that is economically vital to both countries.

These seemingly harmless cash crops are now embedded in local, subnational and national political contestations in both countries. Sesame value chains are being reshaped, with power and profits being used to entrench the grip of political and armed actors who are reinforcing new patterns of land control and driving informal and illicit trade – impacting the coping mechanisms of local communities and threatening to fuel further conflict.

Regional rivalries drive contestation over the Ethiopia supply chain

Internal borders between most of Ethiopia’s regions are marked by boundary disputes, which often degenerate into violent conflict. The most important is between the Tigray and Amhara regions. Since the war began in 2020, the Amhara region has annexed vast areas of western and southern Tigray, which the Amhara region claims were taken from them by Tigray 30 years ago, after the Tigray People’s Liberation Front (TPLF) dominated ethnic coalition came to power.

Conflict has exacerbated a steady decline in formal revenues from sesame exports, dropping over $115 million from 2016 to 2021.

Ethiopia’s exports of spices, oilseeds and pulses brought in over half a billion dollars in 2021, roughly a quarter of the country’s total export revenues and second only to coffee. The sector has been rocked by the war in the north, which accounted for much of Ethiopia’s sesame production, with an estimated 500,000 hectares of sesame fields taken out of cultivation during the 2021 growing season. Conflict has exacerbated a steady decline in formal revenues from sesame exports, dropping over $115 million from 2016 to 2021.

Alongside falling production, the previously integrated value chain has been disrupted and decentralized by political fragmentation and land competition between Amharas and Tigrayans. Before the war, the agricultural sector in Western Tigray/Welkait was dominated by Tigrayan business interests, through the TPLF’s regional endowment fund EFFORT, a business conglomerate including subsidiaries such as Guna Trading House, and Hiwot Agricultural Mechanization.

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Two-minute video explainer: Supply chains, land contestation and conflict in the Horn of Africa

The taking of the area by Amhara forces in late 2020 saw the control over agricultural supply chains shift to actors from the Amhara region, amid contestation between regional officials, businessmen and security actors, backed by political elites. Thousands of displaced ethnic Tigrayan inhabitants of the area have been replaced by ethnic Amharas, enticed to settle there by the Amhara regional government’s offer of grants and leases for land which promise better livelihoods. The sesame they farm is now largely exported through informal and illicit channels, with profits used to reinforce de facto regional control.    

But there is also contestation within the Amhara region over the land and sesame supply chain between sub-regional elites from Gojjam, Gondar and indigenous Welkaites. Welkaites, who were marginalized under TPLF rule, believed that by aligning themselves with powerful Amharas they would reclaim land and influence. But this has not been fully realized, with the local administration reliant on Amhara region subsidies, rather than the federal budget. With little support from the federal government, local Welkait officials are strengthening their ties with Eritrea.

The Ethiopian government’s pursuit of peace with Tigray may lead it to turn away from the Amhara region, which could result in a renewed showdown between Amhara and Tigrayan forces.

At the national level, regional contestation over the control over Western Tigray/Welkait feeds into shifting political alliances between the Amhara, Tigrayans and Oromo which threaten the sustainability of the peace agreement struck between the federal government and TPLF in November 2022 – despite efforts by the government to defer the thorny issue.

While the constitutional return of the land to Tigray remains unlikely anytime soon, there is a feeling that Amhara control over Western Tigray/Welkait is no longer certain. The Ethiopian government’s pursuit of peace with Tigray may lead it to turn away from the Amhara region, despite their alliance during and before the war, which could result in a renewed showdown between Amhara and Tigrayan forces.

The prospect of losing territory could also heighten Amhara nationalist claims on Al Fashaga – the loss of which was partly offset by gaining Western Tigray/Welkait – leading to renewed conflagration with Sudan, outside of federal direction. Eritrea’s presence and alliance with Amhara militias remains a concern, given Asmara’s demonstrable ability to inflame tensions.  

Sudan’s securocrats battle over resources to entrench political power

The war in northern Ethiopia was also used opportunistically by the Sudanese Armed Forces (SAF) to take control of the fertile Al Fashaga borderland. This roughly 250 sq km area had been awarded to Sudan when the boundary was initially demarcated by the British in 1903, a ruling that remained contested by Ethiopia. An uneasy truce had seen Ethiopian farmers cultivate the land under nominal Sudanese administration; a settlement that collapsed in 2020 when thousands of predominantly Amhara farmers were evicted.

Local Sudanese farmers have also lost out – with some not compensated for the loss of lands to their own military, with land given to people from other parts of the country, and through lost relationships with Ethiopian farmers, labourers and investors.

The Sudanese military now allegedly controls more than 90 per cent of the disputed areas and security-linked companies and investors have moved into the lucrative sesame sector, re-routing the supply chain, which used to flow largely through Ethiopian markets. These companies are connected to Sudan’s Military Industrial Corporation, a vast conglomerate of business subsidiaries controlled by SAF – which is headed by General Abdel Fattah al-Burhan.

Competition between Sudanese security actors fuels volatile political rivalries, and further entrenches military control of economic resources.

The commander of the paramilitary Rapid Support Forces, General Mohamed Hamdan Dagolo (or Hemedti), also has interests in agriculture, through his family business Al-Junaid. Both sit at the top of Sudan’s Sovereign Council. Hemedti’s competition with Burhan has seen him develop relations with Ethiopia’s prime minister – counter-balanced by recent rapprochement between Abiy and Burhan – as well as senior Amhara leaders, including over business activities.

Moreover, competition between Sudanese security actors fuels volatile political rivalries, and further entrenches military control of economic resources, undermining civilians at a time when pro-democracy forces are seeking to restore a reform-minded government. One of the key challenges for a new civilian government will be to quickly build up a domestic revenue base to compete with the economic heft of the country’s prominent security institutions, which will demand taking on military-controlled holdings in civic sectors such as agriculture, including sesame.

Informal and illicit trade reinforces conflict dynamics

This context has driven the informalization of trade, with cash crops such as sesame increasingly exported outside of formal channels and connected to other illicit cross-border activities between Ethiopia and Sudan. Indications are that sesame production in Western Tigray/Welkait has recovered significantly during the current 2022/23 harvest season. However, rather than contributing much needed currency to soften Ethiopia’s forex crisis, the Amhara elite-controlled supply chain is primarily being used to secure a variety of regional interests.





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Functions of Gle1 are governed by two distinct modes of self-association [Gene Regulation]

Gle1 is a conserved, essential regulator of DEAD-box RNA helicases, with critical roles defined in mRNA export, translation initiation, translation termination, and stress granule formation. Mechanisms that specify which, where, and when DDXs are targeted by Gle1 are critical to understand. In addition to roles for stress-induced phosphorylation and inositol hexakisphosphate binding in specifying Gle1 function, Gle1 oligomerizes via its N-terminal domain in a phosphorylation-dependent manner. However, a thorough analysis of the role for Gle1 self-association is lacking. Here, we find that Gle1 self-association is driven by two distinct regions: a coiled-coil domain and a novel 10-amino acid aggregation-prone region, both of which are necessary for proper Gle1 oligomerization. By exogenous expression in HeLa cells, we tested the function of a series of mutations that impact the oligomerization domains of the Gle1A and Gle1B isoforms. Gle1 oligomerization is necessary for many, but not all aspects of Gle1A and Gle1B function, and the requirements for each interaction domain differ. Whereas the coiled-coil domain and aggregation-prone region additively contribute to competent mRNA export and stress granule formation, both self-association domains are independently required for regulation of translation under cellular stress. In contrast, Gle1 self-association is dispensable for phosphorylation and nonstressed translation initiation. Collectively, we reveal self-association functions as an additional mode of Gle1 regulation to ensure proper mRNA export and translation. This work also provides further insight into the mechanisms underlying human gle1 disease mutants found in prenatally lethal forms of arthrogryposis.




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Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling [Signal Transduction]

The glucagon receptor (GCGR) activated by the peptide hormone glucagon is a seven-transmembrane G protein–coupled receptor (GPCR) that regulates blood glucose levels. Ubiquitination influences trafficking and signaling of many GPCRs, but its characterization for the GCGR is lacking. Using endocytic colocalization and ubiquitination assays, we have identified a correlation between the ubiquitination profile and recycling of the GCGR. Our experiments revealed that GCGRs are constitutively ubiquitinated at the cell surface. Glucagon stimulation not only promoted GCGR endocytic trafficking through Rab5a early endosomes and Rab4a recycling endosomes, but also induced rapid deubiquitination of GCGRs. Inhibiting GCGR internalization or disrupting endocytic trafficking prevented agonist-induced deubiquitination of the GCGR. Furthermore, a Rab4a dominant negative (DN) that blocks trafficking at recycling endosomes enabled GCGR deubiquitination, whereas a Rab5a DN that blocks trafficking at early endosomes eliminated agonist-induced GCGR deubiquitination. By down-regulating candidate deubiquitinases that are either linked with GPCR trafficking or localized on endosomes, we identified signal-transducing adaptor molecule–binding protein (STAMBP) and ubiquitin-specific protease 33 (USP33) as cognate deubiquitinases for the GCGR. Our data suggest that USP33 constitutively deubiquitinates the GCGR, whereas both STAMBP and USP33 deubiquitinate agonist-activated GCGRs at early endosomes. A mutant GCGR with all five intracellular lysines altered to arginines remains deubiquitinated and shows augmented trafficking to Rab4a recycling endosomes compared with the WT, thus affirming the role of deubiquitination in GCGR recycling. We conclude that the GCGRs are rapidly deubiquitinated after agonist-activation to facilitate Rab4a-dependent recycling and that USP33 and STAMBP activities are critical for the endocytic recycling of the GCGR.




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Wildtype {sigma}1 receptor and the receptor agonist improve ALS-associated mutation-induced insolubility and toxicity [Neurobiology]

Genetic mutations related to ALS, a progressive neurological disease, have been discovered in the gene encoding σ-1 receptor (σ1R). We previously reported that σ1RE102Q elicits toxicity in cells. The σ1R forms oligomeric states that are regulated by ligands. Nevertheless, little is known about the effect of ALS-related mutations on oligomer formation. Here, we transfected NSC-34 cells, a motor neuronal cell line, and HEK293T cells with σ1R-mCherry (mCh), σ1RE102Q-mCh, or nontagged forms to investigate detergent solubility and subcellular distribution using immunocytochemistry and fluorescence recovery after photobleaching. The oligomeric state was determined using crosslinking procedure. σ1Rs were soluble to detergents, whereas the mutants accumulated in the insoluble fraction. Within the soluble fraction, peak distribution of mutants appeared in higher sucrose density fractions. Mutants formed intracellular aggregates that were co-stained with p62, ubiquitin, and phosphorylated pancreatic eukaryotic translation initiation factor-2-α kinase in NSC-34 cells but not in HEK293T cells. The aggregates had significantly lower recovery in fluorescence recovery after photobleaching. Acute treatment with σ1R agonist SA4503 failed to improve recovery, whereas prolonged treatment for 48 h significantly decreased σ1RE102Q-mCh insolubility and inhibited apoptosis. Whereas σ1R-mCh formed monomers and dimers, σ1RE102Q-mCh also formed trimers and tetramers. SA4503 reduced accumulation of the four types in the insoluble fraction and increased monomers in the soluble fraction. The σ1RE102Q insolubility was diminished by σ1R-mCh co-expression. These results suggest that the agonist and WT σ1R modify the detergent insolubility, toxicity, and oligomeric state of σ1RE102Q, which may lead to promising new treatments for σ1R-related ALS.




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Problem Notes for SAS®9 - 66500: A content release on the SAS Risk Governance Framework fails to load when you use SAS 9.4M7 (TS1M7) on the Microsoft Windows operating system

When you log on to the SAS Risk Governance Framework and choose a solution, the web application might fail to load the solution content. When the problem occurs, you continue to see "Loading..." on the screen, an