Chi-Liang Eric Yen
Nov 1, 2008; 49:2283-2301
Thematic Reviews

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.

Undercurrents: The Oversight Board's Trump decision, and Merkel's legacy Audio bhorton.drupal 25 June 2021

Was Facebook right to suspend Trump? And how will Merkel be remembered?

In the wake of the storming of Capitol Hill on 6 January 2021, social media platforms took steps to remove former President Donald Trump from their websites for infringing community standards. This step was welcomed by many, but also raised serious questions about the power of social media companies to limit free speech and censor elected officials. The suspension of President Trump from Facebook was referred to the Oversight Board, an independent body of experts set up to scrutinise the platform’s content moderation decisions.  

In this episode, Ben speaks to Thomas Hughes and Kate Jones about the outcome of the Oversight Board’s inquiry into the Trump suspension, and the wider implications for content moderation on social media.  

Then Lara is joined by Hans Kundnani to assess the political outlook in Germany and reflect on the legacy of outgoing Chancellor Angela Merkel.  

Counter-terrorism measures and sanctions: How to avoid negative consequences for humanitarian action? 9 September 2021 — 2:00PM TO 3:30PM Anonymous (not verified) 21 July 2021 Online

Exploring current endeavours to address the tensions between counter-terrorism measures, sanctions and humanitarian action.

Counter-terrorism measures  address broad forms of support to terrorist acts. Their expansion, internationally and domestically, has given rise to new points of friction with international humanitarian law. Unless the measures include adequate safeguards, they  can impede humanitarian action. Country-specific sanctions imposed for other objectives, such as ending conflicts or protecting civilians, raise similar challenges for humanitarian action. 

These problems are not new, but solutions at international and national level remain elusive. 

At this panel event, which marks the launch of a new Chatham House research paper, panellists explore current endeavours to address the tensions between counter-terrorism measures, sanctions and humanitarian action.

• What are the current dynamics and developments at Security Council level?  
• What are the opportunities now that the UK is developing its independent sanctions strategy? 
• What challenges do counter-terrorism requirements in funding agreements for humanitarian action  pose? 
• What is necessary to make progress?

The trickle-up effect of rights-based climate litigation Expert comment NCapeling 16 November 2021

With governments failing in their pledges and companies accused of ‘green-washing’, human rights-based litigation is increasingly important for accountability.

Tuvalu’s foreign minister addressing COP26 while standing knee-deep in seawater was a stark illustration of how the climate emergency directly and imminently threatens the most basic human rights protected under international law – including to the right to life, self-determination and cultural rights.

Human rights are now a fundamental component of more than 90 per cent of the climate litigation currently taking place outside the US, highlighting the international reach of human rights law and how its emphasis on protecting the most vulnerable helps diverse communities find common arguments for shared goals.

Cases are set to continue and to evolve but three types of claim are emerging, each of which is examined in a new Chatham House briefing paper.

1. Enforcing commitments

One category of cases seeks to hold states accountable for pledges they have made on climate change, such as emission reduction targets made under the framework of the 2015 Paris Agreement. Drawing on human rights obligations, governments can be charged with not taking sufficient steps to implement these pledges.

The case of Leghari v Pakistan (2015) concerned the government’s failure to carry out the National Climate Change Policy of 2012 and the Framework for Implementation of Climate Change Policy (2014-2030). The Lahore High Court held that several of the human rights enshrined in Pakistan’s constitution cover climate change and ‘provide the necessary judicial toolkit to address the government’s response to climate change’.

The court ordered the government to carry out measures such as publishing an adaptation action plan realizable within a few months of the order and establishing a Climate Change Commission to monitor progress.

2. Positive duties to mitigate risks

Many rights-based climate cases are being brought to clarify the scope of states’ positive duties under human rights law to take meaningful steps to protect their citizens against foreseeable risks to life and other rights.

This ‘trickle-up’ effect of human rights was prominent in the case of State of the Netherlands vs the Urgenda Foundation (2019) where the Dutch Supreme Court held that reducing emissions with the highest possible level of ambition amounts to a ‘due diligence standard’ for states to comply with their positive duties to adopt adequate measures to address climate change. Human rights law was also used by the court to fill in the content of the due diligence standards.

There is also a growing trend for rights-based actions to be brought against corporations, such as a recent case which drew on the UN Guiding Principles on Business and Human Rights to define the parameters of Shell’s duty of care and due diligence obligations in relation to carbon emissions under Dutch law. The court ordered Shell to reduce emissions by a net rate of 45 per cent by the end of 2030 – relative to 2019 figures – through its group corporate policy.

3. Avoiding harm in climate action

The global human rights regime is also increasingly invoked in litigation concerning states’ negative obligations to ensure that their climate mitigation and adaptation activities do not themselves contribute to human rights violations (including discrimination) and that states prioritize adaptation measures for those most at risk in a just and equitable way.

As Chatham House’s paper makes clear, this kind of litigation ‘puts pressure on governments to expand their approach to tackling climate change beyond purely a regulatory one to a more holistic strategy’.

Closing the climate justice gap

Climate and environmental litigation grounded in human rights is set to continue given the overwhelming scientific evidence of risks associated with human-induced climate change and the limited confidence in pledges made by states and corporations alike – including those made recently at COP26.

A growing collaboration between civil society organizations and vulnerable communities in relation to both the protection of nature and the enjoyment of their land and cultural rights was evident at COP26, and this alliance will add further momentum to the trend for rights-based climate litigation based on the rights of indigenous and other vulnerable communities, especially on issues such as deforestation.

But more challenges are coming. International human rights law recognizes a duty of international cooperation but there remain significant hurdles for climate-vulnerable communities in developing countries to compel action by richer nations despite the vast debts of ‘carbon colonialism.’

One big issue is the problem of extraterritoriality, as the extent to which states owe obligations to individuals outside their territory is contested. Courts in both Germany and the Netherlands have rejected claimants from developing countries in domestic class actions on this basis. But a recent decision of the UN Committee on the Rights of the Child on a complaint brought by Greta Thunberg and other youth activists against five countries opens the door for further litigation.

One of a number of cases being brought by youth claimants across the world, the committee concluded that a state’s human rights duties can – in some instances – extend to children in other countries. This includes any activities on the territory that host states have the power to prevent from causing ‘transboundary harm’ – such as emissions from the territory – where these activities ‘significantly’ impact the enjoyment of human rights of persons outside the territory.

To date, high-profile rights-based cases have argued for policy change and stronger targets underpinned by binding legislation responsive to the science. Claims are set to become more complex and contested. Building on scientific developments in climate attribution, rights-based litigation is now tackling other difficult questions such as apportioning responsibility and remedial action.

These cases examine both historically high emitters and the public and private actors who either continue specific activities or refrains from action in the face of the overwhelming science linking human activities such as extraction and burning of fossil fuels to deforestation and climatic consequences.

Courts are also likely to explore the duties that states and corporations owe to deliver a ‘just transition’ away from carbon-intensive industries, given the benefits of growth and climate action are already unevenly distributed.

A holistic human-rights based approach

Several states together with civil society are leading the charge for global recognition of the right to a healthy, clean, and sustainable environment in the United Nations (UN) Human Rights Council, and multi-stakeholder processes are defining what effective corporate due diligence looks like.

In addition, UN-appointed special rapporteurs are delivering practical guidance on how to devise solutions which are fair, non-discriminatory, participatory, and climate-resilient without exacerbating inequality – including difficult issues of planned relocation – and UN Human Rights Treaty Bodies are unpacking the duty of international cooperation to act in good faith to address loss and damage.

Recently the Committee on the Elimination of Discrimination Against Women recommended the Marshall Islands, in order to meet its duty to its citizens, should actively seek international cooperation and assistance – including climate change financing – from other countries but in particular the US, whose ‘extraterritorial nuclear testing activities have exacerbated the adverse effects of climate change and natural disasters’ in the islands.

Ukraine: Debunking Russia’s legal justifications Expert comment NCapeling 24 February 2022

Russia is violating international law in Ukraine using baseless allegations, and states’ responses should be guided accordingly.

Russia has begun a large-scale military attack on Ukraine, having first declared it recognizes Donetsk and Luhansk as separate states. It scarcely needs saying Russia is violating international law – violating the prohibition in the United Nations (UN) Charter on the use of force, violating the obligation to respect the sovereignty and territorial integrity of other states, and violating the prohibition on intervention.

But Russia is using the language of the law to defend its actions. In all the recent verbiage of President Vladimir Putin, some attempts at legal arguments can be elicited – but they do not stand up to scrutiny.

Article 2(4) of the UN Charter prohibits the threat or use of force with the only two Charter exceptions to this prohibition being self-defence and action mandated by the UN Security Council. In his speech on 23 February, Putin points to two grounds on which Russia relies on self-defence – defence in aid of the two breakaway republics and self-defence in the light of threats against Russia itself.

Donetsk, Luhansk, and collective self-defence

Putin said ‘the people’s republics of Donbass turned to Russia with a request for help’ and went on to seek to justify his military action under Article 51 of the Charter. But it is only in respect of states that the right of collective self-defence exists – humanitarian intervention on behalf of individuals in a state has not gained a place in international law. And it is only Russia which has recognized the statehood of the two regions.

Putin repeated on 23 February his earlier allegation that the people of the two breakaway republics are being repressed by the Ukraine government, and even that genocide is being committed against them. This baseless allegation is relevant not only to the claim of self-defence on behalf of these regions but also to Russia’s ‘recognition’ of them as separate states.

International law does not give the inhabitants of a part of a state the right to secede from that state. The aspect of self-determination which allows for independence of a ‘people’ applies to peoples in colonies and other overseas territories under the occupation of another state. The other aspect of self-determination is ‘internal’ and comprises the right to freely choose political status and pursue economic, social, and cultural development within the state – as the Minsk accords sought to provide for Donetsk and Luhansk.

There is a somewhat controversial theory in international law that would give a right of secession from a state if the people in question were subject to extreme abuse of human rights and systematic oppression. This is the theory of remedial secession, which some countries, such as Switzerland, used in the International Court of Justice (ICJ) in relation to Kosovo’s declaration of independence from Serbia – an independence still not recognized by Russia.

But the theory has no support from the international courts and, even if it did, Russia itself has stated previously that a right of remedial secession is ‘limited to truly extreme circumstances, such as an outright armed attack by the parent State, threatening the very existence of the people in question’ (see Russia’s submissions to the ICJ in the Kosovo case, para 88).

The facts do not substantiate Russia’s claims anyway. The law is as stated on behalf of the UN Secretary-General on 21 February – that Russia’s decision to recognize the independence of the breakaway regions is a ‘violation of the territorial integrity and sovereignty of Ukraine and inconsistent with the principles of the Charter of the United Nations.’ There are no ‘states’ which can request the use of military force.

Is Ukraine a threat against Russia?

Putin refers to the ‘further expansion of the infrastructure of the North Atlantic Alliance, the military development of the territories of Ukraine’ as creating an ‘anti-Russia’ comprising a ‘real threat not just to our interests, but to the very existence of our state, its sovereignty’.

Article 51 allows for self-defence ‘if an armed attack occurs’. This has been interpreted by many states to include defence against the threat of an imminent attack – for example, there is no requirement to wait until a nuclear strike has begun. But under no interpretation of ‘imminence’ can the situation in Ukraine constitute a threat to Russia. There have been no threats of force against Russia from Ukraine nor from NATO member states. There is nothing to support a legal justification for Russia’s military attack against Ukraine.

The myth of Ukraine never having had ‘real statehood’ also does not give any legal justification for Russian aggression. The UN is based on the ‘principle of the sovereign equality of all its Members’ (Art. 2(1) of the UN Charter). Ukraine retained its membership in the UN at the dissolution of the USSR, having been one of the founding members of the UN as the Ukrainian Soviet Socialist Republic.

What are the legal consequences of Russia’s actions?

Within the UN, it is the Security Council which has the mandate to uphold international peace and security, and act when there is a threat to the peace. But there will be no help from there with Russia’s status as a permanent member holding a veto.

The UN General Assembly may act instead. Since 2014 it has adopted a series of resolutions (the latest on 9 December 2021) requiring Russia to withdraw immediately and unconditionally from Crimea. But the General Assembly does not have the powers of the Security Council, and cannot mandate peacekeepers or the use of force.

In due course there may be the need for a UN Human Rights Commission of Inquiry to be launched if there are breaches of human rights law and international humanitarian law, and human rights cases may be brought against Russia at the European Court of Human Rights. But international institutions do not have the necessary powers to stop what is going on right now.

International law gives the right to Ukraine, being attacked, to call for support from other states. And as well as imposing sanctions, states may wish to consider cyber countermeasures. Some of the recent cyber activity against Ukraine has been attributed by the US, UK, and Australia to the Russian Main Intelligence Unit (GRU).

Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer's diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries.

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Sino-Russian Gas Cooperation: Power of Siberia I and II and Implications for Global LNG Supplies 27 November 2019 — 8:30AM TO 9:30AM Anonymous (not verified) 19 November 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

In a new event in the Sustainable Transitions series, the speaker will present an update of Sino-Russian gas cooperation.

To give a comprehensive account of their impact on global liquefied natural gas (LNG) supplies, he will discuss the following points:

• Gas is scheduled to start flowing from the Power of Siberia I (POS) on 2 December 2019. But what is the background of development of POS 1 and what is its current status and prospects?
• What are the chances of exporting gas through the proposed Altai pipeline? Why is the Mongolia export route so significant? And how will it affect the Central Asian Republics and in particular Turkmenistan’s gas export to China?
• What are the implications of both POS I and Altai gas via Mongolia route in the context of global LNG supply?
• What are the prospects for multilateral pipeline gas cooperation in northeast Asia?
• What are the implications for other Arctic onshore LNG supply, in particular, for Novatek’s Yamal LNG and Arctic LNG 1 and 2 to China on top of POS 1 and Altai gas?

Attendance at this event is by invitation only.

Climate action and gender equality: Can we close the gap on one without the other? 8 March 2021 — 2:30PM TO 4:00PM Anonymous (not verified) 15 February 2021 Online

In partnership with the COP26 presidency, policymakers and experts examine the interrelationship between gender equality and climate action, and highlight innovative examples of policy and practice from around the world.

Marking International Women’s Day, this event organized by the COP26 presidency in partnership with Chatham House, will explore how gender equality and climate action go hand-in-hand. The agreement of the Gender Action Plan (GAP) at COP25 sent the message that the time for gender-responsive climate action is now.

This will be a unique opportunity to hear from policymakers and civil society leaders discussing whether enough is being done, as well as highlighting cutting-edge work around the world and suggesting what the future could hold.

The event will be livestreamed on this event page.

Nuclear, gas and green finance taxonomies in the EU and UK 23 February 2022 — 10:00AM TO 11:00AM Anonymous (not verified) 20 January 2022 Online

Experts discuss EU, UK, and international perspectives on green taxonomy.

This event will address the controversial additions to the EU green finance taxonomy, including the labelling of some nuclear and gas power sources as “green”. Hear perspectives from the UK, EU and international experts.

The UK has committed to creating a green taxonomy to provide a shared understanding of which economic activities count as sustainable. It should be robust and evidence-based, taking an objective and science-based approach to assessing sustainability.

Technical Screening Criteria (TSCs) for the climate change mitigation, and climate change adaptation objectives within the UK green taxonomy will be based on those in the EU Taxonomy. The Government is currently reviewing these and expects to consult on UK draft TSCs in the first quarter of 2022, ahead of legislating by the end of 2022.

In recent weeks the European Commission has proposed controversial additional TSCs for the EU taxonomy, most notably the inclusion of nuclear and natural gas in power generation, which are currently being discussed by Member States and the European Parliament.

The inclusion of controversial power sources not only risks affecting investment and deployment patterns in the net-zero transition, but may also be a threat to the authority of the taxonomy as a whole

Key questions for the UK now include whether and how to address these issues in its own taxonomy, and how to promote a science-based ‘race to the top’ between jurisdictions that can lead to robust international standards.

This Environment and Society Discussion Series event brings expert voices together to discuss EU, UK, and international perspectives, and is co-organized with E3G.

Webinar: Gandhi's Vision for India 15 June 2020 — 12:00PM TO 12:45PM Anonymous (not verified) 9 June 2020

In 1931, Mahatma Gandhi visited Chatham House as part of his campaign for Indian independence. Addressing an overflowing hall, he described the poverty and the religious conflict that plagued India at the time.

Today, India is the world’s fifth largest economy and more than 270 million people have been lifted out of poverty in just a decade. But poverty in India remains widespread and the outbreak of the COVID-19 pandemic is only expected to exacerbate the situation. Meanwhile, the communal violence that erupted in Delhi earlier this year reflects intensifying religious tensions under Prime Minister Narendra Modi.

In this webinar, the speakers discuss Gandhi’s global legacy and to what extent we are seeing a re-awakening of his principles across modern India.

This event is part of a series, held in the context of the Chatham House Centenary in 2020, bringing together historians, practitioners and current policymakers to discuss contemporary problems of international relations.

Constantin Carle and Marlis Hochbruck
Math. Comp. 93 (), 2611-2641.
Abstract, references and article information

Dr. Abiy Tasissa of Tufts University, discusses the mathematics he and colleagues used to study particle collider data, including optimal transport and optimization. Collider physics often result in distributions referred to as jets. Dr. Tasissa and his team used "Earth Mover's Distance" and other mathematical tools to study the shape of jets. "It is interesting for me to see how mathematics can be applied to study these fundamental problems answering fundamental equations in physics, not only at the level of formulating new ideas, which is, in this particular case, a notion of distance, but also how the importance of designing fast optimization algorithms to be able to actually compute these distances," says Dr. Tasissa.

firehouse.ie posted a photo:

firehouse.ie posted a photo:

Claudio Macci and Barbara Pacchiarotti
Theor. Probability and Math. Statist. 111 (), 21-43.
Abstract, references and article information

Chris A.J. Klaassen
Theor. Probability and Math. Statist. 111 (), 9-19.
Abstract, references and article information

Shengyu Tang
Proc. Amer. Math. Soc. 152 (), 5381-5394.
Abstract, references and article information

Frederic Heihoff
Proc. Amer. Math. Soc. 152 (), 5229-5247.
Abstract, references and article information

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Kenta Suzuki of the Massachusetts Institute of Technology (MIT) is awarded the 2025 American Mathematical Society (AMS)-Mathematical Association of America (MAA)-Society for Industrial and Applied Mathematics (SIAM) Frank and Brennie Morgan Prize for his extraordinary research in the representation theory of $p$-adic groups. His papers, including two solo works, represent significant progress in different areas of the field.

From the citation

Suzuki worked on deep problems in representation theory, and he has authored and coauthored six research papers. In particular, he has made important contributions to the representation theory of $p$-adic groups. His results include asymptotics for the dimension of spaces fixed by a congruence subgroup in an admissible representation of $GL(n).$ His joint works include working out the local Langlands correspondence for several rank two $p$-adic groups, and the determination of canonical bases in the subregular quotient of the affine Hecke algebra and its antispherical module, along with their “coherent” categorifications.

Response of Kenta Suzuki

It is an honor for me to receive the Frank and Brennie Morgan Prize. I thank the Morgan family and the AMS, MAA, and SIAM for their generosity. I thank my mentors throughout the years, Toshihiko Nakazawa, Li Li, Michael Zieve, and Colin Hinde, for kindling my interest in mathematics. Toshihiko Nakazawa patiently explored mathematics with me from a young age and continues to inspire me with his insights. I thank Roman Bezrukavnikov, Wei Zhang, Zhiwei Yun, Ivan Losev, Vasily Krylov, and Calder Morton-Ferguson for further stimulating my interest in mathematics at MIT and introducing me to the many wonders of representation theory. Wei Zhang’s unwavering support has motivated me to explore many areas of mathematics. I leave every conversation with Roman Bezrukavnikov with new ideas, and he has helped me grow as a researcher by encouraging me to pursue even my most ambitious ideas. The mathematical community at MIT and Harvard have been supportive and taught me so much, both mathematical and nonmathematical. Finally, I thank my parents, particularly my mother, for supporting me throughout my journey in every possible way. She has been my role model and is one of the most intelligent and charismatic people I know.

Biographical sketch of Kenta Suzuki

Kenta Suzuki is a fourth-year undergraduate at MIT from Tokyo, Japan, and Plymouth, Michigan. Suzuki’s work focuses on the representation theory of $p$-adic groups and geometric representation theory. Suzuki is particularly interested in applying geometric methods to solve problems of representation theory. In his free time, he runs, reads, and is (slowly) learning how to cook.

About the prize

The AMS-MAA-SIAM Frank and Brennie Morgan Prize for Outstanding Research in Mathematics by an Undergraduate Student is awarded annually to an undergraduate (or students for joint work) for outstanding research in mathematics. The prize recipient's research can include more than one paper, however, the paper or papers to be considered for the prize must be completed while the student is an undergraduate. Publication of research is not required.

Established in 1995, the prize is entirely endowed by a gift from Mrs. Frank (Brennie) Morgan. The current prize amount is $1,200.

The prize will be presented at the 2025 Joint Mathematics Meetings in Seattle.

Learn more about the prize and previous recipients.

Contact: AMS Communications

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The American Mathematical Society is dedicated to advancing research and connecting the diverse global mathematical community through our publications, meetings and conferences, MathSciNet, professional services, advocacy, and awareness programs.

UK-based, Jamaica-born dancehall artiste Dubbi believes latest single, ' Side Chick' is a bona fide hit as its popularity has surged on the dancehall scene in the United Kingdom. "It is also streaming well in France and seems to be a real hit on...

A police sergeant who was shot and injured at his home in Portmore, St Catherine, on Thursday night succumbed to his injuries on Monday morning.

A growing number of motor vehicle crashes across Jamaica has been attributed to drivers operating the vehicles under the influence of marijuana, according to Health Minister Dr Christopher Tufton. "The data is clear, we are seeing more people...

Twenty-eight-year-old labourer Michael Ennis, of Manning's Hill district in Manchester, has been charged with smoking ganja in a public place following an incident in May Pen, Clarendon on Monday.

When using the distinct count function in SAS Visual Analytics reports, you might find that a negative value is displayed instead of the actual distinct count: imgalt="distinct_count" src="{fusion_66562_1_disti

Recent studies have suggested that innate immune responses exhibit characteristics associated with memory linked to modulations in both vertebrates and invertebrates. However, the diverse evolutionary paths taken, particularly within the invertebrate taxa, should lead to similarly diverse innate immunity memory processes. Our understanding of innate immune memory in invertebrates primarily comes from studies of the fruit fly Drosophila melanogaster, the generality of which is unclear. Caenorhabditis elegans typically inhabits soil harboring a variety of fatal microbial pathogens; for this invertebrate, the innate immune system and aversive behavior are the major defensive strategies against microbial infection. However, their characteristics of immunological memory remains infantile. Here we discovered an immunological memory that promoted avoidance and suppressed innate immunity during reinfection with bacteria, which we revealed to be specific to the previously exposed pathogens. During this trade-off switch of avoidance and innate immunity, the chemosensory neurons AWB and ADF modulated production of serotonin and dopamine, which in turn decreased expression of the innate immunity-associated genes and led to enhanced avoidance via the downstream insulin-like pathway. Therefore, our current study profiles the immune memories during C. elegans reinfected by pathogenic bacteria and further reveals that the chemosensory neurons, the neurotransmitter(s), and their associated molecular signaling pathways are responsible for a trade-off switch between the two immunological memories.

Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 109 variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (KD) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies.

α-Linked galactose is a common carbohydrate motif in nature that is processed by a variety of glycoside hydrolases from different families. Terminal Galα1–3Gal motifs are found as a defining feature of different blood group and tissue antigens, as well as the building block of the marine algal galactan λ-carrageenan. The blood group B antigen and linear α-Gal epitope can be processed by glycoside hydrolases in family GH110, whereas the presence of genes encoding GH110 enzymes in polysaccharide utilization loci from marine bacteria suggests a role in processing λ-carrageenan. However, the structure–function relationships underpinning the α-1,3-galactosidase activity within family GH110 remain unknown. Here we focus on a GH110 enzyme (PdGH110B) from the carrageenolytic marine bacterium Pseudoalteromonas distincta U2A. We showed that the enzyme was active on Galα1–3Gal but not the blood group B antigen. X-ray crystal structures in complex with galactose and unhydrolyzed Galα1–3Gal revealed the parallel β-helix fold of the enzyme and the structural basis of its inverting catalytic mechanism. Moreover, an examination of the active site reveals likely adaptations that allow accommodation of fucose in blood group B active GH110 enzymes or, in the case of PdGH110, accommodation of the sulfate groups found on λ-carrageenan. Overall, this work provides insight into the first member of a predominantly marine clade of GH110 enzymes while also illuminating the structural basis of α-1,3-galactoside processing by the family as a whole.

12th International Forum on Illegal, Unreported and Unregulated Fishing 18 May 2020 TO 22 May 2020 — 2:00PM TO 3:30PM Anonymous (not verified) 27 September 2019

Proteins in the α-macroglobulin (αM) superfamily use thiol esters to form covalent conjugation products upon their proteolytic activation. αM protease inhibitors use theirs to conjugate proteases and preferentially react with primary amines (e.g. on lysine side chains), whereas those of αM complement components C3 and C4B have an increased hydroxyl reactivity that is conveyed by a conserved histidine residue and allows conjugation to cell surface glycans. Human α2-macroglobulin–like protein 1 (A2ML1) is a monomeric protease inhibitor but has the hydroxyl reactivity–conveying histidine residue. Here, we have investigated the role of hydroxyl reactivity in a protease inhibitor by comparing recombinant WT A2ML1 and the A2ML1 H1084N mutant in which this histidine is removed. Both of A2ML1s' thiol esters were reactive toward the amine substrate glycine, but only WT A2ML1 reacted with the hydroxyl substrate glycerol, demonstrating that His-1084 increases the hydroxyl reactivity of A2ML1's thiol ester. Although both A2ML1s conjugated and inhibited thermolysin, His-1084 was required for the conjugation and inhibition of acetylated thermolysin, which lacks primary amines. Using MS, we identified an ester bond formed between a thermolysin serine residue and the A2ML1 thiol ester. These results demonstrate that a histidine-enhanced hydroxyl reactivity can contribute to protease inhibition by an αM protein. His-1084 did not improve A2ML1's protease inhibition at pH 5, indicating that A2ML1's hydroxyl reactivity is not an adaption to its acidic epidermal environment.

Cation diffusion facilitator (CDF) proteins are a conserved family of divalent transition metal cation transporters. CDF proteins are usually composed of two domains: the transmembrane domain, in which the metal cations are transported through, and a regulatory cytoplasmic C-terminal domain (CTD). Each CDF protein transports either one specific metal or multiple metals from the cytoplasm, and it is not known whether the CTD takes an active regulatory role in metal recognition and discrimination during cation transport. Here, the model CDF protein MamM, an iron transporter from magnetotactic bacteria, was used to probe the role of the CTD in metal recognition and selectivity. Using a combination of biophysical and structural approaches, the binding of different metals to MamM CTD was characterized. Results reveal that different metals bind distinctively to MamM CTD in terms of their binding sites, thermodynamics, and binding-dependent conformations, both in crystal form and in solution, which suggests a varying level of functional discrimination between CDF domains. Furthermore, these results provide the first direct evidence that CDF CTDs play a role in metal selectivity. We demonstrate that MamM's CTD can discriminate against Mn2+, supporting its postulated role in preventing magnetite formation poisoning in magnetotactic bacteria via Mn2+ incorporation.

Aspergillus terreus is an allergenic fungus, in addition to causing infections in both humans and plants. However, the allergens in this fungus are still unknown, limiting the development of diagnostic and therapeutic strategies. We used a proteomic approach to search for allergens, identifying 16 allergens based on two-dimensional immunoblotting with A. terreus susceptible patient sera. We further characterized triose-phosphate isomerase (Asp t 36), one of the dominant IgE (IgE)-reactive proteins. The gene was cloned and expressed in Escherichia coli. Phylogenetic analysis showed Asp t 36 to be highly conserved with close similarity to the triose-phosphate isomerase protein sequence from Dermatophagoides farinae, an allergenic dust mite. We identified four immunodominant epitopes using synthetic peptides, and mapped them on a homology-based model of the tertiary structure of Asp t 36. Among these, two were found to create a continuous surface patch on the 3D structure, rendering it an IgE-binding hotspot. Biophysical analysis indicated that Asp t 36 shows similar secondary structure content and temperature sensitivity with other reported triose-phosphate isomerase allergens. In vivo studies using a murine model displayed that the recombinant Asp t 36 was able to stimulate airway inflammation, as demonstrated by an influx of eosinophils, goblet cell hyperplasia, elevated serum Igs, and induction of Th2 cytokines. Collectively, our results reveal the immunogenic property of Asp t 36, a major allergen from A. terreus, and define a new fungal allergen more broadly. This allergen could serve as a potent candidate for investigating component resolved diagnosis and immunotherapy.

Arabinogalactan proteins (AGPs) are plant proteoglycans with functions in growth and development. However, these functions are largely unexplored, mainly because of the complexity of the sugar moieties. These carbohydrate sequences are generally analyzed with the aid of glycoside hydrolases. The exo-β-1,3-galactanase is a glycoside hydrolase from the basidiomycete Phanerochaete chrysosporium (Pc1,3Gal43A), which specifically cleaves AGPs. However, its structure is not known in relation to its mechanism bypassing side chains. In this study, we solved the apo and liganded structures of Pc1,3Gal43A, which reveal a glycoside hydrolase family 43 subfamily 24 (GH43_sub24) catalytic domain together with a carbohydrate-binding module family 35 (CBM35) binding domain. GH43_sub24 is known to lack the catalytic base Asp conserved among other GH43 subfamilies. Our structure in combination with kinetic analyses reveals that the tautomerized imidic acid group of Gln263 serves as the catalytic base residue instead. Pc1,3Gal43A has three subsites that continue from the bottom of the catalytic pocket to the solvent. Subsite −1 contains a space that can accommodate the C-6 methylol of Gal, enabling the enzyme to bypass the β-1,6–linked galactan side chains of AGPs. Furthermore, the galactan-binding domain in CBM35 has a different ligand interaction mechanism from other sugar-binding CBM35s, including those that bind galactomannan. Specifically, we noted a Gly → Trp substitution, which affects pyranose stacking, and an Asp → Asn substitution in the binding pocket, which recognizes β-linked rather than α-linked Gal residues. These findings should facilitate further structural analysis of AGPs and may also be helpful in engineering designer enzymes for efficient biomass utilization.

The dimeric ectonucleotidase CD73 catalyzes the hydrolysis of AMP at the cell surface to form adenosine, a potent suppressor of the immune response. Blocking CD73 activity in the tumor microenvironment can have a beneficial effect on tumor eradication and is a promising approach for cancer therapy. Biparatopic antibodies binding different regions of CD73 may be a means to antagonize its enzymatic activity. A panel of biparatopic antibodies representing the pairwise combination of 11 parental monoclonal antibodies against CD73 was generated by Fab-arm exchange. Nine variants vastly exceeded the potency of their parental antibodies with ≥90% inhibition of activity and subnanomolar EC50 values. Pairing the Fabs of parents with nonoverlapping epitopes was both sufficient and necessary whereas monovalent antibodies were poor inhibitors. Some parental antibodies yielded potent biparatopics with multiple partners, one of which (TB19) producing the most potent. The structure of the TB19 Fab with CD73 reveals that it blocks alignment of the N- and C-terminal CD73 domains necessary for catalysis. A separate structure of CD73 with a Fab (TB38) which complements TB19 in a particularly potent biparatopic shows its binding to a nonoverlapping site on the CD73 N-terminal domain. Structural modeling demonstrates a TB19/TB38 biparatopic antibody would be unable to bind the CD73 dimer in a bivalent manner, implicating crosslinking of separate CD73 dimers in its mechanism of action. This ability of a biparatopic antibody to both crosslink CD73 dimers and fix them in an inactive conformation thus represents a highly effective mechanism for the inhibition of CD73 activity.

The recent structural elucidation of ex vivo Drosophila Orb2 fibrils revealed a novel amyloid formed by interdigitated Gln and His residue side chains belonging to the prion-like domain. However, atomic-level details on the conformational transitions associated with memory consolidation remain unknown. Here, we have characterized the nascent conformation and dynamics of the prion-like domain (PLD) of Orb2A using a nonconventional liquid-state NMR spectroscopy strategy based on 13C detection to afford an essentially complete set of 13Cα, 13Cβ, 1Hα, and backbone 13CO and 15N assignments. At pH 4, where His residues are protonated, the PLD is disordered and flexible, except for a partially populated α-helix spanning residues 55–60, and binds RNA oligos, but not divalent cations. At pH 7, in contrast, His residues are predominantly neutral, and the Q/H segments adopt minor populations of helical structure, show decreased mobility and start to self-associate. At pH 7, the His residues do not bind RNA or Ca2+, but do bind Zn2+, which promotes further association. These findings represent a remarkable case of structural plasticity, based on which an updated model for Orb2A functional amyloidogenesis is suggested.

27 August 2020

COP27: Navigating a difficult road to Sharm El-Sheikh Expert comment NCapeling 6 July 2022

Against a backdrop of rising urgency, COP27 in Egypt will bring all aspects of climate action into the spotlight – but especially the role of the host country.

As COP26 drew to a close in Glasgow, Egyptian officials announced their priorities for COP27, emphasizing climate finance and climate adaptation – a new approach given previous COPs mainly focused on mitigation, reducing emissions to limit climate damage.

This was followed by the COP27 presidency outlining its vision at MENA Climate Week 2022 to achieve ‘substantive and equal progress’ on all aspects of the negotiations, and Egypt emphasizing its intention to focus on implementing existing carbon reduction targets rather than pushing for further carbon cuts.

Egypt argues it is hosting COP27 on behalf of African nations and that, while it is promoting the interests of the developing world, it will be an impartial arbiter. However it is also useful to consider its priorities from the Egyptian government’s perspective.

Agenda drivers

Egypt has long prioritized climate finance and adaptation because it remains in need of technical and financial support to adapt, especially in agriculture and tourism.

It plans to expand its access to climate funding and investment, an area in which Egypt has been relatively successful as it currently receives 27 per cent of all multilateral climate finance in the MENA region and has issued the region’s first sovereign green bonds.

With public debt currently 94 per cent of GDP, Egyptian officials have also called for debt relief for Egypt and other developing countries.

Egypt’s Climate Change Strategy reflects this approach, aiming to enhance Egypt’s rank on the Climate Change Performance Index in order to ‘attract more investments and acquire more climate funding’.

Limiting the mitigation scope and the focus on finance also echoes Egypt’s own reluctance to make carbon reduction commitments. The Egyptian nationally determined contribution (NDC) – its 2030 pledge under the Paris Agreement – does not include any quantifiable emission reduction targets.

Egypt is one of only a few countries which failed to submit an updated NDC in 2021 and its upcoming update will not include an economy-wide carbon reduction target.

Egypt has also never published a long-term strategy and has no decarbonization plans despite independent estimates it should cut rising emissions by one-quarter by 2030, and by two-thirds by 2050 to be aligned with the Paris Agreement. This partly explains why observers rate Egypt’s climate action as highly insufficient.

Furthermore, Egypt’s championing of ‘moving from pledges to implementation’ without having quantifiable carbon reduction pledges of its own effectively exempts it from both pledging and implementation.

As a developing country, Egypt’s negotiating position is supported by UNFCCC provisions which recognize differentiated responsibilities and respective capabilities of nations.

Its proposal to focus COP27 on the implementation of climate action and finance pledges is important in consolidating progress. But not pushing for more emission reductions at this critical moment risks derailing global decarbonization momentum and undermining global climate action.

According to optimistic estimates, if current climate pledges were implemented the world would still remain on track for 2°C of warming by the end of the century, with far worse impacts than if warming was curbed at 1.5°C.

Under a 2°C scenario, 37 per cent of the global population could regularly be exposed to extreme heat waves compared to 14 per cent in a 1.5°C warmer world, with developing countries expected to be worst-affected.

A 2°C trajectory also runs the risk of tipping points such as the melting of ice sheets in Antarctica and Greenland, triggering runaway climate change. Time to change the warming trajectory is running out as the latest IPCC assessment warns the window of opportunity is now ‘brief and rapidly closing’, and the UN Secretary General recently called for faster carbon cuts by the end of 2022 to avoid a ‘climate catastrophe’.

A different energy transition

Egypt opted not to join any of the voluntary sectoral coalitions at COP26 on reducing methane, clean energy transition, transition to zero-emissions vehicles, or moving beyond oil and gas.

This position is explained by its growing role as an exporter and advocate for fossil gas in the energy transition. Egypt is the second-largest producer of natural gas in Africa and is emerging as a fossil gas hub for the eastern Mediterranean, which is shaping its domestic energy policy.

Its 59GW electricity generation capacity is almost double the peak demand and is dominated by gas-powered electricity generation, which currently represents 42 per cent of all Africa’s gas generation.

Egypt’s climate policy is also shaped by fossil gas, and its national Climate Change Strategy encourages the expansion of gas use by promoting a transition to compressed natural gas for vehicles, the expansion of its domestic natural gas network – despite having universal access to electricity – and shifting to a gas-fuelled shipping sector.

Egypt also voiced support for other African countries to extract and deploy fossil gas and oil resources, making it one of the protagonists of the ‘great fossil gas pushback’. These advocates defend the right of developing countries to deploy fossil gas as a ‘transition fuel’ and champion its necessity to solve energy poverty.

But their position is not shared by all African and developing countries, and is rejected by some civil society groups, who argue it risks locking in greenhouse gases and local emissions for decades as well as delaying future development of low carbon energy systems.

Egypt’s huge spare generation capacity has contributed to a slowdown in renewable energy projects over the past two years. With renewables representing just 6GW, Egypt is expected to miss its renewable energy target for 2022, set at 20 per cent of generating capacity.

Engaging Egypt better

But these positions are more malleable than they seem, and Egypt is open to dialogue – not just on refining the COP27 agenda but also on reviewing its own climate priorities and leveraging its energy sector for a more ambitious transition.

Why Ethiopia must close its political gender gap The World Today mhiggins.drupal 29 July 2022

Women urgently need to gain access to high office if the country hopes to survive, say Hilina Berhanu Degefa and Emebet Getachew.

At the end of 2021, Prime Minister Abiy Ahmed’s government announced the formation of a three-year national dialogue to address Ethiopia’s political crisis, looking at the ongoing civil war and conflict, inflation, unemployment, drought and other urgent domestic issues. 

But, while efforts have been made to ensure the participation of women in this dialogue, it must be more than symbolic otherwise gaps in meaningful gender inclusion could have significant implications on the very survival of the country.
 
One of the challenges for meaningful inclusion is that Ethiopia is a highly patriarchal society. Patriarchal norms and practices permeate all aspects of the country’s social, economic and political life. Women constitute over half of the Ethiopian population and represent 41 per cent of the national parliament.

Nevertheless, most political parties, including those with liberal credentials, are exclusively governed by men, with women taking almost no part in key decision-making processes. As a result, women are relegated to the margins of political and economic activities. 

Though there has been little systematic study of the structural challenges faced by Ethiopian women in politics, women members of political parties encounter many barriers, including political violence, male-coded norms and sexist discourses across Ethiopian society.
 
The nature and scale of political violence perpetrated against women is particularly disempowering and affects their ability to participate in political spaces.

While attitudes to gender equality, sexual violence and gender discrimination are often trivialized, they remain ever-present threats in women’s lives. As late as 2016, a significant minority of men still believed wife-beating to be justified in certain situations. Even when women overcome social pressure to pursue their political ambitions, patriarchal views and practices within political party structures about the role of women significantly undermine their active participation and engagement. 

The political space is even more inaccessible to women with disabilities and in conflict and climate-related crises such as among internally displaced people and in pastoral communities. Male-coded norms ingrained at both party and community levels remain a significant concern. Specifically, sex in exchange for candidacy, inconsiderate working schedules affecting women with children and denial of access to equal information and financial resources are frequently reported as major internal hurdles among political parties.

Closing the gender gap could offer Ethiopia a new beginning

Many political initiatives designed to tackle these gender imbalances often have been driven by short-term political considerations without proper gender-gap assessment and policy analysis. In most cases, the authorities have viewed gender-targeted reforms as acts of benevolence, dispensed by the government, without adopting the legal and financial measures necessary to ensure sustainability and impact.
 
Take, for example, Abiy’s appointment of a 50:50 gender-balanced cabinet in 2018. At the time, much was made about its transformative potential, with the prime minister attracting widespread global approval. Yet, a cabinet reshuffle in 2021 reduced female representation to 36.3 per cent, with far less scrutiny or accountability.

This indicates that gender equality in Ethiopia is not considered a priority but rather an endeavour for more opportune, ‘stable’ times. Without thorough measures that create the conditions for real change, the aspiration of having a gender-balanced cabinet will always be challenging to translate into lasting equal representation.
 
The proposed national dialogue presents an ideal opportunity for Ethiopian women to begin reshaping attitudes and closing the gender gap through their inclusion and participation in the political process. To do so, three issues must be addressed.
 
First, the varying rights of women need to be consolidated, including on identity, constitutional reform and economic issues .

Second, gender equality considerations must be absorbed into mainstream political discourse at all levels.

Third, the experiences of women in the recent war, other ongoing conflicts and past and lingering legacies of political violence targeting women from specific communities, must be acknowledged and remedied. 

If Ethiopia is indeed serious about addressing its asymmetric gender power dynamics, this national dialogue provides an excellent opportunity to begin the process. Genuine participation of women as independent actors, with their own agency, could offer Ethiopia a new beginning.

Purpose: The ⁶⁸Ga-PSMA PET/CT is a commonly used imaging modality in prostate cancers. However, few studies have compared the diagnostic efficiency between ⁶⁸Ga-PSMA and ¹⁸F-FDG PET/CT and evaluated whether a heterogeneous metabolic phenotype (especially PSMA-FDG+ lesions) exists in patients with castration-resistant prostate cancer (CRPC). We determined the added value of ¹⁸F-FDG PET/CT compared to ⁶⁸Ga-PSMA PET/CT in CRPC patients and identified CRPC patients who may benefit from additional ¹⁸F-FDG PET/CT. Methods: Data of 56 patients with CRPC who underwent both ⁶⁸Ga-PSMA and ¹⁸F-FDG PET/CT from May 2018 to February 2021 were retrospectively analysed. Patients were classified into two groups with or without PSMA-FDG+ lesions. The differences in patient characteristics between the two groups and predictors of patients who having at least one PSMA-FDG+ lesion were analysed. Results: Although both the detection rate (75.0% vs. 51.8%, P = 0.004) and positive lesion number (135 vs. 95) of ⁶⁸Ga-PSMA PET/CT were higher than ¹⁸F-FDG PET/CT, there were still 13/56 (23.2%) patients with at least one PSMA-FDG+ lesion. The prostate-specific antigen (PSA) and Gleason score were both higher in the patients with PSMA-FDG+ lesions than in those without PSMA-FDG+ lesions (P = 0.04 and P<0.001, respectively). Multivariate regression analysis showed that the Gleason score (≥8) and PSA (≥7.9 ng/mL) were associated with the detection rate of patients who had PSMA-FDG+ lesions (P = 0.01 and P = 0.04, respectively). The incidences of having PSMA-FDG+ lesions in low-probability (Gleason score<8 and PSA<7.9 ng/mL), medium-probability (Gleason score≥8 and PSA<7.9 ng/mL or Gleason score<8 and PSA≥7.9 ng/mL), and high-probability (Gleason score≥8 and PSA≥7.9 ng/mL) groups were 0%, 21.7%, and 61.5%, respectively (P<0.001). Conclusion: Gleason score and PSA are significant predictors for PSMA-FDG+ lesions, and CRPC patients with high Gleason score and PSA may benefit from additional ¹⁸F-FDG PET/CT.