Sebastian A. Wagner
Oct 1, 2011; 10:M111.013284-M111.013284
Research

Joris J. Benschop
Jul 1, 2007; 6:1198-1214
Research

Guoan Chen
Apr 1, 2002; 1:304-313
Research

William M. Old
Oct 1, 2005; 4:1487-1502
Research

Leigh Anderson
Apr 1, 2006; 5:573-588
Research

Mathias Uhlén
Dec 1, 2005; 4:1920-1932
Research

Albrecht Gruhler
Mar 1, 2005; 4:310-327
Research

Jeffrey C. Silva
Jan 1, 2006; 5:144-156
Research

Linn Fagerberg
Feb 1, 2014; 13:397-406
Research

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

Jürgen Cox
Sep 1, 2014; 13:2513-2526
Technological Innovation and Resources

HIV Type 1 (HIV-1) and simian immunodeficiency virus (SIV) display differential replication kinetics in macrophages. This is because high expression levels of the active host deoxynucleotide triphosphohydrolase sterile α motif domain and histidine-aspartate domain–containing protein 1 (SAMHD1) deplete intracellular dNTPs, which restrict HIV-1 reverse transcription, and result in a restrictive infection in this myeloid cell type. Some SIVs overcome SAMHD1 restriction using viral protein X (Vpx), a viral accessory protein that induces proteasomal degradation of SAMHD1, increasing cellular dNTP concentrations and enabling efficient proviral DNA synthesis. We previously reported that SAMHD1-noncounteracting lentiviruses may have evolved to harbor RT proteins that efficiently polymerize DNA, even at low dNTP concentrations, to circumvent SAMHD1 restriction. Here we investigated whether RTs from SIVmac239 virus lacking a Vpx protein evolve during in vivo infection to more efficiently synthesize DNA at the low dNTP concentrations found in macrophages. Sequence analysis of RTs cloned from Vpx (+) and Vpx (−) SIVmac239–infected animals revealed that Vpx (−) RTs contained more extensive mutations than Vpx (+) RTs. Although the amino acid substitutions were dispersed indiscriminately across the protein, steady-state and pre-steady-state analysis demonstrated that selected SIVmac239 Vpx (−) RTs are characterized by higher catalytic efficiency and incorporation efficiency values than RTs cloned from SIVmac239 Vpx (+) infections. Overall, this study supports the possibility that the loss of Vpx may generate in vivo SIVmac239 RT variants that can counteract the limited availability of dNTP substrate in macrophages.

Lys234 is one of the residues present in class A β-lactamases that is under selective pressure due to antibiotic use. Located adjacent to proton shuttle residue Ser130, it is suggested to play a role in proton transfer during catalysis of the antibiotics. The mechanism underpinning how substitutions in this position modulate inhibitor efficiency and substrate specificity leading to drug resistance is unclear. The K234R substitution identified in several inhibitor-resistant β-lactamase variants is associated with decreased potency of the inhibitor clavulanic acid, which is used in combination with amoxicillin to overcome β-lactamase–mediated antibiotic resistance. Here we show that for CTX-M-14 β-lactamase, whereas Lys234 is required for hydrolysis of cephalosporins such as cefotaxime, either lysine or arginine is sufficient for hydrolysis of ampicillin. Further, by determining the acylation and deacylation rates for cefotaxime hydrolysis, we show that both rates are fast, and neither is rate-limiting. The K234R substitution causes a 1500-fold decrease in the cefotaxime acylation rate but a 5-fold increase in kcat for ampicillin, suggesting that the K234R enzyme is a good penicillinase but a poor cephalosporinase due to slow acylation. Structural results suggest that the slow acylation by the K234R enzyme is due to a conformational change in Ser130, and this change also leads to decreased inhibition potency of clavulanic acid. Because other inhibitor resistance mutations also act through changes at Ser130 and such changes drastically reduce cephalosporin but not penicillin hydrolysis, we suggest that clavulanic acid paired with an oxyimino-cephalosporin rather than penicillin would impede the evolution of resistance.

This article is by Toni Šušnjar.

Warfare and military are an integral part of much of ancient and medieval fantasy. This is no surprise: warfare was a key element in development of society and of history, and much of mythology is also about it. As such, it is difficult for fantasy writers and readers alike to avoid war and military matters in general. And if you are going to do something, try to do it well. Army does not spring from the ground like the spartoi of Jason.

Environment and Geography

Environmental conditions include terrain, climate and resources. All three influence how an army will fight and which weapons it will use.

Terrain can be highly varied, but I will divide it into three categories: mountainous, rolling hills and flat. Mountains and forests – and especially forested mountains – are conductive to infantry warfare. Depending on other conditions (such as society, climate etc.), this can mean either light infantry with focus on ambushes, raiding and guerilla warfare; or heavy infantry, with focus on direct confrontation. Both of these were, at different points, in evidence in Spain and Greece.

Continue reading Building a Fantasy Army — Environment & Society at Mythic Scribes.

This article is by Toni Šušnjar.

Strategy and Enemies

The structure of an army will depend on the strategy, as strategy will determine the army’s role and tasks. A state which carries out expansion through outright territorial conquest will have large numbers of heavy infantry, combat engineers and artillery, and possibly some heavy cavalry as well (e.g. Roman Empire, 10th century Byzantine Empire). If conquest is done by slowly destroying an opponent’s economic and social structures through constant raiding (such as chevauchee or razzia / ghazw), then majority of the army will be light cavalry, with some heavy cavalry support (e.g. Seljuk and Ottoman Empires), and light infantry will be used if terrain is unsuitable for cavalry. If a state is defending against cavalry raids, then light cavalry will be dominant (e.g. 15th century Hungary), whereas heavy cavalry will predominate if enemy raiders are primarily infantry. If enemy armies are too powerful to face in the field, light and heavy cavalry will be used to harass the invading army and cut off its supplies and foraging. In terrain unsuitable for cavalry operations, heavy infantry will be used instead.

Raiding — as a strategy — is generally preferred against a peer opponent, especially if a state cannot have a developed logistical support system.

Continue reading Building a Fantasy Army — Strategy & Organization at Mythic Scribes.

This article is by Toni Šušnjar.

Recruitment and Numbers

The most basic style of recruitment is that of a local militia – rural or urban – where a portion or all of the free men take up arms. Militiamen are usually not highly trained, but they make up for lack of training with motivation: fleeing not only carries social stigma, but is also harshly punished. As such, militias were more effective than what would be expected of “civilians in arms”. Militias almost always depended on relatively cheap and easy to use weapons, though urban militias might have access to more expensive weapons – such as hoplite panoply or crossbows. Tribal militias typically used weapons that were also used for hunting and sport. Peasant levy however was only ever used in a support and harassment role, and often had weapons modified from agricultural implements. Only urban militias could have heavy equipment. A common disadvantage of militia armies is the inability to deploy over long distances and time-frames due to soldiers having a day job; thus, focus on long-term warfare (be it conquest or defence) typically brings about the professionalization of the army. This also means that militias are best used in cases with high political fragmentation – such as city-states.

Continue reading Building a Fantasy Army — Recruitment & Logistics at Mythic Scribes.

This article is by Toni Šušnjar.

In Antiquity and early the Middle Ages, the main weapon was the spear. Only a few exceptions appeared: Roman legions, which used javelins instead, and Macedonian pike phalanx with its sarissa. In the later Middle Ages, the main weapon could be a pike or a polearm (such as polehammer, poleaxe, halberd etc.), before the pike made its return in early modernity. Ranged weapons were not used to cause casualties, but rather to inconvenience the enemies and break up their formation.

Weapons and tactics will adapt to each other, as well as to the terrain and the enemies faced – but adaptations will be done within the boundaries of the society. A society without a significant tradition of horse archery will not counter horse archers with their own, but rather with foot archers. Horse archery was important for nomadic societies, because they could not afford the casualties which resulted from the shock and attrition tactics of the settled societies.

Weapons and armour likewise have a relationship, but since armour is the more difficult to produce of the two, it is developments in armour which typically drive the adaptation of weapons, rather than the other way around.

Continue reading Building a Fantasy Army — Weapons & Tactics at Mythic Scribes.

This article is by Emma Lammers.

Author’s note: neurodivergent is term used to refer to people whose neurological functions differ from the norm because of an innate or acquired condition. Examples of these conditions include autism, learning disabilities, mood disorders, traumatic brain injuries, and more. People who do not have any neurodivergent conditions are considered neurotypical.

To the delight of many readers, more characters in fantasy literature reflect aspects of real-world people than ever before. Today’s heroes can be people of colour, people of any gender or sexual identity, people of nearly any age. Writers are answering the call for more diversity in their work, and oftentimes they do it well, portraying realistic, nuanced characters from marginalized communities.

Some people, however, aren’t as likely to see themselves accurately reflected in the pages of a fantasy story. I’ve searched long and hard to find literary characters who experience autism, anxiety, and sensory processing disorder as I do, and very few of these characters show up in fantasy – a detriment to my favourite genre. Villainous characters are often portrayed as neurodivergent because writers think that this will make them scarier, and you will encounter the occasional hero with post-traumatic stress disorder, but  these depictions tend to lack accuracy, diversity, and consideration for the people who actually have the conditions used in the story.

Continue reading Writing Neurodivergent Characters in Fantasy at Mythic Scribes.

New essay anthology examines the future of the international order News release jon.wallace 7 May 2021

Featuring a new essay by Robin Niblett, Chief Executive of Chatham House, and Leslie Vinjamuri, Director of the US and Americas programme.

“Anchoring the World”, a new anthology, features an important new essay by Robin Niblett, Chief Executive of Chatham House, and Leslie Vinjamuri, Director of the US and Americas programme. The essay, “The Liberal Order Begins At Home”, argues powerfully for the revival of a liberal international order.

The essay collection has been produced by the Lloyd George Study Group on World Order, and celebrates the centennial years of Chatham House, Georgetown University’s School of Foreign Service, and the Council on Foreign Relations.

Robin Niblett said:

“In this excellent collection, some authors argue that the United Nations should continue to anchor the international system, while others argue for the creation of a new Concert of Powers.

“Our essay argues that it is both necessary and possible to revive the idea of a liberal international order: necessary (and urgent) because of heightened global competition with China, and possible only if western democracies repair their deep social and economic problems at home.

“We hope this volume carries forward the fortitude and creative spirit that the School of Foreign Service, Chatham House, and the Council on Foreign Relations have brought to the study and practice of international affairs over the past century.”

The Lloyd George Study Group and book were made possible by the generosity of the family of Robert Lloyd George, the great-grandson of British Prime Minister, David Lloyd George.

Anchoring the World is published by Foreign Affairs magazine.

What is COP29 and why is it important? Explainer jon.wallace 17 October 2024

The COP29 summit will see negotiators try to agree how to finance the climate action the world urgently needs.

COP29, the 29th UN annual conference on climate change, takes place in Baku, Azerbaijan from 11–22 November 2024.

Every COP conference is an important opportunity for international collaboration on climate change. COP29 will have a particular focus on how to make finance available to developing countries for climate action.

COP29 is already contentious, because Azerbaijan’s economy is highly dependent on fossil fuels, the main cause of climate change. That means that Azerbaijan’s government, which will preside over the summit, has a strong incentive to avoid rapid multilateral progress towards phasing out fossil fuels. 

It’s urgent that progress is made at COP29. Climate action lags far behind both what has been promised by countries, and what scientists agree is needed. The impacts of climate change are also rapidly escalating, while backlash against government policies to reduce fossil fuel use is being seen in many places around the world. 

What is a ‘COP’?

The ‘Conference of the Parties’ or ‘COP’ is an annual event that brings together the governments which have signed up to environmental action under the United Nations (UN). 

Governments or ‘parties’ attend the climate change COP if they are part of the United Nations Framework Convention on Climate Change, or the international environmental treaties the Kyoto Protocol (1997) or the landmark and legally binding Paris Agreement (2015).

World leaders, ministers, and negotiators convene at the COP to negotiate and rubber stamp plans to jointly address climate change and its impacts. 

Civil society, businesses, international organizations and the media normally ‘observe’ proceedings to bring transparency, accountability and wider perspectives to the process.

‘Mission 1.5°C’ 

COP28, the 2023 climate conference held in Dubai, was the first of three consecutive COP summits intended to ‘reset’ global climate action – what the UN calls the ‘Roadmap to Mission 1.5°C’ – the ambition to keep global temperatures from rising more than 1.5°C above pre-industrial levels. 

To support continuity and progress across the three COPs, the UAE (COP28), Azerbaijan (COP29) and Brazil (COP30) have formed a COP presidential ‘Troika’ or group of three.

In 2023 the first ‘global stocktake’ of international action to address climate change indicated that the world was far off track for targets set by the Paris Agreement. The ‘UAE Consensus’ agreement, which formed the main output of COP28, set out how parties should respond. 

COP29, the second of the three COPs, is intended to get the finance in place to enable this response. COP30, to be held in Brazil in 2025, will then try to agree how a new round of nationally determined climate plans or ‘contributions’ to global climate efforts (NDCs) should be put into action.

COP29 will be the third consecutive COP held in an authoritarian state, and the second consecutive COP hosted by a petro-state. Taken together, the ‘Troika’ hosts make up the world’s 4th largest oil producer, after the United States, Russia and Saudi Arabia. 

This presents both an opportunity and a risk: the countries are well placed to understand and tackle the core issue of fossil fuel extraction and use. But they also have strong incentives to stall, distract and deflect the negotiations away from phasing out fossil fuels.

Key issues at COP29

Finance – money on the table, and a New Collective Quantified Goal

COP29 has a remit to secure funding for a ‘course correction’ on global climate action. Countries’ revised climate plans (NDCs) are due in February 2025. For developing countries to deliver new ambitious NDCs, however, COP29 must first make clear what finance will be available to help them.

Climate finance is one of the thorniest issues in the negotiations. The previous climate finance goal, of $100 billion per year from developed to developing countries between 2020-25, was symbolic (being a fraction of the sum actually needed) and contentious (developed countries did not meet the target until 2022, and then only with accusations of double-counting). 

A New Collective Quantified Goal (NCQGs), to be agreed at COP29, will need to reflect developing countries’ needs and priorities. Estimates vary, but it is accepted that the scale will be trillions, not billions. To bridge this enormous gap, private finance will need to be mobilized and broader reforms made to global financial architecture. Issues such as subsidies, fossil fuel profits and ‘solidarity levies’ will also need to be on the table. 

Little progress has been made in the run-up to COP29. Parties disagree on who should pay, how much should be paid, what forms the funding should take (loans or grants) and how the funds should be accessed. 

Also up for debate is how funds should be directed – towards mitigating the impacts of climate change (preventing climate change becoming worse), adapting to its effects, or supporting countries to manage loss and damage (climate impacts that have already happened or cannot be avoided).  

In discussions of the NCQG to date, developed countries have consistently called for higher income developing countries, such as China and India, to contribute. 

Such countries have pushed back forcefully against this. For a new goal to be agreed, such divisions will need to be resolved.

Enhanced transparency?

COPs act as showcases for international agreement, but many processes rumble on behind the scenes. COP29 will be an important moment for transparency under the Paris Agreement, as the Parties’ first Biennial Enhanced Transparency Reports (BTRs) are due in December 2024. 

BTRs are an important tool in the Paris Agreement, requiring countries to provide a snapshot of their progress in cutting emissions, setting climate policies, and providing resources for national and international climate action. 

BTRs are meant to build the evidence base for strong NDCs, build trust and promote ambitious climate action. They are also meant to help developing countries showcase achievements and attract climate finance. 

The COP29 presidency has launched the Baku Global Climate Transparency Platform to encourage participation, and support countries in finalising their BTRs. The Platform is meant to provide space for collaboration between government, NGO and private sector stakeholders. 

This is one of the areas in which COP29 host, Azerbaijan, runs into criticism. The country ranks highly on indexes of corruption, and has repeatedly restricted space for NGOs and wider civil society actors through a series of escalating government crackdowns, including imprisonment of environmental activists, in the run-up to the conference.

In conversation with Julien Harneis, UN Assistant Secretary-General 18 November 2024 — 2:30PM TO 3:30PM Anonymous (not verified) 11 November 2024 Chatham House and Online

In this discussion, Julien Harneis will give critical insights into the UN’s humanitarian response in Yemen and the importance of maintaining independent humanitarian assistance.

According to the United Nations, Yemen has faced the world’s worst humanitarian crisis in the last decade, with over 20 million people in need of assistance. Years of ongoing conflict have devastated infrastructure, displaced millions, and caused widespread food insecurity and health emergencies. Access to essential services remains a daily struggle, and the escalating economic collapse has left vulnerable communities facing critical shortages in food, water, and medical supplies.

However, humanitarian actors are continually facing challenges in delivering aid to Yemen due to security threats and supply chain barriers, highlighting the urgent need for coordinated and sustainable international assistance.

UN Assistant Secretary-General and Humanitarian Coordinator for Yemen, Julien Harneis, will provide an account of the humanitarian mission and evolving strategies in Yemen, the impact of regional conflicts in the delivery of aid and discuss other key questions including:

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

Robert W. Mahley
Jan 1, 1999; 40:1-16
Reviews

Chatham House awarded major centenary grant to establish Stavros Niarchos Foundation Wing News Release sysadmin 16 April 2019

Chatham House has been awarded a transformational £10m grant ahead of its upcoming 2020 centenary.

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’.

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.

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.

Strengthening Transatlantic Digital Cooperation

This project explores opportunities for increased cooperation via the transatlantic ‘tech triangle’ of the European Union, United Kingdom and United States.

This project serves as a cross-house initiative (involving the US and Americas Programme, the Europe Programme, the International Law Programme, the Digital Society Initiative and the International Security Programme).

Its long-term goal is to support the emergence of a global vision for technology governance: a vision drawing on democratic values and human rights principles. The project aims to extend the application of these principles to the digital space.

The first phase centres around a knowledge-exchange series, with findings and recommendations disseminated around targeted multilateral events such as G7, the United Nations General Assembly and the 2021 Internet Governance Forum.

Building on this exchange, the second phase will shift its focus to other democratic states and broaden digital cooperation dialogues from like-minded countries in the OECD, in addition to non-Western democracies and under-represented stakeholders from developing countries.

Transatlantic Tech Talks: Cooperation or sovereignty? Audio bhorton.drupal 15 December 2021

A new mini-series from Undercurrents explores international cooperation on regulating the tech sector.

Transatlantic Tech Talks is a three part mini-series on the Undercurrents podcast feed, produced with the support of Microsoft, which explores the state of international cooperation on digital governance between the United States, the UK and Europe.

As technological innovation accelerates, and new digital tools and business models arise, governments are working to develop a framework of regulations to safeguard the rights and interests of their citizens. Not all stakeholders agree, however, on the best way to achieve this. While some advocate a ‘digital cooperation’ approach based on transparency and data-sharing, others are more concerned with maintaining ‘digital sovereignty’.

In the first episode of this series, Ben is joined by Casper Klynge, Harriet Moynihan and Marianne Schneider-Petsinger, who set out the broad context for these debates. They assess where the major government, private sector and civil society actors stand on the question of digital governance, and how they are approaching the international negotiations.

Expert

Expert

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

Erythromycin-resistance methyltransferases are SAM dependent Rossmann fold methyltransferases that convert A2058 of 23S rRNA to m6 2A2058. This modification sterically blocks binding of several classes of antibiotics to 23S rRNA, resulting in a multidrug-resistant phenotype in bacteria expressing the enzyme. ErmC is an erythromycin resistance methyltransferase found in many Gram-positive pathogens, whereas ErmE is found in the soil bacterium that biosynthesizes erythromycin. Whether ErmC and ErmE, which possess only 24% sequence identity, use similar structural elements for rRNA substrate recognition and positioning is not known. To investigate this question, we used structural data from related proteins to guide site-saturation mutagenesis of key residues and characterized selected variants by antibiotic susceptibility testing, single turnover kinetics, and RNA affinity–binding assays. We demonstrate that residues in α4, α5, and the α5-α6 linker are essential for methyltransferase function, including an aromatic residue on α4 that likely forms stacking interactions with the substrate adenosine and basic residues in α5 and the α5-α6 linker that likely mediate conformational rearrangements in the protein and cognate rRNA upon interaction. The functional studies led us to a new structural model for the ErmC or ErmE-rRNA complex.

E. A. Rakhmanov and S. P. Suetin
Trans. Moscow Math. Soc. 83 (), 269-290.
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L. Oeding
Trans. Moscow Math. Soc. 83 (), 227-250.
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A. V. Silantyev
Trans. Moscow Math. Soc. 83 (), 75-149.
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A. P. Starovoitov and N. V. Ryabchenko
Trans. Moscow Math. Soc. 83 (), 15-31.
Abstract, references and article information

Plant-based 'Meat' and Cultured Meat: Revolutionizing the Livestock Sector 10 April 2019 — 4:00PM TO 5:30PM Anonymous (not verified) 14 March 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Consensus is building across the scientific, environmental and public health communities that a radical shift away from excessive meat-eating patterns is urgently needed to tackle the unsustainability of the livestock sector. Recognizing the scale of the challenge ahead, public policymakers, civil society and innovators have increasingly sought to prompt shifts in consumer food choices – away from the most resource-intensive meat products and towards more sustainable alternatives.

Meat analogues – plant-based ‘meat’ and cultured meat also known as ‘lab-grown’ meat – mark a departure from traditional meat alternatives. Both are intended to be indistinguishable from – and in the case of cultured meat biologically equivalent to – animal-derived meat and are marketed principally at meat-eaters. Innovation and investment in meat analogues have increased significantly, but the direction and pace of growth in the meat analogue industry will depend upon a multitude of factors, including public acceptance, civil society support and incumbent industry responses.

This event will explore the challenges of scaling up production and generating demand for meat alternatives. It will also look at the ways policymakers in the UK and EU can impact the direction of the industry while examining what factors will influence consumer acceptance of plant-based ‘meat’ and cultured meat as substitutes for animal-derived meat.

Webinar: On the Front Line: The Impact of COVID-19 on Asia's Migrant Workers 21 May 2020 — 2:00PM TO 2:45PM Anonymous (not verified) 15 May 2020

Asia’s army of migrant workers are on the frontline in confronting the health and economic effects of COVID-19. Lacking formal safety nets, health care access, and facing social dislocation, hundreds of millions across the region are bearing the brunt of the coronavirus lockdown. Asian governments have scrambled to come up with an effective health and humanitarian response, exposing public apathy and significant shortcomings in public policy.

Is better regional coordination necessary to mitigate the impact of the COVID-19 on migrant labourers? Is the private sector in Asia part of the problem or part of the solution?

In this webinar, the speakers will discuss the likely implications of lasting economic damage on the livelihoods of Asia’s migrant workers, as well as responses and measures to effectively mitigate the impact.

Angela Robinson explains the math behind the next generation of cryptographic algorithms. Whenever you log in to a website, send an email, or make an online purchase, you're counting on your data being sent securely, without hackers being able to crack the code. Our standard cryptographic systems hinge on mathematical problems that stump present-day computers, like finding the prime factors of a very large number. But in the coming decades, powerful quantum computers are expected to be able to rapidly solve some such problems, threatening the security of our online communications. To develop new methods that can withstand even the most sophisticated quantum computer, cryptographers are using a wide range of mathematical tools, many of which were originally developed without any real-life applications in mind.

Tsz-Kiu Aaron Chow and Yangyang Li
Trans. Amer. Math. Soc. 377 (), 5993-6020.
Abstract, references and article information

Ahmed Elshafei, Ana Cristina Ferreira, Miguel Sánchez and Abdelghani Zeghib
Trans. Amer. Math. Soc. 377 (), 5837-5862.
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Ming-Lun Hsieh and Shunsuke Yamana
Trans. Amer. Math. Soc. 377 (), 5617-5672.
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Daniel López Neumann
Trans. Amer. Math. Soc. 377 (), 5361-5387.
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Sudip Ranjan Bhuia
Proc. Amer. Math. Soc. 152 (), 5249-5263.
Abstract, references and article information

Forty-six mathematical scientists have been named recipients of AMS-Simons Research Enhancement Grants for Primarily Undergraduate Institution (PUI) Faculty. Each awardee will receive $3,000 per year for three years. 

The grants foster and support research collaboration by full-time mid-career mathematicians at US institutions that do not offer a mathematics doctoral degree.

This year’s grant recipients hail from 42 institutions across 21 US states. The grants will support their research in several different areas, from number theory to applied mathematics.

This is the grant program’s second cohort, said Sarah Bryant, associate vice president of programs. “Over the first two years, we’ve worked with faculty from 75 different institutions, including 19 minority-serving institutions, which shows just how much this program is expanding and making an impact,” Bryant said. She noted that “in the first year, the grants supported 87 trips, helped produce 70 publications and preprints, and gave awardees the resources needed to collaborate and advance their work.”

The grant allows for any activities that will further the awardee’s research program. Expenses include but are not limited to conference participation, institute visits, collaboration travel (awardee or collaborator), computer equipment or software, family-care expenses, and teaching assistants.

Administration of the award by the grantee’s institution is required; annual discretionary funds for a grantee’s department and administrative funds for a grantee's institution will be available at the end of each grant year.

The grants are made possible through funding from the Simons Foundation and the American Mathematical Society (AMS), as well as Eve, Kirsten, Lenore, and Ada of the Menger family.

Applications for the next cohort are anticipated to open on MathPrograms.org on January 9, 2025. Visit the AMS website to view an informational PowerPoint or sign up to receive email updates about the program. Faculty who applied for but did not receive the 2023 or 2024 awards are encouraged to reapply if they are still eligible for the grant.