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

M. Burstein
Nov 1, 1970; 11:583-595
Articles

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

JM Dietschy
Oct 1, 1993; 34:1637-1659
Reviews

Weerapan Khovidhunkit
Jul 1, 2004; 45:1169-1196
Thematic Reviews

AE Christian
Nov 1, 1997; 38:2264-2272
Articles

How can companies defend civic space? 2 February 2021 — 4:00PM TO 5:00PM Anonymous (not verified) 19 January 2021 Online

Panellists discuss how companies can go beyond corporate social responsibility and philanthropy initiatives to protect and support civic freedoms around the world.

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

There is increasing pressure on companies to use their power and profits to engage with social and political causes. In doing so, companies can help to support the ‘shared civic space’ that enables the private sector and civil society organizations to benefit from a society that respects the rule of law and human rights, at a time when many of these rights are under threat around the world.

Many companies have introduced CSR initiatives, due diligence mechanisms and corporate philanthropy. Over 11,000 companies are now signatories to the UN’s Global Compact for sustainable and socially responsible business worldwide.

But as demonstrated by misguided corporate responses to the Black Lives Matter protests this year, there is a danger of corporate activism being perceived as ‘lip service’ rather than genuinely addressing the negative impacts of business operations on civic space.

Recent Chatham House research indicates that meaningful engagement by businesses on such issues must be timely, contextually sensitive and industry-relevant. For example, in 2015, Tiffany & Co. worked with other companies to intervene on behalf of Rafael Marques after he was arrested for reporting on widespread human rights abuses in the Angolan diamond industry. During COVID-19, Microsoft offered free cybersecurity software to healthcare and human rights organizations at increased risk of hacking attacks.

This panel event will draw upon practical examples of private sector support for civic space across different sectors, geographies and political environments.

Why might companies step up to defend freedom of association, expression or political participation even where this comes at a financial or political cost? How can companies resist complicity with governments or regulation that threaten civic space? And what forums exist, or should exist, for developing tactical alliances between companies and civil society actors?

This event is also the launch of a new Chatham House resource, The Role of the Private Sector in Protecting Civic Space.

Persuasion or manipulation? Limiting campaigning online Expert comment NCapeling 15 February 2021

To tackle online disinformation and manipulation effectively, regulators must clarify the dividing line between legitimate and illegitimate campaign practices.

Democracy is at risk, not only from disinformation but from systemic manipulation of public debate online. Evidence shows social media drives control of narratives, polarization, and division on issues of politics and identity. We are now seeing regulators turn their attention to protecting democracy from disinformation and manipulation. But how should they distinguish between legitimate and illegitimate online information practices, between persuasive and manipulative campaigning?

Unregulated, the tactics of disinformation and manipulation have spread far and wide. They are no longer the preserve merely of disaffected individuals, hostile international actors, and authoritarian regimes. Facebook’s periodic reporting on coordinated inauthentic behaviour and Twitter’s on foreign information operations reveal that militaries, governments, and political campaigners in a wide range of countries, including parts of Europe and America, have engaged in manipulative or deceptive information campaigns.

For example, in September 2019, Twitter removed 259 accounts it says were ‘falsely boosting’ public sentiment online that it found to be operated by Spain’s conservative and Christian-democratic political party Partido Popular. In October 2020, Facebook removed accounts with around 400,000 followers linked to Rally Forge, a US marketing firm which Facebook claims was working on behalf of right-wing organisations Turning Point USA and Inclusive Conservation Group. And in December 2020, Facebook took down a network of accounts with more than 6,000 followers, targeting audiences in Francophone Africa and focusing on France’s policies there, finding it linked with individuals associated with the French military.

Public influence on a global scale

Even more revealingly, in its 2020 Global Inventory of Organized Social Media Manipulation, the Oxford Internet Institute (OII) found that in 81 countries, government agencies and/or political parties are using ‘computational propaganda’ in social media to shape public attitudes.

These 81 countries span the world and include not only authoritarian and less democratic regimes but also developed democracies such as many EU member states. OII found that countries with the largest capacity for computational propaganda – which include the UK, US, and Australia – have permanent teams devoted to shaping the online space overseas and at home.

OII categorizes computational propaganda as four types of communication strategy – the creation of disinformation or manipulated content such as doctored images and videos; the use of personal data to target specific segments of the population with disinformation or other false narratives; trolling, doxing or online harassment of political opponents, activists or journalists; and mass-reporting of content or accounts posted or run by opponents as part of gaming the platforms’ automated flagging, demotion, and take-down systems.

Doubtless some of the governments included within OII’s statistics argue their behaviour is legitimate and appropriate, either to disseminate information important to the public interest or to wrestle control of the narrative away from hostile actors. Similarly, no doubt some political campaigners removed by the platforms for alleged engagement in ‘inauthentic behaviour’ or ‘manipulation’ would defend the legitimacy of their conduct.

The fact is that clear limits of acceptable propaganda and information influence operations online do not exist. Platforms still share little information overall about what information operations they see being conducted online. Applicable legal principles such as international human rights law have not yet crystallised into clear rules. As information operations are rarely exposed to public view – with notable exceptions such as the Cambridge Analytica scandal – there is relatively little constraint in media and public scrutiny or censure.

OII’s annual reports and the platforms’ periodic reports demonstrate a continual expansion of deceptive and manipulative practices since 2016, and increasing involvement of private commercial companies in their deployment. Given the power of political influence as a driver, this absence of clear limits may result in ever more sophisticated techniques being deployed in the search for maximal influence.

Ambiguity over reasonable limits on manipulation plays into the hands of governments which regulate ostensibly in the name of combating disinformation, but actually in the interests of maintaining their own control of the narrative and in disregard of the human right to freedom of expression. Following Singapore’s 2019 prohibition of online untruths, 17 governments ranging from Bolivia to Vietnam to Hungary passed regulations during 2020 criminalising ‘fake news’ on COVID-19 while many other governments are alleged to censor opposition arguments or criticisms of official state narratives.

Clear limits are needed. Facebook itself has been calling for societal discussion about the limits of acceptable online behaviour for some time and has issued recommendations of its own.

The European Democracy Action Plan: Aiming to protect pluralism and vigour in democracy

The European Democracy Action Plan (EDAP), which complements the European Commission’s Digital Services Act and Digital Markets Act proposals, is a welcome step. It is ground-breaking in its efforts to protect the pluralism and vigour of European democracies by tackling all forms of online manipulation, while respecting human rights.

While the EDAP tackles disinformation, it also condemns two categories of online manipulation – information influence operations which EDAP describes as ‘coordinated efforts by either domestic or foreign actors to influence a target audience using a range of deceptive means’ and foreign interference, described as ‘coercive and deceptive efforts to disrupt the free formation and expression of individuals’ political will by a foreign state actor or its agents’. These categories include influence operations such as harnessing fake accounts or gaming algorithms, and the suppression of independent information sources through censorship or mass reporting.

But the categories are so broad they risk capturing disinformation practices not only of rogue actors, but also of governments and political campaigners both outside and within the EU. The European Commission plans to work towards refined definitions. Its discussions with member states and other stakeholders should start to determine which practices ought to be tackled as manipulative, and which ought to be tolerated as legitimate campaigning or public information practices.

The extent of the EDAP proposals on disinformation demonstrates the EU’s determination to tackle online manipulation. The EDAP calls for improved practical measures building on the Commission’s 2020 acceleration of effort in the face of COVID-19 disinformation. The Commission is considering how best to impose costs on perpetrators of disinformation, such as by disrupting financial incentives or even imposing sanctions for repeated offences.

Beyond the regulatory and risk management framework proposed by the Digital Services Act (DSA), the Commission says it will issue guidance for platforms and other stakeholders to strengthen their measures against disinformation, building on the existing EU Code of Practice on Disinformation and eventually leading to a strengthened Code with more robust monitoring requirements. These are elements of a broader package of measures in the EDAP to preserve democracy in Europe.

Until there are clear limits, manipulative practices will continue to develop and to spread. More actors will resort to them in order not to be outgunned by opponents. It is hoped forthcoming European discussions – involving EU member state governments, the European Parliament, civil society, academia and the online platforms – will begin to shape at least a European and maybe a global consensus on the limits of information influence, publicly condemning unacceptable practices while safeguarding freedom of expression.

Most importantly, following the example of the EDAP, the preservation of democracy and human rights – rather than the promotion of political or commercial interest – should be the lodestar for those discussions.

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?

Sanctions must not prevent humanitarian work in Ukraine Expert comment NCapeling 30 May 2022

Restrictions on supply of certain items and financial sanctions can impede vital relief unless adequate safeguards are put in place such as exceptions or general licences.

Sanctions play a major role in the response to Russia’s invasion of Ukraine. The United Nations (UN) has not imposed sanctions, but an important number of states have done so. They have imposed a wide array of restrictions and the number of targeted – or ‘designated’ – persons is unprecedented.

The public has been captivated by the freezing of oligarchs’ assets. There is ongoing discussion about seizing them to provide compensation for war damage. Debate continues about how far to ban oil and gas imports.

One aspect of the sanctions has received far less attention, even though it can exacerbate the effect of the conflict on civilians. Some of the trade restrictions and financial sanctions pose immediate and concrete challenges to the capacity of humanitarian organizations to work in Ukraine and in neighbouring states.

Trade sanctions imposed by the European Union (EU) and UK prohibit the export or supply of certain goods and technology in the transport, telecommunications, energy, and oil or mineral exploration sectors to non-government-controlled areas of the Donetsk or Luhansk oblasts, or for use there.

Restricted items include technical equipment which is necessary for humanitarian operations, such as water pumps and refrigerating equipment, but also far more mundane items such as vehicles for transport of persons and goods, and office equipment that are necessary for humanitarian organizations trying to work in the region.

Designations can reduce options for support

Financial sanctions also raise problems. Some are immediately apparent. Significantly for humanitarian operations, the two de facto republics of Donetsk and Luhansk are designated by the EU, the UK, and the US. Consequently, it is prohibited to make funds or assets available to them directly or indirectly.

This prohibition covers the payment of any taxes, licences, and other fees to these authorities, as well as the provision of assets to ministries under their control in the course of humanitarian operations, such as ministries of health and education.

Designations of other entities may also be relevant, such as Russian ‘state enterprises’ which operate in these areas and are the sole providers of commodities necessary for humanitarian response, such as heating fuel.

These are the designations which most obviously impact humanitarian response. However, more than 1,000 persons and entities have been designated and humanitarian organizations must avoid purchasing goods and services from them.

Risk-averse commercial partners

Commercial actors – such as banks, insurers, freight companies and commodity providers – whose services are required by humanitarian organizations must also comply with the sanctions. Experience shows that the due diligence measures adopted by humanitarian organizations do not always allay concerns of risk-averse sectors such as banks.

Fears of violating the sanctions, coupled with the fact humanitarian organizations are rarely profitable clients, have led them to severely restrict the services they provide.

This is not the first occasion the problem has arisen. What is different in relation to Ukraine is the number of designated persons and the ‘sanctions packages’ adopted in quick succession. As compliance officers struggle to keep abreast, their institutions become even more risk-averse.

For UK banks, the situation is exacerbated by the adoption of the Economic Crime (Transparency and Enforcement) Act 2022. This amends existing rules by removing the requirement for the UK Treasury to prove knowledge or reasonable cause to suspect that a transaction violated sanctions, imposing strict liability for sanctions violations.

Time for the UK to follow others

The EU, the US, Switzerland, and other states which have imposed sanctions have sought to mitigate their adverse effects by including safeguards for humanitarian action. Although the UK has largely replicated the measures adopted by the EU in terms of restrictions and designations, it lags behind in including such safeguards.

The UK trade restrictions and financial sanctions do not include exceptions for humanitarian action. While several general licences have been issued, none relate to humanitarian operations.

Instead, the UK measures foresee only the possibility of applying for specific licences – from the Treasury in the case of financial sanctions and the Department of International Trade for trade restrictions. But obtaining specific licences is a time-consuming process which is simply not appropriate for emergency response.

If the UK is to show it is serious about responding to the immense needs caused by the invasion it must introduce appropriate safeguards in its sanctions – either in the form of exceptions or general licences.

What matters is they cover all key humanitarian organizations responding to the Ukraine crisis that are subject to UK sanctions – either because they are UK persons or because their funding agreements with the UK government require them to comply with UK measures.

These include UN agencies, funds and programmes, components of the International Red Cross and Red Crescent Movement, and non-governmental organizations (NGOs) responding to the crisis in Ukraine and neighbouring states. The provision must also clearly extend to commercial entities which provide necessary services for humanitarian operations.

Given the UK recently adopted an exception along similar lines in relation to the Afghanistan sanctions, there is a valuable precedent for Ukraine.

Humanitarian exceptions: A turning point in UN sanctions Expert comment LJefferson 20 December 2022

The UN Security Council has adopted a cross-cutting exception for humanitarian action in UN sanctions. What does it cover? What must happen next?

The UN Security Council has removed an obstacle to humanitarian work. On 9 December 2022, it adopted a resolution establishing a cross-cutting exception to existing – and future – UN financial sanctions for funds or assets necessary for humanitarian assistance and activities to meet basic human needs. In a coup for multilateralism, the council has been able to act, even when the Russian invasion of Ukraine has caused paralysis in other areas.

Resolution 2664 – introduced by Ireland and the US, co-sponsored by 53 states, and adopted by 14 votes in favour, with India abstaining – is the culmination of a decade of engagement between humanitarian organizations and states to find ways of avoiding the adverse impact of sanctions on the most vulnerable: people relying on humanitarian action for survival.

A reminder of the problem

Whilst sanctions are not intended to have adverse humanitarian consequences for civilian populations, aid agencies have argued for years that they do just this. UN financial sanctions prohibit making funds or other assets available directly or indirectly to designated persons or entities. Without adequate safeguards, incidental payments made during humanitarian operations, or relief consignments that are diverted and end up in the hands of such persons or entities can violate this prohibition.

Exceptions in Afghanistan and Haiti sanctions pave the way

Humanitarian actors have been decrying and documenting the impact of sanctions on their operations for years. Ensuring that sanctions did not hinder the COVID-19 response was a turning point in states’ willingness to address the issue.

Movement at Security Council level was gradual, starting off with demands in the renewals of certain country-specific sanctions that measures taken by member states to give effect to them comply with international law. The return to power of the Taliban called for a more radical approach.

In December 2021, the Council adopted a broad exception to the Afghanistan financial sanctions, covering the provision, payment and processing of funds and assets necessary for humanitarian action and for activities to meet basic human needs. A similar exception was adopted – almost unnoticed – in October 2022 in the newly-established Haiti sanctions.

These developments, coupled with the determination of elected Council member Ireland to find solutions, paved the way for the adoption of SCR 2664.

The scope of the humanitarian exception

SCR 2664 introduces a clear and broad exception that addresses the key challenges financial sanctions pose to humanitarian action. The exception expressly refers to the different ways in which funds or assets are allowed to reach designated persons or entities: by the provision of goods or payment of funds by humanitarian actors themselves; by the processing of funds by financial institutions; and by the provision of goods and services by other commercial actors whose services are necessary for humanitarian action such as insurers and freight companies.

The exception is broad in terms of the excluded activities: the provision of funds and assets necessary for humanitarian assistance and activities to meet basic human needs. The UN Somalia sanctions – the first, and for a decade the only, regime to include an express exception – exclude funds necessary for ‘humanitarian assistance’.

SCR 2615 on Afghanistan added the expression ‘activities to meet basic human needs’.  These go beyond humanitarian assistance, and have been interpreted as including activities necessary to sustain essential social services such as health and education, preserve essential community systems, and promote livelihoods and social cohesion.  These are essentially development programmes.  ‘Activities that support basic needs’ should be understood in a similar manner in SCR 2664.

SCR 2664 is not, however, a ‘blanket’ exception.  It only applies to financial sanctions.  These are not the only type of restriction in UN sanctions that can hinder humanitarian action. For example, organizations that send commodities into the Democratic People’s Republic of Korea must still go through the notoriously slow procedure of authorization by the sanctions committee.  Similarly, authorizations are still required for import of demining materials that fall within the scope of arms embargoes.

Opportunities for further engagement and additional safeguards

Recognizing that additional challenges remain, SCR 2664 requests the UN Secretary-General to draft a report on unintended adverse humanitarian consequences of all types of restrictions in UN sanctions. He is asked to include recommendations for minimizing and such unintended consequences, including by the adoption of additional cross-cutting exceptions.

Humanitarian organizations have played a pivotal role in advancing the agenda. SCR 2664 is the result of their relentless engagement with the Security Council. It is not the end of the road. Other restrictions raise problems, and the Council has left the door open to finding ways of addressing them.

Humanitarian actors should seize this opportunity to provide information, identifying the problematic types of restrictions and their consequences on their operations as specifically as possible.

What happens next?

It is UN member states that implement UN sanctions. For SCR 2664 to be truly effective, it is imperative that states give effect to it in domestic law and practice. In doing so, they must not narrow the scope of the exception.

Recent experience in Afghanistan has shown that even in situations when significant safeguards exist, key actors may be unaware of them or unclear as to their precise scope. Financial institutions in particular are fast to de-risk when sanctions are imposed, and remain wary of conducting transactions that they perceive as high-risk even though exceptions permit this.

OFAC – the Office of Foreign Assets Control in the US Treasury – has issued extensive guidance on the Afghanistan sanctions in the form of frequently asked questions.  These have played an extremely important role in ensuring full advantage is taken of the exceptions.

States should follow this example, and adopt guidance to raise awareness of the exception in SCR 2664 and to clarify its scope.

A valuable precedent for autonomous sanctions

SCR 2664 only applies to sanctions adopted by the UN Security Council. It does not extend to autonomous sanctions adopted by states or relevant international organizations such as the EU.

Expert

Expert

Myosins generate force and motion by precisely coordinating their mechanical and chemical cycles, but the nature and timing of this coordination remains controversial. We utilized a FRET approach to examine the kinetics of structural changes in the force-generating lever arm in myosin V. We directly compared the FRET results with single-molecule mechanical events examined by optical trapping. We introduced a mutation (S217A) in the conserved switch I region of the active site to examine how myosin couples structural changes in the actin- and nucleotide-binding regions with force generation. Specifically, S217A enhanced the maximum rate of lever arm priming (recovery stroke) while slowing ATP hydrolysis, demonstrating that it uncouples these two steps. We determined that the mutation dramatically slows both actin-induced rotation of the lever arm (power stroke) and phosphate release (≥10-fold), whereas our simulations suggest that the maximum rate of both steps is unchanged by the mutation. Time-resolved FRET revealed that the structure of the pre– and post–power stroke conformations and mole fractions of these conformations were not altered by the mutation. Optical trapping results demonstrated that S217A does not dramatically alter unitary displacements or slow the working stroke rate constant, consistent with the mutation disrupting an actin-induced conformational change prior to the power stroke. We propose that communication between the actin- and nucleotide-binding regions of myosin assures a proper actin-binding interface and active site have formed before producing a power stroke. Variability in this coupling is likely crucial for mediating motor-based functions such as muscle contraction and intracellular transport.

A. V. Silantyev
Trans. Moscow Math. Soc. 83 (), 75-149.
Abstract, references and article information

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

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

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

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

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

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

Yinji Li, Zhiwei Wang and Xiangyu Zhou
Trans. Amer. Math. Soc. 377 (), 5947-5992.
Abstract, references and article information

Alexandra Kjuchukova, Allison N. Miller, Arunima Ray and Sümeyra Sakallı
Trans. Amer. Math. Soc. 377 (), 5905-5946.
Abstract, references and article information

Carolyn S. Gordon and Michael R. Jablonski
Trans. Amer. Math. Soc. 377 (), 5673-5704.
Abstract, references and article information

firehouse.ie posted a photo:

firehouse.ie posted a photo:

Luiz Ricardo Abreu Melo
Proc. Amer. Math. Soc. 152 (), 5373-5380.
Abstract, references and article information

Xiaoshang Jin
Proc. Amer. Math. Soc. 152 (), 5327-5337.
Abstract, references and article information

R. Gibara and D. Kinzebulatov
St. Petersburg Math. J. 35 (), 445-460.
Abstract, references and article information

Ana Caraiani, Royal Society University Research Fellow and professor of pure mathematics, Imperial College London, has been awarded the 2025 Ruth Lyttle Satter Prize in Mathematics by the American Mathematical Society (AMS). She has been honored for contributions to arithmetic geometry and number theory: in particular, the Langlands program.

From the citation

Ana Caraiani’s work is characterized by a combination of novel ideas and a fearlessness in the face of technical obstacles that would daunt almost any other researcher. This has enabled her to prove several fundamental theorems in the Langlands program.

In the joint paper with Scholze, titled “On the generic part of the cohomology of non-compact unitary Shimura varieties” (Annals of Math., 2024), Caraiani proved very general results about the torsion cohomology classes in non-compact Shimura varieties, strengthening the early results in their 2017 paper in the compact case. The proof is a tour de force, combining perfectoid spaces, a mastery of the trace formula, and a new theory of perverse sheaves in p-adic geometry. These results are of intrinsic interest (for example, they give the first indications of a characteristic p version of Arthur’s conjectures), but they also have many applications throughout the Langlands program. One spectacular application of these results is in her joint paper, “Potential automorphy over CM fields” (with Allen, Calegari, Gee, Helm, Le Hung, Newton, Scholze, Taylor, and Thorne, Annals of Math., 2023), which among other results proves the Ramanujan conjecture for Bianchi modular forms, a problem that had been thought of as being completely out of reach.

The Ramanujan conjecture is of analytic nature, asserting a bound on the eigenvalue of a certain differential operator, but the only way in which cases of it have been proved is via algebraic geometry. In particular, the original Ramanujan conjecture for modular forms was proved by Deligne in the 1970s, as a consequence of his proof of the Weil conjectures. However, in the case of Bianchi modular forms there is no direct relationship with algebraic geometry, and it seems to be impossible to make any direct deductions from the Weil conjectures. Langlands (also in the 1970s) suggested a strategy for proving the Ramanujan conjecture as a consequence of his functoriality conjecture. Caraiani and her coauthors’ proof of the Ramanujan conjecture for Bianchi modular forms proceeds via a variant of Langlands’ strategy, and in particular does not use the Weil conjectures.

Most recently with James Newton, in the paper “On the modularity of elliptic curves over imaginary quadratic fields” (arXiv: 2301.10509), Caraiani has improved upon these results and applied them to the modularity of elliptic curves over imaginary quadratic fields. They come close to completely solving it, with only a small number of exceptions (which constitute 0% of cases).

Response of Ana Caraiani

First, I would like to thank Joan Birman and the AMS for establishing an award that recognizes research contributions by women mathematicians. This is particularly meaningful to me because I looked to many of the previous recipients of the Satter Prize for inspiration at challenging moments in my career. It is a great honour to be selected as a recipient!

I am indebted to my many collaborators, mentors and colleagues who have generously shared their mathematical ideas with me over the years and supported me in different but crucial ways. Special thanks go to Peter Scholze for the wonderful opportunity to collaborate with him on understanding a part of the geometry and cohomology of Shimura varieties, to Richard Taylor for initiating the "ten author" collaboration, which was much more successful than we had originally expected, and to James Newton for our joyful exploration of elliptic curves over imaginary quadratic fields. I also particularly want to acknowledge Jessica Fintzen and Toby Gee for their longstanding friendship and moral support.

Finally, I want to thank my family, especially my husband, Steven, my mother, Zoe, and my daughter, Nadia.

Biographical sketch of Ana Caraiani

Ana Caraiani was born in Bucharest, Romania, in 1984. She received a bachelor's degree in mathematics from Princeton University in 2007 and completed her PhD at Harvard University in 2012. After temporary positions at the University of Chicago, Princeton and the Institute for Advanced Study (IAS), and the University of Bonn, she moved to Imperial College London in 2017, where she is currently a Royal Society University Research Fellow and Professor of Pure Mathematics. She is a Fellow of the AMS, a recipient of an EMS Prize and a New Horizons Prize in Mathematics and was an invited speaker at the 2022 ICM. 

About the prize

Awarded every two years, the Ruth Lyttle Satter Prize in Mathematics recognizes an outstanding contribution to mathematics research by a woman in the previous six years. The prize was established by Joan Birman in honor of her sister, Ruth. The 2025 prize will be recognized during the 2025 Joint Mathematics Meetings in January in Seattle.

Read more and see the list of past recipients.

Contact: AMS Communications

* * * * *

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.

Reggae crooner D'Yani has exclaimed surprise at the momentum building up for his upcoming United Kingdom (UK) tour. "I'm still in shock that the early bird tickets were sold out so quickly, " he told THE WEEKEND STAR. D'Yani, born Andre...

Highly engineered phytases, which sequentially hydrolyze the hexakisphosphate ester of inositol known as phytic acid, are routinely added to the feeds of monogastric animals to improve phosphate bioavailability. New phytases are sought as starting points to further optimize the rate and extent of dephosphorylation of phytate in the animal digestive tract. Multiple inositol polyphosphate phosphatases (MINPPs) are clade 2 histidine phosphatases (HP2P) able to carry out the stepwise hydrolysis of phytate. MINPPs are not restricted by a strong positional specificity making them attractive targets for development as feed enzymes. Here, we describe the characterization of a MINPP from the Gram-positive bacterium Bifidobacterium longum (BlMINPP). BlMINPP has a typical HP2P-fold but, unusually, possesses a large α-domain polypeptide insertion relative to other MINPPs. This insertion, termed the U-loop, spans the active site and contributes to substrate specificity pockets underpopulated in other HP2Ps. Mutagenesis of U-loop residues reveals its contribution to enzyme kinetics and thermostability. Moreover, four crystal structures of the protein along the catalytic cycle capture, for the first time in an HP2P, a large ligand-driven α-domain motion essential to allow substrate access to the active site. This motion recruits residues both downstream of a molecular hinge and on the U-loop to participate in specificity subsites, and mutagenesis identified a mobile lysine residue as a key determinant of positional specificity of the enzyme. Taken together, these data provide important new insights to the factors determining stability, substrate recognition, and the structural mechanism of hydrolysis in this industrially important group of enzymes.

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.

Members of the B-cell lymphoma (BCL-2) protein family regulate mitochondrial outer membrane permeabilization (MOMP), a phenomenon in which mitochondria become porous and release death-propagating complexes during the early stages of apoptosis. Pro-apoptotic BCL-2 proteins oligomerize at the mitochondrial outer membrane during MOMP, inducing pore formation. Of current interest are endogenous factors that can inhibit pro-apoptotic BCL-2 mitochondrial outer membrane translocation and oligomerization. A mitochondrial-derived peptide, Humanin (HN), was reported being expressed from an alternate ORF in the mitochondrial genome and inhibiting apoptosis through interactions with the pro-apoptotic BCL-2 proteins. Specifically, it is known to complex with BAX and BID. We recently reported the fibrillation of HN and BAX into β-sheets. Here, we detail the fibrillation between HN and BID. These fibers were characterized using several spectroscopic techniques, protease fragmentation with mass analysis, and EM. Enhanced fibrillation rates were detected with rising temperatures or pH values and the presence of a detergent. BID fibers are similar to those produced using BAX; however, the structures differ in final conformations of the BCL-2 proteins. BID fibers display both types of secondary structure in the fiber, whereas BAX was converted entirely to β-sheets. The data show that two distinct segments of BID are incorporated into the fiber structure, whereas other portions of BID remain solvent-exposed and retain helical structure. Similar analyses show that anti-apoptotic BCL-xL does not form fibers with humanin. These results support a general mechanism of sequestration of pro-apoptotic BCL-2 proteins into fibers by HN to inhibit MOMP.

16 July 2020

Wenhe Zhu
Dec 29, 2020; 0:RA120.002353v1-mcp.RA120.002353
Research

Yi Liu
Dec 1, 2020; 19:1968-1985
Research

Peter Lasch
Dec 1, 2020; 19:2125-2138
Technological Innovation and Resources

Ryan J Lumpkin
Dec 2, 2020; 0:RA120.002414v1-mcp.RA120.002414
Research

Mitochondrial DNA (mtDNA) encodes proteins and RNAs that support the functions of mitochondria and thereby numerous physiological processes. Mutations of mtDNA can cause mitochondrial diseases and are implicated in aging. The mtDNA within cells is organized into nucleoids within the mitochondrial matrix, but how mtDNA nucleoids are formed and regulated within cells remains incompletely resolved. Visualization of mtDNA within cells is a powerful means by which mechanistic insight can be gained. Manipulation of the amount and sequence of mtDNA within cells is important experimentally and for developing therapeutic interventions to treat mitochondrial disease. This review details recent developments and opportunities for improvements in the experimental tools and techniques that can be used to visualize, quantify, and manipulate the properties of mtDNA within cells.

The kinesin-3 family contains the fastest and most processive motors of the three neuronal transport kinesin families, yet the sequence of states and rates of kinetic transitions that comprise the chemomechanical cycle and give rise to their unique properties are poorly understood. We used stopped-flow fluorescence spectroscopy and single-molecule motility assays to delineate the chemomechanical cycle of the kinesin-3, KIF1A. Our bacterially expressed KIF1A construct, dimerized via a kinesin-1 coiled-coil, exhibits fast velocity and superprocessivity behavior similar to WT KIF1A. We established that the KIF1A forward step is triggered by hydrolysis of ATP and not by ATP binding, meaning that KIF1A follows the same chemomechanical cycle as established for kinesin-1 and -2. The ATP-triggered half-site release rate of KIF1A was similar to the stepping rate, indicating that during stepping, rear-head detachment is an order of magnitude faster than in kinesin-1 and kinesin-2. Thus, KIF1A spends the majority of its hydrolysis cycle in a one-head-bound state. Both the ADP off-rate and the ATP on-rate at physiological ATP concentration were fast, eliminating these steps as possible rate-limiting transitions. Based on the measured run length and the relatively slow off-rate in ADP, we conclude that attachment of the tethered head is the rate-limiting transition in the KIF1A stepping cycle. Thus, KIF1A's activity can be explained by a fast rear-head detachment rate, a rate-limiting step of tethered-head attachment that follows ATP hydrolysis, and a relatively strong electrostatic interaction with the microtubule in the weakly bound post-hydrolysis state.