JF Oram
Dec 1, 1996; 37:2473-2491
Reviews

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

CJ Fielding
Feb 1, 1995; 36:211-228
Reviews

Chatham House Commission on Democracy and Technology in Europe News Release sysadmin 25 July 2019

Our project on Democracy and Technology in Europe is now entering its final phase. Now we want your help in shaping the final report.

Lord Hammond Joins Panel of Senior Advisers News Release NCapeling 10 December 2020

Chatham House is pleased to announce that Lord Hammond of Runnymede is joining our Panel of Senior Advisers.

New Chatham House History Examines our Defining Moments News Release NCapeling 18 January 2021

'A History of Chatham House: its People and Influence from the 1920s to the 2020s' will examine the impact on policymaking of our first 100 years.

Building trust in trade deals – is human rights monitoring the answer? 27 May 2021 — 4:00PM TO 5:15PM Anonymous (not verified) 14 May 2021 Online

Exploring the arguments in favour of more robust human rights monitoring systems and why effective monitoring mechanisms have proved so difficult to get up and running.

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

The recent signing of the EU-China Investment Agreement has reignited arguments about trade and human rights. While many trade agreements envisage human rights monitoring in some shape or form, the monitoring systems that have emerged so far are not especially coherent, systematic or impactful. 

Are the human rights commitments in trade agreements more than just window-dressing?  If so, what kind of monitoring is needed to ensure they are lived up to? 

At this panel event, which marks the launch of a new Chatham House research paper, participants explore the arguments in favour of more robust human rights monitoring systems and why effective monitoring mechanisms have proved so difficult to get up and running in this context. 

• What factors are presently holding governments back, and where is innovation and investment most needed?
• What are the political, economic and structural conditions for fair and effective human rights monitoring of trade agreements? 
• Is human rights monitoring best done unilaterally – or should more effort be put into developing joint approaches? 
• What role might human rights monitoring have to play in governments’ strategies to ‘build back better’ from the COVID-19 pandemic?

Monitoring of trade deals needs a risk-based approach Expert comment NCapeling 24 May 2021

On human rights issues, trading partners must do more than trust to luck.

The recent row within the UK government about the treatment of agricultural products in a proposed new trade deal with Australia provides a reminder that changes to trading arrangements can have social and environmental costs, as well as benefits.

Although the UK government clearly feels political pressure to demonstrate its ‘Global Britain’ credentials with some speedily concluded new deals, rushing ahead without a full understanding of the social, environmental, and human rights implications risks storing up problems for later. In the meantime, calls for better evaluation and monitoring of trade agreements against sustainability-related commitments and goals – ideally with statutory backing – will only get stronger.

EU experiences with these kinds of processes are instructive. For more than 20 years the Directorate General for Trade of the European Commission (DG Trade) has been commissioning sustainability impact assessments (SIAs) from independent consultants in support of trade negotiations, and since 2012 these assessments have explicitly encompassed human rights impacts as a core part of the analysis.

These processes have since been augmented with a programme of periodic ‘ex post’ evaluations of trade agreements to ‘analyse the observed economic, social, human rights, and environmental impacts’ of live trade deals and to make recommendations about any mitigation action which may be needed.

For credibility and objectivity, the Commission outsources much of its sustainability assessment and ex post evaluation activities to independent consultants, who are encouraged to innovate and tailor their approaches subject to broad methodological parameters laid down by the Commission. Over time, experiences with specific assessment and monitoring assignments have enabled external SIA practitioners – and the Commission itself – to progressively strengthen these processes and underlying methodologies.

Yet despite the improvements there remains legitimate questions about whether the human rights aspects of these SIA processes – and subsequent evaluations – are having real policy impact. The difficulty of predicting human rights impacts of trade agreements in advance – as the COVID-19 crisis amply demonstrates – suggests a need for realism about the extent to which a ‘one off’ process, often carried out at a time when there is only ‘agreement in principle’ as to future trading terms, can produce a robust roadmap for heading off future human rights-related risks.

Human rights impact assessments have a potentially valuable role to play in laying down the substantive and structural foundations for future human rights monitoring as part of a broader, iterative, human rights risk management strategy. But the fragmented manner in which many trade agreements approach human rights issues, and the fact that outcomes are the product of negotiation rather than necessarily design, make it difficult to turn this vision into reality.

Controversies surrounding the SIA process for the EU-Mercosur agreement illustrate why striving for more coherence in the identification and subsequent management of human rights-related risks is important. In June 2019, the Commission decided to wrap up negotiations with the South America Mercosur bloc, even though the SIA process for the proposed agreement was still incomplete and the interim and final SIA reports yet to be delivered. Frustrated NGOs made their feelings clear in the form of a formal complaint – and a slap on the wrist from the EU Ombudsman duly followed.

However, when it eventually appeared in December 2020, the final SIA report for the EU-Mercosur deal did include a number of interesting recommendations for responding to specific areas of human rights-related risk identified through the pre-signing assessment process – such as flanking measures designed to address issues pertaining to health, equality, and protection of indigenous peoples, and stressing the need for ‘continuous monitoring’.

Hopefully these recommendations will be proactively followed up, but there are reasons not to be overly optimistic about that. To the extent that these recommendations might have required, or benefitted from, some tweaks to the terms of the trade agreement itself, it was clearly too late. And while there may be opportunities for EU institutions to follow up the recommendations through unilateral ex post evaluation processes, current legal, policy, and institutional arrangements provide few guarantees this will take place.

The credibility of the EU SIA programme has clearly taken a knock because of the problems with the EU-Mercosur process, and stakeholders could be forgiven for questioning whether expending time and effort on engaging in these processes is actually worthwhile. As a first step towards rectifying this, the Commission should be transparent about how it plans to respond to the EU-Mercosur SIA recommendations regarding flanking measures and follow up – ideally consulting with stakeholders about the various human rights monitoring options available.

Looking further ahead, the Commission should be urging SIA practitioners to deal more expansively with the options for follow up human rights monitoring in future SIA reports, setting out recommendations not just on the need for ongoing monitoring of human rights-related issues but on the detail of how this might be done, and how progress towards human rights-related goals could be tracked. And creativity should be encouraged because, as detailed in a newly-published Chatham House research paper, there may be more opportunities for human rights monitoring than first appear.

The SIA process could also provide a forum for exploring complementary measures needed to make future monitoring efforts as effective as possible – jointly and unilaterally; politically, structurally, and resources-wise; both within the framework of the trading relationship and extraneously. The credibility of the process – and hence stakeholder trust – would be further enhanced by commitments from the Commission to be more transparent in future about how different human rights monitoring recommendations laid out in SIAs have been taken into account in subsequent negotiations, in the supervisory arrangements developed for specific trading relationships, and in the implementation of EU trade policy more generally.

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

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

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

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

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

Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β.

Evolving evidence suggests that nicotine may contribute to impaired asthma control by stimulating expression of nerve growth factor (NGF), a neurotrophin associated with airway remodeling and airway hyperresponsiveness. We explored the hypothesis that nicotine increases NGF by reducing lung fibroblast (LF) microRNA-98 (miR-98) and PPARγ levels, thus promoting airway remodeling. Levels of NGF, miR-98, PPARγ, fibronectin 1 (FN1), endothelin-1 (EDN1, herein referred to as ET-1), and collagen (COL1A1 and COL3A1) were measured in human LFs isolated from smoking donors, in mouse primary LFs exposed to nicotine (50 μg/ml), and in whole lung homogenates from mice chronically exposed to nicotine (100 μg/ml) in the drinking water. In selected studies, these pathways were manipulated in LFs with miR-98 inhibitor (anti-miR-98), miR-98 overexpression (miR-98 mimic), or the PPARγ agonist rosiglitazone. Compared with unexposed controls, nicotine increased NGF, FN1, ET-1, COL1A1, and COL3A1 expression in human and mouse LFs and mouse lung homogenates. In contrast, nicotine reduced miR-98 levels in LFs in vitro and in lung homogenates in vivo. Treatment with anti-miR-98 alone was sufficient to recapitulate increases in NGF, FN1, and ET-1, whereas treatment with a miR-98 mimic significantly suppressed luciferase expression in cells transfected with a luciferase reporter linked to the putative seed sequence in the NGF 3'UTR and also abrogated nicotine-induced increases in NGF, FN1, and ET-1 in LFs. Similarly, rosiglitazone increased miR-98 and reversed nicotine-induced increases in NGF, FN1, and ET-1. Taken together, these findings demonstrate that nicotine-induced increases in NGF and other markers of airway remodeling are negatively regulated by miR-98.

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Histone recognition by “reader” modules serves as a fundamental mechanism in epigenetic regulation. Previous studies have shown that Spindlin1 is a reader of histone H3K4me3 as well as “K4me3-R8me2a” and promotes transcription of rDNA or Wnt/TCF4 target genes. Here we show that Spindlin1 also acts as a potent reader of histone H3 “K4me3-K9me3/2” bivalent methylation pattern. Calorimetric titration revealed a binding affinity of 16 nm between Spindlin1 and H3 “K4me3-K9me3” peptide, which is one to three orders of magnitude stronger than most other histone readout events at peptide level. Structural studies revealed concurrent recognition of H3K4me3 and H3K9me3/2 by aromatic pockets 2 and 1 of Spindlin1, respectively. Epigenomic profiling studies showed that Spindlin1 colocalizes with both H3K4me3 and H3K9me3 peaks in a subset of genes enriched in biological processes of transcription and its regulation. Moreover, the distribution of Spindlin1 peaks is primarily associated with H3K4me3 but not H3K9me3, which suggests that Spindlin1 is a downstream effector of H3K4me3 generated in heterochromatic regions. Collectively, our work calls attention to an intriguing function of Spindlin1 as a potent H3 “K4me3-K9me3/2” bivalent mark reader, thereby balancing gene expression and silencing in H3K9me3/2-enriched regions.

Phospholipase Cε (PLCε) is activated downstream of G protein–coupled receptors and receptor tyrosine kinases through direct interactions with small GTPases, including Rap1A and Ras. Although Ras has been reported to allosterically activate the lipase, it is not known whether Rap1A has the same ability or what its molecular mechanism might be. Rap1A activates PLCε in response to the stimulation of β-adrenergic receptors, translocating the complex to the perinuclear membrane. Because the C-terminal Ras association (RA2) domain of PLCε was proposed to the primary binding site for Rap1A, we first confirmed using purified proteins that the RA2 domain is indeed essential for activation by Rap1A. However, we also showed that the PLCε pleckstrin homology (PH) domain and first two EF hands (EF1/2) are required for Rap1A activation and identified hydrophobic residues on the surface of the RA2 domain that are also necessary. Small-angle X-ray scattering showed that Rap1A binding induces and stabilizes discrete conformational states in PLCε variants that can be activated by the GTPase. These data, together with the recent structure of a catalytically active fragment of PLCε, provide the first evidence that Rap1A, and by extension Ras, allosterically activate the lipase by promoting and stabilizing interactions between the RA2 domain and the PLCε core.

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

DNA polymerases are today used throughout scientific research, biotechnology, and medicine, in part for their ability to interact with unnatural forms of DNA created by synthetic biologists. Here especially, natural DNA polymerases often do not have the “performance specifications” needed for transformative technologies. This creates a need for science-guided rational (or semi-rational) engineering to identify variants that replicate unnatural base pairs (UBPs), unnatural backbones, tags, or other evolutionarily novel features of unnatural DNA. In this review, we provide a brief overview of the chemistry and properties of replicative DNA polymerases and their evolved variants, focusing on the Klenow fragment of Taq DNA polymerase (Klentaq). We describe comparative structural, enzymatic, and molecular dynamics studies of WT and Klentaq variants, complexed with natural or noncanonical substrates. Combining these methods provides insight into how specific amino acid substitutions distant from the active site in a Klentaq DNA polymerase variant (ZP Klentaq) contribute to its ability to replicate UBPs with improved efficiency compared with Klentaq. This approach can therefore serve to guide any future rational engineering of replicative DNA polymerases.

RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RecQ C-terminal domain, and an auxiliary element helicase and RNaseD C-terminal (HRDC) domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3'-partial duplex and fork DNA with a moderate processivity and periodically patrols on the ssDNA in the 5'-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA-binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms.

Rhodopsin is a canonical class A photosensitive G protein–coupled receptor (GPCR), yet relatively few pharmaceutical agents targeting this visual receptor have been identified, in part due to the unique characteristics of its light-sensitive, covalently bound retinal ligands. Rhodopsin becomes activated when light isomerizes 11-cis-retinal into an agonist, all-trans-retinal (ATR), which enables the receptor to activate its G protein. We have previously demonstrated that, despite being covalently bound, ATR can display properties of equilibrium binding, yet how this is accomplished is unknown. Here, we describe a new approach for both identifying compounds that can activate and attenuate rhodopsin and testing the hypothesis that opsin binds retinal in equilibrium. Our method uses opsin-based fluorescent sensors, which directly report the formation of active receptor conformations by detecting the binding of G protein or arrestin fragments that have been fused onto the receptor's C terminus. We show that these biosensors can be used to monitor equilibrium binding of the agonist, ATR, as well as the noncovalent binding of β-ionone, an antagonist for G protein activation. Finally, we use these novel biosensors to observe ATR release from an activated, unlabeled receptor and its subsequent transfer to the sensor in real time. Taken together, these data support the retinal equilibrium binding hypothesis. The approach we describe should prove directly translatable to other GPCRs, providing a new tool for ligand discovery and mutant characterization.

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme and transcriptional coactivator and is critical for tumor metabolism. In cancer cells, native tetrameric PKM2 is phosphorylated or acetylated, which initiates a switch to a dimeric/monomeric form that translocates into the nucleus, causing oncogene transcription. However, it is not known how these post-translational modifications (PTMs) disrupt the oligomeric state of PKM2. We explored this question via crystallographic and biophysical analyses of PKM2 mutants containing residues that mimic phosphorylation and acetylation. We find that the PTMs elicit major structural reorganization of the fructose 1,6-bisphosphate (FBP), an allosteric activator, binding site, impacting the interaction with FBP and causing a disruption in oligomerization. To gain insight into how these modifications might cause unique outcomes in cancer cells, we examined the impact of increasing the intracellular pH (pHi) from ∼7.1 (in normal cells) to ∼7.5 (in cancer cells). Biochemical studies of WT PKM2 (wtPKM2) and the two mimetic variants demonstrated that the activity decreases as the pH is increased from 7.0 to 8.0, and wtPKM2 is optimally active and amenable to FBP-mediated allosteric regulation at pHi 7.5. However, the PTM mimetics exist as a mixture of tetramer and dimer, indicating that physiologically dimeric fraction is important and might be necessary for the modified PKM2 to translocate into the nucleus. Thus, our findings provide insight into how PTMs and pH regulate PKM2 and offer a broader understanding of its intricate allosteric regulation mechanism by phosphorylation or acetylation.

Defining discontinuous antigenic epitopes remains a substantial challenge, as exemplified by the case of lipid transfer polyproteins, which are common pollen allergens. Hydrogen/deuterium exchange monitored by NMR can be used to map epitopes onto folded protein surfaces, but only if the complex rapidly dissociates. Modifying the standard NMR-exchange measurement to detect substoichiometric complexes overcomes this time scale limitation and provides new insights into recognition of lipid transfer polyprotein by antibodies. In the future, this new and exciting development should see broad application to a range of tight macromolecular interactions.

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.

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.

A. V. Domrina
Trans. Moscow Math. Soc. 83 (), 201-215.
Abstract, references and article information

A. Kh. Khachatryan, Kh. A. Khachatryan and A. Zh. Narimanyan
Trans. Moscow Math. Soc. 83 (), 183-200.
Abstract, references and article information

A. G. Sergeev, A. Kh. Khachatryan and Kh. A. Khachatryan
Trans. Moscow Math. Soc. 83 (), 55-65.
Abstract, references and article information

Decarbonizing Heat: A New Frontier for Technologies and Business Models 27 February 2019 — 8:15AM TO 9:45AM Anonymous (not verified) 3 December 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Building space and water heating accounts for over 35 percent of global energy consumption - nearly double that of transport. However, there has been limited progress in decarbonizing the sector to date. International cooperation is required to ensure harmonized policies drag low carbon heating technologies down the cost curve to the extent that low carbon heating is cost competitive and affordable. The initial presentations and discussion focus on:

• Demand reduction technologies and policies that speed up transformation of the sector.
• The different challenges for energy efficiency of retrofitting as opposed to new build.
• The impact of electrification on GHG emissions and the power sector.
• The comparative role of national and city level initiatives.

The meeting concludes by looking at the challenges and risks in accelerating the transformation of heating and the lessons that can be learned from other sectors.

The EU’s Un-Common Agricultural Policy 21 October 2019 — 8:30AM TO 10:00AM Anonymous (not verified) 27 September 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Moving Food up the Political Agenda 14 December 2020 — 3:00PM TO 4:30PM Anonymous (not verified) 8 December 2020 Online

How can food system transformation be woven into high level biodiversity, nutrition and climate forums in 2021?

Adverse impacts on food security are expected to worsen as global temperatures continue to rise. As well as feeling the impacts of climate change, food systems drive it in a number of ways. Not only do food systems contribute more to greenhouse gas emissions than any other parts of our lives, they are also the leading driver of biodiversity loss, the largest cause of deforestation and occupy the most land globally.

On our current trajectory, 1.5°C of warming could become a reality in the next 5-10 years. Transforming food systems to meet climate, biodiversity and food security goals is crucial. If left to continue, food alone could take us over 1.5°C this century – even with maximum efforts in the energy sector.

Unprecedented levels of action to transform food systems is required over the next decade. The coming year is described as a ‘super year’ given the numerous high-level global events taking place that cover climate, biodiversity and food security. The year ahead has also been identified as the final opportunity to bring global commitments in line with the goals of the Paris Agreement.

What can be achieved in the super year? How can food system transformation be woven into high level biodiversity, nutrition and climate forums during the super year? How can momentum from the super year be built upon, to ensure meaningful action is taken over the next decade?

Sand: Monitoring and management for a sustainable future 2 March 2021 — 1:00PM TO 2:00PM Anonymous (not verified) 18 February 2021 Online

In partnership with the Global Sand Observatory Initiative, this event outlines the sand challenge, what actions are currently underway to address it, and what else needs to be done.

Please complete your registration on Zoom:

After water, sand is the raw material that the world consumes in the greatest quantity. It is no exaggeration to say that fine sand and coarser materials – the medium-to-coarse-grained pebbles, gravel and rock fragments used in construction – are the building blocks of the modern world.

When bound with cement, sand becomes concrete; when mixed with bitumen, it becomes asphalt; and when heated, it becomes glass. Without sand, we would have no highways, high-rises or high-speed trains. Yet sand – which is used here as shorthand for sand, gravel and crushed rock together – is a resource that is both abundant and finite.

In global terms, it is abundant, especially when compared with many other raw materials, albeit often not available close to where it is needed. It is finite in that the rate at which we are using it far exceeds the natural rate at which it is being replenished by the weathering of rocks by wind and water.

Industrialization, population growth and urbanization have fuelled explosive growth in the demand for sand. Precise data on sand extraction are hard to come by and the lack of data compounds the challenge of managing the resource sustainably.

However, the UN estimates that overall extraction could be in the region of 40 billion tonnes per year, driven primarily by construction sector demand. That equates to 18 kilograms of sand each day for every person on the planet and signals how strategically important these resources are for future sustainable development. Post-COVID-19 recovery investment in infrastructure, digital technologies, tourism and other economic activities are dependent on sand resources.

Current efforts to improve the management of sand resources at local, national and global levels are uneven. This is partly due to unique geological features and geography, but also differences in local manifestations of the ‘sand challenge’, national and regional demand for sand resources, as well as capacities to enforce or implement best practice assessment procedures, extractive practices, environmental management and restoration requirements.

We must put stronger conditions in place for a rapid, just and scaled transition to sustainable sand management. But where to focus our efforts for the greatest positive impact?

Demographics and politics

Analysing political trends based on demographics is growing as the global population changes and traditional political affiliations are replaced.

Major issues for Chatham House research include the impact of the growth of young people in the developing world, significant increases in population aging in the developed world, and the impact of increasing urbanization on political engagement.

Gender and diversity also play an important part in changing political attitudes, while predicting voting behaviour is becoming ever harder to do accurately, as the methods and technology used by younger generations to engage with politics differ hugely from more traditional approaches.

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?

Gurmeet K. Bakshi, Jyoti Garg and Gabriela Olteanu
Math. Comp. 93 (), 3027-3058.
Abstract, references and article information

Pierre Lairez, Eric Pichon-Pharabod and Pierre Vanhove
Math. Comp. 93 (), 2985-3025.
Abstract, references and article information

Torin Greenwood, Jonathan Kariv and Noah Williams
Math. Comp. 93 (), 2959-2983.
Abstract, references and article information

Martin Ehler and Karlheinz Gröchenig
Math. Comp. 93 (), 2885-2919.
Abstract, references and article information

Selim Esedoḡlu, Jiajia Guo and David Li
Math. Comp. 93 (), 2679-2710.
Abstract, references and article information

Buyang Li, Zongze Yang and Zhi Zhou
Math. Comp. 93 (), 2557-2586.
Abstract, references and article information

Tim Chumley explains the connections between random billiards and the science of heat and energy transfer. If you've ever played billiards or pool, you've used your intuition and some mental geometry to plan your shots. Mathematicians have gone a step further, using these games as inspiration for new mathematical problems. Starting from the simple theoretical setup of a single ball bouncing around in an enclosed region, the possibilities are endless. For instance, if the region is shaped like a stadium (a rectangle with semicircles on opposite sides), and several balls start moving with nearly the same velocity and position, their paths in the region soon differ wildly: chaos. Mathematical billiards even have connections to thermodynamics, the branch of physics dealing with heat, temperature, and energy transfer.

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

Otto Overkamp
Trans. Amer. Math. Soc. 377 (), 5863-5903.
Abstract, references and article information

Shoham Letzter
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