gen In conversation with Julien Harneis, UN Assistant Secretary-General By www.chathamhouse.org Published On :: Mon, 11 Nov 2024 10:02:14 +0000 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:What are the priorities and goals of the UN’s current aid plan for Yemen, and how is it designed to reach those most in need?How are recent developments in the Red Sea affecting food security, trade routes, and humanitarian access in Yemen?What strategies are in place to ensure the delivery of humanitarian aid remains independent and neutral?This is a ‘register interest’ event. Confirmations to successful applicants for in-person attendance will be sent on Thursday at 16.00 GMT. Virtual attendees will be granted access to the event.The institute occupies a position of respect and trust, and is committed to fostering inclusive dialogue at all events. Event attendees are expected to uphold this by adhering to our code of conduct. Full Article
gen Undercurrents: Episode 6 - Tribes of Europe, and the International Women's Rights Agenda at the UN By f1.media.brightcove.com Published On :: Thu, 19 Apr 2018 00:00:00 +0100 Full Article
gen Genes, Germs and Geography: The Future of Medicine By f1.media.brightcove.com Published On :: Tue, 24 Apr 2018 00:00:00 +0100 Full Article
gen Argentina: Political Change and the G20 Presidency By f1.media.brightcove.com Published On :: Tue, 05 Jun 2018 00:00:00 +0100 Full Article
gen Undercurrents: Episode 10 - Artificial Intelligence in International Affairs, and Women Drivers in Saudi Arabia By f1.media.brightcove.com Published On :: Fri, 15 Jun 2018 00:00:00 +0100 Full Article
gen Undercurrents: Episode 11 - New Approaches to Peacebuilding, and Gender-Inclusive Growth at the G20 By f1.media.brightcove.com Published On :: Wed, 04 Jul 2018 00:00:00 +0100 Full Article
gen Gender Inequality: Making Technology the Solution, Not the Problem By f1.media.brightcove.com Published On :: Thu, 11 Apr 2019 00:00:00 +0100 Full Article
gen Artificial Intelligence and the Public: Prospects, Perceptions and Implications By f1.media.brightcove.com Published On :: Fri, 28 Jun 2019 00:00:00 +0100 Full Article
gen Undercurrents: Summer Special - Allison Gardner on Artificial Intelligence By f1.media.brightcove.com Published On :: Thu, 08 Aug 2019 00:00:00 +0100 Full Article
gen Human Rights Priorities: An Agenda for Equality and Social Justice By f1.media.brightcove.com Published On :: Tue, 19 Nov 2019 00:00:00 +0000 Full Article
gen Ukraine’s Reform Agenda: Shaping the Future By f1.media.brightcove.com Published On :: Thu, 21 Nov 2019 00:00:00 +0000 Full Article
gen UK General Election 2019: Foreign Policy Implications By f1.media.brightcove.com Published On :: Wed, 11 Dec 2019 00:00:00 +0000 Full Article
gen Undercurrents: Episode 48 - UK Intelligence Agencies, and Paying for Climate Action By f1.media.brightcove.com Published On :: Fri, 20 Mar 2020 00:00:00 +0000 Full Article
gen A simplified method for the preparation of detergent-free lipid rafts By www.jlr.org Published On :: 2005-05-01 Jennifer L. MacdonaldMay 1, 2005; 46:1061-1067Methods Full Article
gen Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase By www.jlr.org Published On :: 2000-02-01 Jorge H. CapdevilaFeb 1, 2000; 41:163-181Reviews Full Article
gen A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent By www.jlr.org Published On :: 1989-04-01 M el-SaadaniApr 1, 1989; 30:627-630Articles Full Article
gen Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL By www.jlr.org Published On :: 2004-06-01 Mohamad NavabJun 1, 2004; 45:993-1007Thematic Reviews Full Article
gen Gene expression regulation by retinoic acid By www.jlr.org Published On :: 2002-11-01 James E. BalmerNov 1, 2002; 43:1773-1808Reviews Full Article
gen Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host By www.jlr.org Published On :: 2004-07-01 Weerapan KhovidhunkitJul 1, 2004; 45:1169-1196Thematic Reviews Full Article
gen Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression By www.jlr.org Published On :: 1996-05-01 K SchoonjansMay 1, 1996; 37:907-925Reviews Full Article
gen Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis By www.jlr.org Published On :: 1996-04-01 IJ GoldbergApr 1, 1996; 37:693-707Reviews Full Article
gen Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI By www.jlr.org Published On :: 1990-03-01 JE HixsonMar 1, 1990; 31:545-548Articles Full Article
gen Strengthening Our Commitment to the Next Generation By www.chathamhouse.org Published On :: Mon, 09 Nov 2020 18:52:16 +0000 Strengthening Our Commitment to the Next Generation News Release NCapeling 9 November 2020 Panel of Young Advisers and Queen Elizabeth II Academy Ambassadors underscore our drive to reach, engage and inspire young people to change their world. Full Article
gen Supporting Next Generation of Leaders in Sustainability By www.chathamhouse.org Published On :: Thu, 28 Jan 2021 21:51:39 +0000 Supporting Next Generation of Leaders in Sustainability News Release NCapeling 28 January 2021 A new programme offering paid internships for young people who are passionate about social, economic, and environmental sustainability has been launched. Full Article
gen Why the next generation is key to protecting human rights By www.chathamhouse.org Published On :: Wed, 23 Jun 2021 13:12:42 +0000 Why the next generation is key to protecting human rights Expert comment LToremark 23 June 2021 Strengthening youth participation in public affairs is essential to building inclusive and democratic societies that respect human rights. Young people have always been drivers of social and economic reform, and today’s global youth population is more numerous and interconnected than ever before. While they have been at the forefront of civic rights movements in recent years, young people are largely excluded from discussions around human rights norms and how to monitor their protection and defence. Today’s global youth population is more numerous and interconnected than ever before. Young people are consistently underrepresented in intergovernmental mechanisms and national dialogues, which not only squanders their potential to contribute to effective solutions but also risks disengagement and disillusionment with multilateralism more broadly, at a time when many are already warning of the fraying of the international liberal order. Although there are actors and initiatives working to lift barriers to youth participation in governance – such as the UN Secretary-General’s Envoy on Youth, Jayathma Wickramanayake, or the UN 2016 Not Too Young To Run campaign – these efforts tend to fall short in effecting real change and rarely translate into institutionalized procedures. While ‘the youth’ is a heterogenous group, comprising different ages, ethnicities, national identities and interests, their participation in realizing human rights is essential to addressing the current challenges and possibilities of human rights for future generations. This will help foster more effective solutions to rights-related challenges, re-build trust in the international human rights framework among younger demographics and broaden and deepen commitments to human rights across generations. Human rights policies and the online environment Young people tend to be more technologically literate than their predecessors and also represent the majority of internet users and social media consumers in many countries. They can therefore play a key role in innovating and imagining rights-based solutions to emerging problems for the human rights framework, such as illegitimate collection of data by governments and companies, microtargeting by online platforms, and the sharing of harmful content online. In many cases, international human rights practices have failed to keep pace with these changes and the challenges they bring. Younger demographics may also approach these novel human rights issues from different starting points. For example, a UK study found that 30 per cent of 18-24 year-olds were ‘unconcerned’ about data privacy compared with only 12 per cent of those aged 55-64, and it has been shown that younger people tend to be more discerning of fake news compared to older generations. There may be a need for human rights institutions and practitioners to acknowledge and bridge these gaps in perspective and understanding to ensure long-term support for proposed solutions. International cooperation for human rights protection It has been suggested that young people have reaped the benefits of previous human rights-based policy reforms and have a strong sense of what rights they are entitled to and why these need to be protected through an international framework. Young people are also generally more supportive of multilateralism compared to their older counterparts, as demonstrated by a 2020 survey by Pew Research Center on global attitudes, which showed that 72 per cent of respondents aged 18-29 stated they have a favourable view of the UN, compared with 58 per cent of respondents aged 50 and older. At a recent Chatham House workshop, young participants from countries as diverse as Lebanon, Kenya and the United States expressed concern that growing hostility towards globalization threatens to undo progress in human rights standards and multilateralism more broadly, progress that they have seen and benefitted from. The rise of nationalist and populist parties has also seen countries shift their attention inwards, as evidenced by former president Trump’s decision to withdraw the US from the Paris Agreement on climate change, and threats by Brazil’s president, Jair Bolsonaro, to follow suit. Engaging more actively with younger individuals on global human rights reform will help ensure the long-term relevance of multilateral cooperation as well as domestic buy-in of human rights commitments. Awareness of the interconnectivity of global problems Young people’s proficiency on online platforms has enabled greater coordination and knowledge sharing without geographical constraints, allowing young activists – like Greta Thunberg – to inspire global movements and foster online discussions about intersectional solutions to modern-day challenges. This intersectional and transnational lens will be a vital component of building solutions to politically or historically complex issues and can be leveraged to foster better understanding of competing human rights claims relating to issues such as land re-distribution in South Africa or limitations on freedom of movement during the COVID-19 pandemic. These democratic forums and platforms will ultimately help build a global community committed to and engaged with human rights. Tokenism can discourage future engagement and dilute the effectiveness of the forums in question. Capturing the next generation’s potential With these concerns and areas of potential in mind, how can human rights institutions and mechanisms create more meaningful avenues for youth input? Recent Chatham House research has suggested that multilateral institutions’ efforts to engage youth has often taken the form of ‘superficial listening’, for example inviting a high-profile youth actor to a one-off event or appointing youth delegates who are not able to participate in formal discussions or mainstream governance forums. While encouraging youth participation in meetings focused on human rights can lead to positive change, tokenism can discourage future engagement and dilute the effectiveness of the forums in question. Capitalizing on the potential of the next generation can be achieved through integrating youth councils and advisers into national and international human rights policy processes, as well as human rights institutions. A few replicable models are already operational, such as the Y7 and the Y20 delegations – the official youth engagement groups for the G7 and G20 – that advance evidence-based proposals to world leaders ahead of the G7 and G20 summits. Subscribe to our weekly newsletterOur flagship newsletter provides a weekly round-up of content, plus receive the latest on events and how to connect with the institute. Enter email address Subscribe At the domestic level, grassroots youth-led movements can help bridge the gap between local constituencies and international policymakers, with youth activists on the ground helping to implement human rights standards and fighting against the spread of misinformation. Strong local networks and civic spaces are essential for pushing back against human rights abuses, and youth activists should be mobilized to connect the efforts of domestic and international bodies to the real issues on the ground; for example, canvassing grassroots youth networks on domestic and traditional customs before implementing development agendas around women’s rights. As well as providing insertion points for youth policy actors, human rights institutions must communicate their goals more effectively to younger generations and promote intergenerational and inclusive dialogue, for example by holding virtual consultations that give access to individuals from different backgrounds. Similarly, they should ask young people about their priorities for human rights reform using regular and accessible surveys or by sharing information on online platforms regularly used by this demographic. This will ensure lasting buy-in from the next generation, essential for the relevance and sustainability of the human rights framework in the years to come. This piece draws upon insights gathered at a workshop hosted by Chatham House in March 2021, which brought together the Institute’s networks of next generation groups including representatives of the QEII Academy Ambassadors, the Panel of Young Advisers, and the Common Futures Conversations community, as well as young members from the South African Institute of International Affairs. Full Article
gen Amyloid precursor protein is a restriction factor that protects against Zika virus infection in mammalian brains [Gene Regulation] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer's diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries. Full Article
gen Genetic evidence for partial redundancy between the arginine methyltransferases CARM1 and PRMT6 [Signal Transduction] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss. We thus performed a screen of type I PRMTs, which revealed that PRMT6 can also deposit the H3R17me2a mark in vitro. CARM1 knockout mice are perinatally lethal and display a reduced fetal size, whereas PRMT6 null mice are viable, which permits the generation of double knockouts. Embryos that are null for both CARM1 and PRMT6 are noticeably smaller than CARM1 null embryos, providing in vivo evidence of redundancy. Mouse embryonic fibroblasts (MEFs) from the double knockout embryos display an absence of the H3R17me2a mark during mitosis and increased signs of DNA damage. Moreover, using the combination of CARM1 and PRMT6 inhibitors suppresses the cell proliferation of WT MEFs, suggesting a synergistic effect between CARM1 and PRMT6 inhibitions. These studies provide direct evidence that PRMT6 also deposits the H3R17me2a mark and acts redundantly with CARM1. Full Article
gen Stop codon read-through of mammalian MTCH2 leading to an unstable isoform regulates mitochondrial membrane potential [Gene Regulation] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3' UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3' UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through–deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential. Full Article
gen MicroRNA-98 reduces nerve growth factor expression in nicotine-induced airway remodeling [Gene Regulation] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 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. Full Article
gen Inhibition of the SUV4-20 H1 histone methyltransferase increases frataxin expression in Friedreich's ataxia patient cells [Gene Regulation] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The molecular mechanisms of reduced frataxin (FXN) expression in Friedreich's ataxia (FRDA) are linked to epigenetic modification of the FXN locus caused by the disease-associated GAA expansion. Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target. Using a human FXN–GAA–Luciferase repeat expansion genomic DNA reporter model of FRDA, we screened the Structural Genomics Consortium epigenetic probe collection. We found that pharmacological inhibition of the SUV4-20 methyltransferases by the tool compound A-196 increased the expression of FXN by ∼1.5-fold in the reporter cell line. In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells, A-196 increased FXN expression by up to 2-fold, an effect not seen in WT cells. SUV4-20 inhibition was accompanied by a reduction in H4K20me2 and H4K20me3 and an increase in H4K20me1, but only modest (1.4–7.8%) perturbation in genome-wide expression was observed. Finally, based on the structural activity relationship and crystal structure of A-196, novel small molecule A-196 analogs were synthesized and shown to give a 20-fold increase in potency for increasing FXN expression. Overall, our results suggest that histone methylation is important in the regulation of FXN expression and highlight SUV4-20 H1 as a potential novel therapeutic target for FRDA. Full Article
gen China already leads 4 of the 15 U.N. specialized agencies — and is aiming for a 5th By www.chathamhouse.org Published On :: Thu, 05 Mar 2020 10:58:21 +0000 Source The Washington Post URL https://www.washingtonpost.com/politics/2020/03/03/china-already-leads-4-15-un-s... Release date 03 March 2020 Expert Courtney J. Fung In the news type Op-ed Hide date on homepage Full Article
gen Intransigent Netanyahu brings Groundhog Day for Israel By www.chathamhouse.org Published On :: Fri, 06 Mar 2020 16:29:53 +0000 Source Arab News URL https://www.arabnews.com/node/1634966 Release date 29 February 2020 Expert Professor Yossi Mekelberg In the news type Op-ed Hide date on homepage Full Article
gen For China’s coronavirus diplomacy to succeed, Beijing must dial up generosity and downplay ideology By www.chathamhouse.org Published On :: Wed, 06 May 2020 17:31:39 +0000 Source South China Morning Post URL https://www.scmp.com/comment/opinion/article/3079971/chinas-coronavirus-diplomac... Release date 16 April 2020 Expert Dr Yu Jie In the news type Op-ed Hide date on homepage Full Article
gen The insurgency in northern Mozambique has got worse. Why? By www.chathamhouse.org Published On :: Wed, 06 May 2020 17:41:31 +0000 Source Mail & Guardian URL https://mg.co.za/article/2020-03-31-the-insurgency-in-northern-mozambique-has-go... Release date 31 March 2020 Expert Dr Alex Vines OBE In the news type Op-ed Hide date on homepage Full Article
gen A Deep-Diving Sub. A Deadly Fire. And Russia’s Secret Undersea Agenda By www.chathamhouse.org Published On :: Wed, 13 May 2020 15:37:45 +0000 Source New York Times URL https://www.nytimes.com/2020/04/20/world/europe/russian-submarine-fire-losharik.... Release date 20 April 2020 Expert Mathieu Boulègue In the news type Op-ed Hide date on homepage Full Article
gen Libya’s Gen. Hifter declared military rule last month. That hasn’t happened By www.chathamhouse.org Published On :: Wed, 27 May 2020 12:11:33 +0000 Source The Washington Post URL https://www.washingtonpost.com/politics/2020/05/22/libyas-gen-hifter-declared-mi... Release date 22 May 2020 Expert Tim Eaton In the news type Op-ed Hide date on homepage Full Article
gen Molecular basis for histone H3 “K4me3-K9me3/2” methylation pattern readout by Spindlin1 [Gene Regulation] By www.jbc.org Published On :: 2020-12-04T00:06:06-08:00 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. Full Article
gen Building better polymerases: Engineering the replication of expanded genetic alphabets [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 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. Full Article
gen Multilevel interpolations for the generalized Nikishin system on a tree graph By www.ams.org Published On :: Tue, 01 Oct 2024 14:21 EDT V. G. Lysov Trans. Moscow Math. Soc. 83 (), 291-304. Abstract, references and article information Full Article
gen On a class of degenerate hypoelliptic polynomials By www.ams.org Published On :: Tue, 01 Oct 2024 14:21 EDT H. G. Kazaryan and V. N. Margaryan Trans. Moscow Math. Soc. 83 (), 151-181. Abstract, references and article information Full Article
gen Moving Food up the Political Agenda By www.chathamhouse.org Published On :: Tue, 08 Dec 2020 16:43:59 +0000 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? Full Article
gen Climate action and gender equality: Can we close the gap on one without the other? By www.chathamhouse.org Published On :: Mon, 15 Feb 2021 16:04:18 +0000 Climate action and gender equality: Can we close the gap on one without the other? 8 March 2021 — 2:30PM TO 4:00PM Anonymous (not verified) 15 February 2021 Online In partnership with the COP26 presidency, policymakers and experts examine the interrelationship between gender equality and climate action, and highlight innovative examples of policy and practice from around the world. Marking International Women’s Day, this event organized by the COP26 presidency in partnership with Chatham House, will explore how gender equality and climate action go hand-in-hand. The agreement of the Gender Action Plan (GAP) at COP25 sent the message that the time for gender-responsive climate action is now. This will be a unique opportunity to hear from policymakers and civil society leaders discussing whether enough is being done, as well as highlighting cutting-edge work around the world and suggesting what the future could hold. The event will be livestreamed on this event page. Full Article
gen Artificial Intelligence Apps Risk Entrenching India’s Socio-economic Inequities By www.chathamhouse.org Published On :: Wed, 14 Mar 2018 15:35:52 +0000 Artificial Intelligence Apps Risk Entrenching India’s Socio-economic Inequities Expert comment sysadmin 14 March 2018 Artificial intelligence applications will not be a panacea for addressing India’s grand challenges. Data bias and unequal access to technology gains will entrench existing socio-economic fissures. — Participants at an AI event in Bangalore. Photo: Getty Images. Artificial intelligence (AI) is high on the Indian government’s agenda. Some days ago, Prime Minister Narendra Modi inaugurated the Wadhwani Institute for Artificial Intelligence, reportedly India’s first research institute focused on AI solutions for social good. In the same week, Niti Aayog CEO Amitabh Kant argued that AI could potentially add $957 billion to the economy and outlined ways in which AI could be a ‘game changer’. During his budget speech, Finance Minister Arun Jaitley announced that Niti Aayog would spearhead a national programme on AI; with the near doubling of the Digital India budget, the IT ministry also announced the setting up of four committees for AI-related research. An industrial policy for AI is also in the pipeline, expected to provide incentives to businesses for creating a globally competitive Indian AI industry. Narratives on the emerging digital economy often suffer from technological determinism — assuming that the march of technological transformation has an inner logic, independent of social choice and capable of automatically delivering positive social change. However, technological trajectories can and must be steered by social choice and aligned with societal objectives. Modi’s address hit all the right notes, as he argued that the ‘road ahead for AI depends on and will be driven by human intentions’. Emphasising the need to direct AI technologies towards solutions for the poor, he called upon students and teachers to identify ‘the grand challenges facing India’ – to ‘Make AI in India and for India’. To do so, will undoubtedly require substantial investments in R&D, digital infrastructure and education and re-skilling. But, two other critical issues must be simultaneously addressed: data bias and access to technology gains. While computers have been mimicking human intelligence for some decades now, a massive increase in computational power and the quantity of available data are enabling a process of ‘machine learning.’ Instead of coding software with specific instructions to accomplish a set task, machine learning involves training an algorithm on large quantities of data to enable it to self-learn; refining and improving its results through multiple iterations of the same task. The quality of data sets used to train machines is thus a critical concern in building AI applications. Much recent research shows that applications based on machine learning reflect existing social biases and prejudice. Such bias can occur if the data set the algorithm is trained on is unrepresentative of the reality it seeks to represent. If for example, a system is trained on photos of people that are predominantly white, it will have a harder time recognizing non-white people. This is what led a recent Google application to tag black people as gorillas. Alternatively, bias can also occur if the data set itself reflects existing discriminatory or exclusionary practices. A recent study by ProPublica found for example that software that was being used to assess the risk of recidivism in criminals in the United States was twice as likely to mistakenly flag black defendants as being at higher risk of committing future crimes. The impact of such data bias can be seriously damaging in India, particularly at a time of growing social fragmentation. It can contribute to the entrenchment of social bias and discriminatory practices, while rendering both invisible and pervasive the processes through which discrimination occurs. Women are 34 per cent less likely to own a mobile phone than men – manifested in only 14 per cent of women in rural India owning a mobile phone, while only 30 per cent of India’s internet users are women. Women’s participation in the labour force, currently at around 27 per cent, is also declining, and is one of the lowest in South Asia. Data sets used for machine learning are thus likely to have a marked gender bias. The same observations are likely to hold true for other marginalized groups as well. Accorded to a 2014 report, Muslims, Dalits and tribals make up 53 per cent of all prisoners in India; National Crime Records Bureau data from 2016 shows in some states, the percentage of Muslims in the incarcerated population was almost three times the percentage of Muslims in the overall population. If AI applications for law and order are built on this data, it is not unlikely that it will be prejudiced against these groups. (It is worth pointing out that the recently set-up national AI task force is comprised of mostly Hindu men – only two women are on the task force, and no Muslims or Christians. A recent article in the New York Times talked about AI’s ‘white guy problem’; will India suffer from a ‘Hindu male bias’?) Yet, improving the quality, or diversity, of data sets may not be able to solve the problem. The processes of machine learning and reasoning involve a quagmire of mathematical functions, variables and permutations, the logic of which are not readily traceable or predictable. The dazzle of AI-enabled efficiency gains must not blind us to the fact that while AI systems are being integrated into key socio-economic systems, their accuracy and logic of reasoning have not been fully understood or studied. The other big challenge stems from the distribution of AI-led technology gains. Even if estimates of AI contribution to GDP are correct, the adoption of these technologies is likely to be in niches within the organized sector. These industries are likely to be capital- rather than labour-intensive, and thus unlikely to contribute to large-scale job creation. At the same time, AI applications can most readily replace low- to medium-skilled jobs within the organized sector. This is already being witnessed in the outsourcing sector – where basic call and chat tasks are now automated. Re-skilling will be important, but it is unlikely that those who lose their jobs will also be those who are being re-skilled – the long arch of technological change and societal adaptation is longer than that of people’s lives. The contractualization of work, already on the rise, is likely to further increase as large industries prefer to have a flexible workforce to adapt to technological change. A shift from formal employment to contractual work can imply a loss of access to formal social protection mechanisms, increasing the precariousness of work for workers. The adoption of AI technologies is also unlikely in the short- to medium-term in the unorganized sector, which engages more than 80 per cent of India’s labor force. The cost of developing and deploying AI applications, particularly in relation to the cost of labour, will inhibit adoption. Moreover, most enterprises within the unorganized sector still have limited access to basic, older technologies – two-thirds of the workforce are employed in enterprises without electricity. Eco-system upgrades will be important but incremental. Given the high costs of developing AI-based applications, most start-ups are unlikely to be working towards creating bottom-of-the-pyramid solutions. Access to AI-led technology gains is thus likely to be heavily differentiated – a few high-growth industries can be expected, but these will not necessarily result in the welfare of labour. Studies show that labour share of national income, especially routine labour, has been declining steadily across developing countries. We should be clear that new technological applications themselves are not going to transform or disrupt this trend – rather, without adequate policy steering, these trends will be exacerbated. Policy debates about AI applications in India need to take these two issues seriously. AI applications will not be a panacea for addressing ‘India’s grand challenges’. Data bias and unequal access to technology gains will entrench existing socio-economic fissures, even making them technologically binding. In addition to developing AI applications and creating a skilled workforce, the government needs to prioritize research that examines the complex social, ethical and governance challenges associated with the spread of AI-driven technologies. Blind technological optimism might entrench rather than alleviate the grand Indian challenge of inequity and growth. This article was originally published in the Indian Express. Full Article
gen Gender and equality By www.chathamhouse.org Published On :: Thu, 16 Jan 2020 13:23:41 +0000 Gender and equality Exploring empowerment in areas such as women’s rights, equality and discrimination, the sharing of unpaid work, and the role of gender in achieving the SDGs. nfaulds-adams… 16 January 2020 Many women are still excluded from economic decision-making within their own household, receive lower salaries than men, and work longer hours. They are also often excluded from the labour market, do not have access to finance, and are denied property rights. Wider areas of interest include examining the potential for foreign policies that prioritize gender equality, the physical, cultural and practical challenges to integrating women into close combat roles in the military, and the future of women in peace and security. Equality and diversity research work also examines why people from black and minority ethnic groups still do less well in terms of education and the jobs they do than people from other groups, and considers the rights of workers across the world. It is strongly linked with promoting human rights and freedoms, based on principles such as dignity and respect. Full Article
gen Rational group algebras of generalized strongly monomial groups: Primitive idempotents and units By www.ams.org Published On :: Mon, 21 Oct 2024 15:01 EDT Gurmeet K. Bakshi, Jyoti Garg and Gabriela Olteanu Math. Comp. 93 (), 3027-3058. Abstract, references and article information Full Article
gen Convergence, finiteness and periodicity of several new algorithms of ????-adic continued fractions By www.ams.org Published On :: Mon, 21 Oct 2024 15:01 EDT Zhaonan Wang and Yingpu Deng Math. Comp. 93 (), 2921-2942. Abstract, references and article information Full Article
gen Convergence analysis of Laguerre approximations for analytic functions By www.ams.org Published On :: Mon, 21 Oct 2024 15:01 EDT Haiyong Wang Math. Comp. 93 (), 2861-2884. Abstract, references and article information Full Article
gen Generalized Korn’s inequalities for piecewise ????¹ and ????² vector fields By www.ams.org Published On :: Mon, 21 Oct 2024 15:01 EDT David M. Williams and Qingguo Hong Math. Comp. 93 (), 2587-2609. Abstract, references and article information Full Article
gen Pinpointing How Genes Interact By www.ams.org Published On :: Thu, 21 Oct 2021 14:38:14 -0400 Lorin Crawford explains how he uses math to analyze interactions between genes. Your DNA (the biological instruction manual in all of your cells) contains a mind-boggling amount of information represented in roughly 20,000 genes that encode proteins, plus a similar number of genes with other functions. As the cost of analyzing an individual's DNA has plummeted, it has become possible to search the entire human genome for genetic variants that are associated with traits such as height or susceptibility to certain diseases. Sometimes, one gene has a straightforward impact on the trait. But in many cases, the effect of one gene variant depends on which variants of other genes are present, a phenomenon called "epistasis." Studying such interactions involves huge datasets encompassing the DNA of hundreds of thousands of people. Mathematically, that requires time-intensive calculations with massive matrices and a good working knowledge of statistics. Full Article
gen Corrigendum to “The Class Number one Problem for the Normal CM-fields of degree 32” By www.ams.org Published On :: Thu, 31 Oct 2024 16:22 EDT Soun-Hi Kwon Trans. Amer. Math. Soc. 377 (), 6021-6022. Abstract, references and article information Full Article