1,234 research outputs found

    Computing Equilibria of Prediction Markets via Persuasion

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    We study the computation of equilibria in prediction markets in perhaps the most fundamental special case with two players and three trading opportunities. To do so, we show equivalence of prediction market equilibria with those of a simpler signaling game with commitment introduced by Kong and Schoenebeck (2018). We then extend their results by giving computationally efficient algorithms for additional parameter regimes. Our approach leverages a new connection between prediction markets and Bayesian persuasion, which also reveals interesting conceptual insights

    A Yersinia Effector with Enhanced Inhibitory Activity on the NF-κB Pathway Activates the NLRP3/ASC/Caspase-1 Inflammasome in Macrophages

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    A type III secretion system (T3SS) in pathogenic Yersinia species functions to translocate Yop effectors, which modulate cytokine production and regulate cell death in macrophages. Distinct pathways of T3SS-dependent cell death and caspase-1 activation occur in Yersinia-infected macrophages. One pathway of cell death and caspase-1 activation in macrophages requires the effector YopJ. YopJ is an acetyltransferase that inactivates MAPK kinases and IKKβ to cause TLR4-dependent apoptosis in naïve macrophages. A YopJ isoform in Y. pestis KIM (YopJKIM) has two amino acid substitutions, F177L and K206E, not present in YopJ proteins of Y. pseudotuberculosis and Y. pestis CO92. As compared to other YopJ isoforms, YopJKIM causes increased apoptosis, caspase-1 activation, and secretion of IL-1β in Yersinia-infected macrophages. The molecular basis for increased apoptosis and activation of caspase-1 by YopJKIM in Yersinia-infected macrophages was studied. Site directed mutagenesis showed that the F177L and K206E substitutions in YopJKIM were important for enhanced apoptosis, caspase-1 activation, and IL-1β secretion. As compared to YopJCO92, YopJKIM displayed an enhanced capacity to inhibit phosphorylation of IκB-α in macrophages and to bind IKKβ in vitro. YopJKIM also showed a moderately increased ability to inhibit phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1β secretion occurred in IKKβ-deficient macrophages infected with Y. pestis expressing YopJCO92, confirming that the NF-κB pathway can negatively regulate inflammasome activation. K+ efflux, NLRP3 and ASC were important for secretion of IL-1β in response to Y. pestis KIM infection as shown using macrophages lacking inflammasome components or by the addition of exogenous KCl. These data show that caspase-1 is activated in naïve macrophages in response to infection with a pathogen that inhibits IKKβ and MAPK kinases and induces TLR4-dependent apoptosis. This pro-inflammatory form of apoptosis may represent an early innate immune response to highly virulent pathogens such as Y. pestis KIM that have evolved an enhanced ability to inhibit host signaling pathways

    Neural Network Parameterizations of Electromagnetic Nucleon Form Factors

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    The electromagnetic nucleon form-factors data are studied with artificial feed forward neural networks. As a result the unbiased model-independent form-factor parametrizations are evaluated together with uncertainties. The Bayesian approach for the neural networks is adapted for chi2 error-like function and applied to the data analysis. The sequence of the feed forward neural networks with one hidden layer of units is considered. The given neural network represents a particular form-factor parametrization. The so-called evidence (the measure of how much the data favor given statistical model) is computed with the Bayesian framework and it is used to determine the best form factor parametrization.Comment: The revised version is divided into 4 sections. The discussion of the prior assumptions is added. The manuscript contains 4 new figures and 2 new tables (32 pages, 15 figures, 2 tables

    Photonics and fracture toughness of heterogeneous composite materials

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    Fracture toughness measures the resistance of a material to fracture. This fundamental property is used in diverse engineering designs including mechanical, civil, materials, electronics and chemical engineering applications. In spite of the advancements made in the past 40 years, the evaluation of this remains challenging for extremely heterogeneous materials such as composite concretes. By taking advantage of the optical properties of a thin birefringent coating on the surface of opaque, notched composite concrete beams, here we sense the evolution of the maximum shear stress distribution on the beams under loading. The location of the maximum deviator stress is tracked ahead of the crack tip on the experimental concrete samples under the ultimate load, and hence the effective crack length is characterised. Using this, the fracture toughness of a number of heterogeneous composite beams is evaluated and the results compare favourably well with other conventional methods using combined experimental and numerical/analytical approaches. Finally a new model, correlating the optically measured shear stress concentration factor and flexural strength with the fracture toughness of concretes is proposed. The current photonics-based study could be vital in evaluating the fracture toughness of even opaque and complex heterogeneous materials more effectively in future

    Phenotyping progenies for complex architectural traits: a strategy for 1-year-old apple trees (Malus x domestica Borkh.)

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    International audienceThe aim of this study was to define a methodology for describing architectural traits in a quantitative way on tree descendants. Our strategy was to collect traits related to both tree structural organization, resulting from growth and branching, and tree form and then to select among these traits relevant descriptors on the basis of their genetic parameters. Because the complexity of tree architecture increases with tree age, we chose to describe the trees in the early stages of development. The study was carried out on a 1-year-old apple progeny derived from two parent cultivars with contrasted architecture. A large number of variables were collected at different positions and scales within the trees. Broad-sense heritability and genetic correlations were estimated and the within tree variability was analyzed for variables measured on long sylleptic axillary shoots (LSAS). These results were combined to select heritable and not correlated variables. Finally, the selection of variables proposed combines topological with geometric traits measured on both trunks and LSAS: (1) on the trunk, mean internode length, and number of sylleptic axillary shoots; (2) on axillary shoots, conicity, bending, and number of sylleptic axillary shoots born at order 3. The trees of the progeny were partitioned on the basis of these variables. The putative agronomic interest of the selected variables with respect to the subsequent tree development is discussed

    The extraordinary evolutionary history of the reticuloendotheliosis viruses

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    The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

    Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach

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    BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made

    Direct Interaction of Endogenous Kv Channels with Syntaxin Enhances Exocytosis by Neuroendocrine Cells

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    K+ efflux through voltage-gated K+ (Kv) channels can attenuate the release of neurotransmitters, neuropeptides and hormones by hyperpolarizing the membrane potential and attenuating Ca2+ influx. Notably, direct interaction between Kv2.1 channels overexpressed in PC12 cells and syntaxin has recently been shown to facilitate dense core vesicle (DCV)-mediated release. Here, we focus on endogenous Kv2.1 channels and show that disruption of their interaction with native syntaxin after ATP-dependent priming of the vesicles by Kv2.1 syntaxin–binding peptides inhibits Ca2+ -triggered exocytosis of DCVs from cracked PC12 cells in a specific and dose-dependent manner. The inhibition cannot simply be explained by the impairment of the interaction of syntaxin with its SNARE cognates. Thus, direct association between endogenous Kv2.1 and syntaxin enhances exocytosis and in combination with the Kv2.1 inhibitory effect to hyperpolarize the membrane potential, could contribute to the known activity dependence of DCV release in neuroendocrine cells and in dendrites where Kv2.1 commonly expresses and influences release

    An approach to classifying human resources constraints to attaining health-related Millennium Development Goals

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    BACKGROUND: For any wide-ranging effort to scale up health-related priority interventions, human resources for health (HRH) are likely to be a key to success. This study explores constraints related to human resources in the health sector for achieving the Millennium Development Goals (MDGs) in low-income countries. METHODS AND FRAMEWORK: The analysis drew on information from a variety of publicly-available sources and principally on data presented in published papers in peer-reviewed journals. For classifying HRH constraints an analytical framework was used that considers constraints at five levels: individual characteristics, the health service delivery level, the health sector level, training capacities and the sociopolitical and economic context of a country. RESULTS AND DISCUSSION: At individual level, the decision to enter, remain and serve in the health sector workforce is influenced by a series of social, economic, cultural and gender-related determinants. For example, to cover the health needs of the poorest it is necessary to employ personnel with specific social, ethnic and cultural characteristics. At health-service level, the commitment of health staff is determined by a number of organizational and management factors. The workplace environment has a great impact not only on health worker performance, but also on the comprehensiveness and efficiency of health service delivery. At health-sector level, the use of monetary and nonmonetary incentives is of crucial importance for having the accurate skill mix at the appropriate place. Scaling up of priority interventions is likely to require significant investments in initial and continuous training. Given the lead time required to produce new health workers, such investments must occur in the early phases of scaling up. At the same time coherent national HRH policies are required for giving direction on HRH development and linking HRH into health-sector reform issues, the scaling-up of priority interventions, poverty reduction strategies, and training approaches. Multisectoral collaboration and the sociopolitical and economic context of a country determine health sector workforce development and potential emigration. CONCLUSIONS: Key determinants of success for achieving international development goals are closely related to human-resource development
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