1,306 research outputs found

    Backward Induction Foundations of the Shapley Value

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    We present a noncooperative game model of coalitional bargaining, closely based on that of Gul (1989) but solvable by backward induction. In this game, Gul's condition of “value additivity” does not suffice to ensure the existence of a subgame perfect Nash equilibrium that supports the Shapley value, but a related condition—“no positive value-externalities”—does. Multiple equilibria can arise only in the event of ties, and with a mild restriction on tie-break rules these equilibria all support the Shapley value

    Genetic variants in ALDH1B1 and alcohol dependence risk in a British and Irish population: A bioinformatic and genetic study

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    Alcohol is metabolized in the liver via the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Polymorphisms in the genes encoding these enzymes, which are common in East Asian populations, can alter enzyme kinetics and hence the risk of alcohol dependence and its sequelae. One of the most important genetic variants, in this regards, is the single nucleotide polymorphism (SNP) rs671 in ALDH2, the gene encoding the primary acetaldehyde metabolizing enzyme ALDH2. However, the protective allele of rs671 is absent in most Europeans although ALDH1B1, which shares significant sequence homology with ALDH2, contains several, potentially functional, missense SNPs that do occur in European populations. The aims of this study were: (i) to use bioinformatic techniques to characterize the possible effects of selected variants in ALDH1B1 on protein structure and function; and, (ii) to genotype three missense and one stop-gain, protein-altering, non-synonymous SNPs in 1478 alcohol dependent cases and 1254 controls of matched British and Irish ancestry. No significant allelic associations were observed between the three missense SNPs and alcohol dependence risk. The minor allele frequency of rs142427338 (Gln378Ter) was higher in alcohol dependent cases than in controls (allelic P = 0.19, OR = 2.98, [0.62-14.37]) but as this SNP is very rare the study was likely underpowered to detect an association with alcohol dependence risk. This potential association will needs to be further evaluated in other large, independent European populations

    Drinking behaviour and rs738409:g in pnpla3 are associated with slower recovery of liver function following severe alcoholic hepatitis

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    Abstract PWE-079 published in Gut, vol 66, suppl 2 (July 2017), pages A166-A167

    The effect of clozapine on mRNA expression for genes encoding G protein-coupled receptors and the protein components of clathrin-mediated endocytosis.

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    Clathrin-mediated endocytosis (CME) is an intracellular trafficking mechanism for packaging cargo, including G protein-coupled receptors (GPCRs), into clathrin-coated vesicles (CCVs). The antipsychotic chlorpromazine inhibits CCV assembly of adaptor protein AP2 whereas clozapine increases serotonin2A receptor internalization. We hypothesized that clozapine alters the expression of CME genes modulating vesicle turnover and GPCR internalization

    Identification of rare nonsynonymous variants in SYNE1/CPG2 in bipolar affective disorder

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    Background: Bipolar affective disorder (BPD) is a severe mood disorder with a prevalence of ∼ 1.5% in the population. The pathogenesis of BPD is poorly understood; however, a strong heritable component has been identified. Previous genome-wide association studies have indicated a region on 6q25, coding for the SYNE1 gene, which increases disease susceptibility. SYNE1 encodes the synaptic nuclear envelope protein-1, nesprin-1. A brain-specific splice variant of SYNE1, CPG2 encoding candidate plasticity gene 2, has been identified. The intronic single-nucleotide polymorphism with the strongest genome-wide significant association in BPD, rs9371601, is present in both SYNE1 and CPG2. / Methods: We screened 937 BPD samples for genetic variation in SYNE1 exons 14–33, which covers the CPG2 region, using high-resolution melt analysis. In addition, we screened two regions of increased transcriptional activity, one of them proposed to be the CPG2 promoter region. / Results and Conclusion: We identified six nonsynonymous and six synonymous variants. We genotyped three rare nonsynonymous variants, rs374866393, rs148346599 and rs200629713, in a total of 1099 BPD samples and 1056 controls. Burden analysis of these rare variants did not show a significant association with BPD. However, nine patients are compound heterozygotes for variants in SYNE1/CPG2, suggesting that rare coding variants may contribute significantly towards the complex genetic architecture underlying BPD. Imputation analysis in our own wholegenome sequencing sample of 99 BPD individuals identified an additional eight risk variants in the CPG2 region of SYNE1

    Constitutional Validity of Zoning Under the Police Power

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    The City Beautiful Movement: Weeks/Gates Mills and the Rural Response

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    Steven McQuillin looks at the historic Gates Mills community and how its development was influenced by advancements in transportation and by the Gates Mills Improvement Society’s established principles. Abstract; originally published in Western Reserve Studies Symposium (11th:1996 : Cleveland, Ohio

    Cities of Ancient Greece

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