466,601 research outputs found

    Genome-wide association studies of the self-rating of effects of ethanol (SRE).

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    The level of response (LR) to alcohol as measured with the Self-Report of the Effects of Alcohol Retrospective Questionnaire (SRE) evaluates the number of standard drinks usually required for up to four effects. The need for a higher number of drinks for effects is genetically influenced and predicts higher risks for heavy drinking and alcohol problems. We conducted genome-wide association study (GWAS) in the African-American (COGA-AA, N = 1527 from 309 families) and European-American (COGA-EA, N = 4723 from 956 families) subsamples of the Collaborative Studies on the Genetics of Alcoholism (COGA) for two SRE scores: SRE-T (average of first five times of drinking, the period of heaviest drinking, and the most recent 3 months of consumption) and SRE-5 (the first five times of drinking). We then meta-analyzed the two COGA subsamples (COGA-AA + EA). Both SRE-T and SRE-5 were modestly heritable (h2 : 21%-31%) and genetically correlated with alcohol dependence (AD) and DSM-IV AD criterion count (rg : 0.35-0.76). Genome-wide significant associations were observed (SRE-T: chromosomes 6, rs140154945, COGA-EA P = 3.30E-08 and 11, rs10647170, COGA-AA+EA P = 3.53E-09; SRE-5: chromosome13, rs4770359, COGA-AA P = 2.92E-08). Chromosome 11 was replicated in an EA dataset from the National Institute on Alcohol Abuse and Alcoholism intramural program. In silico functional analyses and RNA expression analyses suggest that the chromosome 6 locus is an eQTL for KIF25. Polygenic risk scores derived using the COGA SRE-T and SRE-5 GWAS predicted 0.47% to 2.48% of variances in AD and DSM-IV AD criterion count in independent datasets. This study highlights the genetic contribution of alcohol response phenotypes to the etiology of alcohol use disorders

    D-modules on Smooth Toric Varieties

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    Let X be a smooth toric variety. David Cox introduced the homogeneous coordinate ring S of X and its irrelevant ideal B. Extending well-known results on projective space, Cox established the following: (1) the category of quasi-coherent sheaves on X is equivalent to the category of graded S-modules modulo B-torsion, (2) the variety X is a geometric quotient of Spec(S) V(B) by a suitable torus action. We provide the D-module version of these results. More specifically, let A denote the ring of differential operators on Spec(S). We show that the category of D-modules on X is equivalent to a subcategory of graded A-modules modulo B-torsion. Additionally, we prove that the characteristic variety of a D-module is a geometric quotient of an open subset of the characteristic variety of the associated A-module and that holonomic D-modules correspond to holonomic A-modules.Comment: AMS-LaTeX, 28 page

    Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute intra-axonal amyloid-β accumulation and independently accelerates the development of tau abnormalities

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    Alzheimer\u27s disease (AD) is a neurodegenerative disorder characterized pathologically by progressive neuronal loss, extracellular plaques containing the amyloid-β (Aβ) peptides, and neurofibrillary tangles composed of hyperphosphorylated tau proteins. Aβ is thought to act upstream of tau, affecting its phosphorylation and therefore aggregation state. One of the major risk factors for AD is traumatic brain injury (TBI). Acute intra-axonal Aβ and diffuse extracellular plaques occur in ∼30% of human subjects after severe TBI. Intra-axonal accumulations of tau but not tangle-like pathologies have also been found in these patients. Whether and how these acute accumulations contribute to subsequent AD development is not known, and the interaction between Aβ and tau in the setting of TBI has not been investigated. Here, we report that controlled cortical impact TBI in 3xTg-AD mice resulted in intra-axonal Aβ accumulations and increased phospho-tau immunoreactivity at 24 h and up to 7 d after TBI. Given these findings, we investigated the relationship between Aβ and tau pathologies after trauma in this model by systemic treatment of Compound E to inhibit γ-secretase activity, a proteolytic process required for Aβ production. Compound E treatment successfully blocked posttraumatic Aβ accumulation in these injured mice at both time points. However, tau pathology was not affected. Our data support a causal role for TBI in acceleration of AD-related pathologies and suggest that TBI may independently affect Aβ and tau abnormalities. Future studies will be required to assess the behavioral and long-term neurodegenerative consequences of these pathologies

    The quantum capacity with symmetric side channels

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    We present an upper bound for the quantum channel capacity that is both additive and convex. Our bound can be interpreted as the capacity of a channel for high-fidelity quantum communication when assisted by a family of channels that have no capacity on their own. This family of assistance channels, which we call symmetric side channels, consists of all channels mapping symmetrically to their output and environment. The bound seems to be quite tight, and for degradable quantum channels it coincides with the unassisted channel capacity. Using this symmetric side channel capacity, we find new upper bounds on the capacity of the depolarizing channel. We also briefly indicate an analogous notion for distilling entanglement using the same class of (one-way) channels, yielding one of the few entanglement measures that is monotonic under local operations with one-way classical communication (1-LOCC), but not under the more general class of local operations with classical communication (LOCC).Comment: 10 pages, 4 figure

    Pairwise alignment incorporating dipeptide covariation

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    Motivation: Standard algorithms for pairwise protein sequence alignment make the simplifying assumption that amino acid substitutions at neighboring sites are uncorrelated. This assumption allows implementation of fast algorithms for pairwise sequence alignment, but it ignores information that could conceivably increase the power of remote homolog detection. We examine the validity of this assumption by constructing extended substitution matrixes that encapsulate the observed correlations between neighboring sites, by developing an efficient and rigorous algorithm for pairwise protein sequence alignment that incorporates these local substitution correlations, and by assessing the ability of this algorithm to detect remote homologies. Results: Our analysis indicates that local correlations between substitutions are not strong on the average. Furthermore, incorporating local substitution correlations into pairwise alignment did not lead to a statistically significant improvement in remote homology detection. Therefore, the standard assumption that individual residues within protein sequences evolve independently of neighboring positions appears to be an efficient and appropriate approximation

    The effect of nanocoatings enriched with essential oils on ‘Rocha’ pear long storage

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    The effect of coating 'Rocha' pears with alginate-based nanoemulsions enriched with lemongrass essential oil (LG) or citral (Cit) was investigated. Fruit were treated with the nanoemulsions: sodium alginate 2% (w/w) + citral 1% (w/w) (Cit1%); sodium alginate 2% (w/w) + citral 2% (w/w) (Cit2%); sodium alginate 2% (w/w) + lemongrass 1.25% (w/w) (LG1.25%); sodium alginate 2% (w/w) + lemongrass 2.5% (w/w) (LG2.5%). Then, fruit were stored at 0 °C and at 95% relative humidity, for six months. Fruit samples were taken after two, four and six months, and then placed at 22 °C. Upon removal and after 7 d shelf-life, fruit were evaluated for colour CIE (L*, h◦), firmness, soluble solids content (SSC), titratable acidity (TA), weight loss, electrolytic leakage, microbial growth, symptoms of superficial scald and internal browning. All nanoemulsions had droplets in the nano range <500 nm, showed uniformity of particle size and stable dispersion. Cit-nanoemulsions had lower droplet size and higher stability than LG. No nanoemulsion showed cytotoxicity. Coatings reduced fruit colour evolution and preserved better firmness than control. After shelf-life, better firmness was found in LG-coated fruit. Coatings did not affect SSC and TA. Microbial growth was below the safety limits in all treatments. Fruit treated with LG-nanoemulsions did not show scald symptoms and panelists preferred LG1.25% coated fruit. Cit2% treated fruit showed the highest scald and internal browning symptoms, while LG1.25% did not show any disorders. This study suggests that LG-nanocoatings have the potential for preserving the quality of 'Rocha' pear.FCT (SFRH/BPD/108831/2015); UID/BIA/04325/2019/ UID/Multi/00631/2019/ UID/AMB/50017/2019info:eu-repo/semantics/publishedVersio

    On computing explanations in argumentation

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    Copyright © 2015, Association for the Advancement of Artificial Intelligence (www.aaai.org). All rights reserved.Argumentation can be viewed as a process of generating explanations. However, existing argumentation semantics are developed for identifying acceptable arguments within a set, rather than giving concrete justifications for them. In this work, we propose a new argumentation semantics, related admissibility, designed for giving explanations to arguments in both Abstract Argumentation and Assumption-based Argumentation. We identify different types of explanations defined in terms of the new semantics. We also give a correct computational counterpart for explanations using dispute forests
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