342 research outputs found

    The Economics of Small Worlds

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    We examine a simple economic model of network formation where agents benefit from indirect relationships. We show that small-world features—short path lengths between nodes together with highly clustered link structures—necessarily emerge for a wide set of parameters

    The Economics of Small Worlds

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    We examine a simple economic model of network formation where agents benefit from indirect relationships. We show that small-world features - -- short path lengths between nodes together with highly clustered link structures --- necessarily emerge for a wide set of parameters.networks, small worlds

    Homophily and Long-Run Integration in Social Networks

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    We model network formation when heterogeneous nodes enter sequentially and form connections through both random meetings and network-based search, but with type-dependent biases. We show that there is "long-run integration," whereby the composition of types in sufficiently old nodes' neighborhoods approaches the global type distribution, provided that the network-based search is unbiased. However, younger nodes' connections still reflect the biased meetings process. We derive the type-based degree distributions and group-level homophily patterns when there are two types and location-based biases. Finally, we illustrate aspects of the model with an empirical application to data on citations in physics journals.Comment: 39 pages, 2 figure

    GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome

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    Time-resolved ChIP-chip can be utilized to monitor the genome-wide dynamics of the GINS complex, yielding quantitative information on replication fork movement.Replication forks progress at remarkably uniform rates across the genome, regardless of location.GINS progression appears to be arrested, albeit with very low frequency, at sites of highly transcribed genes.Comparison of simulation with data leads to novel biological insights regarding the dynamics of replication fork progressio

    Epithelial NAD+ depletion drives mitochondrial dysfunction and contributes to intestinal inflammation

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    IntroductionWe have previously demonstrated that a pathologic downregulation of peroxisome proliferator-activated receptor–gamma coactivator 1-alpha (PGC1α) within the intestinal epithelium contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism underlying downregulation of PGC1α expression and activity during IBD is not yet clear.MethodsMice (male; C57Bl/6, Villincre/+;Pgc1afl/fl mice, and Pgc1afl/fl) were subjected to experimental colitis and treated with nicotinamide riboside. Western blot, high-resolution respirometry, nicotinamide adenine dinucleotide (NAD+) quantification, and immunoprecipitation were used to in this study.ResultsWe demonstrate a significant depletion in the NAD+ levels within the intestinal epithelium of mice undergoing experimental colitis, as well as humans with ulcerative colitis. While we found no decrease in the levels of NAD+-synthesizing enzymes within the intestinal epithelium of mice undergoing experimental colitis, we did find an increase in the mRNA level, as well as the enzymatic activity, of the NAD+-consuming enzyme poly(ADP-ribose) polymerase-1 (PARP1). Treatment of mice undergoing experimental colitis with an NAD+ precursor reduced the severity of colitis, restored mitochondrial function, and increased active PGC1α levels; however, NAD+ repletion did not benefit transgenic mice that lack PGC1α within the intestinal epithelium, suggesting that the therapeutic effects require an intact PGC1α axis.DiscussionOur results emphasize the importance of PGC1α expression to both mitochondrial health and homeostasis within the intestinal epithelium and suggest a novel therapeutic approach for disease management. These findings also provide a mechanistic basis for clinical trials of nicotinamide riboside in IBD patients

    GeneDB--an annotation database for pathogens.

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    GeneDB (http://www.genedb.org) is a genome database for prokaryotic and eukaryotic pathogens and closely related organisms. The resource provides a portal to genome sequence and annotation data, which is primarily generated by the Pathogen Genomics group at the Wellcome Trust Sanger Institute. It combines data from completed and ongoing genome projects with curated annotation, which is readily accessible from a web based resource. The development of the database in recent years has focused on providing database-driven annotation tools and pipelines, as well as catering for increasingly frequent assembly updates. The website has been significantly redesigned to take advantage of current web technologies, and improve usability. The current release stores 41 data sets, of which 17 are manually curated and maintained by biologists, who review and incorporate data from the scientific literature, as well as other sources. GeneDB is primarily a production and annotation database for the genomes of predominantly pathogenic organisms

    The American Association for the Surgery of Trauma renal injury grading scale: Implications of the 2018 revisions for injury reclassification and predicting bleeding interventions.

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    BackgroundIn 2018, the American Association for the Surgery of Trauma (AAST) published revisions to the renal injury grading system to reflect the increased reliance on computed tomography scans and non-operative management of high-grade renal trauma (HGRT). We aimed to evaluate how these revisions will change the grading of HGRT and if it outperforms the original 1989 grading in predicting bleeding control interventions.MethodsData on HGRT were collected from 14 Level-1 trauma centers from 2014 to 2017. Patients with initial computed tomography scans were included. Two radiologists reviewed the scans to regrade the injuries according to the 1989 and 2018 AAST grading systems. Descriptive statistics were used to assess grade reclassifications. Mixed-effect multivariable logistic regression was used to measure the predictive ability of each grading system. The areas under the curves were compared.ResultsOf the 322 injuries included, 27.0% were upgraded, 3.4% were downgraded, and 69.5% remained unchanged. Of the injuries graded as III or lower using the 1989 AAST, 33.5% were upgraded to grade IV using the 2018 AAST. Of the grade V injuries, 58.8% were downgraded using the 2018 AAST. There was no statistically significant difference in the overall areas under the curves between the 2018 and 1989 AAST grading system for predicting bleeding interventions (0.72 vs. 0.68, p = 0.34).ConclusionAbout one third of the injuries previously classified as grade III will be upgraded to grade IV using the 2018 AAST, which adds to the heterogeneity of grade IV injuries. Although the 2018 AAST grading provides more anatomic details on injury patterns and includes important radiologic findings, it did not outperform the 1989 AAST grading in predicting bleeding interventions.Level of evidencePrognostic and Epidemiological Study, level III

    The Economic Consequences of Social-Network Structure

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    We survey the literature on the economic consequences of the structure of social networks. We develop a taxonomy of "macro" and "micro" characteristics of social-interaction networks and discuss both the theoretical and empirical findings concerning the role of those characteristics in determining learning, diffusion, decisions, and resulting behaviors. We also discuss the challenges of accounting for the endogeneity of networks in assessing the relationship between the patterns of interactions and behaviors

    Cooperation in anonymous dynamic social networks

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    Abstract We study the extent to which cooperative behavior can be sustained in large, anonymous, evolving social networks. Individuals strategically form relationships under a social matching protocol and engage in prisoner's dilemma interactions with their partners. We characterize a class of equilibria that support cooperation as a stationary outcome. When cooperation is possible, its level is uniquely determined. While neither community enforcement nor contagion mechanisms have force in our setting, the endogenous dynamics of the social network imply that cooperation allows an individual to gradually accumulate a large network of profitable interactions, while defection results in social marginalization. Even as players become perfectly patient, equilibrium allows for full cooperation, only autarky, or the coexistence of cooperation and defection, depending on payoffs. Smaller levels of cooperation can be sustained by a form of exclusivity among cooperators. * We than
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