4 resultados para Atwood, Margaret, 1939-. The Penelopiad

em Boston University Digital Common


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BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS:We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate [greater than or equal to]80%, minor allele frequency [greater than or equal to]10%, Hardy-Weinberg test p [greater than or equal to] 0.001).RESULTS:In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value < 10-5). The two sets of SNPs were in high linkage disequilibrium (minimum r2 = 0.58). The top 30 SNPs for generalized estimating equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. CONCLUSION: Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging.

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This dissertation analyzes the theological and ethical convictions that led the people of the Plateau Vivarais-Lignon to shelter thousands of refugees between 1939 and 1945. It does so by examining the themes of narrative identity, hospitality, character formation, nonviolence, and the contextual witness of church tradition. Though a number of studies have been published about the rescue activity in this region of France during World War II, none have thoroughly analyzed the theological nature of this activity. Using the Plateau Vivarais-Lignon as a case study in theological ethics, the dissertation draws on historical sources as well as the work of contemporary theologians and ethicists to understand, interpret, and analyze the witness of this community. After situating its rescue and resistance work within the Huguenot narrative of persecution and exile, I examine the theological convictions of the Reformed pastor of Le Chambon-sur-Lignon, André Trocmé, who played a key role in making the Plateau a place of refuge during the Holocaust. The study highlights the importance of narrative in the actions of this community and discusses the relationship between narrative, character, and ethics. It then examines the nonviolent commitments of key leaders of the rescue effort, using this analysis as a springboard to engage in broader theological reflection about the ethics of nonviolence. After examining the radical hospitality practiced on the Plateau in light of biblical narratives and Reformed history, I investigate the counter-cultural nature of Christian hospitality. The study concludes by analyzing the nature and witness of the church in light of the legacy of the Plateau Vivarais-Lignon. The dissertation suggests that increased academic and ecclesial attention be given to the relationship between narrative and character, the counter-cultural shape of Christian hospitality, and the active nature of nonviolence. It presents an in-depth analysis of the theological and ethical convictions of the people of the Plateau Vivarais-Lignon, arguing that their witness has ongoing significance for communities of faith as they grapple with how to form disciples, relate to the wider society, welcome strangers, and communicate God's shalom in a world of violence.

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How does the brain make decisions? Speed and accuracy of perceptual decisions covary with certainty in the input, and correlate with the rate of evidence accumulation in parietal and frontal cortical "decision neurons." A biophysically realistic model of interactions within and between Retina/LGN and cortical areas V1, MT, MST, and LIP, gated by basal ganglia, simulates dynamic properties of decision-making in response to ambiguous visual motion stimuli used by Newsome, Shadlen, and colleagues in their neurophysiological experiments. The model clarifies how brain circuits that solve the aperture problem interact with a recurrent competitive network with self-normalizing choice properties to carry out probablistic decisions in real time. Some scientists claim that perception and decision-making can be described using Bayesian inference or related general statistical ideas, that estimate the optimal interpretation of the stimulus given priors and likelihoods. However, such concepts do not propose the neocortical mechanisms that enable perception, and make decisions. The present model explains behavioral and neurophysiological decision-making data without an appeal to Bayesian concepts and, unlike other existing models of these data, generates perceptual representations and choice dynamics in response to the experimental visual stimuli. Quantitative model simulations include the time course of LIP neuronal dynamics, as well as behavioral accuracy and reaction time properties, during both correct and error trials at different levels of input ambiguity in both fixed duration and reaction time tasks. Model MT/MST interactions compute the global direction of random dot motion stimuli, while model LIP computes the stochastic perceptual decision that leads to a saccadic eye movement.