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We explore the ability of a simple simulated annealing procedure to assemble native-like structures from fragments of unrelated protein structures with similar local sequences using Bayesian scoring functions. Environment and residue pair specific contributions to the scoring functions appear as the first two terms in a series expansion for the residue(More)
CONTEXT Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN Estrogen plus progestin component of the Women's(More)
CONTEXT The Women's Health Initiative (WHI) trial of estrogen plus progestin was stopped early because of adverse effects, including an increased risk of stroke in the estrogen plus progestin group. OBJECTIVE To assess the effect of estrogen plus progestin on ischemic and hemorrhagic stroke and in subgroups, and to determine whether the effect of estrogen(More)
Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls(More)
ANOVA type models are considered for a regression function or for the logarithm of a probability function, conditional probability function, density function, conditional density function, hazard function, conditional hazard function, or spectral density function. Polynomial splines are used to model the main eeects, and their tensor products are used to(More)
Interactions are frequently at the center of interest in single-nucleotide polymorphism (SNP) association studies. When interacting SNPs are in the same gene or in genes that are close in sequence, such interactions may suggest which haplotypes are associated with a disease. Interactions between unrelated SNPs may suggest genetic pathways. Unfortunately,(More)
Polynomial splines and their tensor products are used to estimate the conditional log-hazard function based on possibly censored, positive response data and one or more covariates. An automatic procedure involving the maximum likelihood method, stepwise addition, stepwise deletion and BIC is used to select the nal model. The possible models contain(More)
In this paper we investigate the power to identify gene x gene interactions in genome-wide association studies. In our analysis we focus on two-stage analyses: analyses in which we only test for interactions between single nucleotide polymorphisms that show some marginal effect. We give two algorithms to compute significance levels for such an analyses. One(More)
Previous analyses of gene expression in a mouse model of Huntington's disease (R6/2) indicated that an N-terminal fragment of mutant huntingtin causes downregulation of striatal signaling genes and particularly those normally induced by cAMP and retinoic acid. The present study expands the regional and temporal scope of this previous work by assessing(More)