Stanford University

About: Stanford University is a education organization based out in Stanford, California, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 125751 authors who have published 320347 publications receiving 21892059 citations. The organization is also known as: Leland Stanford Junior University & University of Stanford.

The Relative Power of Family-Based and Case-Control Designs for Linkage Disequilibrium Studies of Complex Human Diseases I. DNA Pooling

Abstract: We consider statistics for analyzing a variety of family-based and nonfamily-based designs for detecting linkage disequilibrium of a marker with a disease susceptibility locus. These designs include sibships with parents, sibships without parents, and use of unrelated controls. We also provide formulas for and evaluate the relative power of different study designs using these statistics. In this first paper in the series, we derive statistical tests based on data derived from DNA pooling experiments and describe their characteristics. Although designs based on affected and unaffected sibs without parents are usually robust to population stratification, they suffer a loss of power compared with designs using parents or unrelateds as controls. Although increasing the number of unaffected sibs improves power, the increase is generally not substantial. Designs including sibships with multiple affected sibs are typically the most powerful, with any of these control groups, when the disease allele frequency is low. When the allele frequency is high, however, designs with unaffected sibs as controls do not retain this advantage. In designs with parents, having an affected parent has little impact on the power, except for rare dominant alleles, where the power is increased compared with families with no affected parents. Finally, we also demonstrate that for sibships with parents, only the parents require individual genotyping to derive the TDT statistic, whereas all the offspring can be pooled. This can potentially lead to considerable savings in genotyping, especially for multiplex sibships. The formulas and tables we derive should provide some guidance to investigators designing nuclear family-based linkage disequilibrium studies for complex diseases.

Cloud-based simulations on Google Exacycle reveal ligand modulation of GPCR activation pathways

Abstract: Simulations can provide tremendous insight into the atomistic details of biological mechanisms, but micro- to millisecond timescales are historically only accessible on dedicated supercomputers. We demonstrate that cloud computing is a viable alternative that brings long-timescale processes within reach of a broader community. We used Google's Exacycle cloud-computing platform to simulate two milliseconds of dynamics of a major drug target, the G-protein-coupled receptor β2AR. Markov state models aggregate independent simulations into a single statistical model that is validated by previous computational and experimental results. Moreover, our models provide an atomistic description of the activation of a G-protein-coupled receptor and reveal multiple activation pathways. Agonists and inverse agonists interact differentially with these pathways, with profound implications for drug design.

Control of combustion-generated nitrogen oxide emissions: Technology driven by regulation

Abstract: Nitrogen oxides in the atmosphere contribute to photochemical smog, to the formation of acid rain precursors, to the destruction of ozone in the stratosphere and to global warming. Over the past 150 years, global emissions of nitrogen oxides into the atmosphere have been increasing steadily. A significant amount of the nitrogen oxide emissions is attributed to combustion of biomass and fossil fuels. Increasingly stringent NOx emissions regulations are being implemented in a number of industrialized countries. These regulations have driven and continue to drive the development of NOx emissions control techniques. This paper reviews existing and some emerging technologies for reduction of NOx emissions from combustion sources and examines the prospects of these technologies for meeting stricter emissions regulations. Both combustion modification and post-combustion methods for NOx reduction are considered. The important role of research on the chemistry of nitrogen oxides in combustion gases in development and optimization of emissions control techniques is described.