Predicting functionally important SNP classes based on negative selection

<p>Abstract</p> <p>Background</p> <p>With the advent of cost-effective genotyping technologies, genome-wide association studies allow researchers to examine hundreds of thousands of single nucleotide polymorphisms (SNPs) for association with human disease. Recently, many researchers applying this strategy have detected strong associations to disease with SNP markers that are either not in linkage disequilibrium with any nonsynonymous SNP or large distances from any annotated gene. In such cases, no well-established standard practice for effective SNP selection for follow-up studies exists. We aim to identify and prioritize groups of SNPs that are more likely to affect phenotypes in order to facilitate efficient SNP selection for follow-up studies.</p> <p>Results</p> <p>Based on the annotations available in the Ensembl database, we categorized SNPs in the human genome into classes related to regulatory attributes, such as epigenetic modifications and transcription factor binding sites, in addition to classes related to gene structure and cross-species conservation. Using the distribution of derived allele frequencies (DAF) within each class, we assessed the strength of natural selection for each class relative to the genome as a whole. We applied this DAF analysis to Perlegen resequenced SNPs genome-wide. Regulatory elements annotated by Ensembl such as specific histone methylation sites as well as classes defined by cross-species conservation showed negative selection in comparison to the genome as a whole.</p> <p>Conclusions</p> <p>These results highlight which annotated classes are under purifying selection, have putative functional importance, and contain SNPs that are strong candidates for follow-up studies after genome-wide association. Such SNP annotation may also be useful in interpreting results of whole-genome sequencing studies.</p

Proposition 8: California Law after In re Lance W. and People v. Castro

Until recently, California provided a relatively high level of constitutional protection to criminal defendants. With the passage of Proposition 8 in 1982, the California voters expressed their desire to decrease this level of protection in order to remove impediments to the effective prosecution of criminally accuseds. This comment will examine two of the major provisions of Proposition 8 and their effect on California law in light of major cases decided by the California Supreme Court in 1985

How Protostellar Outflows Help Massive Stars Form

We consider the effects of an outflow on radiation escaping from the infalling envelope around a massive protostar. Using numerical radiative transfer calculations, we show that outflows with properties comparable to those observed around massive stars lead to significant anisotropy in the stellar radiation field, which greatly reduces the radiation pressure experienced by gas in the infalling envelope. This means that radiation pressure is a much less significant barrier to massive star formation than has previously been thought.Comment: 4 pages, 2 figures, emulateapj, accepted for publication in ApJ Letter

A study of the effects of micro-gravity on seed germination

This study will identify characteristics of seed germination dependent upon gravity. To accomplish this objective, four different seed types will be germinated in space and then be compared to a control group germinated on Earth. Both the experimental and control groups will be analyzed on the cellular level for the size of cells, structural anomalies, and gravitational effects. The experiment will be conducted in a Get Away Special Canister (GAS Can no. 608) owned by the U.S. Space and Rocket Center and designed for students. The GAS Can will remain in the cargo bay of the Space Shuttle with minimal astronaut interaction

Why Should We Care About CARE-HF?

Previous trials of cardiac resynchronization therapy (CRT) have suggested that this therapy can significantly improve functional class and exercise capacity during short-term follow-up. The impact of this therapy on morbidity and mortality has only recently been reported. The Cardiac Resynchronization-Heart Failure (CARE-HF) study has definitively shown that CRT significantly reduces mortality (36%, p < 0.002) in patients with NYHA functional class III and IV heart failure and ventricular dyssynchrony. This study also shows that CRT reverses ventricular remodeling and improves myocardial performance progressively for at least 18 months. In heart failure patients, the CARE-HF and Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) (the earlier major morbidity/mortality trial) studies together show the unequivocal benefit for CRT therapy and CRT therapy with back-up defibrillation to significantly reduce mortality and hospitalization compared with optimal medical therapy. Both studies suggest the benefit of adding the implantable cardiac defibrillator to CRT devices, as over one-third of deaths in the CRT-pacemaker arm of both the COMPANION and CARE-HF studies were sudden

Molecular Line Emission from Massive Protostellar Disks: Predictions for ALMA and the EVLA

We compute the molecular line emission of massive protostellar disks by solving the equation of radiative transfer through the cores and disks produced by the recent radiation-hydrodynamic simulations of Krumholz, Klein, & McKee. We find that in several representative lines the disks show brightness temperatures of hundreds of Kelvin over velocity channels ~10 km s^-1 wide, extending over regions hundreds of AU in size. We process the computed intensities to model the performance of next-generation radio and submillimeter telescopes. Our calculations show that observations using facilities such as the EVLA and ALMA should be able to detect massive protostellar disks and measure their rotation curves, at least in the nearest massive star-forming regions. They should also detect significant sub-structure and non-axisymmetry in the disks, and in some cases may be able to detect star-disk velocity offsets of a few km s^-1, both of which are the result of strong gravitational instability in massive disks. We use our simulations to explore the strengths and weaknesses of different observational techniques, and we also discuss how observations of massive protostellar disks may be used to distinguish between alternative models of massive star formation.Comment: 15 pages, 9 figures, emulateapj format, accepted for publication in ApJ. Resolution of figures severely degraded to fit within size limits. Download the full paper from http://www.astro.princeton.edu/~krumholz/recent.htm

Designing for Incentives: Better Information Sharing for Better Software Engineering

Software-reliant systems permeate all aspects of modern society. The resulting interconnectedness and associated com- plexity has resulted in a proliferation of diverse stakeholders with conflicting goals. Thus, contemporary software engi- neering is plagued by incentive conflicts, in settling on design features, allocating resources during the development of products, and allocating computational resources at run- time. In this position paper, we describe some of these problems and outline a research agenda in bridging to the economic theory of mechanism design, which seeks to align incentives in multi-agent systems with private information and conflicting goals. The ultimate goal is to advance a principled methodology for the design of incentive-compatible approaches to manage the dynamic processes of software engineering.Engineering and Applied Science