A renormalization approach for the 2D Anderson model at the band edge: Scaling of the localization volume

We study the localization volumes $V$ (participation ratio) of electronic wave functions in the 2d-Anderson model with diagonal disorder. Using a renormalization procedure, we show that at the band edges, i.e. for energies $E\approx \pm 4$, $V$ is inversely proportional to the variance \var of the site potentials. Using scaling arguments, we show that in the neighborhood of $E=\pm 4$, $V$ scales as V=\var^{-1}g((4-\ve E\ve)/\var) with the scaling function $g(x)$. Numerical simulations confirm this scaling ansatz

M-BISON: Microarray-based integration of data sources using networks

BACKGROUND: The accurate detection of differentially expressed (DE) genes has become a central task in microarray analysis. Unfortunately, the noise level and experimental variability of microarrays can be limiting. While a number of existing methods partially overcome these limitations by incorporating biological knowledge in the form of gene groups, these methods sacrifice gene-level resolution. This loss of precision can be inappropriate, especially if the desired output is a ranked list of individual genes. To address this shortcoming, we developed M-BISON (Microarray-Based Integration of data SOurces using Networks), a formal probabilistic model that integrates background biological knowledge with microarray data to predict individual DE genes. RESULTS: M-BISON improves signal detection on a range of simulated data, particularly when using very noisy microarray data. We also applied the method to the task of predicting heat shock-related differentially expressed genes in S. cerevisiae, using an hsf1 mutant microarray dataset and conserved yeast DNA sequence motifs. Our results demonstrate that M-BISON improves the analysis quality and makes predictions that are easy to interpret in concert with incorporated knowledge. Specifically, M-BISON increases the AUC of DE gene prediction from .541 to .623 when compared to a method using only microarray data, and M-BISON outperforms a related method, GeneRank. Furthermore, by analyzing M-BISON predictions in the context of the background knowledge, we identified YHR124W as a potentially novel player in the yeast heat shock response. CONCLUSION: This work provides a solid foundation for the principled integration of imperfect biological knowledge with gene expression data and other high-throughput data sources

Medication decision-making for patients with renal insufficiency in inpatient and outpatient care at a US Veterans Affairs Medical Centre: a qualitative, cognitive task analysis.

BackgroundMany studies identify factors that contribute to renal prescribing errors, but few examine how healthcare professionals (HCPs) detect and recover from an error or potential patient safety concern. Knowledge of this information could inform advanced error detection systems and decision support tools that help prevent prescribing errors.ObjectiveTo examine the cognitive strategies that HCPs used to recognise and manage medication-related problems for patients with renal insufficiency.DesignHCPs submitted documentation about medication-related incidents. We then conducted cognitive task analysis interviews. Qualitative data were analysed inductively.SettingInpatient and outpatient facilities at a major US Veterans Affairs Medical Centre.ParticipantsPhysicians, nurses and pharmacists who took action to prevent or resolve a renal-drug problem in patients with renal insufficiency.OutcomesEmergent themes from interviews, as related to recognition of renal-drug problems and decision-making processes.ResultsWe interviewed 20 HCPs. Results yielded a descriptive model of the decision-making process, comprised of three main stages: detect, gather information and act. These stages often followed a cyclical path due largely to the gradual decline of patients' renal function. Most HCPs relied on being vigilant to detect patients' renal-drug problems rather than relying on systems to detect unanticipated cues. At each stage, HCPs relied on different cognitive cues depending on medication type: for renally eliminated medications, HCPs focused on gathering renal dosing guidelines, while for nephrotoxic medications, HCPs investigated the need for particular medication therapy, and if warranted, safer alternatives.ConclusionsOur model is useful for trainees so they can gain familiarity with managing renal-drug problems. Based on findings, improvements are warranted for three aspects of healthcare systems: (1) supporting the cyclical nature of renal-drug problem management via longitudinal tracking mechanisms, (2) providing tools to alleviate HCPs' heavy reliance on vigilance and (3) supporting HCPs' different decision-making needs for renally eliminated versus nephrotoxic medications

Coherent Functional Modules Improve Transcription Factor Target Identification, Cooperativity Prediction, and Disease Association

Transcription factors (TFs) are fundamental controllers of cellular regulation that function in a complex and combinatorial manner. Accurate identification of a transcription factor's targets is essential to understanding the role that factors play in disease biology. However, due to a high false positive rate, identifying coherent functional target sets is difficult. We have created an improved mapping of targets by integrating ChIP-Seq data with 423 functional modules derived from 9,395 human expression experiments. We identified 5,002 TF-module relationships, significantly improved TF target prediction, and found 30 high-confidence TF-TF associations, of which 14 are known. Importantly, we also connected TFs to diseases through these functional modules and identified 3,859 significant TF-disease relationships. As an example, we found a link between MEF2A and Crohn's disease, which we validated in an independent expression dataset. These results show the power of combining expression data and ChIP-Seq data to remove noise and better extract the associations between TFs, functional modules, and disease

Robertson-Walker fluid sources endowed with rotation characterised by quadratic terms in angular velocity parameter

Einstein's equations for a Robertson-Walker fluid source endowed with rotation Einstein's equations for a Robertson-Walker fluid source endowed with rotation are presented upto and including quadratic terms in angular velocity parameter. A family of analytic solutions are obtained for the case in which the source angular velocity is purely time-dependent. A subclass of solutions is presented which merge smoothly to homogeneous rotating and non-rotating central sources. The particular solution for dust endowed with rotation is presented. In all cases explicit expressions, depending sinusoidally on polar angle, are given for the density and internal supporting pressure of the rotating source. In addition to the non-zero axial velocity of the fluid particles it is shown that there is also a radial component of velocity which vanishes only at the poles. The velocity four-vector has a zero component between poles

The relationship between human semen parameters and environmental exposure to polychlorinated biphenyls and p,p′p,p'-DDE

Scientific and public concern exists about potential reproductive health effects of persistent chlorinated organic chemicals, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE, the most stable daughter compound of DDT). To explore the hypothesis that environmental exposures to PCBs and DDE are associated with altered semen parameters, we conducted a cross-sectional study of 212 male partners of subfertile couples who presented to the Massachusetts General Hospital Andrology Laboratory. Semen parameters were analyzed as both a continuous measure and dichotomized based on World Health Organization reference values for sperm concentration (< 20 million/mL), motility (< 50% motile), and Kruger strict criteria for morphology (< 4% normal). The comparison group for the dichotomized analysis was men with all three semen parameters above the reference values. In serum, 57 PCB congeners and $p,p'$-DDE were measured by congener-specific analysis using gas chromatography with electron capture detection. There were dose-response relationships among PCB-138 and sperm motility (odds ratio per tertile, adjusted for age, abstinence, and smoking, and $p$-value for trend were, respectively, 1.00, 1.68, 2.35, and $p$-value = 0.03) and morphology (1.00, 1.36, 2.53, $p$-value = 0.04). There was limited evidence of an inverse relationship between sum of PCBs, as well as those PCBs classified as cytochrome P450 enzyme inducers, with sperm motility and sperm morphology, as well as limited evidence of an inverse association between $p,p'$-DDE and sperm motility. The lack of a consistent relationship among semen parameters and other individual PCB congeners and groupings of congeners may indicate a difference in spermatotoxicity between congeners

Fractal Analysis of Protein Potential Energy Landscapes

The fractal properties of the total potential energy V as a function of time t are studied for a number of systems, including realistic models of proteins (PPT, BPTI and myoglobin). The fractal dimension of V(t), characterized by the exponent \gamma, is almost independent of temperature and increases with time, more slowly the larger the protein. Perhaps the most striking observation of this study is the apparent universality of the fractal dimension, which depends only weakly on the type of molecular system. We explain this behavior by assuming that fractality is caused by a self-generated dynamical noise, a consequence of intermode coupling due to anharmonicity. Global topological features of the potential energy landscape are found to have little effect on the observed fractal behavior.Comment: 17 pages, single spaced, including 12 figure

Design of the Spitzer Space Telescope Heritage Archive

It is predicted that Spitzer Space Telescope’s cryogen will run out in April 2009, and the final reprocessing for the cryogenic mission is scheduled to end in April 2011, at which time the Spitzer archive will be transferred to the NASA/IPAC Infrared Science Archive (IRSA) for long-term curation. The Spitzer Science Center (SSC) and IRSA are collaborating to design and deploy the Spitzer Heritage Archive (SHA), which will supersede the current Spitzer archive. It will initially contain the raw and final reprocessed cryogenic science products, and will eventually incorporate the final products from the Warm mission. The SHA will be accompanied by tools deemed necessary to extract the full science content of the archive and by comprehensive documentation

An integrative method for scoring candidate genes from association studies: application to warfarin dosing

BackgroundA key challenge in pharmacogenomics is the identification of genes whose variants contribute to drug response phenotypes, which can include severe adverse effects. Pharmacogenomics GWAS attempt to elucidate genotypes predictive of drug response. However, the size of these studies has severely limited their power and potential application. We propose a novel knowledge integration and SNP aggregation approach for identifying genes impacting drug response. Our SNP aggregation method characterizes the degree to which uncommon alleles of a gene are associated with drug response. We first use pre-existing knowledge sources to rank pharmacogenes by their likelihood to affect drug response. We then define a summary score for each gene based on allele frequencies and train linear and logistic regression classifiers to predict drug response phenotypes.ResultsWe applied our method to a published warfarin GWAS data set comprising 181 individuals. We find that our method can increase the power of the GWAS to identify both VKORC1 and CYP2C9 as warfarin pharmacogenes, where the original analysis had only identified VKORC1. Additionally, we find that our method can be used to discriminate between low-dose (AUROC=0.886) and high-dose (AUROC=0.764) responders.ConclusionsOur method offers a new route for candidate pharmacogene discovery from pharmacogenomics GWAS, and serves as a foundation for future work in methods for predictive pharmacogenomics

Age of the Universe: Influence of the Inhomogeneities on the global Expansion-Factor

For the first time we calculate quantitatively the influence of inhomogeneities on the global expansion factor by averaging the Friedmann equation. In the framework of the relativistic second-order Zel'dovich-approximation scheme for irrotational dust we use observational results in form of the normalisation constant fixed by the COBE results and we check different power spectra, namely for adiabatic CDM, isocurvature CDM, HDM, WDM, Strings and Textures. We find that the influence of the inhomogeneities on the global expansion factor is very small. So the error in determining the age of the universe using the Hubble constant in the usual way is negligible. This does not imply that the effect is negligible for local astronomical measurements of the Hubble constant. Locally the determination of the redshift-distance relation can be strongly influenced by the peculiar velocity fields due to inhomogeneities. Our calculation does not consider such effects, but is contrained to comparing globally homogeneous and averaged inhomogeneous matter distributions. In addition we relate our work to previous treatments.Comment: 10 pages, version accepted by Phys. Rev.