Optical Spectroscopy of Diffuse Ionized Gas in M31

We have obtained sensitive long-slit spectra of Diffuse Ionized Gas (DIG) in the Andromeda Galaxy, M31, covering the wavelength range of 3550-6850 Angs. By co-adding extracted DIG spectra, we reached a 1 sigma uncertainty of 9.3E-19 ergs/s/cm^{2}/arcsec^{2} corresponding to .46 pc/cm^{6} in Emission Measure. We present average spectra of DIG at four brightness levels with Emission Measures ranging from 9 to 59 pc/cm^{6}. We present the first measurements of [OII]\lambda3727 and [OIII]\lambda5007 of the truly diffuse ionized medium in the disk of an external spiral galaxy. We find that I_[OII]/I_H\alpha=.9-1.4. The [OIII] line is weak (I_[OIII]/I_H\beta = .5), but stronger than in the Galactic DIG. Measurements of [NII]\lambda6583 and [SII](\lambda6717+\lambda6731) are also presented. The [SII] lines are clearly stronger than typical HII regions (I_[SII]/I_H\alpha = .5 compared to .2). Overall, the line ratios are in agreement with predictions of photoionization models for diffuse gas exposed to a dilute stellar radiation field, but the line ratios of the DIG in M31 are somewhat different than observed for Galactic DIG. The differences indicate a less diluted radiation field in the DIG of M31's spiral arms compared to DIG in the Solar Neighborhood of the Milky Way. We have also detected HeI\lambda5876 emission from the brightest DIG in M31. The HeI line appears to be stronger than in the Galactic DIG, possibly indicating that most of the Helium in the bright DIG in M31 is fully ionized. However, this result is somewhat tentative.Comment: Fig. 5 corrected and other minor changes. Paper accepted to ApJ. 21 pages, Latex, incl. 5 fig. & 1 tab., submitted to Ap

The Political De-Determination of Legal Rules and the Contested Meaning of the ‘No Bailout’ Clause

Traditional debates on legal theory have devoted a great deal of attention to the question of the determinacy of legal rules. With the aid of social sciences and linguistics, this article suggests a way out of the ‘determinate-indeterminate’ dichotomy that has dominated the academic debate on the topic so far. Instead, a dynamic approach is proposed, in which rules are deemed to undergo processes of political ‘de-determination’ and ‘re-determination’. To illustrate this, the article uses the example of Art. 125 of the Treaty on the Functioning of the European Union, the ‘no bailout’ provision, which played a major role in the management of the Euro-crisis. As will be shown, with the start of the crisis, this provision, whose meaning was once scarcely controversial, became the object of intense interpretative disagreement. As it became politically relevant, the rule also became the site of interpretative competitions, until the intervention of the European Court of Justice disambiguated and redefined its meaning

GIFtS: annotation landscape analysis with GeneCards

<p>Abstract</p> <p>Background</p> <p>Gene annotation is a pivotal component in computational genomics, encompassing prediction of gene function, expression analysis, and sequence scrutiny. Hence, quantitative measures of the annotation landscape constitute a pertinent bioinformatics tool. GeneCards^®is a gene-centric compendium of rich annotative information for over 50,000 human gene entries, building upon 68 data sources, including Gene Ontology (GO), pathways, interactions, phenotypes, publications and many more.</p> <p>Results</p> <p>We present the GeneCards Inferred Functionality Score (GIFtS) which allows a quantitative assessment of a gene's annotation status, by exploiting the unique wealth and diversity of GeneCards information. The GIFtS tool, linked from the GeneCards home page, facilitates browsing the human genome by searching for the annotation level of a specified gene, retrieving a list of genes within a specified range of GIFtS value, obtaining random genes with a specific GIFtS value, and experimenting with the GIFtS weighting algorithm for a variety of annotation categories. The bimodal shape of the GIFtS distribution suggests a division of the human gene repertoire into two main groups: the high-GIFtS peak consists almost entirely of protein-coding genes; the low-GIFtS peak consists of genes from all of the categories. Cluster analysis of GIFtS annotation vectors provides the classification of gene groups by detailed positioning in the annotation arena. GIFtS also provide measures which enable the evaluation of the databases that serve as GeneCards sources. An inverse correlation is found (for GIFtS>25) between the number of genes annotated by each source, and the average GIFtS value of genes associated with that source. Three typical source prototypes are revealed by their GIFtS distribution: genome-wide sources, sources comprising mainly highly annotated genes, and sources comprising mainly poorly annotated genes. The degree of accumulated knowledge for a given gene measured by GIFtS was correlated (for GIFtS>30) with the number of publications for a gene, and with the seniority of this entry in the HGNC database.</p> <p>Conclusion</p> <p>GIFtS can be a valuable tool for computational procedures which analyze lists of large set of genes resulting from wet-lab or computational research. GIFtS may also assist the scientific community with identification of groups of uncharacterized genes for diverse applications, such as delineation of novel functions and charting unexplored areas of the human genome.</p

Cis and Trans Effects of Human Genomic Variants on Gene Expression

This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731).

Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P &lt; 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

But Not Both:The Exclusive Disjunction in Qualitative Comparative Analysis (QCA)

The application of Boolean logic using Qualitative Comparative Analysis (QCA) is becoming more frequent in political science but is still in its relative infancy. Boolean ‘AND’ and ‘OR’ are used to express and simplify combinations of necessary and sufficient conditions. This paper draws out a distinction overlooked by the QCA literature: the difference between inclusive- and exclusive-or (OR and XOR). It demonstrates that many scholars who have used the Boolean OR in fact mean XOR, discusses the implications of this confusion and explains the applications of XOR to QCA. Although XOR can be expressed in terms of OR and AND, explicit use of XOR has several advantages: it mirrors natural language closely, extends our understanding of equifinality and deals with mutually exclusive clusters of sufficiency conditions. XOR deserves explicit treatment within QCA because it emphasizes precisely the values that make QCA attractive to political scientists: contextualization, confounding variables, and multiple and conjunctural causation

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

GENOMEPOP: A program to simulate genomes in populations

<p>Abstract</p> <p>Background</p> <p>There are several situations in population biology research where simulating DNA sequences is useful. Simulation of biological populations under different evolutionary genetic models can be undertaken using backward or forward strategies. Backward simulations, also called coalescent-based simulations, are computationally efficient. The reason is that they are based on the history of lineages with surviving offspring in the current population. On the contrary, forward simulations are less efficient because the entire population is simulated from past to present. However, the coalescent framework imposes some limitations that forward simulation does not. Hence, there is an increasing interest in forward population genetic simulation and efficient new tools have been developed recently. Software tools that allow efficient simulation of large DNA fragments under complex evolutionary models will be very helpful when trying to better understand the trace left on the DNA by the different interacting evolutionary forces. Here I will introduce GenomePop, a forward simulation program that fulfills the above requirements. The use of the program is demonstrated by studying the impact of intracodon recombination on global and site-specific <it>dN/dS </it>estimation.</p> <p>Results</p> <p>I have developed algorithms and written software to efficiently simulate, forward in time, different Markovian nucleotide or codon models of DNA mutation. Such models can be combined with recombination, at inter and intra codon levels, fitness-based selection and complex demographic scenarios.</p> <p>Conclusion</p> <p>GenomePop has many interesting characteristics for simulating SNPs or DNA sequences under complex evolutionary and demographic models. These features make it unique with respect to other simulation tools. Namely, the possibility of forward simulation under General Time Reversible (GTR) mutation or GTR×MG94 codon models with intra-codon recombination, arbitrary, user-defined, migration patterns, diploid or haploid models, constant or variable population sizes, etc. It also allows simulation of fitness-based selection under different distributions of mutational effects. Under the 2-allele model it allows the simulation of recombination hot-spots, the definition of different frequencies in different populations, etc. GenomePop can also manage large DNA fragments. In addition, it has a scaling option to save computation time when simulating large sequences and population sizes under complex demographic and evolutionary situations. These and many other features are detailed in its web page <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p