VLBI and Archival VLA and WSRT Observations of the GRB 030329 Radio Afterglow

We present VLBI and archival Karl G. Jansky Very Large Array (VLA) and Westerbork Synthesis Radio Telescope (WSRT) observations of the radio afterglow from the gamma-ray burst (GRB) of 2003 March 29 (GRB 030329) taken between 672 and 2032 days after the burst. The EVLA and WSRT data suggest a simple power law decay in the flux at 5 GHz, with no clear signature of any rebrightening from the counter jet. We report an unresolved source at day 2032 of size $1.18\pm0.13$ mas, which we use in conjunction with the expansion rate of the burst to argue for the presence of a uniform, ISM-like circumburst medium. We develop a semi-analytic method to model gamma-ray burst afterglows, and apply it to the 5 GHz light curve to perform burst calorimetry. A limit of $< 0.067$ mas yr$^{-1}$ is placed on the proper motion, supporting the standard afterglow model for gamma-ray bursts.Comment: 24 pages, 5 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Intra-Firm Wage Dispersion and Firm Performance: Evidence from Linked Employer-Employee Data

Cet article analyse la relation entre la dispersion salariale intra-firme et la performance au sein de grandes entreprises belges à partir de données appareillées employeur-employé. Sur base de la méthodologie de Winter-Ebmer et Zweimüller (1999), nous trouvons une relation positive et significative entre la dispersion salariale au sein des entreprises et les profits par tête. Ce résultat est obtenu en contrôlant pour les caractéristiques des travailleurs et des entreprises ainsi qu'en abordant le problème potentiel de la simultanéité. Nos estimations indiquent également que l'intensité de la relation est plus forte pour les ouvriers ainsi qu'au sein des entreprises avec un degréélevé de monitoring. Ces résultats correspondent davantage à la théorie des 'tournois' qu'aux modèles de 'coopération'. Copyright WWZ and Helbing & Lichtenhahn Verlag AG 2004.

Novel Nonnucleoside Inhibitor of Hepatitis C Virus RNA-Dependent RNA Polymerase

A novel nonnucleoside inhibitor of hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp), [(1R)-5-cyano-8-methyl-1-propyl-1,3,4,9-tetrahydropyano[3,4-b]indol-1-yl] acetic acid (HCV-371), was discovered through high-throughput screening followed by chemical optimization. HCV-371 displayed broad inhibitory activities against the NS5B RdRp enzyme, with 50% inhibitory concentrations ranging from 0.3 to 1.8 μM for 90% of the isolates derived from HCV genotypes 1a, 1b, and 3a. HCV-371 showed no inhibitory activity against a panel of human polymerases, including mitochondrial DNA polymerase gamma, and other unrelated viral polymerases, demonstrating its specificity for the HCV polymerase. A single administration of HCV-371 to cells containing the HCV subgenomic replicon for 3 days resulted in a dose-dependent reduction of the steady-state levels of viral RNA and protein. Multiple treatments with HCV-371 for 16 days led to a >3-log(10) reduction in the HCV RNA level. In comparison, multiple treatments with a similar inhibitory dose of alpha interferon resulted in a 2-log(10) reduction of the viral RNA level. In addition, treatment of cells with a combination of HCV-371 and pegylated alpha interferon resulted in an additive antiviral activity. Within the effective antiviral concentrations of HCV-371, there was no effect on cell viability and metabolism. The intracellular antiviral specificity of HCV-371 was demonstrated by its lack of activity in cells infected with several DNA or RNA viruses. Fluorescence binding studies show that HCV-371 binds the NS5B with an apparent dissociation constant of 150 nM, leading to high selectivity and lack of cytotoxicity in the antiviral assays

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

Contains fulltext : 118576.pdf (publisher's version ) (Open Access)Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes