Radial Velocity Studies of Close Binary Stars.VIII

Radial-velocity measurements and sine-curve fits to the orbital velocity variations are presented for the seventh set of ten close binary systems: V410 Aur, V523 Cas, QW Gem, V921 Her, V2357 Oph, V1130 Tau, HN UMa, HX UMa, HD 93917, NSV 223. All systems, but three (V523 Cas, HD 93917, NSV 223), were discovered photometrically by the Hipparcos mission. All systems are double-lined (SB2) binaries and all, but the detached, very close system V1130 Tau, are contact binaries. The broadening-function permitted improvement of the orbital elements for V523 Cas, which was the only system observed before for radial velocity variations. Spectroscopic/visual companions were detected for V410 Aur and HX UMa.Comment: AASTeX5, 4 figures, 3 tables, to appear AJ, June 200

Radial Velocity Studies of Close Binary Stars. IX

Radial-velocity measurements and sine-curve fits to the orbital velocity variations are presented for the eighth set of ten close binary systems: AB And, V402 Aur, V445 Cep, V2082 Cyg, BX Dra, V918 Her, V502 Oph, V1363 Ori, KP Peg, V335 Peg. Half of the systems (V445 Cep, V2082 Cyg, V918 Her, V1363 Ori, V335 Peg) were discovered photometrically by the Hipparcos mission and all systems are double-lined (SB2) contact binaries. The broadening function method permitted improvement of the orbital elements for AB And and V502 Oph. The other systems have been observed for radial velocity variations for the first time; in this group are five bright (V<7.5) binaries: V445 Cep, V2082 Cyg, V918 Her, KP Peg and V335 Peg. Several of the studied systems are prime candidates for combined light and radial-velocity synthesis solutions.Comment: 17+ pages, 2 tables, 4 figure

Radial Velocity Studies of Close Binary Stars.VI

Radial-velocity measurements and sine-curve fits to the orbital velocity variations are presented for the sixth set of ten close binary systems: SV Cam, EE Cet, KR Com, V410 Cyg, GM Dra, V972 Her, ET Leo, FS Leo, V2388 Oph, II UMa. All systems except FS Leo are double-lined spectroscopic binaries. The type of FS Leo is unknown while SV Cam is a close, detached binary; all remaining systems are contact binaries. Eight binaries (all except SV Cam and V401 Cyg) are the recent photometric discoveries of the Hipparcos satellite project. Five systems, EE Cet, KR Com, V401 Cyg, V2388 Oph, II UMa, are members of visual/spectroscopic triple systems. We were able to observe the close binary system EE Cet separately of its companion, but in the remaining four systems we could separate the spectral components only through the use of the broadening-function approach. Several of the studied systems are prime candidates for combined light and radial-velocity synthesis solutions.Comment: AASTeX5, 5 figures, 2 tables, modified after the AJ revie

Stochastic Modeling of B Lymphocyte Terminal Differentiation and Its Suppression by Dioxin

<p>Abstract</p> <p>Background</p> <p>Upon antigen encounter, naïve B lymphocytes differentiate into antibody-secreting plasma cells. This humoral immune response is suppressed by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxin-like compounds, which belong to the family of aryl hydrocarbon receptor (AhR) agonists.</p> <p>Results</p> <p>To achieve a better understanding of the immunotoxicity of AhR agonists and their associated health risks, we have used computer simulations to study the behavior of the gene regulatory network underlying B cell terminal differentiation. The core of this network consists of two coupled double-negative feedback loops involving transcriptional repressors Bcl-6, Blimp-1, and Pax5. Bifurcation analysis indicates that the feedback network can constitute a bistable system with two mutually exclusive transcriptional profiles corresponding to naïve B cells and plasma cells. Although individual B cells switch to the plasma cell state in an all-or-none fashion when stimulated by the polyclonal activator lipopolysaccharide (LPS), stochastic fluctuations in gene expression make the switching event probabilistic, leading to heterogeneous differentiation response among individual B cells. Moreover, stochastic gene expression renders the dose-response behavior of a population of B cells substantially graded, a result that is consistent with experimental observations. The steepness of the dose response curve for the number of plasma cells formed vs. LPS dose, as evaluated by the apparent Hill coefficient, is found to be inversely correlated to the noise level in Blimp-1 gene expression. Simulations illustrate how, through AhR-mediated repression of the AP-1 protein, TCDD reduces the probability of LPS-stimulated B cell differentiation. Interestingly, stochastic simulations predict that TCDD may destabilize the plasma cell state, possibly leading to a reversal to the B cell phenotype.</p> <p>Conclusion</p> <p>Our results suggest that stochasticity in gene expression, which renders a graded response at the cell population level, may have been exploited by the immune system to launch humoral immune response of a magnitude appropriately tuned to the antigen dose. In addition to suppressing the initiation of the humoral immune response, dioxin-like compounds may also disrupt the maintenance of the acquired immunity.</p

PLoS Biol

The Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were developed to address the lack of reproducibility in biomedical animal studies and improve the communication of research findings. While intended to guide the preparation of peer-reviewed manuscripts, the principles of transparent reporting are also fundamental for in vivo databases. Here, we describe the benefits and challenges of applying the guidelines for the International Mouse Phenotyping Consortium (IMPC), whose goal is to produce and phenotype 20,000 knockout mouse strains in a reproducible manner across ten research centres. In addition to ensuring the transparency and reproducibility of the IMPC, the solutions to the challenges of applying the ARRIVE guidelines in the context of IMPC will provide a resource to help guide similar initiatives in the future

Nat Genet

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.Comment in : Genetic differential calculus. [Nat Genet. 2015] Comment in : Scaling up phenotyping studies. [Nat Biotechnol. 2015