Direct observation of the picosecond dynamics of I_2-Ar fragmentation

Picosecond real‐time observations of the dynamics of I_2–Ar fragmentation are reported. The state‐to‐state rates, k(ν^i,,ν^f,), are directly measured and related to the homogeneous broadening of the initial state, and to product state distributions in the exit channel. Comparisons with different theories of vibrational (and electronic) predissociation are made

Roles of binding elements, FOXL2 domains, and interactions with cJUN and SMADs in regulation of FSHβ.

We previously identified FOXL2 as a critical component in FSHβ gene transcription. Here, we show that mice deficient in FOXL2 have lower levels of gonadotropin gene expression and fewer LH- and FSH-containing cells, but the same level of other pituitary hormones compared to wild-type littermates, highlighting a role of FOXL2 in the pituitary gonadotrope. Further, we investigate the function of FOXL2 in the gonadotrope cell and determine which domains of the FOXL2 protein are necessary for induction of FSHβ transcription. There is a stronger induction of FSHβ reporter transcription by truncated FOXL2 proteins, but no induction with the mutant lacking the forkhead domain. Specifically, FOXL2 plays a role in activin induction of FSHβ, functioning in concert with activin-induced SMAD proteins. Activin acts through multiple promoter elements to induce FSHβ expression, some of which bind FOXL2. Each of these FOXL2-binding sites is either juxtaposed or overlapping with a SMAD-binding element. We determined that FOXL2 and SMAD4 proteins form a higher order complex on the most proximal FOXL2 site. Surprisingly, two other sites important for activin induction bind neither SMADs nor FOXL2, suggesting additional factors at work. Furthermore, we show that FOXL2 plays a role in synergistic induction of FSHβ by GnRH and activin through interactions with the cJUN component of the AP1 complex that is necessary for GnRH responsiveness. Collectively, our results demonstrate the necessity of FOXL2 for proper FSH production in mice and implicate FOXL2 in integration of transcription factors at the level of the FSHβ promoter

Survey sequencing and radiation hybrid mapping to construct comparative maps.

In MURPHY WJ (ed.) Phylogenomics, Humana Press. (Methods in Molecular Biology, 422)International audienceRadiation hybrid (RH) mapping has become one of the most well-established techniques for economically and efficiently navigating genomes of interest. The success of the technique relies on random chromosome breakage of a target genome, which is then captured by recipient cells missing a preselected marker. Selection for hybrid cells that have DNA fragments bearing the marker of choice, plus a random set of DNA fragments from the initial irradiation, generates a set of cell lines that recapitulates the genome of the target organism several-fold. Markers or genes of interest are analyzed by PCR using DNA isolated from each cell line. Statistical tools are applied to determine both the linear order of markers on each chromosome, and the confidence of each placement. The resolution of the resulting map relies on many factors, most notably the degree of breakage from the initial radiation as well as the number of hybrid clones and mean retention value.A high-resolution RH map of a genome derived from low pass or survey sequencing (coverage from 1 to 2 times) can provide essentially the same comparative data on gene order that is derived from high-coverage (greater than x7) genome sequencing. When combined with fluorescence in situ hybridization, RH maps are complete and ordered blueprints for each chromosome. They give information about the relative order and spacing of genes and markers, and allow investigators to move between target and reference genomes, such as those of mouse or human, with ease although the approach is not limited to mammal genomes

VLA observations of water masers towards 6.7 GHz methanol maser sources

22 GHz water and 6.7 GHz methanol masers are usually thought as signposts of early stages of high-mass star formation but little is known about their associations and the physical environments they occur in. The aim was to obtain accurate positions and morphologies of the water maser emission and relate them to the methanol maser emission recently mapped with Very Long Baseline Interferometry. A sample of 31 methanol maser sources was searched for 22 GHz water masers using the VLA and observed in the 6.7 GHz methanol maser line with the 32 m Torun dish simultaneously. Water maser clusters were detected towards 27 sites finding 15 new sources. The detection rate of water maser emission associated with methanol sources was as high as 71%. In a large number of objects (18/21) the structure of water maser is well aligned with that of the extended emission at 4.5 $\mu$m confirming the origin of water emission from outflows. The sources with methanol emission with ring-like morphologies, which likely trace a circumstellar disk/torus, either do not show associated water masers or the distribution of water maser spots is orthogonal to the major axis of the ring. The two maser species are generally powered by the same high-mass young stellar object but probe different parts of its environment. The morphology of water and methanol maser emission in a minority of sources is consistent with a scenario that 6.7 GHz methanol masers trace a disc/torus around a protostar while the associated 22 GHz water masers arise in outflows. The majority of sources in which methanol maser emission is associated with the water maser appears to trace outflows. The two types of associations might be related to different evolutionary phases.Comment: accepted by Astronomy & Astrophysic

Levosimendan for the prevention of acute organ dysfunction in sepsis

BACKGROUND Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. METHODS We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events. RESULTS The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04). CONCLUSIONS The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials number, ISRCTN12776039.

Design, analysis and test verification of advanced encapsulation systems, phase 2 program results

Optical, electrical isolation, thermal structural, structural deflection, and thermal tests are reported. The utility of the optical, series capacitance, and structural deflection models was verified

Peer mentorship and positive effects on student mentor and mentee retention and academic success

This study examined how the introduction of peer mentorship in an undergraduate health and social welfare programme at a large northern university affected student learning. Using an ethnographic case study approach, the study draws upon data collected from a small group of mentors and their mentees over a period of one academic year using interviews, reflective journals, assessment and course evaluation data. Analysis of the data collected identified a number of key findings: peer mentorship improves assessment performance for both mentee and mentor; reduces stress and anxiety, enhances participation and engagement in the academic community, and adds value to student outcomes