Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans

Acknowledgments We are grateful to the Ian Fraser Cytometry Centre and our Mass Spetrometry and qPCR Facilities for help with the flow cytometry, glutathione and qRT-PCR assays, respectively. We also thank our many colleagues in the CRISP Consortium and in the medical mycology and systems biology communities for insightful discussions. Funding: This work was supported by the CRISP project (Combinatorial Responses In Stress Pathways), which was funded by the UK Biotechnology and Biological Research Council (www.bbsrc.ac.uk): AJPB, KH, CG, ADM, NARG, MT, MCR. (Research Grants; BB/F00513X/1, BB/F005210/1-2). AJPB and JQ received additional support from the BBSRC (Research Grants; BB/K016393/1; BB/K017365/1). NARG and AJPB were also supported by the Wellcome Trust (www.wellcome.ac.uk), (Grants: 080088; 097377). AJPB was also supported by the European Research Council (http://erc.europa.eu/), (STRIFE Advanced Grant; ERC-2009-AdG-249793). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Carbon ion acceleration from thin foil targets irradiated by ultrahigh-contrast, ultraintense laser pulses

In this study, ion acceleration from thin planar target foils irradiated by ultrahigh-contrast (10(10)), ultrashort (50 fs) laser pulses focused to intensities of 7 x 10(20) W cm(-2) is investigated experimentally. Target normal sheath acceleration (TNSA) is found to be the dominant ion acceleration mechanism when the target thickness is >= 50 nm and laser pulses are linearly polarized. Under these conditions, irradiation at normal incidence is found to produce higher energy ions than oblique incidence at 35 degrees with respect to the target normal. Simulations using one-dimensional (1D) boosted and 2D particle-in-cell codes support the result, showing increased energy coupling efficiency to fast electrons for normal incidence. The effects of target composition and thickness on the acceleration of carbon ions are reported and compared to calculations using analytical models of ion acceleration

The discourse dynamics approach to metaphor and metaphor-led discourse analysis

The use of metaphor as a tool to uncover people's ideas, attitudes, and values through analysis of discourse is demonstrated and illustrated with data collected in a social science research project. A 'discourse dynamics' approach to metaphor situated within a complexity/dynamic systems perspective is developed. This approach is turned into a method of 'metaphor-led discourse analysis' which is described in detail, using a focus group discussion to illustrate the procedure: transcription, metaphor identification, coding metaphors and using software, and finding patterns of metaphor use from coded data. The reasoning that justifies decisions at each stage of the procedure is made explicit so that the trustworthiness of the method can be maximized. The method of metaphor-led discourse analysis has been developed through a series of empirical projects to be accessible and relevant to social science researchers as well as to metaphor scholars

Organizational Culture and Physician Satisfaction with Dimensions of Group Practice

To assess the extent to which the organizational culture of physician group practices is associated with individual physician satisfaction with the managerial and organizational capabilities of the groups. Study Design and Methods . Physician surveys from 1997 to 1998 assessing the culture of their medical groups and their satisfaction with six aspects of group practice. Organizational culture was conceptualized using the Competing Values framework, yielding four distinct cultural types. Physician-level data were aggregated to the group level to attain measures of organizational culture. Using hierarchical linear modeling, individual physician satisfaction with six dimensions of group practice was predicted using physician-level variables and group-level variables. Separate models for each of the four cultural types were estimated for each of the six satisfaction measures, yielding a total of 24 models. Sample Studied . Fifty-two medical groups affiliated with 12 integrated health systems from across the U.S., involving 1,593 physician respondents (38.3 percent response rate). Larger medical groups and multispecialty groups were over-represented compared with the U.S. as a whole. Principal Findings . Our models explain up to 31 percent of the variance in individual physician satisfaction with group practice, with individual organizational culture scales explaining up to 5 percent of the variance. Group-level predictors: group (i.e., participatory) culture was positively associated with satisfaction with staff and human resources, technological sophistication, and price competition. Hierarchical (i.e., bureaucratic) culture was negatively associated with satisfaction with managerial decision making, practice level competitiveness, price competition, and financial capabilities. Rational (i.e., task-oriented) culture was negatively associated with satisfaction with staff and human resources, and price competition. Developmental (i.e., risk-taking) culture was not significantly associated with any of the satisfaction measures. In some of the models, being a single-specialty group (compared with a primary care group) and a group having a higher percent of male physicians were positively associated with satisfaction with financial capabilities. Physician-level predictors: individual physicians' ratings of organizational culture were significantly related to many of the satisfaction measures. In general, older physicians were more satisfied than younger physicians with many of the satisfaction measures. Male physicians were less satisfied with data capabilities. Primary care physicians (versus specialists) were less satisfied with price competition. Conclusion . Some dimensions of physician organizational culture are significantly associated with various aspects of individual physician satisfaction with group practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/1/j.1475-6773.2006.00648.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/2/HESR+648+Appendix+A.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/3/HESR+648+Appendix+C.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/4/HESR+648+Appendix+B.pd

Qatar-1b: a hot Jupiter orbiting a metal-rich K dwarf star

We report the discovery and initial characterisation of Qatar-1b, a hot Jupiter orbiting a metal-rich K dwarf star, the first planet discovered by the Alsubai Project exoplanet transit survey. We describe the strategy used to select candidate transiting planets from photometry generated by the Alsubai Project instrument. We examine the rate of astrophysical and other false positives found during the spectroscopic reconnaissance of the initial batch of candidates. A simultaneous fit to the follow-up radial velocities and photometry of Qatar-1b yield a planetary mass of 1.09+/-0.08 Mjup and a radius of 1.16+/-0.05 Rjup. The orbital period and separation are 1.420033 days and 0.0234 AU for an orbit assumed to be circular. The stellar density, effective temperature and rotation rate indicate an age greater than 4 Gyr for the system.Comment: 8 pages, 5 figures, submitted to Monthly Notices of the Royal Astronomical Societ

Qatar-2: A K dwarf orbited by a transiting hot Jupiter and a more massive companion in an outer orbit

We report the discovery and initial characterization of Qatar-2b, a hot Jupiter transiting a V = 13.3 mag K dwarf in a circular orbit with a short period, P_ b = 1.34 days. The mass and radius of Qatar-2b are M_p = 2.49 M_j and R_p = 1.14 R_j, respectively. Radial-velocity monitoring of Qatar-2 over a span of 153 days revealed the presence of a second companion in an outer orbit. The Systemic Console yielded plausible orbits for the outer companion, with periods on the order of a year and a companion mass of at least several M_j. Thus Qatar-2 joins the short but growing list of systems with a transiting hot Jupiter and an outer companion with a much longer period. This system architecture is in sharp contrast to that found by Kepler for multi-transiting systems, which are dominated by objects smaller than Neptune, usually with tightly spaced orbits that must be nearly coplanar

Relativistic plasma surfaces as an efficient second harmonic generator

We report on the characterization of the specular reflection of 50 fs laser pulses in the intensity range 10(17)-10(21)Wcm(-2) obliquely incident with p-polarization onto solid density plasmas. These measurements show that the absorbed energy fraction remains approximately constant and that second harmonic generation (SHG) achieves efficiencies of 22 +/- 8% for intensities approaching 10(21)Wcm(-2). A simple model based on the relativistic oscillating mirror concept reproduces the observed intensity scaling, indicating that this is the dominant process involved for these conditions. This method may prove to be superior to SHG by sum frequency mixing in crystals as it is free from dispersion and retains high spatial coherence at high intensity

Xanthine oxidase inhibition and white matter hyperintensity progression following ischaemic stroke and transient ischaemic attack (XILO-FIST): a multicentre, double-blinded, randomised, placebo-controlled trial

BACKGROUND: People who experience an ischaemic stroke are at risk of recurrent vascular events, progression of cerebrovascular disease, and cognitive decline. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity (WMH) progression and blood pressure (BP) following ischaemic stroke or transient ischaemic attack (TIA). METHODS: In this multicentre, prospective, randomised, double-blinded, placebo-controlled trial conducted in 22 stroke units in the United Kingdom, we randomly assigned participants within 30-days of ischaemic stroke or TIA to receive oral allopurinol 300 mg twice daily or placebo for 104 weeks. All participants had brain MRI performed at baseline and week 104 and ambulatory blood pressure monitoring at baseline, week 4 and week 104. The primary outcome was the WMH Rotterdam Progression Score (RPS) at week 104. Analyses were by intention to treat. Participants who received at least one dose of allopurinol or placebo were included in the safety analysis. This trial is registered with ClinicalTrials.gov, NCT02122718. FINDINGS: Between 25th May 2015 and the 29th November 2018, 464 participants were enrolled (232 per group). A total of 372 (189 with placebo and 183 with allopurinol) attended for week 104 MRI and were included in analysis of the primary outcome. The RPS at week 104 was 1.3 (SD 1.8) with allopurinol and 1.5 (SD 1.9) with placebo (between group difference −0.17, 95% CI −0.52 to 0.17, p = 0.33). Serious adverse events were reported in 73 (32%) participants with allopurinol and in 64 (28%) with placebo. There was one potentially treatment related death in the allopurinol group. INTERPRETATION: Allopurinol use did not reduce WMH progression in people with recent ischaemic stroke or TIA and is unlikely to reduce the risk of stroke in unselected people. FUNDING: The British Heart Foundation and the UK Stroke Association