Examination of Fluconazole-Induced Alopecia in an Animal Model and Human Cohort.

Fluconazole-induced alopecia is a significant problem for patients receiving long-term therapy. We evaluated the hair cycle changes of fluconazole in a rat model and investigated potential molecular mechanisms. Plasma and tissue levels of retinoic acid were not found to be causal. Human patients with alopecia attributed to fluconazole also underwent detailed assessment and in both our murine model and human cohort fluconazole induced telogen effluvium. Future work further examining the mechanism of fluconazole-induced alopecia should be undertaken

Transiting Exoplanet Studies and Community Targets for JWST's Early Release Science Program

The James Webb Space Telescope will revolutionize transiting exoplanet atmospheric science due to its capability for continuous, long-duration observations and its larger collecting area, spectral coverage, and spectral resolution compared to existing space-based facilities. However, it is unclear precisely how well JWST will perform and which of its myriad instruments and observing modes will be best suited for transiting exoplanet studies. In this article, we describe a prefatory JWST Early Release Science (ERS) program that focuses on testing specific observing modes to quickly give the community the data and experience it needs to plan more efficient and successful future transiting exoplanet characterization programs. We propose a multi-pronged approach wherein one aspect of the program focuses on observing transits of a single target with all of the recommended observing modes to identify and understand potential systematics, compare transmission spectra at overlapping and neighboring wavelength regions, confirm throughputs, and determine overall performances. In our search for transiting exoplanets that are well suited to achieving these goals, we identify 12 objects (dubbed "community targets") that meet our defined criteria. Currently, the most favorable target is WASP-62b because of its large predicted signal size, relatively bright host star, and location in JWST's continuous viewing zone. Since most of the community targets do not have well-characterized atmospheres, we recommend initiating preparatory observing programs to determine the presence of obscuring clouds/hazes within their atmospheres. Measurable spectroscopic features are needed to establish the optimal resolution and wavelength regions for exoplanet characterization. Other initiatives from our proposed ERS program include testing the instrument brightness limits and performing phase-curve observations.(Abridged)Comment: This is a white paper that originated from an open discussion at the Enabling Transiting Exoplanet Science with JWST workshop held November 16 - 18, 2015 at STScI (http://www.stsci.edu/jwst/science/exoplanets). Accepted for publication in PAS

Spectroscopic Time-series Performance of JWST/NIRSpec from Commissioning Observations

We report on JWST commissioning observations of the transiting exoplanet HAT-P-14 b, obtained using the Bright Object Time Series (BOTS) mode of the NIRSpec instrument with the G395H/F290LP grating/filter combination ($3-5\mu$m). While the data were used primarily to verify that the NIRSpec BOTS mode is working as expected, and to enable it for general scientific use, they yield a precise transmission spectrum which we find is featureless down to the precision level of the instrument, consistent with expectations given HAT-P-14~b's small scale-height and hence expected atmospheric features. The exquisite quality and stability of the \emph{JWST/NIRSpec} transit spectrum -- almost devoid of any systematic effects -- allowed us to obtain median uncertainties of 50-60 ppm in this wavelength range at a resolution of $R=100$ in a single exposure, which is in excellent agreement with pre-flight expectations and close to the (or at the) photon-noise limit for a $J = 9.094$, F-type star like HAT-P-14. These observations showcase the ability of NIRSpec/BOTS to perform cutting-edge transiting exoplanet atmospheric science, setting the stage for observations and discoveries to be made in Cycle 1 and beyond.Comment: 16 pages, 14 figures; part of the PASP Focus Issue "JWST Time-Series Observations: Commissioning Performance". Paper after the first round of referee comments; inputs welcom

Are Women Who Work in Bars, Guesthouses and Similar Facilities a Suitable Study Population for Vaginal Microbicide Trials in Africa?

BACKGROUND: A feasibility study was conducted to investigate whether an occupational at-risk cohort of women in Mwanza, Tanzania are a suitable study population for future phase III vaginal microbicide trials. METHODOLOGY/PRINCIPAL FINDINGS: 1573 women aged 16-54 y working in traditional and modern bars, restaurants, hotels, guesthouses or as local food-handlers were enrolled at community-based reproductive health clinics, provided specimens for HIV/STI and pregnancy testing, and asked to attend three-monthly clinical follow-up visits for 12-months. HIV positive and negative women were eligible to enter the feasibility study and to receive free reproductive health services at any time. HIV prevalence at baseline was 26.5% (417/1573). HIV incidence among 1156 sero-negative women attending at baseline was 2.9/100PYs. Among 1020 HIV sero-negative, non-pregnant women, HIV incidence was 2.0/100PYs, HSV-2 incidence 12.7/100PYs and pregnancy rate 17.8/100PYs. Retention at three-months was 76.3% (778/1020). Among 771 HIV sero-negative, non-pregnant women attending at three-months, subsequent follow-up at 6, 9 and 12-months was 83.7%, 79.6%, and 72.1% respectively. Older women, those who had not moved home or changed their place of work in the last year, and women working in traditional bars or as local food handlers had the highest re-attendance. CONCLUSIONS/SIGNIFICANCE: Women working in food outlets and recreational facilities in Tanzania and other parts of Africa may be a suitable study population for microbicide and other HIV prevention trials. Effective locally-appropriate strategies to address high pregnancy rates and early losses to follow-up are essential to minimise risk to clinical trials in these settings

Crystal Structures of Malonyl-Coenzyme A Decarboxylase Provide Insights into Its Catalytic Mechanism and Disease-Causing Mutations

Malonyl-coenzyme A decarboxylase (MCD) is found from bacteria to humans, has important roles in regulating fatty acid metabolism and food intake, and is an attractive target for drug discovery. We report here four crystal structures of MCD from human, Rhodopseudomonas palustris, Agrobacterium vitis, and Cupriavidus metallidurans at up to 2.3 Å resolution. The MCD monomer contains an N-terminal helical domain involved in oligomerization and a C-terminal catalytic domain. The four structures exhibit substantial differences in the organization of the helical domains and, consequently, the oligomeric states and intersubunit interfaces. Unexpectedly, the MCD catalytic domain is structurally homologous to those of the GCN5-related N-acetyltransferase superfamily, especially the curacin A polyketide synthase catalytic module, with a conserved His-Ser/Thr dyad important for catalysis. Our structures, along with mutagenesis and kinetic studies, provide a molecular basis for understanding pathogenic mutations and catalysis, as well as a template for structure-based drug design

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Description and performance of track and primary-vertex reconstruction with the CMS tracker

A description is provided of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices. Despite the very hostile environment at the LHC, the performance obtained with these algorithms is found to be excellent. For tbar t events under typical 2011 pileup conditions, the average track-reconstruction efficiency for promptly-produced charged particles with transverse momenta of pT > 0.9GeV is 94% for pseudorapidities of |η| < 0.9 and 85% for 0.9 < |η| < 2.5. The inefficiency is caused mainly by hadrons that undergo nuclear interactions in the tracker material. For isolated muons, the corresponding efficiencies are essentially 100%. For isolated muons of pT = 100GeV emitted at |η| < 1.4, the resolutions are approximately 2.8% in pT, and respectively, 10μm and 30μm in the transverse and longitudinal impact parameters. The position resolution achieved for reconstructed primary vertices that correspond to interesting pp collisions is 10–12μm in each of the three spatial dimensions. The tracking and vertexing software is fast and flexible, and easily adaptable to other functions, such as fast tracking for the trigger, or dedicated tracking for electrons that takes into account bremsstrahlung

Alignment of the CMS tracker with LHC and cosmic ray data

© CERN 2014 for the benefit of the CMS collaboration, published under the terms of the Creative Commons Attribution 3.0 License by IOP Publishing Ltd and Sissa Medialab srl. Any further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation and DOI.The central component of the CMS detector is the largest silicon tracker ever built. The precise alignment of this complex device is a formidable challenge, and only achievable with a significant extension of the technologies routinely used for tracking detectors in the past. This article describes the full-scale alignment procedure as it is used during LHC operations. Among the specific features of the method are the simultaneous determination of up to 200 000 alignment parameters with tracks, the measurement of individual sensor curvature parameters, the control of systematic misalignment effects, and the implementation of the whole procedure in a multi-processor environment for high execution speed. Overall, the achieved statistical accuracy on the module alignment is found to be significantly better than 10μm