One ring to rule them all? Another cellular responsibility for PCNA

To prevent duplication or loss of genomic regions during DNA replication, it is essential that the entire genome is copied precisely once every S phase. Cells achieve this by mutually exclusive regulation of origin firing and licensing. A crucial protein that is involved in origin licensing is chromatin licensing and DNA replication factor 1 (CDT1) and, therefore, activity of this protein must be strictly controlled. Four recent articles have demonstrated that proliferating cell nuclear antigen (PCNA), an essential sliding clamp used in replication and DNA repair, has a crucial role in this process by mediating the proteasomal degradation of CDT1

Optimizing future dark energy surveys for model selection goals

We demonstrate a methodology for optimizing the ability of future dark energy surveys to answer model selection questions, such as `Is acceleration due to a cosmological constant or a dynamical dark energy model?'. Model selection Figures of Merit are defined, exploiting the Bayes factor, and surveys optimized over their design parameter space via a Monte Carlo method. As a specific example we apply our methods to generic multi-fibre baryon acoustic oscillation spectroscopic surveys, comparable to that proposed for SuMIRe PFS, and present implementations based on the Savage-Dickey Density Ratio that are both accurate and practical for use in optimization. It is shown that whilst the optimal surveys using model selection agree with those found using the Dark Energy Task Force (DETF) Figure of Merit, they provide better informed flexibility of survey configuration and an absolute scale for performance; for example, we find survey configurations with close to optimal model selection performance despite their corresponding DETF Figure of Merit being at only 50% of its maximum. This Bayes factor approach allows us to interpret the survey configurations that will be good enough for the task at hand, vital especially when wanting to add extra science goals and in dealing with time restrictions or multiple probes within the same project.Comment: 12 pages, 16 figure

Formation of octapod MnO nanoparticles with enhanced magnetic properties through kinetically-controlled thermal decomposition of polynuclear manganese complexes

Polynuclear manganese complexes are used as precursors for the synthesis of manganese oxide nanoparticles (MnO NPs). Altering the thermal decomposition conditions can shift the nanoparticle product from spherical, thermodynamically-driven NPs to unusual, kinetically-controlled octapod structures. The resulting increased surface area profoundly alters the NP's surface-dependent magnetism and may have applications in nanomedicine

Systematic review of symptom clusters in cardiovascular disease

Background: Although individual symptoms and symptom trajectories for various cardiovascular conditions have been reported, there is limited research identifying the symptom clusters that may provide a better understanding of patients’ experiences with heart disease. Aims: To summarize the state of the science in symptom cluster research for patients with acute coronary syndrome, myocardial infarction, coronary artery bypass surgery, and heart failure through systematic review and to provide direction for the translation of symptom cluster research into the clinical setting. Methods: Databases were searched for articles from January 2000 through to May 2015 using MESH terms “symptoms, symptom clusters, acute coronary syndrome (ACS), myocardial infarction (MI), coronary heart disease (CHD), ischemic heart disease (IHD), heart failure (HF), coronary artery bypass surgery (CABS), cluster analyses, and latent classes.” The search was limited to human studies, English language articles, and original articles investigating symptom clusters in individuals with heart disease. Fifteen studies meeting the criteria were included. Results: For patients with ACS and MI, younger persons were more likely to experience clusters with the most symptoms. Older adults were more likely to experience clusters with the lowest number of symptoms and more diffuse and milder symptom clusters that are less reflective of classic ACS presentations. For HF patients, symptom clusters frequently included physical and emotional/cognitive components; edema clustered in only three studies. Symptom expression was congruent across geographical regions and cultures. Conclusions: The findings demonstrated similarities in symptom clusters during ACS, MI, and HF, despite multiple methods and analyses. These results may help clinicians to prepare at-risk patients for proper treatment-seeking and symptom self-management behaviors

Dispersed Fringe Sensing Analysis - DFSA

Dispersed Fringe Sensing (DFS) is a technique for measuring and phasing segmented telescope mirrors using a dispersed broadband light image. DFS is capable of breaking the monochromatic light ambiguity, measuring absolute piston errors between segments of large segmented primary mirrors to tens of nanometers accuracy over a range of 100 micrometers or more. The DFSA software tool analyzes DFS images to extract DFS encoded segment piston errors, which can be used to measure piston distances between primary mirror segments of ground and space telescopes. This information is necessary to control mirror segments to establish a smooth, continuous primary figure needed to achieve high optical quality. The DFSA tool is versatile, allowing precise piston measurements from a variety of different optical configurations. DFSA technology may be used for measuring wavefront pistons from sub-apertures defined by adjacent segments (such as Keck Telescope), or from separated sub-apertures used for testing large optical systems (such as sub-aperture wavefront testing for large primary mirrors using auto-collimating flats). An experimental demonstration of the coarse-phasing technology with verification of DFSA was performed at the Keck Telescope. DFSA includes image processing, wavelength and source spectral calibration, fringe extraction line determination, dispersed fringe analysis, and wavefront piston sign determination. The code is robust against internal optical system aberrations and against spectral variations of the source. In addition to the DFSA tool, the software package contains a simple but sophisticated MATLAB model to generate dispersed fringe images of optical system configurations in order to quickly estimate the coarse phasing performance given the optical and operational design requirements. Combining MATLAB (a high-level language and interactive environment developed by MathWorks), MACOS (JPL s software package for Modeling and Analysis for Controlled Optical Systems), and DFSA provides a unique optical development, modeling and analysis package to study current and future approaches to coarse phasing controlled segmented optical systems

Upper-Room Ultraviolet Light and Negative Air Ionization to Prevent Tuberculosis Transmission

Background Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air. Methods and Findings For 535 consecutive days, exhaust air from an HIV-TB ward in Lima, Perú, was passed through three guinea pig air-sampling enclosures each housing approximately 150 guinea pigs, using a 2-d cycle. On UV-off days, ward air passed in parallel through a control animal enclosure and a similar enclosure containing negative ionizers. On UV-on days, UV lights and mixing fans were turned on in the ward, and a third animal enclosure alone received ward air. TB infection in guinea pigs was defined by monthly tuberculin skin tests. All guinea pigs underwent autopsy to test for TB disease, defined by characteristic autopsy changes or by the culture of Mycobacterium tuberculosis from organs. 35% (106/304) of guinea pigs in the control group developed TB infection, and this was reduced to 14% (43/303) by ionizers, and to 9.5% (29/307) by UV lights (both p < 0.0001 compared with the control group). TB disease was confirmed in 8.6% (26/304) of control group animals, and this was reduced to 4.3% (13/303) by ionizers, and to 3.6% (11/307) by UV lights (both p < 0.03 compared with the control group). Time-to-event analysis demonstrated that TB infection was prevented by ionizers (log-rank 27; p < 0.0001) and by UV lights (log-rank 46; p < 0.0001). Time-to-event analysis also demonstrated that TB disease was prevented by ionizers (log-rank 3.7; p = 0.055) and by UV lights (log-rank 5.4; p = 0.02). An alternative analysis using an airborne infection model demonstrated that ionizers prevented 60% of TB infection and 51% of TB disease, and that UV lights prevented 70% of TB infection and 54% of TB disease. In all analysis strategies, UV lights tended to be more protective than ionizers. Conclusions Upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes

Type I interferons (IFNs) are important for host defense from viral infections, acting to restrict viral production in infected cells and to promote antiviral immune responses. However, the type I IFN system has also been associated with severe lung inflammatory disease in response to respiratory syncytial virus (RSV). Which cells produce type I IFNs upon RSV infection and how this directs immune responses to the virus, and potentially results in pathological inflammation, is unclear. Here, we show that alveolar macrophages (AMs) are the major source of type I IFNs upon RSV infection in mice. AMs detect RSV via mitochondrial antiviral signaling protein (MAVS)–coupled retinoic acid–inducible gene 1 (RIG-I)–like receptors (RLRs), and loss of MAVS greatly compromises innate immune restriction of RSV. This is largely attributable to loss of type I IFN–dependent induction of monocyte chemoattractants and subsequent reduced recruitment of inflammatory monocytes (infMo) to the lungs. Notably, the latter have potent antiviral activity and are essential to control infection and lessen disease severity. Thus, infMo recruitment constitutes an important and hitherto underappreciated, cell-extrinsic mechanism of type I IFN–mediated antiviral activity. Dysregulation of this system of host antiviral defense may underlie the development of RSV-induced severe lung inflammation