2,285 research outputs found
Structure of Frequency-Interacting RNA Helicase from \u3ci\u3eNeurospora crassa\u3c/i\u3e Reveals High Flexibility in a Domain Critical for Circadian Rhythm and RNA Surveillance
The FRH (frequency-interacting RNA helicase) protein is the Neurospora crassa homolog of yeast Mtr4, an essential RNA helicase that plays a central role in RNA metabolism as an activator of the nuclear RNA exosome. FRH is also a required component of the circadian clock, mediating protein interactions that result in the rhythmic repression of gene expression. Here we show that FRH unwinds RNA substrates in vitro with a kinetic profile similar to Mtr4, indicating that while FRH has acquired additional functionality, its core helicase function remains intact. In contrast with the earlier FRH structures, a new crystal form of FRH results in an ATP binding site that is undisturbed by crystal contacts and adopts a conformation consistent with nucleotide binding and hydrolysis. Strikingly, this new FRH structure adopts an arch domain conformation that is dramatically altered from previous structures. Comparison of the existing FRH structures reveals conserved hinge points that appear to facilitate arch motion. Regions in the arch have been previously shown to mediate a variety of protein-protein interactions critical for RNA surveillance and circadian clock functions. The conformational changes highlighted in the FRH structures provide a platform for investigating the relationship between arch dynamics and Mtr4/FRH function
Attributable costs of enterococcal bloodstream infections in a nonsurgical hospital cohort
BACKGROUND: Vancomycin-resistant enterococcal (VRE) bloodstream infections (BSI) are associated with increased morbidity and mortality. OBJECTIVE: To determine the attributable costs of vancomycin-sensitive (VSE) and VRE BSI and the independent impact of vancomycin-resistance on hospital costs. METHODS: A retrospective cohort study was conducted of 21,154 non-surgical patients admitted to an academic medical center between 2002 and 2003. Using administrative data, attributable hospital costs (inflation adjusted to 2,250 (95% confidence interval [CI], 2,880) in the standard GLS model and 1,588–4,479 (95% CI, 5,732) in the standard GLS model and 3,170–5,282 (8,043) for VSE BSI and 1,579–1,713 (95% CI, 2,192) in the standard GLS model and 1,214–$1,968) in the propensity-score weighted GLS model. Attributable length of stay ranged from 1.1–2.2 days for VSE BSI and 2.2–3.5 days for VRE BSI cases. CONCLUSIONS: VSE and VRE BSI were independently associated with hospital costs and length of stay. Vancomycin-resistance was associated with increased costs
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The evolution of mapping habitat for northern spotted owls (Strix occidentalis caurina): A comparison of photo-interpreted, Landsat-based, and lidar-based habitat maps
Wildlife habitat mapping has evolved at a rapid pace over the last few decades. Beginning with simple, often subjective,
hand-drawn maps, habitat mapping now involves complex species distribution models (SDMs) using
mapped predictor variables derived from remotely sensed data. For species that inhabit large geographic areas,
remote sensing technology is often essential for producing range wide maps. Habitat monitoring for northern
spotted owls (Strix occidentalis caurina), whose geographic covers about 23 million ha, is based on SDMs that
use Landsat Thematic Mapper imagery to create forest vegetation data layers using gradient nearest neighbor
(GNN) methods. Vegetation data layers derived from GNN are modeled relationships between forest inventory
plot data, climate and topographic data, and the spectral signatures acquired by the satellite. When used as predictor
variables for SDMs, there is some transference of the GNN modeling error to the final habitat map.
Recent increases in the use of light detection and ranging (lidar) data, coupled with the need to produce spatially
accurate and detailed forest vegetation maps have spurred interest in its use for SDMs and habitat mapping. Instead
of modeling predictor variables from remotely sensed spectral data, lidar provides direct measurements of
vegetation height for use in SDMs. We expect a SDM habitat map produced from directly measured predictor variables
to be more accurate than one produced from modeled predictors.
We used maximum entropy (Maxent) SDM modeling software to compare predictive performance and estimates
of habitat area between Landsat-based and lidar-based northern spotted owl SDMs and habitat maps.
We explored the differences and similarities between these maps, and to a pre-existing aerial photo-interpreted
habitat map produced by local wildlife biologists. The lidar-based map had the highest predictive
performance based on 10 bootstrapped replicate models (AUC = 0.809 ± 0.011), but the performance of
the Landsat-based map was within acceptable limits (AUC = 0.717 ± 0.021). As is common with photo-interpreted
maps, there was no accuracy assessment available for comparison. The photo-interpreted map produced
the highest and lowest estimates of habitat area, depending on which habitat classes were included
(nesting, roosting, and foraging habitat = 9962 ha, nesting habitat only = 6036 ha). The Landsat-based map
produced an estimate of habitat area that was within this range (95% CI: 6679–9592 ha), while the lidar-based
map produced an area estimate similar to what was interpreted by local wildlife biologists as nesting (i.e., high
quality) habitat using aerial imagery (95% CI: 5453–7216). Confidence intervals of habitat area estimates from
the SDMs based on Landsat and lidar overlapped.
We concluded that both Landsat- and lidar-based SDMs produced reasonable maps and area estimates for northern
spotted owl habitat within the study area. The lidar-based map was more precise and spatially similar to
what local wildlife biologists considered spotted owl nesting habitat. The Landsat-based map provided a less precise
spatial representation of habitat within the relatively small geographic confines of the study area, but habitat
area estimates were similar to both the photo-interpreted and lidar-based maps.
Photo-interpreted maps are time consuming to produce, subjective in nature, and difficult to replicate. SDMs provide
a framework for efficiently producing habitat maps that can be replicated as habitat conditions change over
time, provided that comparable remotely sensed data are available. When the SDM uses predictor variables extracted
from lidar data, it can produce a habitat map that is both accurate and useful at large and small spatial scales. In comparison, SDMs using Landsat-based data are more appropriate for large scale analyses of amounts
and general spatial patterns of habitat at regional scales.Keywords: GNN,
Landsat TM,
Northern spotted owl,
Maxent,
Species distribution modeling,
Lidar,
Habitat suitabilit
An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein
Campylobacter jejuni is a Gram-negative food-borne pathogen associated with gastroenteritis in humans as well as cases of the autoimmune disease Guillain Barre syndrome. C. jejuni is asaccharolytic because it lacks an active glycolytic pathway for the use of sugars as a carbon source. This suggests an increased reliance on amino acids as nutrients and indeed the genome sequence of this organism indicates the presence of a number of amino acid uptake systems. Cj0982, also known as CjaA, is a putative extracytoplasmic solute receptor for one such uptake system as well as a major surface antigen and vaccine candidate. The crystal structure of Cj0982 reveals a two-domain protein with density in the enclosed cavity between the domains that clearly defines the presence of a bound cysteine ligand. Fluorescence titration experiments were used to demonstrate that Cj0982 binds cysteine tightly and specifically with a K-d of similar to 10(-7) M consistent with a role as a receptor for a high- affinity transporter. These data imply that Cj0982 is the binding protein component of an ABC-type cysteine transporter system and that cysteine uptake is important in the physiology of C. jejuni
Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140217/1/sur.2013.9999.pd
The ACS Nearby Galaxy Survey Treasury
The ACS Nearby Galaxy Survey Treasury (ANGST) is a systematic survey to
establish a legacy of uniform multi-color photometry of resolved stars for a
volume-limited sample of nearby galaxies (D<4 Mpc). The survey volume
encompasses 69 galaxies in diverse environments, including close pairs, small &
large groups, filaments, and truly isolated regions. The galaxies include a
nearly complete range of morphological types spanning a factor of ~10^4 in
luminosity and star formation rate. The survey data consists of images taken
with ACS on HST, supplemented with archival data and new WFPC2 imaging taken
after the failure of ACS. Survey images include wide field tilings covering the
full radial extent of each galaxy, and single deep pointings in uncrowded
regions of the most massive galaxies in the volume. The new wide field imaging
in ANGST reaches median 50% completenesses of m_F475W=28.0 mag, m_F606W=27.3
mag, and m_F814W=27.3 mag, several magnitudes below the tip of the red giant
branch (TRGB). The deep fields reach magnitudes sufficient to fully resolve the
structure in the red clump. The resulting photometric catalogs are publicly
accessible and contain over 34 million photometric measurements of >14 million
stars. In this paper we present the details of the sample selection, imaging,
data reduction, and the resulting photometric catalogs, along with an analysis
of the photometric uncertainties (systematic and random), for both the ACS and
WFPC2 imaging. We also present uniformly derived relative distances measured
from the apparent magnitude of the TRGB.Comment: 54 pages, including 24 pages of figures and 16 pages of tables.
Project website and data available at http://www.nearbygalaxies.org/ . Data
is also available through MAST. Scheduled to appear in the Astrophysical
Journal Supplements. (Replaced to fix several figures that were damaged
during compression
Bichromatic beam splitter for three-level atoms
We investigate schemes for the clean splitting of beams of three-level atoms using two standing-wave laser fields within an optical cavity. The proposed beam splitter is shown to work for atoms in the Λ ladder, and ssV configurations. For appropriate values of Rabi frequencies and detunings, we obtain a triangular type of potential for the atomic states of interest. As well as modeling the coherent evolution of the systems, we have used quantum Monte Carlo wave-function methods to model the effects of spontaneous emission on the resulting diffraction pattern, finding significant differences between the three configurations. We also investigate the limits of the Raman-Nath approximation for our systems, using the symmetric split-operator technique to include the effects of the kinetic term in the Hamiltonian. We also present the results of calculations in which the split output beams are recombined, demonstrating the expected interference for differently prepared input beams. In comparison with two-level beam splitters using a single standing wave, we obtain a superior splitting, while, in comparison with magneto-optical beam splitters, our system possesses the worthwhile practical advantages of experimental simplicity
Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017
Objective: To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients. Participants: A multispecialty task force of 16 international experts in critical care medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine. Design/Methods: The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members. Results: The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60min of < 9 g/dL) after cosyntropin (250 g) administration and a random plasma cortisol of < 10 g/dL may be used by clinicians. We suggest against using plasma-free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using IV hydrocortisone < 400mg/day for 3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO(2) < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence). Conclusions: Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force
Critical Illness-Related Corticosteroid Insufficiency (CIRCI): A Narrative Review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)
Objective: To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI). Participants: A multi-specialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Data Sources: Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews. Results: Three major pathophysiologic events were considered to constitute CIRCI: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids. The dysregulation of the HPA axis is complex, involving multidirectional crosstalk between the CRH/ACTH pathways, autonomic nervous system, vasopressinergic system, and immune system. Recent studies have demonstrated that plasma clearance of cortisol is markedly reduced during critical illness, explained by suppressed expression and activity of the primary cortisol-metabolizing enzymes in the liver and kidney. Despite the elevated cortisol levels during critical illness, tissue resistance to glucocorticoids is believed to occur due to insufficient glucocorticoid alpha-mediated anti-inflammatory activity. Conclusions: Novel insights into the pathophysiology of CIRCI add to the limitations of the current diagnostic tools to identify at-risk patients and may also impact how corticosteroids are used in patients with CIRCI
Measurement of the scintillation time spectra and pulse-shape discrimination of low-energy beta and nuclear recoils in liquid argon with DEAP-1
The DEAP-1 low-background liquid argon detector was used to measure
scintillation pulse shapes of electron and nuclear recoil events and to
demonstrate the feasibility of pulse-shape discrimination (PSD) down to an
electron-equivalent energy of 20 keV.
In the surface dataset using a triple-coincidence tag we found the fraction
of beta events that are misidentified as nuclear recoils to be (90% C.L.) for energies between 43-86 keVee and for a nuclear recoil
acceptance of at least 90%, with 4% systematic uncertainty on the absolute
energy scale. The discrimination measurement on surface was limited by nuclear
recoils induced by cosmic-ray generated neutrons. This was improved by moving
the detector to the SNOLAB underground laboratory, where the reduced background
rate allowed the same measurement with only a double-coincidence tag.
The combined data set contains events. One of those, in the
underground data set, is in the nuclear-recoil region of interest. Taking into
account the expected background of 0.48 events coming from random pileup, the
resulting upper limit on the electronic recoil contamination is
(90% C.L.) between 44-89 keVee and for a nuclear recoil
acceptance of at least 90%, with 6% systematic uncertainty on the absolute
energy scale.
We developed a general mathematical framework to describe PSD parameter
distributions and used it to build an analytical model of the distributions
observed in DEAP-1. Using this model, we project a misidentification fraction
of approx. for an electron-equivalent energy threshold of 15 keV for
a detector with 8 PE/keVee light yield. This reduction enables a search for
spin-independent scattering of WIMPs from 1000 kg of liquid argon with a
WIMP-nucleon cross-section sensitivity of cm, assuming
negligible contribution from nuclear recoil backgrounds.Comment: Accepted for publication in Astroparticle Physic
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