269 research outputs found
A draft map of the mouse pluripotent stem cell spatial proteome.
Knowledge of the subcellular distribution of proteins is vital for understanding cellular mechanisms. Capturing the subcellular proteome in a single experiment has proven challenging, with studies focusing on specific compartments or assigning proteins to subcellular niches with low resolution and/or accuracy. Here we introduce hyperLOPIT, a method that couples extensive fractionation, quantitative high-resolution accurate mass spectrometry with multivariate data analysis. We apply hyperLOPIT to a pluripotent stem cell population whose subcellular proteome has not been extensively studied. We provide localization data on over 5,000 proteins with unprecedented spatial resolution to reveal the organization of organelles, sub-organellar compartments, protein complexes, functional networks and steady-state dynamics of proteins and unexpected subcellular locations. The method paves the way for characterizing the impact of post-transcriptional and post-translational modification on protein location and studies involving proteome-level locational changes on cellular perturbation. An interactive open-source resource is presented that enables exploration of these data.The authors thank Andreas Hühmer, Philip Remes, Jesse Canterbury and Graeme McAlister of Thermo Fisher Scientific, San Jose, CA, USA, for their advice regarding operation of the Orbitrap Fusion. We also thank Mike Deery for assistance with checking sample integrity on the mass spectrometers in the Cambridge Centre for Proteomics on equipment purchased via a Wellcome Trust grant (099135/Z/12/Z ), and Brian Hendrich of the Wellcome Trust-MRC Stem Cell Institute in Cambridge and Sean Munro of the MRC Laboratory of Molecular Biology in Cambridge for insightful comments about the data. AC was supported by BBSRC grant (BB/D526088/1). C.M.M. and L.G. were supported by European Union 7th Framework Program (PRIMEXS project, grant agreement number 262067), L.M.B was supported by a BBSRC Tools and Resources Development Fund (Award BB/K00137X/1), and P.C.H. was supported by an ERC Advanced Investigator grant to A.M.A. A.G. was funded through the Alexander S. Onassis Public Benefit Foundation, the Foundation for Education and European Culture (IPEP) and the Embiricos Trust Scholarship of Jesus College Cambridge. T.H. was supported by Commonwealth Split Site PhD Scholarship. T.N. was supported by an ERASMUS Placement scholarshipThis is the final version of the article. It was first available from NPG via http://dx.doi.org/10.1038/ncomms999
Prevention of ventilator-associated pneumonia: the multimodal approach of the spanish ICU pneumonia zero program.
Objectives:
The “Pneumonia Zero” project is a nationwide multimodal intervention based on the simultaneous implementation of a comprehensive evidence-based bundle measures to prevent ventilator-associated pneumonia in critically ill patients admitted to the ICU.
Design:
Prospective, interventional, and multicenter study.
Setting:
A total of 181 ICUs throughout Spain.
Patients:
All patients admitted for more than 24 hours to the participating ICUs between April 1, 2011, and December 31, 2012.
Intervention:
Ten ventilator-associated pneumonia prevention measures were implemented (seven were mandatory and three highly recommended). The database of the National ICU-Acquired Infections Surveillance Study (Estudio Nacional de Vigilancia de Infecciones Nosocomiales [ENVIN]) was used for data collection. Ventilator-associated pneumonia rate was expressed as incidence density per 1,000 ventilator days. Ventilator-associated pneumonia rates from the incorporation of the ICUs to the project, every 3 months, were compared with data of the ENVIN registry (April–June 2010) as the baseline period. Ventilator-associated pneumonia rates were adjusted by characteristics of the hospital, including size, type (public or private), and teaching (postgraduate) or university-affiliated (undergraduate) status.
Measurements and Main Results:
The 181 participating ICUs accounted for 75% of all ICUs in Spain. In a total of 171,237 ICU admissions, an artificial airway was present on 505,802 days (50.0% of days of stay in the ICU). A total of 3,474 ventilator-associated pneumonia episodes were diagnosed in 3,186 patients. The adjusted ventilator-associated pneumonia incidence density rate decreased from 9.83 (95% CI, 8.42–11.48) per 1,000 ventilator days in the baseline period to 4.34 (95% CI, 3.22–5.84) after 19–21 months of participation.
Conclusions:
Implementation of the bundle measures included in the “Pneumonia Zero” project resulted in a significant reduction of more than 50% of the incidence of ventilator-associated pneumonia in Spanish ICUs. This reduction was sustained 21 months after implementation
Evaluation of a system to feedback information on Public Health: the experience of Area 2 of the Community of Madrid
BACKGROUND: In January 2000 the Public Health Service of Area 2, in the Region of Madrid, began to publish a weekly sheet on epidemiological and public health information (HISP) addressed to health professionals working in the Area. The aim of the present study was to estimate to how extend the "HISP" was known among health professionals of Area 2, and also to estimate the suitability and usefulness of its contents, during 2000. METHODS: A postal survey was carried out among a random sample of professionals working in Area 2. A descriptive analysis of main variables was done, variables associated to the knowledge of the "HISP" were investigated. Epi Info 2000 program was used for the analysis. RESULTS: The response rate was 79.7%. The best evaluated content was that related to epidemic outbreaks. An association between knowing the "HISP" and knowing the regional epidemiological bulletin (Boletin Epidemiológico de la Comunidad de Madrid) was found (OR = 9.3, IC 95% = 2.9-29.5), and also an association between knowing the "HISP" and being a physician (OR = 4.3, IC: 1.5-12.6, p = 0.005). CONCLUSIONS: The "HISP" has a good acceptance among health professionals of Area 2. They were more interested in contents related to stressful situations. It is necessary to improve the diffusion of information on public health among nursing professionals. Fundamento: En enero del año 2000 el Servicio de Salud Pública del Área Sanitaria 2 de la Comunidad de Madrid, inició la edición semanal de una Hoja de Información en Salud Pública (HISP) dirigida a los profesionales de la salud del Área. El presente trabajo tiene como objetivo estimar el conocimiento, aceptabilidad, utilidad y difusión de la HISP durante el año 2000.
Métodos: Se realizó una encuesta por correo a una muestra de profesionales sanitarios del Área 2. Tras un análisis descriptivo se investigó, mediante análisis multivariante, qué factores explicaban que un profesional del Área conociera la HISP. Se utilizó el programa Epi Info 2000.
Resultados: La tasa de respuesta fue del 79,7%. El apartado mejor valorado fue el de alertas en salud pública. Se encontró una asociación entre conocer la HISP y conocer el Boletín Epidemiológico de la Comunidad de Madrid (OR=9,3, IC 95%=2,9-29,5), y entre ser médico y recibir información de salud pública (OR=4,3, IC:1,5-12,6, p=0,005).
Conclusiones: La HISP ha tenido buena aceptación entre los profesionales sanitarios del Área 2 que valoran más los contenidos relacionados con situaciones estresantes. Es necesario mejorar la difusión de la información de salud pública entre los profesionales de enfermería
The 2HWC HAWC Observatory Gamma Ray Catalog
We present the first catalog of TeV gamma-ray sources realized with the
recently completed High Altitude Water Cherenkov Observatory (HAWC). It is the
most sensitive wide field-of-view TeV telescope currently in operation, with a
1-year survey sensitivity of ~5-10% of the flux of the Crab Nebula. With an
instantaneous field of view >1.5 sr and >90% duty cycle, it continuously
surveys and monitors the sky for gamma ray energies between hundreds GeV and
tens of TeV.
HAWC is located in Mexico at a latitude of 19 degree North and was completed
in March 2015. Here, we present the 2HWC catalog, which is the result of the
first source search realized with the complete HAWC detector. Realized with 507
days of data and represents the most sensitive TeV survey to date for such a
large fraction of the sky. A total of 39 sources were detected, with an
expected contamination of 0.5 due to background fluctuation. Out of these
sources, 16 are more than one degree away from any previously reported TeV
source. The source list, including the position measurement, spectrum
measurement, and uncertainties, is reported. Seven of the detected sources may
be associated with pulsar wind nebulae, two with supernova remnants, two with
blazars, and the remaining 23 have no firm identification yet.Comment: Submitted 2017/02/09 to the Astrophysical Journa
The Sensitivity of HAWC to High-Mass Dark Matter Annihilations
The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view
detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in
central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC
will observe gamma rays and cosmic rays with an array of water Cherenkov
detectors. The full HAWC array is scheduled to be operational in Spring 2015.
In this paper, we study the HAWC sensitivity to the gamma-ray signatures of
high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be
sensitive to diverse searches for dark matter annihilation, including
annihilation from extended dark matter sources, the diffuse gamma-ray emission
from dark matter annihilation, and gamma-ray emission from non-luminous dark
matter subhalos. Here we consider the HAWC sensitivity to a subset of these
sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the
Galactic center. We simulate the HAWC response to gamma rays from these sources
in several well-motivated dark matter annihilation channels. If no gamma-ray
excess is observed, we show the limits HAWC can place on the dark matter
cross-section from these sources. In particular, in the case of dark matter
annihilation into gauge bosons, HAWC will be able to detect a narrow range of
dark matter masses to cross-sections below thermal. HAWC should also be
sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The
constraints placed by HAWC on the dark matter cross-section from known sources
should be competitive with current limits in the mass range where HAWC has
similar sensitivity. HAWC can additionally explore higher dark matter masses
than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR
Observation of the Crab Nebula with the HAWC Gamma-Ray Observatory
The Crab Nebula is the brightest TeV gamma-ray source in the sky and has been
used for the past 25 years as a reference source in TeV astronomy, for
calibration and verification of new TeV instruments. The High Altitude Water
Cherenkov Observatory (HAWC), completed in early 2015, has been used to observe
the Crab Nebula at high significance across nearly the full spectrum of
energies to which HAWC is sensitive. HAWC is unique for its wide field-of-view,
nearly 2 sr at any instant, and its high-energy reach, up to 100 TeV. HAWC's
sensitivity improves with the gamma-ray energy. Above 1 TeV the
sensitivity is driven by the best background rejection and angular resolution
ever achieved for a wide-field ground array.
We present a time-integrated analysis of the Crab using 507 live days of HAWC
data from 2014 November to 2016 June. The spectrum of the Crab is fit to a
function of the form . The data is well-fit with values of
, , and
log when
is fixed at 7 TeV and the fit applies between 1 and 37 TeV. Study of the
systematic errors in this HAWC measurement is discussed and estimated to be
50\% in the photon flux between 1 and 37 TeV.
Confirmation of the Crab flux serves to establish the HAWC instrument's
sensitivity for surveys of the sky. The HAWC survey will exceed sensitivity of
current-generation observatories and open a new view of 2/3 of the sky above 10
TeV.Comment: Submitted 2017/01/06 to the Astrophysical Journa
Daily monitoring of TeV gamma-ray emission from Mrk 421, Mrk 501, and the Crab Nebula with HAWC
We present results from daily monitoring of gamma rays in the energy range
to TeV with the first 17 months of data from the High
Altitude Water Cherenkov (HAWC) Observatory. Its wide field of view of 2
steradians and duty cycle of % are unique features compared to other TeV
observatories that allow us to observe every source that transits over HAWC for
up to hours each sidereal day. This regular sampling yields
unprecedented light curves from unbiased measurements that are independent of
seasons or weather conditions. For the Crab Nebula as a reference source we
find no variability in the TeV band. Our main focus is the study of the TeV
blazars Markarian (Mrk) 421 and Mrk 501. A spectral fit for Mrk 421 yields a
power law index and
an exponential cut-off
TeV. For Mrk 501, we find an index and exponential cut-off TeV. The light curves for both sources show clear
variability and a Bayesian analysis is applied to identify changes between flux
states. The highest per-transit fluxes observed from Mrk 421 exceed the Crab
Nebula flux by a factor of approximately five. For Mrk 501, several transits
show fluxes in excess of three times the Crab Nebula flux. In a comparison to
lower energy gamma-ray and X-ray monitoring data with comparable sampling we
cannot identify clear counterparts for the most significant flaring features
observed by HAWC.Comment: 18 pages, 10 figures, accepted for publication in The Astrophysical
Journa
All-particle cosmic ray energy spectrum measured by the HAWC experiment from 10 to 500 TeV
We report on the measurement of the all-particle cosmic ray energy spectrum
with the High Altitude Water Cherenkov (HAWC) Observatory in the energy range
10 to 500 TeV. HAWC is a ground based air-shower array deployed on the slopes
of Volcan Sierra Negra in the state of Puebla, Mexico, and is sensitive to
gamma rays and cosmic rays at TeV energies. The data used in this work were
taken from 234 days between June 2016 to February 2017. The primary cosmic-ray
energy is determined with a maximum likelihood approach using the particle
density as a function of distance to the shower core. Introducing quality cuts
to isolate events with shower cores landing on the array, the reconstructed
energy distribution is unfolded iteratively. The measured all-particle spectrum
is consistent with a broken power law with an index of prior to
a break at ) TeV, followed by an index of . The
spectrum also respresents a single measurement that spans the energy range
between direct detection and ground based experiments. As a verification of the
detector response, the energy scale and angular resolution are validated by
observation of the cosmic ray Moon shadow's dependence on energy.Comment: 16 pages, 11 figures, 4 tables, submission to Physical Review
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