3,365 research outputs found
ARID1A influences HDAC1/BRD4 activity, intrinsic proliferative capacity and breast cancer treatment response.
Using genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens to understand endocrine drug resistance, we discovered ARID1A and other SWI/SNF complex components as the factors most critically required for response to two classes of estrogen receptor-alpha (ER) antagonists. In this context, SWI/SNF-specific gene deletion resulted in drug resistance. Unexpectedly, ARID1A was also the top candidate in regard to response to the bromodomain and extraterminal domain inhibitor JQ1, but in the opposite direction, with loss of ARID1A sensitizing breast cancer cells to bromodomain and extraterminal domain inhibition. We show that ARID1A is a repressor that binds chromatin at ER cis-regulatory elements. However, ARID1A elicits repressive activity in an enhancer-specific, but forkhead box A1-dependent and active, ER-independent manner. Deletion of ARID1A resulted in loss of histone deacetylaseâ1 binding, increased histoneâ4 lysine acetylation and subsequent BRD4-driven transcription and growth. ARID1A mutations are more frequent in treatment-resistant disease, and our findings provide mechanistic insight into this process while revealing rational treatment strategies for these patients
Diagnosing Clostridioides difficile infections with molecular diagnostics: multicenter evaluation of revogene C. difficile assay
Clostridioides difficile infections are a significant threat to our healthcare system, and rapid and accurate diagnostics are crucial to implement the necessary infection prevention and control measurements. Nucleic acid amplification tests are such reliable diagnostic tools for the detection of toxigenic Clostridioides difficile strains directly from stool specimens. In this multicenter evaluation, we determined the performance of the revogene C. difficile assay. The analysis was conducted on prospective stool specimens collected from six different sites in Europe. The performance of the revogene C. difficile assay was compared to the different routine diagnostic methods and, for a subset of the specimens, against toxigenic culture. In total, 2621 valid stool specimens were tested, and the revogene C. difficile assay displayed a sensitivity/specificity of 97.1% [93.3-99.0] and 98.9% [98.5-99.3] for identification of Clostridioides difficile infection. Discrepancy analysis using additional methods improved this performance to 98.8% [95.8-99.9] and 99.6% [99.2-99.8], respectively. In comparison to toxigenic culture, the revogene C. difficile assay displayed a sensitivity/specificity of 93.0% [86.1-97.1] and 99.5% [98.7-99.9], respectively. These results indicate that the revogene C. difficile assay is a robust and reliable aid in the diagnosis of Clostridioides difficile infections.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This study was supported by grants from GenePOC, now part of Meridian Biosciences.published version, accepted versio
Detailed spectral and morphological analysis of the shell type SNR RCW 86
Aims: We aim for an understanding of the morphological and spectral
properties of the supernova remnant RCW~86 and for insights into the production
mechanism leading to the RCW~86 very high-energy gamma-ray emission. Methods:
We analyzed High Energy Spectroscopic System data that had increased
sensitivity compared to the observations presented in the RCW~86 H.E.S.S.
discovery publication. Studies of the morphological correlation between the
0.5-1~keV X-ray band, the 2-5~keV X-ray band, radio, and gamma-ray emissions
have been performed as well as broadband modeling of the spectral energy
distribution with two different emission models. Results:We present the first
conclusive evidence that the TeV gamma-ray emission region is shell-like based
on our morphological studies. The comparison with 2-5~keV X-ray data reveals a
correlation with the 0.4-50~TeV gamma-ray emission.The spectrum of RCW~86 is
best described by a power law with an exponential cutoff at TeV and a spectral index of ~. A static
leptonic one-zone model adequately describes the measured spectral energy
distribution of RCW~86, with the resultant total kinetic energy of the
electrons above 1 GeV being equivalent to 0.1\% of the initial kinetic
energy of a Type I a supernova explosion. When using a hadronic model, a
magnetic field of ~100G is needed to represent the measured data.
Although this is comparable to formerly published estimates, a standard
E spectrum for the proton distribution cannot describe the gamma-ray
data. Instead, a spectral index of ~1.7 would be required, which
implies that ~erg has been transferred into
high-energy protons with the effective density cm^-3. This
is about 10\% of the kinetic energy of a typical Type Ia supernova under the
assumption of a density of 1~cm^-3.Comment: accepted for publication by A&
Observation of two new baryon resonances
Two structures are observed close to the kinematic threshold in the mass spectrum in a sample of proton-proton collision data, corresponding
to an integrated luminosity of 3.0 fb recorded by the LHCb experiment.
In the quark model, two baryonic resonances with quark content are
expected in this mass region: the spin-parity and
states, denoted and .
Interpreting the structures as these resonances, we measure the mass
differences and the width of the heavier state to be
MeV,
MeV,
MeV, where the first and second
uncertainties are statistical and systematic, respectively. The width of the
lighter state is consistent with zero, and we place an upper limit of
MeV at 95% confidence level. Relative
production rates of these states are also reported.Comment: 17 pages, 2 figure
The exceptionally powerful TeV gamma-ray emitters in the Large Magellanic Cloud
The Large Magellanic Cloud, a satellite galaxy of the Milky Way, has been
observed with the High Energy Stereoscopic System (H.E.S.S.) above an energy of
100 billion electron volts for a deep exposure of 210 hours. Three sources of
different types were detected: the pulsar wind nebula of the most energetic
pulsar known N 157B, the radio-loud supernova remnant N 132D and the largest
non-thermal X-ray shell - the superbubble 30 Dor C. The unique object SN 1987A
is, surprisingly, not detected, which constrains the theoretical framework of
particle acceleration in very young supernova remnants. These detections reveal
the most energetic tip of a gamma-ray source population in an external galaxy,
and provide via 30 Dor C the unambiguous detection of gamma-ray emission from a
superbubble.Comment: Published in Science Magazine (Jan. 23, 2015). This ArXiv version has
the supplementary online material incorporated as an appendix to the main
pape
Measurement of the CKM angle Îł from a combination of B±âDh± analyses
A combination of three LHCb measurements of the CKM angle Îł is presented. The decays B±âD K± and
B±âDϱ are used, where D denotes an admixture of D0 and D0 mesons, decaying into K+Kâ, Ï+Ïâ, K±Ïâ, K±ÏâϱÏâ, K0SÏ+Ïâ, or K0S K+Kâ ïŹnal states. All measurements use a dataset corresponding to 1.0 fbâ1 of integrated luminosity. Combining results from B±âD K± decays alone a best-ïŹt value of
Îł =72.0⊠is found, and conïŹdence intervals are set
Îł â [56.4,86.7]⊠at 68% CL,
Îł â [42.6,99.6]⊠at 95% CL.
The best-ïŹt value of Îł found from a combination of results from B±âDϱ decays alone, is Îł =18.9âŠ,
and the conïŹdence intervals
Îł â [7.4,99.2]⊠âȘ [167.9,176.4]⊠at 68% CL
are set, without constraint at 95% CL. The combination of results from B± â D K± and B± â Dϱ
decays gives a best-ïŹt value of Îł =72.6⊠and the conïŹdence intervals
Îł â [55.4,82.3]⊠at 68% CL,
Îł â [40.2,92.7]⊠at 95% CL
are set. All values are expressed modulo 180âŠ, and are obtained taking into account the effect of D0âD0
mixing
Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma)
The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma
and Bs0 -> phi gamma has been measured using 0.37 fb-1 of pp collisions at a
centre of mass energy of sqrt(s) = 7 TeV, collected by the LHCb experiment. The
value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) = 1.12 +/- 0.08
^{+0.06}_{-0.04} ^{+0.09}_{-0.08}, where the first uncertainty is statistical,
the second systematic and the third is associated to the ratio of fragmentation
fractions fs/fd. Using the world average for BR(B0 -> K*0 gamma) = (4.33 +/-
0.15) x 10^{-5}, the branching fraction BR(Bs0 -> phi gamma) is measured to be
(3.9 +/- 0.5) x 10^{-5}, which is the most precise measurement to date.Comment: 15 pages, 1 figure, 2 table
- âŠ