303 research outputs found
Radiogenic and Muon-Induced Backgrounds in the LUX Dark Matter Detector
The Large Underground Xenon (LUX) dark matter experiment aims to detect rare
low-energy interactions from Weakly Interacting Massive Particles (WIMPs). The
radiogenic backgrounds in the LUX detector have been measured and compared with
Monte Carlo simulation. Measurements of LUX high-energy data have provided
direct constraints on all background sources contributing to the background
model. The expected background rate from the background model for the 85.3 day
WIMP search run is
~events~keV~kg~day
in a 118~kg fiducial volume. The observed background rate is
~events~keV~kg~day,
consistent with model projections. The expectation for the radiogenic
background in a subsequent one-year run is presented.Comment: 18 pages, 12 figures / 17 images, submitted to Astropart. Phy
Signal yields, energy resolution, and recombination fluctuations in liquid xenon
This work presents an analysis of monoenergetic electronic recoil peaks in
the dark-matter-search and calibration data from the first underground science
run of the Large Underground Xenon (LUX) detector. Liquid xenon charge and
light yields for electronic recoil energies between 5.2 and 661.7 keV are
measured, as well as the energy resolution for the LUX detector at those same
energies. Additionally, there is an interpretation of existing measurements and
descriptions of electron-ion recombination fluctuations in liquid xenon as
limiting cases of a more general liquid xenon re- combination fluctuation
model. Measurements of the standard deviation of these fluctuations at
monoenergetic electronic recoil peaks exhibit a linear dependence on the number
of ions for energy deposits up to 661.7 keV, consistent with previous LUX
measurements between 2-16 keV with H. We highlight similarities in liquid
xenon recombination for electronic and nuclear recoils with a comparison of
recombination fluctuations measured with low-energy calibration data.Comment: 11 pages, 12 figures, 3 table
Histone Deacetylase 9 Activates IKK to Regulate Atherosclerotic Plaque Vulnerability
Rationale: Arterial inflammation manifested as atherosclerosis is the leading cause of mortality worldwide. Genome-wide association studies have identified a prominent role of histone deacetylase 9 (HDAC9) in atherosclerosis and its clinical complications including stroke and myocardial infarction.
Objective: To determine the mechanisms linking HDAC9 to these vascular pathologies and explore its therapeutic potential for atheroprotection.
Methods and Results: We studied the effects of Hdac9 on features of plaque vulnerability using bone marrow reconstitution experiments and pharmacological targeting with a small molecule inhibitor in hyperlipidemic mice. We further employed two-photon and intravital microscopy to study endothelial activation and leukocyte-endothelial interactions. We show that hematopoietic Hdac9 deficiency reduces lesional macrophage content whilst increasing fibrous cap thickness thus conferring plaque stability. We demonstrate that HDAC9 binds to IKKα and β resulting in their deacetylation and subsequent activation, which drives inflammatory responses in both macrophages and endothelial cells. Pharmacological inhibition of HDAC9 with the class IIa HDAC inhibitor TMP195 attenuates lesion formation by reducing endothelial activation and leukocyte recruitment along with limiting pro-inflammatory responses in macrophages. Transcriptional profiling using RNA-Seq revealed that TMP195 downregulates key inflammatory pathways consistent with inhibitory effects on IKKβ. TMP195 mitigates the progression of established lesions and inhibits the infiltration of inflammatory cells. Moreover, TMP195 diminishes features of plaque vulnerability and thereby enhances plaque stability in advanced lesions. Ex vivo treatment of monocytes from patients with established atherosclerosis reduced the production of inflammatory cytokines including IL-1β and IL-6.
Conclusions: Our findings identify HDAC9 as a regulator of atherosclerotic plaque stability and IKK activation thus providing a mechanistic explanation for the prominence of HDAC9 as a vascular risk locus in genome-wide association studies. Its therapeutic inhibition may provide a potent lever to alleviate vascular inflammation
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