Ectopic Expression Of Pericentric HSATII RNA Results In Nuclear RNA Accumulation, MeCP2 Recruitment, And Cell Division Defects

Within the pericentric regions of human chromosomes reside large arrays of tandemly repeated satellite sequences. Expression of the human pericentric satellite HSATII is prevented by extensive heterochromatin silencing in normal cells, yet in many cancer cells, HSATII RNA is aberrantly expressed and accumulates in large nuclear foci in cis. Expression and aggregation of HSATII RNA in cancer cells is concomitant with recruitment of key chromatin regulatory proteins including methyl-CpG binding protein 2 (MeCP2). While HSATII expression has been observed in a wide variety of cancer cell lines and tissues, the effect of its expression is unknown. We tested the effect of stable expression of HSATII RNA within cells that do not normally express HSATII. Ectopic HSATII expression in HeLa and primary fibroblast cells leads to focal accumulation of HSATII RNA in cis and triggers the accumulation of MeCP2 onto nuclear HSATII RNA bodies. Further, long-term expression of HSATII RNA leads to cell division defects including lagging chromosomes, chromatin bridges, and other chromatin defects. Thus, expression of HSATII RNA in normal cells phenocopies its nuclear accumulation in cancer cells and allows for the characterization of the cellular events triggered by aberrant expression of pericentric satellite RNA

Targeting host glycolysis as a strategy for antimalarial development

Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anemia is a known dose-limiting side effect of these inhibitors and presents a major caveat to development of antiglycolytic therapies. We developed specific inhibitors of enolase - a critical enzyme in glycolysis - and validated their metabolic and cellular effects on human erythrocytes. Enolase inhibition increases erythrocyte susceptibility to oxidative damage and induces rapid and premature erythrocyte senescence, rather than direct hemolysis. We apply our model of red cell toxicity to address questions regarding erythrocyte glycolytic disruption in the context o

Selection of the silicon sensor thickness for the Phase-2 upgrade of the CMS Outer Tracker

During the operation of the CMS experiment at the High-Luminosity LHC the silicon sensors of the Phase-2 Outer Tracker will be exposed to radiation levels that could potentially deteriorate their performance. Previous studies had determined that planar float zone silicon with n-doped strips on a p-doped substrate was preferred over p-doped strips on an n-doped substrate. The last step in evaluating the optimal design for the mass production of about 200 m$^{2}$ of silicon sensors was to compare sensors of baseline thickness (about 300 μm) to thinned sensors (about 240 μm), which promised several benefits at high radiation levels because of the higher electric fields at the same bias voltage. This study provides a direct comparison of these two thicknesses in terms of sensor characteristics as well as charge collection and hit efficiency for fluences up to 1.5 × 10$^{15}$ n$_{eq}$/cm$^{2}$. The measurement results demonstrate that sensors with about 300 μm thickness will ensure excellent tracking performance even at the highest considered fluence levels expected for the Phase-2 Outer Tracker

Test beam performance of a CBC3-based mini-module for the Phase-2 CMS Outer Tracker before and after neutron irradiation

The Large Hadron Collider (LHC) at CERN will undergo major upgrades to increase the instantaneous luminosity up to 5–7.5×10$^{34}$ cm$^{-2}$s$^{-1}$. This High Luminosity upgrade of the LHC (HL-LHC) will deliver a total of 3000–4000 fb-1 of proton-proton collisions at a center-of-mass energy of 13–14 TeV. To cope with these challenging environmental conditions, the strip tracker of the CMS experiment will be upgraded using modules with two closely-spaced silicon sensors to provide information to include tracking in the Level-1 trigger selection. This paper describes the performance, in a test beam experiment, of the first prototype module based on the final version of the CMS Binary Chip front-end ASIC before and after the module was irradiated with neutrons. Results demonstrate that the prototype module satisfies the requirements, providing efficient tracking information, after being irradiated with a total fluence comparable to the one expected through the lifetime of the experiment

Multiplicity and rapidity dependence of strange hadron production in pp, pPb, and PbPb collisions at the LHC

Peer reviewe

Search for narrow resonances in dilepton mass spectra in proton-proton collisions at root s=13 TeV and combination with 8 TeV data

Peer reviewe

Search for heavy gauge W ' bosons in events with an energetic lepton and large missing transverse momentum at root s=13TeV

Peer reviewe

Alignment of the CMS silicon tracker during commissioning with cosmic rays

The CMS silicon tracker, consisting of 1440 silicon pixel and 15 148 silicon strip detector modules, has been aligned using more than three million cosmic ray charged particles, with additional information from optical surveys. The positions of the modules were determined with respect to cosmic ray trajectories to an average precision of 3-4 microns RMS in the barrel and 3-14 microns RMS in the endcap in the most sensitive coordinate. The results have been validated by several studies, including laser beam cross-checks, track fit self-consistency, track residuals in overlapping module regions, and track parameter resolution, and are compared with predictions obtained from simulation. Correlated systematic effects have been investigated. The track parameter resolutions obtained with this alignment are close to the design performance

Measurement of B-s(0) meson production in pp and PbPb collisions at root S-NN=5.02 TeV

The production cross sections of B-s(0) mesons and charge conjugates are measured in proton-proton (pp) and PbPb collisions via the exclusive decay channel B-s(0)-> J/ psi phi ->mu(+) mu(-) K+K- at a center-of-mass energy of 5.02 TeV per nucleon pair and within the rapidity range vertical bar y vertical bar <2.4 using the CMS detector at the LHC. The pp measurement is performed as a function of transverse momentum (P-T) of the B-s(0), mesons in the range of 7 to 50 GeV/c and is compared to the predictions of perturbative QCD calculations. The B s production yield in PbPb collisions is measured in two F t intervals, 7 to 15 and 15 to 50 GeV/c, and compared to the yield in pp collisions in the same kinematic region. The nuclear modification factor (R-AA) is found to be 1.5 +/- 0.6(stat) +/- 0.5(syst) for 7-15 GeV/c, and 0.87 +/- 0.30(stat) +/- 0.1 7(syst) for 15-50 GeV/c, respectively. Within current uncertainties, the B-s(0) results are consistent with models of strangeness enhancement, and suppression by parton energy loss, as observed for the B+ mesons. Published by Elsevier B.V.Peer reviewe