The Transcriptional Response in Human Umbilical Vein Endothelial Cells Exposed to Insulin: A Dynamic Gene Expression Approach

BACKGROUND: In diabetes chronic hyperinsulinemia contributes to the instability of the atherosclerotic plaque and stimulates cellular proliferation through the activation of the MAP kinases, which in turn regulate cellular proliferation. However, it is not known whether insulin itself could increase the transcription of specific genes for cellular proliferation in the endothelium. Hence, the characterization of transcriptional modifications in endothelium is an important step for a better understanding of the mechanism of insulin action and the relationship between endothelial cell dysfunction and insulin resistance. METHODOLOGY AND PRINCIPAL FINDINGS: The transcriptional response of endothelial cells in the 440 minutes following insulin stimulation was monitored using microarrays and compared to a control condition. About 1700 genes were selected as differentially expressed based on their treated minus control profile, thus allowing the detection of even small but systematic changes in gene expression. Genes were clustered in 7 groups according to their time expression profile and classified into 15 functional categories that can support the biological effects of insulin, based on Gene Ontology enrichment analysis. In terms of endothelial function, the most prominent processes affected were NADH dehydrogenase activity, N-terminal myristoylation domain binding, nitric-oxide synthase regulator activity and growth factor binding. Pathway-based enrichment analysis revealed "Electron Transport Chain" significantly enriched. Results were validated on genes belonging to "Electron Transport Chain" pathway, using quantitative RT-PCR. CONCLUSIONS: As far as we know, this is the first systematic study in the literature monitoring transcriptional response to insulin in endothelial cells, in a time series microarray experiment. Since chronic hyperinsulinemia contributes to the instability of the atherosclerotic plaque and stimulates cellular proliferation, some of the genes identified in the present work are potential novel candidates in diabetes complications related to endothelial dysfunction

Determination of jet calibration and energy resolution in proton–proton collisions at s = 8 TeV using the ATLAS detector

Abstract: The jet energy scale, jet energy resolution, and their systematic uncertainties are measured for jets reconstructed with the ATLAS detector in 2012 using proton–proton data produced at a centre-of-mass energy of 8 TeV with an integrated luminosity of 20fb-1. Jets are reconstructed from clusters of energy depositions in the ATLAS calorimeters using the anti-kt algorithm. A jet calibration scheme is applied in multiple steps, each addressing specific effects including mitigation of contributions from additional proton–proton collisions, loss of energy in dead material, calorimeter non-compensation, angular biases and other global jet effects. The final calibration step uses several in situ techniques and corrects for residual effects not captured by the initial calibration. These analyses measure both the jet energy scale and resolution by exploiting the transverse momentum balance in γ + jet, Z + jet, dijet, and multijet events. A statistical combination of these measurements is performed. In the central detector region, the derived calibration has a precision better than 1% for jets with transverse momentum 150GeV<pT< 1500 GeV, and the relative energy resolution is (8.4±0.6)% for pT=100GeV and (23±2)% for pT=20GeV. The calibration scheme for jets with radius parameter R=1.0, for which jets receive a dedicated calibration of the jet mass, is also discussed

Combination of the W boson polarization measurements in top quark decays using ATLAS and CMS data at s = 8 TeV

Abstract: The combination of measurements of the W boson polarization in top quark decays performed by the ATLAS and CMS collaborations is presented. The measurements are based on proton-proton collision data produced at the LHC at a centre-of-mass energy of 8 TeV, and corresponding to an integrated luminosity of about 20 fb−1 for each experiment. The measurements used events containing one lepton and having different jet multiplicities in the final state. The results are quoted as fractions of W bosons with longitudinal (F0), left-handed (FL), or right-handed (FR) polarizations. The resulting combined measurements of the polarization fractions are F0 = 0.693 ± 0.014 and FL = 0.315 ± 0.011. The fraction FR is calculated from the unitarity constraint to be FR = −0.008 ± 0.007. These results are in agreement with the standard model predictions at next-to-next-to-leading order in perturbative quantum chromodynamics and represent an improvement in precision of 25 (29)% for F0 (FL) with respect to the most precise single measurement. A limit on anomalous right-handed vector (VR), and left- and right-handed tensor (gL, gR) tWb couplings is set while fixing all others to their standard model values. The allowed regions are [−0.11, 0.16] for VR, [−0.08, 0.05] for gL, and [−0.04, 0.02] for gR, at 95% confidence level. Limits on the corresponding Wilson coefficients are also derived