SETD2 haploinsufficiency for microtubule methylation is an early driver of genomic instability in renal cell carcinoma

Loss of the short arm of chromosome 3 (3p) occurs early in >95% of clear cell renal cell carcinoma (ccRCC). Nearly ubiquitous 3p loss in ccRCC suggests haploinsufficiency for 3p tumor suppressors as early drivers of tumorigenesis. We previously reported methyltransferase SETD2, which trimethylates H3 histones on lysine 36 (H3K36me3) and is located in the 3p deletion, to also trimethylate microtubules on lysine 40 (aTubK40me3) during mitosis, with aTubK40me3 required for genomic stability. We now show that monoallelic, Setd2-deficient cells retaining H3K36me3, but not aTubK40me3, exhibit a dramatic increase in mitotic defects and micronuclei count, with increased viability compared with biallelic loss. In SETD2-inactivated human kidney cells, rescue with a pathogenic SETD2 mutant deficient for microtubule (aTubK40me3), but not histone (H3K36me3) methylation, replicated this phenotype. Genomic instability (micronuclei) was also a hallmark of patient-derived cells from ccRCC. These data show that the SETD2 tumor suppressor displays a haploinsufficiency phenotype disproportionately impacting microtubule methylation and serves as an early driver of genomic instability. Significance: Loss of a single allele of a chromatin modifier plays a role in promoting oncogenesis, underscoring the growing relevance of tumor suppressor haploinsufficiency in tumorigenesis

A New Class of Bianchi Type-I Cosmological Models in Scalar-Tensor Theory of Gravitation and Late Time Acceleration

A new class of a spatially homogeneous and anisotropic Bianchi type-I cosmological models of the universe for perfect fluid distribution within the framework of scalar-tensor theory of gravitation proposed by Saez and Ballester (Phys. Lett. 113:467, 1986) is investigated. To prevail the deterministic solutions we choose the different scale factors which yield time-dependent deceleration parameters (DP) representing models which generate a transition of the universe from the early decelerated phase to the recent accelerating phase. Three different physically viable models of the universe are obtained in which their anisotropic solutions may enter to some isotropic inflationary era. The modified Einstein's field equations are solved exactly and the models are found to be in good concordance with recent observations. Some physical and geometric properties of the models are also discussed.Comment: 16 pages, 8 figure

Accelerating Bianchi Type-V Cosmology with Perfect Fluid and Heat Flow in Saez-Ballester Theory

In this paper we discuss the law of variation of scale factor $a = (t^{k}e^{t})^{\frac{1}{n}}$ which yields a time-dependent deceleration parameter (DP) representing a new class of models that generate a transition of universe from the early decelerated phase to the recent accelerating phase. Exact solutions of Einstein's modified field equations with perfect fluid and heat conduction are obtained within the framework of Saez-Ballester scalar-tensor theory of gravitation and the model is found to be in good agreement with recent observations. We find, for n = 3, k = 1, the present value of DP in derived model as q_0 = -0.67 which is very near to the observed value of DP at present epoch. We find that the time-dependent DP is sensible for the present day Universe and give an earmark description of evolution of universe. Some physical and geometric properties of the models are also discussed.Comment: 12 pages, 5 figure

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Measurement of the inclusive 3-jet production differential cross section in proton-proton collisions at 7 TeV and determination of the strong coupling constant in the TeV range

This paper presents a measurement of the inclusive 3-jet production differential cross section at a proton–proton centre-of-mass energy of 7 TeV using data corresponding to an integrated luminosity of 5 fb-1 collected with the CMS detector. The analysis is based on the three jets with the highest transverse momenta. The cross section is measured as a function of the invariant mass of the three jets in a range of 445–3270 GeV and in two bins of the maximum rapidity of the jets up to a value of 2. A comparison between the measurement and the prediction from perturbative QCD at next-to-leading order is performed. Within uncertainties, data and theory are in agreement. The sensitivity of the observable to the strong coupling constant αS is studied. A fit to all data points with 3-jet masses larger than 664 GeV gives a value of the strong coupling constant of αS(MZ)=0.1171±0.0013(exp)-0.0047+0.0073(theo)

Measurements of the t(t)Overbar charge asymmetry using the dilepton decay channel in pp collisions at root s=7 TeV

The tt¯ charge asymmetry in proton-proton collisions at s√ = 7 TeV is measured using the dilepton decay channel (ee, e μ , or μμ ). The data correspond to a total integrated luminosity of 5.0 fb −1 , collected by the CMS experiment at the LHC. The tt and lepton charge asymmetries, defined as the differences in absolute values of the rapidities between the reconstructed top quarks and antiquarks and of the pseudorapidities between the positive and negative leptons, respectively, are measured to be A C = −0 . 010 ± 0 . 017 (stat . ) ± 0 . 008 (syst . ) and AlepC = 0 . 009 ± 0 . 010 (stat . ) ± 0 . 006 (syst . ). The lepton charge asymmetry is also measured as a function of the invariant mass, rapidity, and transverse momentum of the tt¯ system. All measurements are consistent with the expectations of the standard model

Measurement of the differential cross section for top quark pair production in pp collisions at √s=8 TeV

The normalized differential cross section for top quark pair (tt¯) production is measured in pp collisions at a centre-of-mass energy of 8TeV at the CERN LHC using the CMS detector in data corresponding to an integrated luminosity of 19.7fb-1. The measurements are performed in the lepton+jets (e/μ++jets) and in the dilepton e+e-, μ+μ-, and e±μ∓) decay channels. The tt¯ cross section is measured as a function of the kinematic properties of the charged leptons, the jets associated to b quarks, the top quarks, and the tt¯ system. The data are compared with several predictions from perturbative quantum chromodynamic up to approximate next-to-next-to-leading-order precision. No significant deviations are observed relative to the standard model predictions. © 2015, CERN for the benefit of the CMS collaboration

Measurement of prompt Jψ\psi pair production in pp collisions at \sqrt s = 7 Tev

Production of prompt J/ ψ meson pairs in proton-proton collisions at s s√ = 7 TeV is measured with the CMS experiment at the LHC in a data sample corresponding to an integrated luminosity of about 4.7 fb −1 . The two J/ ψ mesons are fully reconstructed via their decays into μ + μ − pairs. This observation provides for the first time access to the high-transverse-momentum region of J/ ψ pair production where model predictions are not yet established. The total and differential cross sections are measured in a phase space defined by the individual J/ ψ transverse momentum ( p T J/ ψ ) and rapidity (| y J/ ψ |): | y J/ ψ | 6.5 GeV/ c ; 1.2 4.5 GeV/ c . The total cross section, assuming unpolarized prompt J/ ψ pair production is 1.49 ± 0.07 (stat) ±0.13 (syst) nb. Different assumptions about the J/ ψ polarization imply modifications to the cross section ranging from −31% to +27%