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

Applications of electrified dust and dust devil electrodynamics to Martian atmospheric electricity

Atmospheric transport and suspension of dust frequently brings electrification, which may be substantial. Electric fields of 10 kVm-1 to 100 kVm-1 have been observed at the surface beneath suspended dust in the terrestrial atmosphere, and some electrification has been observed to persist in dust at levels to 5 km, as well as in volcanic plumes. The interaction between individual particles which causes the electrification is incompletely understood, and multiple processes are thought to be acting. A variation in particle charge with particle size, and the effect of gravitational separation explains to, some extent, the charge structures observed in terrestrial dust storms. More extensive flow-based modelling demonstrates that bulk electric fields in excess of 10 kV m-1 can be obtained rapidly (in less than 10 s) from rotating dust systems (dust devils) and that terrestrial breakdown fields can be obtained. Modelled profiles of electrical conductivity in the Martian atmosphere suggest the possibility of dust electrification, and dust devils have been suggested as a mechanism of charge separation able to maintain current flow between one region of the atmosphere and another, through a global circuit. Fundamental new understanding of Martian atmospheric electricity will result from the ExoMars mission, which carries the DREAMS (Dust characterization, Risk Assessment, and Environment Analyser on the Martian Surface)-MicroARES (Atmospheric Radiation and Electricity Sensor) instrumentation to Mars in 2016 for the first in situ measurements

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe

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

Search for the associated production of the Higgs boson with a top-quark pair

A search for the standard model Higgs boson produced in association with a top-quark pair t t ¯ H (tt¯H) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb −1 and 19.7 fb −1 collected in pp collisions at center-of-mass energies of 7 TeV and 8 TeV respectively. The search is based on the following signatures of the Higgs boson decay: H → hadrons, H → photons, and H → leptons. The results are characterized by an observed t t ¯ H tt¯H signal strength relative to the standard model cross section, μ = σ/σ SM ,under the assumption that the Higgs boson decays as expected in the standard model. The best fit value is μ = 2.8 ± 1.0 for a Higgs boson mass of 125.6 GeV

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)