The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling

The kinases MSK1 and MSK2 are activated 'downstream' of the p38 and Erk1/2 mitogen-activated protein kinases. Here we found that MSK1 and MSK2 were needed to limit the production of proinflammatory cytokines in response to stimulation of primary macrophages with lipopolysaccharide. By inducing transcription of the mitogen-activated protein kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10, MSK1 and MSK2 exerted many negative feedback mechanisms. Deficiency in MSK1 and MSK2 prevented the binding of phosphorylated transcription factors CREB and ATF1 to the promoters of the genes encoding interleukin 10 and DUSP1. Mice doubly deficient in MSK1 and MSK2 were hypersensitive to lipopolysaccharide-induced endotoxic shock and showed prolonged inflammation in a model of toxic contact eczema induced by phorbol 12-myristate 13-acetate. Our results establish MSK1 and MSK2 as key components of negative feedback mechanisms needed to limit Toll-like receptor-driven inflammation.</p

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for high-mass dilepton resonances in pp collisions at s√=8 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to dielectron or dimuon final states. Results are presented from an analysis of proton-proton (pp) collisions at a center-of-mass energy of 8 TeV corresponding to an integrated luminosity of 20.3  fb−1 in the dimuon channel. A narrow resonance with Standard Model Z couplings to fermions is excluded at 95% confidence level for masses less than 2.79 TeV in the dielectron channel, 2.53 TeV in the dimuon channel, and 2.90 TeV in the two channels combined. Limits on other model interpretations are also presented, including a grand-unification model based on the E6 gauge group, Z∗ bosons, minimal Z' models, a spin-2 graviton excitation from Randall-Sundrum models, quantum black holes, and a minimal walking technicolor model with a composite Higgs boson

Addendum to ‘measurement of the tt̄ production cross-section using eμ events with b-tagged jets in pp collisions at √s= 7 and 8 TeV with the ATLAS detector’

The ATLAS measurement of the inclusive top quark pair (tt̄) cross-section σtt̄ in proton–proton collisions at √s=8 TeV has been updated using the final 2012 luminosity calibration. The updated cross-section result is: σtt¯=242.9±1.7±5.5±5.1±4.2pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, knowledge of the integrated luminosity and of the LHC beam energy. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. The measurement of the ratio of tt̄ cross-sections at √s=8 TeV and √s=7 TeV, and the √s=8 TeV fiducial measurement corresponding to the experimental acceptance of the leptons, have also been updated. The most precise measurement of the tt̄ cross-section (σtt̄) in proton–proton collisions at √s=8 TeV from the ATLAS Collaboration was made using events with an opposite-charge electron–muon pair and one or two b-tagged jets [1], and used a preliminary calibration of the integrated luminosity. The luminosity calibration has been finalised since [2] with a total uncertainty of 1.9%, corresponding to a substantial improvement on the previous uncertainty of 2.8%. Since the uncertainty on the integrated luminosity contributed 3.1% of the total 4.3% uncertainty on the σtt¯ measurement reported in [1], a significant improvement in the measurement is possible by using the new luminosity calibration, as documented in this Addendum. The new calibration corresponds to an integrated luminosity of 20.2 fb−¹ for the √s=8 TeV sample, a decrease of 0.2%. The cross-section was recomputed taking into account the effects on both the conversion of the tt¯ event yield to a cross-section, and the background estimates, giving a result of: σtt¯=242.9±1.7±5.5±5.1±4.2pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, knowledge of the integrated luminosity, and of the LHC beam energy, giving a total uncertainty of 8.8 pb (3.6 %). The result is consistent with the theoretical prediction of 252.9−14.5+13.3 pb, calculated at next-to-next-to-leading-order with next-to-next-to-leading-logarithmic soft gluon terms with the top++ 2.0 program [3] as discussed in detail in Ref. [1]. The updated value of the ratio of cross-sections Rtt¯=σtt¯(8 TeV)/σtt¯(7 TeV) is: Rtt¯=1.328±0.024±0.015±0.038±0.001, with uncertainties defined as above, adding in quadrature to a total of 0.047. The largest uncertainty comes from the uncertainties on the integrated luminosities, considered to be uncorrelated between the √s=7 TeV and √s=8 TeV datasets. This result is 2.1σ below the expectation of 1.430±0.013 calculated from top++ 2.0 as discussed in Ref. [1]. The updated fiducial cross-sections, for a tt¯ decay producing an eμ pair within a given fiducial region, are shown in Table 1, updating Table 5 of Ref. [1]. The results are given both for the analysis requirements of pT>25GeV and |η|30GeV and |η|<2.4. They are given separately for the two cases where events with either one or both leptons coming from t→W→τ→ℓ rather than the direct decay t→W→ℓ(ℓ=e or μ) are included, or where the contributions involving τ decays are subtracted. The results shown for the √s=7 TeV data sample are unchanged with respect to those in Ref. [1]. The results for the top quark pole mass and limits on light supersymmetric top squarks presented in Ref. [1] are derived from √s=7 TeV and √s=8 TeV cross-section measurements taken together, and would be only slightly improved by the luminosity update described here

Search for new phenomena in the dijet mass distribution using pp collision data at √s = 8 TeV with the ATLAS detector

Dijet events produced in LHC proton-proton collisions at a center-of-mass energy √s=8  TeV are studied with the ATLAS detector using the full 2012 data set, with an integrated luminosity of 20.3  fb−1. Dijet masses up to about 4.5 TeV are probed. No resonancelike features are observed in the dijet mass spectrum. Limits on the cross section times acceptance are set at the 95% credibility level for various hypotheses of new phenomena in terms of mass or energy scale, as appropriate. This analysis excludes excited quarks with a mass below 4.06 TeV, color-octet scalars with a mass below 2.70 TeV, heavy W′ bosons with a mass below 2.45 TeV, chiral W∗ bosons with a mass below 1.75 TeV, and quantum black holes with six extra space-time dimensions with threshold mass below 5.66 TeV