GC-Rich Sequence Elements Recruit PRC2 in Mammalian ES Cells

Polycomb proteins are epigenetic regulators that localize to developmental loci in the early embryo where they mediate lineage-specific gene repression. In Drosophila, these repressors are recruited to sequence elements by DNA binding proteins associated with Polycomb repressive complex 2 (PRC2). However, the sequences that recruit PRC2 in mammalian cells have remained obscure. To address this, we integrated a series of engineered bacterial artificial chromosomes into embryonic stem (ES) cells and examined their chromatin. We found that a 44 kb region corresponding to the Zfpm2 locus initiates de novo recruitment of PRC2. We then pinpointed a CpG island within this locus as both necessary and sufficient for PRC2 recruitment. Based on this causal demonstration and prior genomic analyses, we hypothesized that large GC-rich elements depleted of activating transcription factor motifs mediate PRC2 recruitment in mammals. We validated this model in two ways. First, we showed that a constitutively active CpG island is able to recruit PRC2 after excision of a cluster of activating motifs. Second, we showed that two 1 kb sequence intervals from the Escherichia coli genome with GC-contents comparable to a mammalian CpG island are both capable of recruiting PRC2 when integrated into the ES cell genome. Our findings demonstrate a causal role for GC-rich sequences in PRC2 recruitment and implicate a specific subset of CpG islands depleted of activating motifs as instrumental for the initial localization of this key regulator in mammalian genomes.Burroughs Wellcome FundCharles E. Culpeper FoundationMassachusetts General HospitalBroad Institute of MIT and Harvar

Effect of Supplementation with Zinc and Other Micronutrients on Malaria in Tanzanian Children: A Randomised Trial

Hans Verhoef and colleagues report findings from a randomized trial conducted among Tanzanian children at high risk for malaria. Children in the trial received either daily oral supplementation with either zinc alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. The investigators did not find evidence from this study that zinc or multi-nutrients protected against malaria episodes

Search for anomalous couplings in the W tb vertex from the measurement of double differential angular decay rates of single top quarks produced in the t-channel with the ATLAS detector

The electroweak production and subsequent decay of single top quarks is determined by the properties of the Wtb vertex. This vertex can be described by the complex parameters of an effective Lagrangian. An analysis of angular distributions of the decay products of single top quarks produced in the t -channel constrains these parameters simultaneously. The analysis described in this paper uses 4.6 fb−1 of proton-proton collision data at √s =7 TeV collected with the ATLAS detector at the LHC. Two parameters are measured simultaneously in this analysis. The fraction f 1 of decays containing transversely polarised W bosons is measured to be 0.37 ± 0.07 (stat.⊕syst.). The phase δ − between amplitudes for transversely and longitudinally polarised W bosons recoiling against left-handed b-quarks is measured to be −0.014π ± 0.036π (stat.⊕syst.). The correlation in the measurement of these parameters is 0.15. These values result in two-dimensional limits at the 95% confidence level on the ratio of the complex coupling parameters g R and V L, yielding Re[g R /V L] ∈ [−0.36, 0.10] and Im[g R /V L] ∈ [−0.17, 0.23] with a correlation of 0.11. The results are in good agreement with the predictions of the Standard Model

Modelling Z → ττ processes in ATLAS with τ-embedded Z → μμ data

This paper describes the concept, technical realisation and validation of a largely data-driven method to model events with Z→ττ decays. In Z→μμ events selected from proton-proton collision data recorded at √s=8 TeV with the ATLAS experiment at the LHC in 2012, the Z decay muons are replaced by τ leptons from simulated Z→ττ decays at the level of reconstructed tracks and calorimeter cells. The τ lepton kinematics are derived from the kinematics of the original muons. Thus, only the well-understood decays of the Z boson and τ leptons as well as the detector response to the τ decay products are obtained from simulation. All other aspects of the event, such as the Z boson and jet kinematics as well as effects from multiple interactions, are given by the actual data. This so-called τ-embedding method is particularly relevant for Higgs boson searches and analyses in ττ final states, where Zarrowττ decays constitute a large irreducible background that cannot be obtained directly from data control samples. In this paper, the relevant concepts are discussed based on the implementation used in the ATLAS Standard Model H→ττ analysis of the full datataset recorded during 2011 and 2012

Measurements of the top quark branching ratios into channels with leptons and quarks with the ATLAS detector

We thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWFW and FWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; EPLANET, ERC and NSRF, European Union; IN2P3-CNRS, CEA-DSM/IRFU, France; GNSF, Georgia; BMBF, DFG, HGF Helmholtz Association, MPG and AvH Foundation, Germany; GSRT and NSRF, Greece; RGC, Hong Kong SAR, China; ISF, MINERVA, GIF, I-CORE and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; BRF and RCN, Norway; MNiSW and NCN, Poland; GRICES and FCT, Portugal; MNE/IFA, Romania; MES of Russia and NRC KI, Russian Federation; JINR; MSTD, Serbia; MSSR, Slovakia; ARRS and MIZŠ, Slovenia; DST/NRF, South Africa; MINECO, Spain; SRC and Wallenberg Foundation, Sweden; SER, SNSF and Cantons of Bern and Geneva, Switzerland; NSC, Taiwan; TAEK, Turkey; STFC, the Royal Society and Leverhulme Trust, United Kingdom; DOE and NSF, United States of America. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) and BNL (USA) and in the Tier-2 facilities worldwide

Determination of the ratio of b-quark fragmentation fractions fs/fd in pp collisions at √s = 7 TeV with the ATLAS Detector

With an integrated luminosity of 2.47  fb−1 recorded by the ATLAS experiment at the LHC, the exclusive decays B 0s→J/ψϕ and B0d→J/ψK*0 of B mesons produced in pp collisions at √s=7  TeV are used to determine the ratio of fragmentation fractions fs/fd. From the observed B0s→J/ψϕ and B0d→J/ψK*0 yields, the quantity (fs/fd)[B(B0s→J/ψϕ)/B(B 0d→J/ψK*0)] is measured to be 0.199±0.004(stat)±0.008(syst). Using a recent theory prediction for [B(B0s→J/ψϕ)/B(B0d→J/ψK*0)] yields (fs/fd)=0.240±0.004(stat)±0.010(syst)±0.017(th). This result is based on a new approach that provides a significant improvement of the world average

Measurement of the tt̄W and tt̄Z production cross sections in pp collisions at √s = 8 TeV with the ATLAS detector

The production cross sections of top-quark pairs in association with massive vector bosons have been measured using data from pp collisions at s√ = 8 TeV. The dataset corresponds to an integrated luminosity of 20.3 fb−¹ collected by the ATLAS detector in 2012 at the LHC. Final states with two, three or four leptons are considered. A fit to the data considering the tt̄W and tt̄Z processes simultaneously yields a significance of 5.0σ (4.2σ) over the background-only hypothesis for tt¯Wtt¯W (tt̄Z) production. The measured cross sections are σtt̄W = 369 + 100−91 fb and σtt̄Z = 176 + 58−52 fb. The background-only hypothesis with neither tt̄W nor tt̄Z production is excluded at 7.1σ. All measurements are consistent with next-to-leading-order calculations for the tt̄W and tt̄Z processes

Searches for Higgs boson pair production in the hh→bbττ, γγWW∗, γγbb, bbbb channels with the ATLAS detector

Searches for both resonant and nonresonant Higgs boson pair production are performed in the hh→bbττ, γγWW∗ final states using 20.3  fb−1 of pp collision data at a center-of-mass energy of 8 TeV recorded with the ATLAS detector at the Large Hadron Collider. No evidence of their production is observed and 95% confidence-level upper limits on the production cross sections are set. These results are then combined with the published results of the hh→γγbb, bbbb analyses. An upper limit of 0.69 (0.47) pb on the nonresonant hh production is observed (expected), corresponding to 70 (48) times the SM gg→hh cross section. For production via narrow resonances, cross-section limits of hh production from a heavy Higgs boson decay are set as a function of the heavy Higgs boson mass. The observed (expected) limits range from 2.1 (1.1) pb at 260 GeV to 0.011 (0.018) pb at 1000 GeV. These results are interpreted in the context of two simplified scenarios of the Minimal Supersymmetric Standard Model

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Search for the electroweak production of supersymmetric particles in sqrt(s)=8 TeV pp collisions with the ATLAS detector

The ATLAS experiment has performed extensive searches for the electroweak production of charginos, neutralinos, and staus. This article summarizes and extends the search for electroweak supersymmetry with new analyses targeting scenarios not covered by previously published searches. New searches use vectorboson fusion production, initial-state radiation jets, and low-momentum lepton final states, as well as multivariate analysis techniques to improve the sensitivity to scenarios with small mass splittings and low-production cross sections. Results are based on 20 fb−1 of proton-proton collision data at √s = 8 TeV recorded with the ATLAS experiment at the Large Hadron Collider. No significant excess beyond Standard Model expectations is observed. The new and existing searches are combined and interpreted in terms of 95% confidence-level exclusion limits in simplified models, where a single production process and decay mode is assumed, as well as within phenomenological supersymmetric models