Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Exclusive J/psi Photoproduction off Protons in Ultraperipheral p-Pb Collisions at root s(NN)=5.02 TeV

We present the first measurement at the LHC of exclusive J/psi photoproduction off protons, in ultraperipheral proton-lead collisions at root s(NN) = 5.02 TeV. Events are selected with a dimuon pair produced either in the rapidity interval, in the laboratory frame, 2.5 J/psi + p) are 33.2 +/- 2.2(stat) +/- 3.2(syst) +/- 0.7(theor) nb in p-Pb and 284 +/- 36(stat)(-32)(+27)(syst) +/- 26(theor) nb in Pb-p collisions. We measure this process up to about 700 GeV in the gamma p center of mass, which is a factor of two larger than the highest energy studied at HERA. The data are consistent with a power law dependence of the J/psi photoproduction cross section in gamma p energies from about 20 to 700 GeV, or equivalently, from Bjorken x scaling variable between similar to 2 x 10(-2) and similar to 2 x 10(-5), thus indicating no significant change in the gluon density behavior of the proton between HERA and LHC energies

Measurement of the inclusive differential jet cross section in pp collisions at root s=2.76 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The ALICE Collaboration at the CERN Large Hadron Collider reports the first measurement of the inclusive differential jet cross section at mid-rapidity in pp collisions at root s = 2.76 TeV, with integrated luminosity of 13.6 nb(-1). Jets are measured over the transverse momentum range 20 to 125 GeV/c and are corrected to the particle level. Calculations based on Next-to-Leading Order perturbative QCD are in good agreement with the measurements. The ratio of inclusive jet cross sections for jet radii R = 0.2 and R = 0.4 is reported, and is also well reproduced by a Next-to-Leading Order perturbative QCD calculation when hadronization effects are included. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.72241763262272State Committee of Science, ArmeniaCalouste Gulbenkian Foundation from Lisbon, ArmeniaSwiss Fonds Kidagan, ArmeniaConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financiadora de Estudos e Projetos (FINEP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Natural Science Foundation of China (NSFC)Chinese Ministry of Education (CMOE)Ministry of Science and Technology of China (MSTC)Ministry of Education and Youth of the Czech RepublicDanish Natural Science Research CouncilCarlsberg FoundationDanish National Research FoundationThe European Research Council under the European Community's Seventh Framework ProgrammeHelsinki Institute of PhysicsAcademy of FinlandFrench CNRS-IN2P3, France'Region Pays de Loire', France'Region Alsace', France'Region Auvergne', FranceCEA, FranceGerman BMBFHelmholtz AssociationGeneral Secretariat for Research and Technology, Ministry of Development, GreeceHungarian OTKANational Office for Research and Technology (NKTH)Department of Atomic Energy of the Government of IndiaDepartment of Science and Technology of the Government of IndiaIstituto Nazionale di Fisica Nucleate (INFN), ItalyCentro Fermi - Museo Storico della Fisica e Centro Studi e Ricerche "Enrico Fermi", ItalyMEXT Grant-in-Aid for Specially Promoted Research, JapanJoint Institute for Nuclear Research, DubnaNational Research Foundation of Korea (NRF)CONACYT, MexicoDGAPA, MexicoALFA-ECHELEN Program (High-Energy Physics Latin-American-European Network)Stichting voor Fundamenteel Onderzoek der Materie (FOM), NetherlandsNederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO), NetherlandsResearch Council of Norway (NFR)Polish Ministry of Science and Higher EducationNational Authority for Scientific Research - NASR (Autoritatea Nationala pentru Cercetare Stiintifica - ANCS)Ministry of Education and Science of Russian FederationInternational Science and Technology CenterRussian Academy of SciencesRussian Federal Agency of Atomic EnergyRussian Federal Agency for Science and InnovationsCERN-INTASMinistry of Education of SlovakiaDepartment of Science and Technology, South AfricaCIEMAT, CubaEELA, CubaMinisterio de Educacion y Ciencia of Spain, CubaXunta de Galicia (Conselleria de Educacion), CubaCEADEN, CubaCubaenergia, CubaIAEA (International Atomic Energy Agency)Swedish Research Council (VR)Knut & Alice Wallenberg Foundation (KAW)Ukraine Ministry of Education and ScienceUnited Kingdom Science and Technology Facilities Council (STFC)The United States Department of EnergyUnited States National Science FoundationState of TexasState of OhioConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Measurement of charged jet suppression in Pb-Pb collisions at sNN\sqrt{s_{NN}}=2.76TeV

A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at $\sqrt{s_{NN}}$=2.76TeV is reported. Jets are reconstructed from charged particles using the anti-$k_T$ jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |$\eta$|<0.5. The transverse momentum p_T of charged particles is measured down to 0.15 GeV/c which gives access to the low p_T fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R=0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high p_T leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with R=0.2 and R=0.3 is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with R<0.3.A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at $\sqrt{s_{\rm NN}}=2.76$ TeV is reported. Jets are reconstructed from charged particles using the anti-$k_{\rm T}$ jet algorithm with jet resolution parameters $R$ of $0.2$ and $0.3$ in pseudo-rapidity $|\eta|<0.5$. The transverse momentum $p_{\rm T}$ of charged particles is measured down to $0.15$ GeV/$c$ which gives access to the low $p_{\rm T}$ fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter $R=0.3$ considered in the analysis. The fragmentation bias introduced by selecting jets with a high $p_{\rm T}$ leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with $R=0.2$ and $R=0.3$ is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with $R<0.3$

Measurement of electrons from semileptonic heavy-flavor hadron decays in pp collisions at root s=2.76 TeV

The p(T)-differential production cross section of electrons from semileptonic decays of heavy-flavor hadrons has been measured at midrapidity in proton-proton collisions at root s = 2.76 TeV in the transverse momentum range 0.5 < p(T) < 12 GeV/c with the ALICE detector at the LHC. The analysis was performed using minimum bias events and events triggered by the electromagnetic calorimeter. Predictions from perturbative QCD calculations agree with the data within the theoretical and experimental uncertainties

Long-range angular correlations of pi, K and p in p-Pb collisions at root s(NN)=5.02 TeV

Angular correlations between unidentified charged trigger particles and various species of charged associated particles (unidentified particles, pions, kaons, protons and antiprotons) are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV in the transverse-momentum range 0.3 < p(T) < 4 GeV/c. The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range vertical bar n(lab)vertical bar < 0.8. Fourier coefficients are extracted from the long-range correlations projected onto the azimuthal angle difference and studied as a function of p(T) and in intervals of event multiplicity. In high-multiplicity events, the second-order coefficient for protons, 4, is observed to be smaller than that for pions, v(2)(pi), up to about p(T) = 2 GeV/c. To reduce correlations due to jets, the per-trigger yield measured in low-multiplicity events is subtracted from that in high-multiplicity events. A two-ridge structure is obtained for all particle species. The Fourier decomposition of this structure shows that the second-order coefficients for pions and kaons are similar. The v(2)(p) is found to be smaller at low P-T and larger at higher p(T) than v(2)(pi), with a crossing occurring at about 2 GeV/c. This is qualitatively similar to the elliptic-flow pattern observed in heavy-ion collisions. A mass ordering effect at low transverse momenta is consistent with expectations from hydrodynamic model calculations assuming a collectively expanding system. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.7264169916417