The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

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

Measurements of differential cross-sections in top-quark pair events with a high transverse momentum top quark and limits on beyond the Standard Model contributions to top-quark pair production with the ATLAS detector at √s = 13 TeV

Cross-section measurements of top-quark pair production where the hadronically decaying top quark has transverse momentum greater than 355 GeV and the other top quark decays into ℓνb are presented using 139 fb−1 of data collected by the ATLAS experiment during proton-proton collisions at the LHC. The fiducial cross-section at s = 13 TeV is measured to be σ = 1.267 ± 0.005 ± 0.053 pb, where the uncertainties reflect the limited number of data events and the systematic uncertainties, giving a total uncertainty of 4.2%. The cross-section is measured differentially as a function of variables characterising the tt¯ system and additional radiation in the events. The results are compared with various Monte Carlo generators, including comparisons where the generators are reweighted to match a parton-level calculation at next-to-next-to-leading order. The reweighting improves the agreement between data and theory. The measured distribution of the top-quark transverse momentum is used to search for new physics in the context of the effective field theory framework. No significant deviation from the Standard Model is observed and limits are set on the Wilson coefficients of the dimension-six operators OtG and Otq(8), where the limits on the latter are the most stringent to date. [Figure not available: see fulltext.]

Search for new phenomena in high-mass diphoton final states using 37 fb−1 of proton–proton collisions collected at √s = 13 TeV with the ATLAS detector

Searches for new phenomena in high-mass diphoton final states with the ATLAS experiment at the LHC are presented. The analysis is based on pp collision data corresponding to an integrated luminosity of 36.7 fb−1 at a centre-of-mass energy √s = 13 TeV recorded in 2015 and 2016. Searches are performed for resonances with spin 0, as predicted by theories with an extended Higgs sector, and for resonances with spin 2, using a warped extra-dimension model as a benchmark model, as well as for non-resonant signals, assuming a large extra-dimension scenario. No significant deviation from the Standard Model is observed. Upper limits are placed on the production cross section times branching ratio to two photons as a function of the resonance mass. In addition, lower limits are set on the ultraviolet cutoff scale in the large extra-dimensions model

Measurement of VH, H → b b ¯ production as a function of the vector-boson transverse momentum in 13 TeV pp collisions with the ATLAS detector

Cross-sections of associated production of a Higgs boson decaying into bottom-quark pairs and an electroweak gauge boson, W or Z, decaying into leptons are measured as a function of the gauge boson transverse momentum. The measurements are performed in kinematic fiducial volumes defined in the `simplified template cross-section' framework. The results are obtained using 79.8 fb-1 of proton-proton collisions recorded by the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13 TeV. All measurements are found to be in agreement with the Standard Model predictions, and limits are set on the parameters of an effective Lagrangian sensitive to modifications of the Higgs boson couplings to the electroweak gauge bosons

Measurements of differential cross-sections in four-lepton events in 13 TeV proton-proton collisions with the ATLAS detector

Measurements of four-lepton differential and integrated fiducial cross-sections in events with two same-flavour, opposite-charge electron or muon pairs are presented. The data correspond to 139 fb−1 of s√ = 13 TeV proton-proton collisions, collected by the ATLAS detector during Run 2 of the Large Hadron Collider (2015–2018). The final state has contributions from a number of interesting Standard Model processes that dominate in different four-lepton invariant mass regions, including single Z boson production, Higgs boson production and on-shell ZZ production, with a complex mix of interference terms, and possible contributions from physics beyond the Standard Model. The differential cross-sections include the four-lepton invariant mass inclusively, in slices of other kinematic variables, and in different lepton flavour categories. Also measured are dilepton invariant masses, transverse momenta, and angular correlation variables, in four regions of four-lepton invariant mass, each dominated by different processes. The measurements are corrected for detector effects and are compared with state-of-the-art Standard Model calculations, which are found to be consistent with the data. The Z → 4ℓ branching fraction is extracted, giving a value of (4.41 ± 0.30) × 10−6. Constraints on effective field theory parameters and a model based on a spontaneously broken B − L gauge symmetry are also evaluated. Further reinterpretations can be performed with the provided information

Search for pair production of third-generation scalar leptoquarks decaying into a top quark and a τ-lepton in pp collisions at s√ = 13 TeV with the ATLAS detector

A search for pair production of third-generation scalar leptoquarks decaying into a top quark and a τ-lepton is presented. The search is based on a dataset of pp collisions at s√ = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Events are selected if they have one light lepton (electron or muon) and at least one hadronically decaying τ -lepton, or at least two light leptons. In addition, two or more jets, at least one of which must be identified as containing b-hadrons, are required. Six final states, defined by the multiplicity and flavour of lepton candidates, are considered in the analysis. Each of them is split into multiple event categories to simultaneously search for the signal and constrain several leading backgrounds. The signal-rich event categories require at least one hadronically decaying τ-lepton candidate and exploit the presence of energetic final-state objects, which is characteristic of signal events. No significant excess above the Standard Model expectation is observed in any of the considered event categories, and 95% CL upper limits are set on the production cross section as a function of the leptoquark mass, for different assumptions about the branching fractions into tτ and bν. Scalar leptoquarks decaying exclusively into tτ are excluded up to masses of 1.43 TeV while, for a branching fraction of 50% into tτ, the lower mass limit is 1.22 TeV

Muon reconstruction and identification efficiency in ATLAS using the full Run 2 pp collision data set at \sqrt{s}=13 TeV

This article documents the muon reconstruction and identification efficiency obtained by the ATLAS experiment for 139 \hbox {fb}^{-1} of pp collision data at \sqrt{s}=13 TeV collected between 2015 and 2018 during Run 2 of the LHC. The increased instantaneous luminosity delivered by the LHC over this period required a reoptimisation of the criteria for the identification of prompt muons. Improved and newly developed algorithms were deployed to preserve high muon identification efficiency with a low misidentification rate and good momentum resolution. The availability of large samples of Z\rightarrow \mu \mu and J/\psi \rightarrow \mu \mu decays, and the minimisation of systematic uncertainties, allows the efficiencies of criteria for muon identification, primary vertex association, and isolation to be measured with an accuracy at the per-mille level in the bulk of the phase space, and up to the percent level in complex kinematic configurations. Excellent performance is achieved over a range of transverse momenta from 3 GeV to several hundred GeV, and across the full muon detector acceptance of |\eta |<2.7

Measurement of Higgs boson production in the diphoton decay channel in pp collisions at center-of-mass energies of 7 and 8 TeV with the ATLAS detector

A measurement of the production processes of the recently discovered Higgs boson is performed in the two-photon final state using 4.5  fb[superscript −1] of proton-proton collisions data at √s=7  TeV and 20.3  fb[superscript −1] at √s=8  TeV collected by the ATLAS detector at the Large Hadron Collider. The number of observed Higgs boson decays to diphotons divided by the corresponding Standard Model prediction, called the signal strength, is found to be μ=1.17±0.27 at the value of the Higgs boson mass measured by ATLAS, m[subscript H]=125.4  GeV. The analysis is optimized to measure the signal strengths for individual Higgs boson production processes at this value of m[subscript H]. They are found to be μ[subscript ggF]=1.32±0.38, μ[subscript VBF]=0.8±0.7, μ[subscript WH]=1.0±1.6, μ[subscript ZH]=0.1[superscript +3.7 subscript −0.1], and μ[subscript t [bar over t] H] =1.6[superscript +2.7 subscript −1.8], for Higgs boson production through gluon fusion, vector-boson fusion, and in association with a W or Z boson or a top-quark pair, respectively. Compared with the previously published ATLAS analysis, the results reported here also benefit from a new energy calibration procedure for photons and the subsequent reduction of the systematic uncertainty on the diphoton mass resolution. No significant deviations from the predictions of the Standard Model are found.European Organization for Nuclear ResearchUnited States. Dept. of EnergyNational Science Foundation (U.S.)Brookhaven National Laborator