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  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Landes Bioscience. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
  • Jiang, X., et al. (författare)
  • Shared heritability and functional enrichment across six solid cancers
  • 2019
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
  • Campbell, PJ, et al. (författare)
  • Pan-cancer analysis of whole genomes
  • 2020
  • Ingår i: Nature. - : Nature Publishing Group. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
  • Tidskriftsartikel (refereegranskat)
  • Phu, Vu Dinh, et al. (författare)
  • Burden of Hospital Acquired Infections and Antimicrobial Use in Vietnamese Adult Intensive Care Units
  • 2016
  • Ingår i: PLoS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203 .- 1932-6203. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Vietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs). We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs) across Vietnam. Methods Monthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08: 00 a.m. on the survey day were included. Results Among 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing). Pneumonia accounted for 79.4% (804/1012) of HAIs Most HAIs (84.5% [855/1012]) were acquired in the survey hospital with 42.5% (363/855) acquired prior to ICU admission and 57.5% (492/855) developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76), urinary catheter (OR 2.12), no involvement of a family member in patient care (OR 1.94), and surgery after admission (OR 1.66). 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 [24.4%]), Pseudomonas aeruginosa (100/726 [13.8%]), and Klebsiella pneumoniae (84/726 [11.6%]), with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/ 3287) patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively). Conclusion A high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts.
  • Aad, G., et al. (författare)
  • A measurement of the ratio of the W and Z cross sections with exactly one associated jet in pp collisions at root s=7 TeV with ATLAS
  • 2012
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier. - 0370-2693 .- 1873-2445. ; 708:3-5, s. 221-240
  • Tidskriftsartikel (refereegranskat)abstract
    • The ratio of production cross sections of the W and Z bosons with exactly one associated jet is presented as a function of jet transverse momentum threshold. The measurement has been designed to maximise cancellation of experimental and theoretical uncertainties, and is reported both within a particle-level kinematic range corresponding to the detector acceptance and as a total cross-section ratio. Results are obtained with the ATLAS detector at the LHC in pp collisions at a centre-of-mass energy of 7 TeV using an integrated luminosity of 33 pb(-1). The results are compared with perturbative leading-order, leading-log, and next-to-leading-order QCD predictions, and are found to agree within experimental and theoretical uncertainties. The ratio is measured for events with a single jet with p(T) > 30 GeV to be 8.73 +/- 0.30(stat) +/- 0.40(syst) in the electron channel, and 8.49 +/- 0.23(stat) +/- 0.33(syst) in the muon channel. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved.
  • Aad, G., et al. (författare)
  • A search for flavour changing neutral currents in top-quark decays in pp collision data collected with the ATLAS detector at root s=7 TeV
  • 2012
  • Ingår i: Journal of High Energy Physics. - : Springer. - 1029-8479 .- 1126-6708. ; :9
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for flavour changing neutral current (FCNC) processes in top-quark decays by the ATLAS Collaboration is presented. Data collected from pp collisions at the LHC at a centre-of-mass energy of root s = 7 TeV during 2011, corresponding to an integrated luminosity of 2.1 fb(-1), were used. A search was performed for top-quark pair-production events, with one top quark decaying through the t -> Zq FCNC (q = u, c) channel, and the other through the Standard Model dominant mode t -> Wb. Only the decays of the Z boson to charged leptons and leptonic W-boson decays were considered as signal. Consequently, the final-state topology is characterised by the presence of three isolated charged leptons, at least two jets and missing transverse momentum from the undetected neutrino. No evidence for an FCNC signal was found. An upper limit on the t -> Zq branching ratio of BR(t -> Zq) < 0.73% is set at the 95% confidence level.
  • Aad, G., et al. (författare)
  • A search for t(t)over-bar resonances in lepton plus jets events with highly boosted top quarks collected in pp collisions at root s=7 TeV with the ATLAS detector
  • 2012
  • Ingår i: Journal of High Energy Physics. - : Springer. - 1029-8479 .- 1126-6708. ; :9
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for resonant production of high-mass top-quark pairs is performed on 2.05 fb(-1) of proton-proton collisions at root s = 7 TeV collected in 2011 with the ATLAS experiment at the Large Hadron Collider. This analysis of the lepton+jets final state is specifically designed for the particular topology that arises from the decay of highly boosted top quarks. The observed t (t) over bar invariant mass spectrum is found to be compatible with the Standard Model prediction and 95% credibility level upper limits are derived on the t (t) over bar production rate through new massive states. An upper limit of 0.7 pb is set on the production cross section times branching fraction of a narrow 1 TeV resonance. A Kaluza-Klein gluon with a mass smaller than 1.5 TeV is excluded.
  • Aad, G., et al. (författare)
  • A search for t (t)over-bar resonances with the ATLAS detector in 2.05 fb(-1) of proton-proton collisions at root s=7 TeV
  • 2012
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer. - 1434-6044 .- 1434-6052. ; 72:7
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for top quark pair resonances in final states containing at least one electron or muon has been performed with the ATLAS experiment at the CERN Large Hadron Collider. The search uses a data sample corresponding to an integrated luminosity of 2.05 fb(-1), which was recorded in 2011 at a proton-proton centre-of-mass energy of 7 TeV. No evidence for a resonance is found and limits are set on the production cross-section times branching ratio to t (t) over bar for narrow and wide resonances. For narrow Z' bosons, the observed 95 % Bayesian credibility level limits range from 9.3 pb to 0.95 pb for masses in the range of m(Z') = 500 GeV to m(Z') = 1300 GeV. The corresponding excluded mass region for a leptophobic topcolour Z' boson (Kaluza-Klein gluon excitation in the Randall-Sundrum model) is m(Z') < 880 GeV (m(gKK) < 1130 GeV).
  • Aad, G., et al. (författare)
  • A study of the material in the ATLAS inner detector using secondary hadronic interactions
  • 2012
  • Ingår i: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • The ATLAS inner detector is used to reconstruct secondary vertices due to hadronic interactions of primary collision products, so probing the location and amount of material in the inner region of ATLAS. Data collected in 7 TeV pp collisions at the LHC, with a minimum bias trigger, are used for comparisons with simulated events. The reconstructed secondary vertices have spatial resolutions ranging from similar to 200 mu m to 1 mm. The overall material description in the simulation is validated to within an experimental uncertainty of about 7%. This will lead to a better understanding of the reconstruction of various objects such as tracks, leptons, jets, and missing transverse momentum.
  • Aad, G., et al. (författare)
  • ATLAS measurements of the properties of jets for boosted particle searches
  • 2012
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - : American Physical Society. - 1550-2368 .- 1550-7998. ; 86:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements are presented of the properties of high transverse momentum jets, produced in proton-proton collisions at a center-of-mass energy of root s = 7 TeV. The data correspond to an integrated luminosity of 35 pb(-1) and were collected with the ATLAS detector in 2010. Jet mass, width, eccentricity, planar flow and angularity are measured for jets reconstructed using the anti-k(t) algorithm with distance parameters R 0: 6 and 1.0, with transverse momentum p(T) > 300 GeV and pseudorapidity vertical bar eta vertical bar < 2. The measurements are compared to the expectations of Monte Carlo generators that match leading-logarithmic parton showers to leading-order, or next-to-leading-order, matrix elements. The generators describe the general features of the jets, although discrepancies are observed in some distributions.
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