1. |
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2. |
- Campbell, PJ, et al.
(author)
-
Pan-cancer analysis of whole genomes
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. 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 promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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3. |
- Aaltonen, T., et al.
(author)
-
Tevatron Run II combination of the effective leptonic electroweak mixing angle
- 2018
-
In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:11
-
Journal article (peer-reviewed)abstract
- Drell-Yan lepton pairs produced in the process p (p) over bar -> l(+)l(-) + X through an intermediate gamma*/Z boson have an asymmetry in their angular distribution related to the spontaneous symmetry breaking of the electroweak force and the associated mixing of its neutral gauge bosons. The CDF and D0 experiments have measured the effective-leptonic electroweak mixing parameter sin(2) theta(lept)(eff) using electron and muon pairs selected from the full Tevatron proton-antiproton data sets collected in 2001-2011, corresponding to 9-10 fb(-1) of integrated luminosity. The combination of these measurements yields the most precise result from hadron colliders, sin(2)theta(lept)(eff) = 0.23148 +/- 0.00033. This result is consistent with, and approaches in precision, the best measurements from electron-positron colliders. The standard model inference of the on-shell electroweak mixing parameter sin(2) theta(W), or equivalently the W-boson mass M-W, using the ZFITTER software package yields sin(2) theta(W) = 0.22324 +/- 0.00033 or equivalently, M-W = 80.367 +/- 0.017 GeV/c(2).
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4. |
- Abelev, B., et al.
(author)
-
Freeze-out radii extracted from three-pion cumulants in pp, p-Pb and Pb-Pb collisions at the LHC
- 2014
-
In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 739, s. 139-151
-
Journal article (peer-reviewed)abstract
- In high-energy collisions, the spatio-temporal size of the particle production region can be measured using the Bose-Einstein correlations of identical bosons at low relative momentum. The source radii are typically extracted using two-pion correlations, and characterize the system at the last stage of interaction, called kinetic freeze-out. In low-multiplicity collisions, unlike in high-multiplicity collisions, two-pion correlations are substantially altered by background correlations, e. g. mini-jets. Such correlations can be suppressed using three-pion cumulant correlations. We present the first measurements of the size of the system at freeze-out extracted from three-pion cumulant correlations in pp, p-Pb and Pb-Pb collisions at the LHC with ALICE. At similar multiplicity, the invariant radii extracted in p-Pb collisions are found to be 5-15% larger than those in pp, while those in Pb-Pb are 35-55% larger than those in p-Pb. Our measurements disfavor models which incorporate substantially stronger collective expansion in p-Pb as compared to pp collisions at similar multiplicity. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license
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5. |
- Abelev, B., et al.
(author)
-
Measurement of electrons from semileptonic heavy-flavor hadron decays in pp collisions at root s=2.76 TeV
- 2015
-
In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 91:1
-
Journal article (peer-reviewed)abstract
- 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.
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6. |
- Abelev, B., et al.
(author)
-
Measurement of visible cross sections in proton-lead collisions at root s(NN)=5.02 TeV in van der Meer scans with the ALICE detector
- 2014
-
In: Journal of Instrumentation. - 1748-0221. ; 9
-
Journal article (peer-reviewed)abstract
- In 2013, the Large Hadron Collider provided proton-lead and lead-proton collisions at the center-of-mass energy per nucleon pair root s(NN) = 5.02 TeV. Van der Meer scans were performed for both configurations of colliding beams, and the cross section was measured for two reference processes, based on particle detection by the T0 and V0 detectors, with pseudo-rapidity coverage 4.6 < eta < 4.9, -3.3 < eta < -3.0 and 2.8 < eta < 5.1, -3.7 < eta < -1.7, respectively. Given the asymmetric detector acceptance, the cross section was measured separately for the two configurations. The measured visible cross sections are used to calculate the integrated luminosity of the proton-lead and lead-proton data samples, and to indirectly measure the cross section for a third, configuration-independent, reference process, based on neutron detection by the Zero Degree Calorimeters.
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7. |
- Abelev, B., et al.
(author)
-
Multiplicity dependence of pion, kaon, proton and lambda production in p-Pb collisions at root s(NN)=5.02 TeV
- 2014
-
In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 728, s. 25-38
-
Journal article (peer-reviewed)abstract
- In this Letter, comprehensive results on pi(+/-), K-+/-, K-S(0), p((p) over bar) and A((A) over bar) production at mid-rapidity (0 < y(CMS) < 0.5) in p-Pb collisions at root s(NN) = 5.02 TeV, measured by the ALICE detector at the LHC, are reported. The transverse momentum distributions exhibit a hardening as a function of event multiplicity, which is stronger for heavier particles. This behavior is similar to what has been observed in pp and Pb-Pb collisions at the LHC. The measured pr distributions are compared to d-Au, Au-Au and Pb-Pb results at lower energy and with predictions based on QCD-inspired and hydrodynamic models. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.
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8. |
- Abelev, B., et al.
(author)
-
Technical Design Report for the Upgrade of the ALICE Inner Tracking System
- 2014
-
In: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 41:8
-
Journal article (peer-reviewed)abstract
- LICE (A Large Ion Collider Experiment) is studying the physics of strongly interacting matter, and in particular the properties of the Quark–Gluon Plasma (QGP), using proton–proton, proton–nucleus and nucleus–nucleus collisions at the CERN LHC (Large Hadron Collider). The ALICE Collaboration is preparing a major upgrade of the experimental apparatus, planned for installation in the second long LHC shutdown in the years 2018–2019. A key element of the ALICE upgrade is the construction of a new, ultra-light, high-resolution Inner Tracking System (ITS) based on monolithic CMOS pixel detectors. The primary focus of the ITS upgrade is on improving the performance for detection of heavy-flavour hadrons, and of thermal photons and low-mass di-electrons emitted by the QGP. With respect to the current detector, the new Inner Tracking System will significantly enhance the determination of the distance of closest approach to the primary vertex, the tracking efficiency at low transverse momenta, and the read-out rate capabilities. This will be obtained by seven concentric detector layers based on a 50 μm thick CMOS pixel sensor with a pixel pitch of about 30×30 μm2. This document, submitted to the LHCC (LHC experiments Committee) in September 2013, presents the design goals, a summary of the R&D activities, with focus on the technical implementation of the main detector components, and the projected detector and physics performance.
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9. |
- Abelev, B., et al.
(author)
-
Centrality, rapidity and transverse momentum dependence of J/Psi suppression in Pb-Pb collisions at root(NN)-N-S=2.76TeV
- 2014
-
In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 734, s. 314-327
-
Journal article (peer-reviewed)abstract
- The inclusive J/.nuclear modification factor (R-AA) in Pb-Pb collisions at root(NN)-N-S = 2.76TeVhas been measured by ALICE as a function of centrality in the e+ e-decay channel at mid-rapidity (| y| < 0.8) and as a function of centrality, transverse momentum and rapidity in the + -decay channel at forward-rapidity (2.5 < y < 4). The J/.yields measured in Pb-Pb are suppressed compared to those in ppcollisions scaled by the number of binary collisions. The RAAintegrated over a centrality range corresponding to 90% of the inelastic Pb-Pb cross section is 0.72 - 0.06(stat.) - 0.10(syst.) at mid-rapidity and 0.58 - 0.01(stat.) - 0.09(syst.) at forward-rapidity. At low transverse momentum, significantly larger values of RAAare measured at forward-rapidity compared to measurements at lower energy. These features suggest that a contribution to the J/.yield originates from charm quark (re) combination in the deconfined partonic medium. (C) 2014 The Authors. Published by Elsevier B. V.
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10. |
- Abelev, B, et al.
(author)
-
Directed Flow of Charged Particles at Midrapidity Relative to the Spectator Plane in Pb-Pb Collisions at sqrt[s_{NN}]=2.76 TeV.
- 2013
-
In: Physical Review Letters. - 1079-7114. ; 111:23
-
Journal article (peer-reviewed)abstract
- The directed flow of charged particles at midrapidity is measured in Pb-Pb collisions at sqrt[s_{NN}]=2.76 TeV relative to the collision symmetry plane defined by the spectator nucleons. A negative slope of the rapidity-odd directed flow component with approximately 3 times smaller magnitude than found at the highest RHIC energy is observed. This suggests a smaller longitudinal tilt of the initial system and disfavors the strong fireball rotation predicted for the LHC energies. The rapidity-even directed flow component is measured for the first time with spectators and found to be independent of pseudorapidity with a sign change at transverse momenta p_{T} between 1.2 and 1.7 GeV/c. Combined with the observation of a vanishing rapidity-even p_{T} shift along the spectator deflection this is strong evidence for dipolelike initial density fluctuations in the overlap zone of the nuclei. Similar trends in the rapidity-even directed flow and the estimate from two-particle correlations at midrapidity, which is larger by about a factor of 40, indicate a weak correlation between fluctuating participant and spectator symmetry planes. These observations open new possibilities for investigation of the initial conditions in heavy-ion collisions with spectator nucleons.
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11. |
- Abelev, B., et al.
(author)
-
Energy dependence of the transverse momentum distributions of charged particles in pp collisions measured by ALICE
- 2013
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:12
-
Journal article (peer-reviewed)abstract
- Differential cross sections of charged particles in inelastic pp collisions as a function of pT have been measured at root s = 0.9, 2.76 and 7 TeV at the LHC. The pT spectra are compared to NLO-pQCD calculations. Though the differential cross section for an individual root s cannot be described by NLO-pQCD, the relative increase of cross section with root s is in agreement with NLO-pQCD. Based on these measurements and observations, procedures are discussed to construct pp reference spectra at root s = 2.76 and 5.02 TeV up to pT = 50 GeV/c as required for the calculation of the nuclear modification factor in nucleus-nucleus and proton-nucleus collisions.
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12. |
- Abelev, B., et al.
(author)
-
J/psi production and nuclear effects in p-Pb collisions at=5.02 TeV
- 2014
-
In: Journal of High Energy Physics. - 1029-8479. ; :2
-
Journal article (peer-reviewed)abstract
- Inclusive J/psi production has been studied with the ALICE detector in p-Pb collisions at the nucleon-nucleon center of mass energy = 5.02 TeV at the CERN LHC. The measurement is performed in the center of mass rapidity domains 2.03 < y (cms) < 3.53 and -4.46 < y (cms) < -2.96, down to zero transverse momentum, studying the mu (+) mu (-) decay mode. In this paper, the J/psi production cross section and the nuclear modification factor R (pPb) for the rapidities under study are presented. While at forward rapidity, corresponding to the proton direction, a suppression of the J/psi yield with respect to binary-scaled pp collisions is observed, in the backward region no suppression is present. The ratio of the forward and backward yields is also measured differentially in rapidity and transverse momentum. Theoretical predictions based on nuclear shadowing, as well as on models including, in addition, a contribution from partonic energy loss, are in fair agreement with the experimental results.
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13. |
- Abelev, B., et al.
(author)
-
K*(892)(0) and phi(1020) production in Pb-Pb collisions at root s(NN)=2.76 TeV
- 2015
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:2
-
Journal article (peer-reviewed)abstract
- The yields of the K*(892)(0) and phi(1020) resonances are measured in Pb-Pb collisions at root s(NN) = 2.76 TeV through their hadronic decays using the ALICE detector. The measurements are performed in multiple centrality intervals at mid-rapidity (vertical bar y vertical bar < 0.5) in the transverse-momentum ranges 0.3 < p(T) < 5 GeV/c for the K*(892)(0) and 0.5 < p(T) < 5 GeV/c for the phi(1020). The yields of K*(892)(0) are suppressed in central Pb-Pb collisions with respect to pp and peripheral Pb-Pb collisions (perhaps due to rescattering of its decay products in the hadronic medium), while the longer-lived phi(1020) meson is not suppressed. These particles are also used as probes to study the mechanisms of particle production. The shape of the pT distribution of the phi(1020) meson, but not its yield, is reproduced fairly well by hydrodynamic models for central Pb-Pb collisions. In central Pb-Pb collisions at low and intermediate p(T), the p/phi(1020) ratio is flat in p(T), while the p/pi and phi(1020)/pi ratios show a pronounced increase and have similar shapes to each other. These results indicate that the shapes of the p(T) distributions of these particles in central Pb-Pb collisions are determined predominantly by the particle masses and radial flow. Finally, phi(1020) production in Pb-Pb collisions is enhanced, with respect to the yield in pp collisions and the yield of charged pions, by an amount similar to the Lambda and Xi.
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14. |
- Abelev, B, et al.
(author)
-
K_{S}^{0} and Λ Production in Pb-Pb Collisions at sqrt[s_{NN}]=2.76 TeV.
- 2013
-
In: Physical Review Letters. - 1079-7114. ; 111:22
-
Journal article (peer-reviewed)abstract
- The ALICE measurement of K_{S}^{0} and Λ production at midrapidity in Pb-Pb collisions at sqrt[s_{NN}]=2.76 TeV is presented. The transverse momentum (p_{T}) spectra are shown for several collision centrality intervals and in the p_{T} range from 0.4 GeV/c (0.6 GeV/c for Λ) to 12 GeV/c. The p_{T} dependence of the Λ/K_{S}^{0} ratios exhibits maxima in the vicinity of 3 GeV/c, and the positions of the maxima shift towards higher p_{T} with increasing collision centrality. The magnitude of these maxima increases by almost a factor of three between most peripheral and most central Pb-Pb collisions. This baryon excess at intermediate p_{T} is not observed in pp interactions at sqrt[s]=0.9 TeV and at sqrt[s]=7 TeV. Qualitatively, the baryon enhancement in heavy-ion collisions is expected from radial flow. However, the measured p_{T} spectra above 2 GeV/c progressively decouple from hydrodynamical-model calculations. For higher values of p_{T}, models that incorporate the influence of the medium on the fragmentation and hadronization processes describe qualitatively the p_{T} dependence of the Λ/K_{S}^{0} ratio.
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15. |
- Abelev, B., et al.
(author)
-
Long-range angular correlations of pi, K and p in p-Pb collisions at root s(NN)=5.02 TeV
- 2013
-
In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 726:1-3, s. 164-177
-
Journal article (peer-reviewed)abstract
- 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.
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16. |
- Abelev, B., et al.
(author)
-
Measurement of quarkonium production at forward rapidity in collisions at TeV
- 2014
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 74:8
-
Journal article (peer-reviewed)abstract
- The inclusive production cross sections at forward rapidity of , , (1S) and (2S) are measured in collisions at with the ALICE detector at the LHC. The analysis is based on a data sample corresponding to an integrated luminosity of 1.35 pb. Quarkonia are reconstructed in the dimuon-decay channel and the signal yields are evaluated by fitting the invariant mass distributions. The differential production cross sections are measured as a function of the transverse momentum and rapidity , over the ranges GeV/c for , GeV/c for all other resonances and for . The measured cross sections integrated over and , and assuming unpolarized quarkonia, are: b, b, nb and nb, where the first uncertainty is statistical and the second one is systematic. The results are compared to measurements performed by other LHC experiments and to theoretical models.
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17. |
- Abelev, B., et al.
(author)
-
Multi-strange baryon production at mid-rapidity in Pb-Pb collisions at root s(NN)=2.76 TeV
- 2014
-
In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 728, s. 216-227
-
Journal article (peer-reviewed)abstract
- The production of Xi(-) and Omega(-) baryons and their anti-particles in Pb-Pb collisions root s(NN) = 2.76 TeV has been measured using the ALICE detector. The transverse momentum spectra at mid-rapidity (vertical bar y vertical bar < 0.5) for charged Xi and Omega hyperons have been studied in the range 0.6 < P-T < 8.0 GeV/c and 1.2 < p(T) < 7.0 GeV/c, respectively, and in several centrality intervals (from the most central 0-.10% to the most peripheral 60-80% collisions). These spectra have been compared with the predictions of recent hydrodynamic models. In particular, the Krakow and EPOS models give a satisfactory description of the data, with the latter covering a wider P-T range. Mid-rapidity yields, integrated over p(T), have been determined. The hyperon-to-pion ratios are similar to those at RHIC: they rise smoothly with centrality up to < N-part > similar to 150 and saturate thereafter. The enhancements (yields per participant nucleon relative to those in pp collisions) increase both with the strangeness content of the baryon and with centrality, but are less pronounced than at lower energies. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.
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18. |
- Abelev, B., et al.
(author)
-
Multiplicity dependence of two-particle azimuthal correlations in pp collisions at the LHC
- 2013
-
In: Journal of High Energy Physics. - 1029-8479. ; :9
-
Journal article (peer-reviewed)abstract
- We present the measurements of particle pair yields per trigger particle obtained from di-hadron azimuthal correlations in pp collisions at root s = 0.9, 2.76, and 7TeV recorded with the ALICE detector. The yields are studied as a function of the charged particle multiplicity. Taken together with the single particle yields the pair yields provide information about parton fragmentation at low transverse momenta, as well as on the contribution of multiple parton interactions to particle production. Data are compared to calculations using the PYTHIA6, PYTHIA8, and PHOJET event generators.
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19. |
- Abelev, B., et al.
(author)
-
Performance of the ALICE experiment at the CERN LHC
- 2014
-
In: International Journal of Modern Physics A. - 0217-751X. ; 29:24
-
Research review (peer-reviewed)abstract
- ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables.
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20. |
- Abelev, B., et al.
(author)
-
Production of charged pions, kaons and protons at large transverse momenta in pp and Pb-Pb collisions at root s(NN)=2.76 TeV
- 2014
-
In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 736, s. 196-207
-
Journal article (peer-reviewed)abstract
- Transverse momentum spectra of pi(+/-), K-+/- and p((p) over bar) up to p(T) = 20 GeV/c at mid-rapidity in pp, peripheral (60-80%) and central (0-5%) Pb-Pb collisions at v root s(NN) = 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pionratios both show a distinct peak at p(T) approximate to 3 GeV/c in central Pb-Pb collisions. Below the peak, p(T) < 3 GeV/c, both ratios are in good agreement with hydrodynamical calculations, suggesting that the peak itself is dominantly the result of radial flow rather than anomalous hadronization processes. For p(T) > 10 GeV/c particle ratios in pp and Pb-Pb collisions are in agreement and the nuclear modification factors for pi(+/-), K-+/- and p((p) over bar) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license
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21. |
- Abelev, B., et al.
(author)
-
Two- and three-pion quantum statistics correlations in Pb-Pb collisions at root S-NN=2.76 TeV at the CERN Large Hadron Collider
- 2014
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 89:2
-
Journal article (peer-reviewed)abstract
- Correlations induced by quantum statistics are sensitive to the spatiotemporal extent as well as dynamics of particle-emitting sources in heavy-ion collisions. In addition, such correlations can be used to search for the presence of a coherent component of pion production. Two- and three-pion correlations of same and mixed charge are measured at low relative momentum to estimate the coherent fraction of charged pions in Pb-Pb collisions at root S-NN = 2.76 TeV at the CERN Large Hadron Collider with ALICE. The genuine three-pion quantum statistics correlation is found to be suppressed relative to the two-pion correlation based on the assumption of fully chaotic pion emission. The suppression is observed to decrease with triplet momentum. The observed suppression at low triplet momentum may correspond to a coherent fraction in charged-pion emission of 23% +/- 8%.
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22. |
- Bravo, L, et al.
(author)
-
- 2021
-
swepub:Mat__t
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23. |
- Tabiri, S, et al.
(author)
-
- 2021
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swepub:Mat__t
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24. |
- Joffrin, E., et al.
(author)
-
Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
-
In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
-
Research review (peer-reviewed)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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25. |
- Abazov, V. M., et al.
(author)
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Measurement of the Effective Weak Mixing Angle in p¯p→Z/γ∗→ℓ+ℓ− Events
- 2018
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 120:24
-
Journal article (peer-reviewed)abstract
- We present a measurement of the effective weak mixing angle parameter sin(2)theta(l)(eff) in p (p) over bar -> Z/gamma* -> mu(+)mu(-) events at a center-of-mass energy of 1.96 TeV, collected by the D0 detector at the Fermilab Tevatron Collider and corresponding to 8.6 fb(-1) of integrated luminosity. The measured value of sin(2)theta(l)(eff)[mu mu] = 0.23016 +/- 0.00064 is further combined with the result from the D0 measurement in p (p) over bar -> Z/gamma* -> e(+)e(-) events, resulting in sin(2)theta(l)(eff)[comb] = 0.23095 +/- 0.00040. This combined result is the most precise measurement from a single experiment at a hadron collider and is the most precise determination using the coupling of the Z/gamma* to light quarks.
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26. |
- Algaba, Juan-Carlos, et al.
(author)
-
Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
-
In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Research review (peer-reviewed)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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27. |
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- 2019
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Journal article (peer-reviewed)
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28. |
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29. |
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30. |
- Yin, X., et al.
(author)
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Vertical Sandwich Gate-All-Around Field-Effect Transistors with Self-Aligned High-k Metal Gates and Small Effective-Gate-Length Variation
- 2020
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In: IEEE Electron Device Letters. - : Institute of Electrical and Electronics Engineers Inc.. - 0741-3106 .- 1558-0563. ; 41:1, s. 8-11
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Journal article (peer-reviewed)abstract
- A new type of vertical nanowire (NW)/nanosheet (NS) field-effect transistors (FETs), termed vertical sandwich gate-all-around (GAA) FETs (VSAFETs), is presented in this work. Moreover, an integration flow that is compatible with processes used in the mainstream industry is proposed for the VSAFETs. Si/SiGe epitaxy, isotropic quasi-atomic-layer etching (qALE), and gate replacement were used to fabricate pVSAFETs for the first time. Vertical GAA FETs with self-aligned high-k metal gates and a small effective-gate-length variation were obtained. Isotropic qALE, including Si-selective etching of SiGe, was developed to control the diameter/thickness of the NW/NS channels. NWs with a diameter of 10 nm and NSs with a thickness of 20 nm were successfully fabricated, and good device characteristics were obtained. Finally, the device performance was investigated and is discussed in this work. © 2019 IEEE.
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32. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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.
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33. |
- Wang, H. Y., et al.
(author)
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Cellular Analysis and Comparative Transcriptomics Reveal the Tolerance Mechanisms of Candida tropicalis Toward Phenol
- 2020
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In: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 11
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Journal article (peer-reviewed)abstract
- Phenol is a ubiquitous pollutant and can contaminate natural water resources. Hence, the removal of phenol from wastewater is of significant importance. A series of biological methods were used to remove phenol based on the natural ability of microorganisms to degrade phenol, but the tolerance mechanism of phenol-degraded strains to phenol are not very clear. Morphological observation on Candida tropicalis showed that phenol caused the reactive oxygen species (ROS) accumulation, damaging the mitochondrial and the endoplasmic reticulum. On the basis of transcriptome data and cell wall susceptibility analysis, it was found that C. tropicalis prevented phenol-caused cell damage through improvement of cell wall resistance, maintenance of high-fidelity DNA replication, intracellular protein homeostasis, organelle integrity, and kept the intracellular phenol concentration at a low level through cell-wall remodeling and removal of excess phenol via MDR/MXR transporters. The knowledge obtained will promote the genetic modification of yeast strains in general to tolerate the high concentrations of phenol and improve their efficiency of phenol degradation.
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34. |
- Zhang, Y., et al.
(author)
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Association between estimated glomerular filtration rate and 10-year atherosclerotic cardiovascular disease risk among community residents in Shanghai, China
- 2022
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In: Nutrition, Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753.
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Journal article (peer-reviewed)abstract
- Background and aims: The association between the estimated glomerular filtration rate (eGFR) and atherosclerotic cardiovascular disease (ASCVD) risk is unknown. We aimed to evaluate whether eGFR can be used as a predictor in ASCVD risk assessment. Methods and results: Using baseline data from 28,187 participants from Shanghai Suburban Adult Cohort and Biobank study, we adopted Pooled Cohort Equations (PCEs) and Prediction for ASCVD Risk in China (China-PAR) to estimate 10-year ASCVD risk. Multivariate logistic regression was used to analyze the relationship between 10-year ASCVD risk and eGFR. The receiver operating characteristic (ROC) curve was used to evaluate predictive value of eGFR for 10-year high ASCVD risk. Compared with normal eGFR, both men and women with reduced eGFR had a higher prevalence of ASCVD risk factors. With the decrease of eGFR level, the median of 10-year ASCVD risk gradually increased. For men, the adjusted odds ratios (95% confidence interval (CI)) of 10-year high ASCVD risk by PCEs associated with eGFR (60–74 and <60 mL/min/1.73 m2) were 1.52 (95%CI:1.17–1.99) and 2.51 (95%CI:1.27–4.97). The corresponding result was significant only for eGFR < 60 mL/min/1.73 m2, OR of 1.57 (1.14–2.18) for women. Using China-PAR, the adjusted OR of 10-year high risk associated with eGFR < 60 mL/min/1.73 m2 was 1.82 (1.40–2.38) in men. ROC indicated that eGFR has a good predictive value for 10-year high ASCVD risk. Conclusion: eGFR may be an important risk factor in predicting and stratifying ASCVD risk. Consideration should be given to integrating eGFR into existing risk assessment tools to improve predictive performance. © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University
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35. |
- Zhang, Y., et al.
(author)
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Prediction of 10-year atherosclerotic cardiovascular disease risk among community residents in Shanghai, China - a comparative analysis of risk algorithms
- 2021
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In: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 31:7, s. 2058-2067
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Journal article (peer-reviewed)abstract
- Background and aims: The accuracy of various 10-year atherosclerotic cardiovascular disease (ASCVD) risk models has been debatable. We compared two risk algorithms and explored clustering patterns across different risk stratifications among community residents in Shanghai. Methods and results: A total of 28,201 residents (aged 40-74 years old) who were free of ASCVD were selected from the Shanghai Survey in China. The 10-year ASCVD risk was estimated by applying the 2013 Pooled Cohort Equations (PCEs) and Prediction for ASCVD Risk in China (China-PAR). The agreement was assessed between PCEs and China-PAR using Cohen's kappa statistics. The mean absolute 10-year ASCVD risk calculated by PCEs and China-PAR was about 10.0% and 6.0%, respectively. PCEs estimated that 44.9% of participants [with a 95% confidence interval (CI):44.0%-45.8%] were at high risk, while China-PAR estimated only 16.7% (95%CI:15.8%-18.0%) were at high risk. In both models, the percentage of high ASCVD risk was higher for participants who were older, men, less educated, current smokers, drinkers and manual workers. Among high-risk individuals, almost all participants (PCEs:90.5%; China-PAR:98.6%) had at least one risk factor; hypertension being the most prevalent. The concordance between PCEs and China-PAR was moderate (kappa:0.428, 95%CI: 0.420-0.434) with a better agreement for women (kappa:0.503,95%CI: 0.493-0.513) than for men (kappa:0.211,95%CI: 0.201-0.221). Conclusion: The proportion of participants with a 10-year ASCVD high risk predicted by China PAR was lower than the results of the PCEs. The risk stratifications of the two algorithms were inconsistent in terms of demographic and life-behaviour characteristics. (C) 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
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38. |
- Gao, X, et al.
(author)
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Longitudinal patient-reported outcomes 1 year after thoracoscopic segmentectomy versus lobectomy for early-stage lung cancer: a multicentre, prospective cohort study protocol
- 2023
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In: BMJ open. - : BMJ. - 2044-6055. ; 13:1, s. e067841-
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Journal article (peer-reviewed)abstract
- Segmentectomy and lobectomy are the main surgical procedures for early-stage lung cancer. However, few studies have analysed patient-reported outcomes after segmentectomy versus lobectomy. This study aims to compare patient-reported outcomes—such as symptoms, daily functioning and quality of life—between thoracoscopic segmentectomy and lobectomy for early-stage lung cancer during the 1 year after surgery.Methods and analysisOverall, 788 newly diagnosed patients with early-stage lung cancer (tumour size ≤2 cm), who are scheduled to undergo thoracoscopic segmentectomy or lobectomy, will be recruited in this multicentre, prospective cohort study. The patients will receive standardised care after surgery. The Perioperative Symptom Assessment for Lung Surgery—a validated lung cancer surgery-specific scale—will be used to assess the symptoms and functions at baseline, at discharge and monthly after discharge for 1 year. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Lung Cancer module 29 will be used to assess the patients’ quality of life at the same time points. The primary outcome will be the shortness of breath scores during the first year after thoracoscopic segmentectomy and lobectomy and will be compared using mixed-effects models. The secondary outcomes will include other symptoms, indicators of daily functioning, quality of life scores and traditional clinical outcomes. These will be compared using mixed-effects models and the Student’s t-test, non-parametric test or Χ2test. Propensity score matching will be used to ensure an even distribution of known confounders between the groups.Ethics and disseminationThe Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital approved this study (approval number: SCCHEC-02-2022-002). All participants will be instructed to provide informed consent. The manuscript is based on protocol version 3.0. The study results will be presented at medical conferences and published in peer-reviewed journals.Trial registration numberChiCTR2200060753.
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39. |
- Sun, Q., et al.
(author)
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Prevalence and cardiovascular risk factors of asymptomatic intracranial arterial stenosis : the Kongcun Town Study in Shandong, China
- 2020
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 27:4, s. 729-735
-
Journal article (peer-reviewed)abstract
- Background and purpose This study was to investigate the prevalence and cardiovascular risk factors (CRFs) of asymptomatic intracranial atherosclerotic stenosis (aICAS) amongst middle-aged and older adults living in rural communities in China. Methods This population-based study included 2019 subjects (aged >= 40 years, 52.3% women) who were free of stroke and living in rural communities in China. From October 2017 to May 2018, data on demographics, CRFs and health conditions were collected through face-to-face interviews, physical examination and laboratory tests. Asymptomatic ICAS was detected through a two-phase procedure: a screening phase with transcranial Doppler ultrasound, followed by a diagnostic phase with magnetic resonance angiography examination. Multivariable logistic regression models were used to analyse CRFs associated with aICAS. Results Of the 2019 participants, aICAS was detected in 153 persons. The overall prevalence of aICAS was 7.6%, and the prevalence of moderate-to-severe aICAS was 5.0%. The multi-adjusted odds ratio (95% confidence interval) of aICAS associated with CRFs was 2.40 (1.56-3.69) for hypertension, 1.91 (1.32-2.76) for high hypersensitive C-reactive protein, 1.68 (1.14-2.49) for diabetes and 1.61 (1.08-2.41) for overweight or obesity. When these four CRFs were aggregated, compared with participants without any of these factors, the multi-adjusted odds ratios (95% confidence interval) of aICAS for persons concurrently having one, two and three or more of these factors were 1.14 (0.52-2.48), 2.91 (1.42-5.99) and 5.51 (2.64-11.50), respectively (P for linear trend <0.001). Conclusions Asymptomatic ICAS is common amongst rural-dwelling middle-aged and older Chinese people. Hypertension, diabetes, overweight or obesity and high hypersensitive C-reactive protein, especially when coexisting, are strongly associated with aICAS.
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40. |
- Xiang, Y., et al.
(author)
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Kinetic, Thermodynamic, and Crystallographic Studies of 2-Triazolylthioacetamides as Verona Integron-Encoded Metallo-beta-Lactamase 2 (VIM-2) Inhibitor
- 2020
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In: Biomolecules. - : MDPI AG. - 2218-273X. ; 10:1
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Journal article (peer-reviewed)abstract
- Inhibition of beta-lactamases presents a promising strategy to restore the beta-lactams antibacterial activity to resistant bacteria. In this work, we found that aromatic carboxyl substituted 2-triazolylthioacetamides 1a-j inhibited VIM-2, exhibiting an IC50 value in the range of 20.6-58.6 mu M. The structure-activity relationship study revealed that replacing the aliphatic carboxylic acid with aromatic carboxyl improved the inhibitory activity of 2-triazolylthioacetamides against VIM-2. 1a-j (16 mg/mL) restored the antibacterial activity of cefazolin against E. coli cell expressing VIM-2, resulting in a 4-8-fold reduction in MICs. The isothermal titration calorimetry (ITC) characterization suggested that the primary binding 2-triazolylthioacetamide (1b, 1c, or 1h) to VIM-2 was a combination of entropy and enthalpy contributions. Further, the crystal structure of VIM-2 in complex with 1b was obtained by co-crystallization with a hanging-drop vapour-diffusion method. The crystal structure analysis revealed that 1b bound to two Zn(II) ions of the enzyme active sites, formed H-bound with Asn233 and structure water molecule, and interacted with the hydrophobic pocket of enzyme activity center utilizing hydrophobic moieties; especially for the phenyl of aromatic carboxyl which formed pi-pi stacking with active residue His263. These studies confirmed that aromatic carboxyl substituted 2-triazolylthioacetamides are the potent VIM-2 inhibitors scaffold and provided help to further optimize 2-triazolylthioacetamides as VIM-2 even or broad-spectrum M beta Ls inhibitors.
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41. |
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42. |
- Chen, DS, et al.
(author)
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Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
-
Journal article (peer-reviewed)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
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43. |
- Labit, B., et al.
(author)
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Dependence on plasma shape and plasma fueling for small edge-localized mode regimes in TCV and ASDEX Upgrade
- 2019
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:8
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Journal article (peer-reviewed)abstract
- © 2019 Institute of Physics Publishing. All rights reserved. Within the EUROfusion MST1 work package, a series of experiments has been conducted on AUG and TCV devices to disentangle the role of plasma fueling and plasma shape for the onset of small ELM regimes. On both devices, small ELM regimes with high confinement are achieved if and only if two conditions are fulfilled at the same time. Firstly, the plasma density at the separatrix must be large enough (ne,sep/nG ∼ 0.3), leading to a pressure profile flattening at the separatrix, which stabilizes type-I ELMs. Secondly, the magnetic configuration has to be close to a double null (DN), leading to a reduction of the magnetic shear in the extreme vicinity of the separatrix. As a consequence, its stabilizing effect on ballooning modes is weakened.
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44. |
- Li, Q., et al.
(author)
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Discovery of new strains for furfural degradation using adaptive laboratory evolution in Saccharomyces cerevisiae
- 2023
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In: Journal of Hazardous Materials. - 0304-3894. ; 459
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Journal article (peer-reviewed)abstract
- In industrial production, the excessive discharge of furfural can pose harm to soil microorganisms, aquatic an-imals and plants, as well as humans. Therefore, it is crucial to develop efficient and cost-effective methods for degrading furfural in the environment. Currently, the use of Saccharomyces cerevisiae for furfural degradation in water has shown effectiveness, but there is a need to explore improved efficiency and tolerance in S. cerevisiae for this purpose. In this study, we isolated and evolved highly efficient furfural degradation strains, namely YBA_08 and F60C. These strains exhibited remarkable capabilities, degrading 59% and 99% furfural in the YPD medium after 72 h of incubation, significantly higher than the 31% achieved by the model strain S288C. Through analysis of the efficient degradation mechanism in the evolutionary strain F60C, we discovered a 326% increase in the total amount of NADH and NADPH. This increase likely promotes faster furfural degradation through intracel-lular aldehyde reductases. Moreover, the decrease in NADPH content led to a 406% increase in glutathione content at the background level, which protects cells from damage caused by reactive oxygen species. Mutations and differential expression related to cell cycle and cell wall synthesis were observed, enabling cell survival in the presence of furfural and facilitating rapid furfural degradation and growth recovery. Based on these findings, it is speculated that strains YBA_08 and F60C have the potential to contribute to furfural degradation in water and the production of furfuryl alcohol, ethanol, and FDCA in biorefinery processes.
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46. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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47. |
- Meyer, H.F., et al.
(author)
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Overview of physics studies on ASDEX Upgrade
- 2019
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
-
Research review (peer-reviewed)abstract
- The ASDEX Upgrade (AUG) programme, jointly run with the EUROfusion MST1 task force, continues to significantly enhance the physics base of ITER and DEMO. Here, the full tungsten wall is a key asset for extrapolating to future devices. The high overall heating power, flexible heating mix and comprehensive diagnostic set allows studies ranging from mimicking the scrape-off-layer and divertor conditions of ITER and DEMO at high density to fully non-inductive operation (q 95 = 5.5, ) at low density. Higher installed electron cyclotron resonance heating power 6 MW, new diagnostics and improved analysis techniques have further enhanced the capabilities of AUG. Stable high-density H-modes with MW m-1 with fully detached strike-points have been demonstrated. The ballooning instability close to the separatrix has been identified as a potential cause leading to the H-mode density limit and is also found to play an important role for the access to small edge-localized modes (ELMs). Density limit disruptions have been successfully avoided using a path-oriented approach to disruption handling and progress has been made in understanding the dissipation and avoidance of runaway electron beams. ELM suppression with resonant magnetic perturbations is now routinely achieved reaching transiently . This gives new insight into the field penetration physics, in particular with respect to plasma flows. Modelling agrees well with plasma response measurements and a helically localised ballooning structure observed prior to the ELM is evidence for the changed edge stability due to the magnetic perturbations. The impact of 3D perturbations on heat load patterns and fast-ion losses have been further elaborated. Progress has also been made in understanding the ELM cycle itself. Here, new fast measurements of and E r allow for inter ELM transport analysis confirming that E r is dominated by the diamagnetic term even for fast timescales. New analysis techniques allow detailed comparison of the ELM crash and are in good agreement with nonlinear MHD modelling. The observation of accelerated ions during the ELM crash can be seen as evidence for the reconnection during the ELM. As type-I ELMs (even mitigated) are likely not a viable operational regime in DEMO studies of 'natural' no ELM regimes have been extended. Stable I-modes up to have been characterised using -feedback. Core physics has been advanced by more detailed characterisation of the turbulence with new measurements such as the eddy tilt angle - measured for the first time - or the cross-phase angle of and fluctuations. These new data put strong constraints on gyro-kinetic turbulence modelling. In addition, carefully executed studies in different main species (H, D and He) and with different heating mixes highlight the importance of the collisional energy exchange for interpreting energy confinement. A new regime with a hollow profile now gives access to regimes mimicking aspects of burning plasma conditions and lead to nonlinear interactions of energetic particle modes despite the sub-Alfvénic beam energy. This will help to validate the fast-ion codes for predicting ITER and DEMO.
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48. |
- Tang, J, et al.
(author)
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Cancer cells escape p53's tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation
- 2021
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In: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 40:35, s. 5416-5426
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Journal article (peer-reviewed)abstract
- The inactivation of tumor-suppressor genes contributes heavily to oncogenesis. The mutation of TP53 has been well-studied and recognized as a major factor in the development of tumors. Yet other means of p53 inactivation has not been well-elucidated. We previously identified a hypermethylated gene ZDHHC1 that suppresses tumor growth when the expression was restored, but the specific mechanism was yet to be found. The protein product of ZDHHC1 is an S-palmitoyltransferase and we have identified p53 as a substrate for ZDHHC1-mediated palmitoylation, specifically at the C135, C176, and C275 residues. The novel form of post-translational modification of p53 is required for the nuclear translocation of the tumor suppressor. p53 recruited DNMT3A to ZDHHC1 promoter and is responsible for the hypermethylation of ZDHHC1. The epigenetic feedback loop formed by ZDHHC1 and p53 sheds light on the inactivation of p53 without the presence of genetic mutations.
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