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1.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 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.
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2.
  • Wang, Zhaoming, et al. (författare)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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3.
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4.
  • Abdoullaye, Doukary, et al. (författare)
  • Permanent genetic resources added to molecular ecology resources database 1 August 2009 - 30 September 2009
  • 2010
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:1, s. 232-236
  • Tidskriftsartikel (refereegranskat)abstract
    • This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross-tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate-A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides.
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5.
  • Tang, Ting-Ting, et al. (författare)
  • Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.
  • 2011
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 6:9, s. e24272-
  • Tidskriftsartikel (refereegranskat)abstract
    • Animal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought to elucidate the mechanism of T(reg-)cell defects in CHF patients.
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6.
  • Abelev, B., et al. (författare)
  • Centrality, rapidity and transverse momentum dependence of J/Psi suppression in Pb-Pb collisions at root(NN)-N-S=2.76TeV
  • 2014
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 734, s. 314-327
  • Tidskriftsartikel (refereegranskat)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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7.
  • Abelev, B, et al. (författare)
  • Directed Flow of Charged Particles at Midrapidity Relative to the Spectator Plane in Pb-Pb Collisions at sqrt[s_{NN}]=2.76 TeV.
  • 2013
  • Ingår i: Physical Review Letters. - 1079-7114. ; 111:23
  • Tidskriftsartikel (refereegranskat)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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8.
  • Abelev, B., et al. (författare)
  • Energy dependence of the transverse momentum distributions of charged particles in pp collisions measured by ALICE
  • 2013
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:12
  • Tidskriftsartikel (refereegranskat)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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9.
  • Abelev, B., et al. (författare)
  • Freeze-out radii extracted from three-pion cumulants in pp, p-Pb and Pb-Pb collisions at the LHC
  • 2014
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 739, s. 139-151
  • Tidskriftsartikel (refereegranskat)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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10.
  • Abelev, B., et al. (författare)
  • J/psi production and nuclear effects in p-Pb collisions at=5.02 TeV
  • 2014
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :2
  • Tidskriftsartikel (refereegranskat)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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11.
  • Abelev, B, et al. (författare)
  • K_{S}^{0} and Λ Production in Pb-Pb Collisions at sqrt[s_{NN}]=2.76 TeV.
  • 2013
  • Ingår i: Physical Review Letters. - 1079-7114. ; 111:22
  • Tidskriftsartikel (refereegranskat)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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12.
  • Abelev, B., et al. (författare)
  • Long-range angular correlations of pi, K and p in p-Pb collisions at root s(NN)=5.02 TeV
  • 2013
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 726:1-3, s. 164-177
  • Tidskriftsartikel (refereegranskat)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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13.
  • Abelev, B., et al. (författare)
  • Measurement of quarkonium production at forward rapidity in collisions at TeV
  • 2014
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 74:8
  • Tidskriftsartikel (refereegranskat)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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14.
  • Abelev, B., et al. (författare)
  • 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
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 9
  • Tidskriftsartikel (refereegranskat)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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15.
  • Abelev, B., et al. (författare)
  • Multi-strange baryon production at mid-rapidity in Pb-Pb collisions at root s(NN)=2.76 TeV
  • 2014
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 728, s. 216-227
  • Tidskriftsartikel (refereegranskat)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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16.
  • Abelev, B., et al. (författare)
  • Multiplicity dependence of pion, kaon, proton and lambda production in p-Pb collisions at root s(NN)=5.02 TeV
  • 2014
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 728, s. 25-38
  • Tidskriftsartikel (refereegranskat)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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17.
  • Abelev, B., et al. (författare)
  • Multiplicity dependence of two-particle azimuthal correlations in pp collisions at the LHC
  • 2013
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :9
  • Tidskriftsartikel (refereegranskat)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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18.
  • Abelev, B., et al. (författare)
  • Performance of the ALICE experiment at the CERN LHC
  • 2014
  • Ingår i: International Journal of Modern Physics A. - 0217-751X. ; 29:24
  • Forskningsöversikt (refereegranskat)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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19.
  • Abelev, B., et al. (författare)
  • 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
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 736, s. 196-207
  • Tidskriftsartikel (refereegranskat)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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20.
  • Abelev, B., et al. (författare)
  • Technical Design Report for the Upgrade of the ALICE Inner Tracking System
  • 2014
  • Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 41:8
  • Tidskriftsartikel (refereegranskat)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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21.
  • Abelev, B., et al. (författare)
  • 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
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 89:2
  • Tidskriftsartikel (refereegranskat)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.
  • Ding, Jun-Li, et al. (författare)
  • Attenuation of Acute Pancreatitis by Peroxisome Proliferator-Activated Receptor-α in Rats: The Effect on Toll-Like Receptor Signaling Pathways
  • 2013
  • Ingår i: Pancreas. - : Lippincott, Williams and Wilkins. - 0885-3177 .- 1536-4828. ; 42:1, s. 114-122
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The peroxisome proliferator-activated receptor-α (PPAR-α) has attracted considerable attention for its anti-inflammatory properties; however, Toll-like receptor (TLR) pathways have an essential proinflammatory role in acute pancreatitis (AP). This study aimed to evaluate the attenuation of inflammation by PPAR-α and to investigate the interaction between PPAR-α and TLR pathways in AP.Methods: Acute pancreatitis was induced in rats by administration of cerulein. The PPAR-α agonist WY14643 and/or antagonist MK886 was administered. The severity of AP was determined by measuring serum amylase, lipase, Ca2+, pathological changes, myeloperoxidase activity, serum levels of interleukin (IL)-6, and intercellular adhesion molecule-1 (ICAM-1). The TLR2 and TLR4 messenger RNA (mRNA) and proteins were determined by real-time reverse transcriptase polymerase chain reaction and Western blotting, respectively. The mRNA expressions of target molecules of TLR pathways, including IL-6, IL-10, ICAM-1, and tumor necrosis factor α were also measured.Results: Treatment with WY14643 significantly decreased amylase, lipase, myeloperoxidase activity, pathological scores, IL-6, and ICAM-1 levels. The TLR2 and TLR4 mRNA and proteins were markedly decreased after treatment with WY14643, along with IL-6, ICAM-1, and tumor necrosis factor α mRNA levels. However, these effects were completely reversed by the coadministration of MK886.Conclusions: Activation of PPAR-α played a protective role in AP, partially mediated by modulation of TLR pathways.
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23.
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24.
  • Jacobs, Kevin B, et al. (författare)
  • Detectable clonal mosaicism and its relationship to aging and cancer.
  • 2012
  • Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
  • Tidskriftsartikel (refereegranskat)abstract
    • In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
  •  
25.
  • Liu, Shiping, et al. (författare)
  • Population Genomics Reveal Recent Speciation and Rapid Evolutionary Adaptation in Polar Bears
  • 2014
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 157:4, s. 785-794
  • Tidskriftsartikel (refereegranskat)abstract
    • Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.
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26.
  • Rajaraman, Preetha, et al. (författare)
  • Genome-wide association study of glioma and meta-analysis
  • 2012
  • Ingår i: Human Genetics. - : SPRINGER. - 0340-6717 .- 1432-1203. ; 131:12, s. 1877-1888
  • Tidskriftsartikel (refereegranskat)abstract
    • Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.
  •  
27.
  • Wang, Xiaodong (Alice), et al. (författare)
  • The ability of wood to buffer highly acidic and alkaline adhesives
  • 2010
  • Ingår i: Wood and Fiber Science. - 0735-6161. ; 42:3, s. 398-405
  • Tidskriftsartikel (refereegranskat)abstract
    • The ability of wood to buffer and mitigate the effects of strongly acidic or alkaline environ- ments produced near the glue line by extreme pH structural adhesives was evaluated. The pH values of wood, cured adhesives, and mixtures of the two in water slurries were determined for different wood types. The pHs of slurries of seven highly alkaline phenol–formaldehyde adhesives were lowered when the adhesive was cured in the presence of wood dust with effects increasing with the proportion of wood in the mixture. The “acidities” or amounts of alkali needed to adjust the slurries to pH 12.5 were relatively high for all species because of weak acid groups in wood that dissociate at pH greater than 8. This explains the ability of wood to buffer highly alkaline adhesives. The pHs of slurries of two acidic melamine–urea–formaldehyde adhesives increased in the presence of wood, but the effect was less significant compared with the alkaline adhesives. Similarly, the “alkalinities” or amounts of acid required to adjust the slurries to pH 3 were relatively low. Aspen veneer samples had a greater effect on adhesive pH than spruce and Douglas-fir. These effects will help mitigate potentially adverse effects of strongly alkaline or acidic adhesives on wood adhesive bond strength.
  •  
28.
  • Wang, Xiaodong, et al. (författare)
  • Effects of pH on lap-shear strength for aspen veneer
  • 2013
  • Ingår i: Wood and Fiber Science. - 0735-6161. ; 45:3, s. 294-302
  • Tidskriftsartikel (refereegranskat)abstract
    • This study is one part of a whole project called "Impact of Extreme pH of Structural Adhesives on Bond Durability." The objective of this study was to evaluate effects of pH on wood-adhesive bond strength and chemical change in aspen (Populus tremuloides Michx) wood caused by extreme pH exposures. Aspen veneer lap-shear samples were tested for maximum stress (N/mm2) and wood failure (%) after exposure to soaking in different buffered solutions (pH = 2.0, 2.5, 3.0; water, 10.0, 11.0, 11.5, 12.0, and 12.5) for 1, 4, and 7 mo. One set of samples stored in laboratory conditions was also tested as a control at each test time. Results indicated that bond strength and wood failure decreased after 4- and 7-mo exposures to acidic conditions but did not change significantly under alkaline exposures. However, the buffered acidic solutions (pH = 2.0 and 3.0) did not cause a measurable chemical change in aspen wood, whereas losses in hemicellulose and lignin were found after aspen wood specimens had been exposed to pH > 11.0 buffered solutions.
  •  
29.
  •  
30.
  • Yang, Jia-Xiang, et al. (författare)
  • Facile synthesis, optical properties and theoretical calculation of two novel two-photon absorption chromophores
  • 2010
  • Ingår i: Journal of Luminescence. - : Elsevier BV. - 0022-2313 .- 1872-7883. ; 130:4, s. 654-659
  • Tidskriftsartikel (refereegranskat)abstract
    • Two heterocycle-based derivatives that can be used as two-photon absorption chromophore, 9-butyl-3-(2,6-diphenylpyridin-4-yl)-9H-carbazole (BDPYC) and 9-butyl-3-(4-(2, 6-diphenylpyridin-4-yl)styryl)-9H-carbazole (BDPSC) have been successfully synthesized and fully characterized by elemental analysis, IR, H-1 NMR, C-13 NMR and MS. The molecules possess D-pi-A structures, but have different pi bridge. The 9-butylcarbazole is used as a donor (D), and the pyridine ring is used as an acceptor (A). One- and two-photon absorption and excited fluorescence properties in various solvents were experimentally investigated. Two-photon initiated optical data recording experiments have been carried Out under 740 nm laser radiation, and the possible mechanism of optical data storage is discussed based on theoretical calculations.
  •  
31.
  • Yu, Weifang, et al. (författare)
  • Cystatin C Deficiency Promotes Epidermal Dysplasia in K14-HPV16 Transgenic Mice
  • 2010
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cysteine protease cathepsins are important in extracellular matrix protein degradation, cell apoptosis, and angiogenesis. Mice lacking cathepsins are protected from tumor progression in several animal models, suggesting that the regulation of cathepsin activities controls the growth of various malignant tumors. Methods and Results: We tested the role of cathepsins using a mouse model of multistage epithelial carcinogenesis, in which the human keratin-14 promoter/enhancer drove the expression of human papillomavirus type 16 (HPV16) early region E6/E7 transgenes. During the progression of premalignant dysplasia, we observed increased expression of cysteine protease cathepsin S, but concomitantly reduced expression of cathepsin endogenous inhibitor cystatin C in the skin tissue extract. Absence of cystatin C in these transgenic mice resulted in more progression of dysplasia to carcinoma in situ on the face, ear, chest, and tail. Chest and ear skin extract real time PCR and immunoblot analysis, mouse serum sample ELISA, tissue immunohistological analysis, and tissue extract-mediated in vitro elastinolysis and collagenolysis assays demonstrated that cystatin C deficiency significantly increased cathepsin expression and activity. In skin from both the chest and ear, we found that the absence of cystatin C reduced epithelial cell apoptosis but increased proliferation. From the same tissue preparations, we detected significantly higher levels of pro-angiogenic laminin 5-derived c2 peptides and concurrently increased neovascularization in cystatin C-deficient mice, compared to those from wild-type control mice. Conclusion: Enhanced cathepsin expression and activity in cystatin C-deficient mice contributed to the progression of dysplasia by altering premalignant tissue epithelial proliferation, apoptosis, and neovascularization.
  •  
32.
  • Zhang, Yaolin, et al. (författare)
  • Evaluation of block shear properties of selected extreme-PH structural adhesives by short term exposure test.
  • 2010
  • Ingår i: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 120:2, s. 657-665
  • Tidskriftsartikel (refereegranskat)abstract
    • Nine structural adhesives with varying pH were selected to examine the effect of adhesive pH on wood–adhesive bond quality. The adhesives evaluated included four highly alkaline phenol–formaldehyde, one intermediate pH phenol–resorcinol–formaldehyde, two acidic melamine–urea–formaldehyde, and two acidic melamine–formaldehyde resins. Block shear specimens were prepared using Douglas-fir and black spruce wood. The adhesive performance was evaluated by measuring the shear properties (strength and wood failure) of the specimens tested at the dry and vacuum–pressure–redry (VPD) conditions. Adhesive pH, test condition, and wood species showed significant effects on shear properties. The different adhesives performed differently at the dry and VPD conditions. The high-pH adhesives (phenol–formaldehyde and phenol–resorcinol–formaldehyde) showed similar high wood failures at both test conditions and performed better than the low-pH adhesives (melamine–formaldehyde and melamine–urea–formaldehyde), especially after the VPD conditioning. The low-pH adhesives showed high wood failure at the dry condition, but wood failure decreased significantly after VPD conditioning for both species, indicating that the low-pH adhesives were less durable than the high-pH adhesives. High-pH adhesives did not have a negative impact on the strength of the bonded specimens.
  •  
33.
  • Zhang, Yaolin, et al. (författare)
  • Impact of Curing Condition on pH and Alkalinity/ Acidity of Structural Wood Adhesives
  • 2010
  • Ingår i: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 117:5, s. 2888-2898
  • Tidskriftsartikel (refereegranskat)abstract
    • Nine formulations were selected for evalu- ating the effect of different curing methods on pH and alkalinity or acidity of various structural wood adhesives. These included four phenol–formaldehyde (PF) resins with high pH, one phenol–resorcinol–formaldehyde (PRF) resin with intermediate pH, two melamine–urea–formalde- hyde (MUF) resins, and two melamine–formaldehyde (MF) resins with low pH. The four curing methods used in the study were: (1) curing at 102–105C for 1 h (based on CSA O112.6-1977), (2) four-hour curing at 66C fol- lowed by 1-hour curing at 150C (based on ASTM D1583- 01), (3) curing at room temperature overnight (based on ASTM D 1583-01), and (4) cured adhesive squeezed out from glue lines of bonded shear block samples. The effect of the different methods on pH and alkalinity/acidity of the cured adhesive depended strongly on the individual adhesives. For the PF, the alkalinity was different for the different formulations in the liquid form, while in the cured form, the difference in the alkalinity depended on the curing method used. The MF and the MUF were the adhesives most affected by the method used. In particular, the MUF showed much higher cured film pH values when cured by method 2 compared to the other three methods, while both the cured MF and MUF exhibited quite variable acidity values when cured with the different methods. The PRF showed reasonably uniform cured film pH but varying acidity values when cured with the different methods.
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34.
  •  
35.
  • Zhou, Xiang-Yu, et al. (författare)
  • TRAF6 as the Key Adaptor of TLR4 Signaling Pathway Is Involved in Acute Pancreatitis
  • 2010
  • Ingår i: PANCREAS. - 0885-3177. ; 39:3, s. 359-366
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To study the potential role of tumor necrosis factor receptor-associated factor 6 (TRAF6) as the key adaptor of the toll-like receptor 4 (TLR4) signaling pathway in acute pancreatitis (AP) in mice. Methods: Acute pancreatitis was induced by 7 intraperitoneal injections of cerulein in TLR4-deficient (TLR4-Def) and TLR4 wild-type (TLR4-WT) mice. Inflammatory severity was scored and evaluated based on pathological study. TRAF6 expression was determined by reverse transcriptase polymerase chain reaction, Western blot, and immunohistochemistry. Results: Acute pancreatitis was successfully induced in both mice strains, but the inflammatory progression was different. In TLR4-Def mice, pancreatic inflammation was blunt and mild first, then became increasingly intensive and peaked at the later stage, whereas in the TLR4-WT mice, the response was fast initiated and peaked at the early stage of AP, then alleviated gradually. TRAF6 expression in TLR4-Def mice was significantly higher than that in the TLR4-WT mice. Immunohistochemistry located TRAF6 expressed mainly in the pancreatic acinar cells. Conclusions: The TLR4-TRAF6 signaling pathway is critically involved in AP. Other signaling pathways beyond TLR4 may participate in the pancreatic inflammatory process via TRAF6. As a convergence point of the TLR4-dependent and the TLR4-independent signaling pathways, TRAF6 plays an important role in AP.
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36.
  • Zhu, Zhen-Long, et al. (författare)
  • Cytoplasmic expression of p33(ING1b) is correlated with tumorigenesis and progression of human esophageal squamous cell carcinoma.
  • 2013
  • Ingår i: Oncology letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 5:1, s. 161-166
  • Tidskriftsartikel (refereegranskat)abstract
    • p33(ING1b), a newly discovered candidate tumor suppressor gene and a nuclear protein, belongs to the inhibitor of growth gene family. Previous studies have shown that p33(ING1b) is involved in the restriction of cell growth and proliferation, apoptosis, tumor anchorage-independent growth, cellular senescence, maintenance of genomic stability and modulation of cell cycle checkpoints. Loss of nuclear p33(ING1b) has been observed in melanoma, seminoma, papillary thyroid carcinoma, oral squamous cell carcinoma, breast ductal cancer and acute lymphoblastic leukemia. Inactivation and/or decreased expression of p33(ING1b) have been reported in various types of cancer, including head and neck squamous cell, breast, lung, stomach, blood and brain malignancies. Since little is known about the clinicopathological significance of p33(ING1b) in esophageal squamous cell carcinoma (ESCC), this study aimed to investigate the association of p33(ING1b) expression with clinicopathological variables and particularly interesting new cysteine-histidine rich protein (PINCH) in patients with ESCC. p33(ING1b) expression was examined by immunohistochemistry in 20 normal esophageal mucosa and in 64 ESCC specimens. The results revealed that the positive expression of p33(ING1b) protein in normal squamous cells was localized in the nucleus alone and the positive rate was 95%, while in ESCCs, the positive expression was mainly in the cytoplasm, together with nuclear expression, and the positive rate was 36% (P<0.0001). Furthermore, the cases with lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without metastasis (P=0.001). The cytoplasmic expression of p33(ING1b) was positively related to PINCH expression (P<0.0001) in ESCC, and the cases positive for both proteins had a high lymph node metastasis rate (P=0.001). In conclusion, p33(ING1b) cellular compartmental shift from the nucleus to the cytoplasm may cause loss of normal cellular function and play a central role in the tumorigenesis and metastasis of ESCC.
  •  
37.
  • Zhu, Zhen-Long, et al. (författare)
  • PINCH expression and its clinicopathological significance in gastric adenocarcinoma
  • 2012
  • Ingår i: Disease Markers. - : IOS Press. - 0278-0240 .- 1875-8630. ; 33:4, s. 171-178
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Particularly interesting new cysteine-histidine rich protein (PINCH) is an important component of the local adhesion complexes and upregulated in several types of malignancies, and involved in the incidence and development of tumours. PINCH expression is also independently correlated with poorer survival in patients with colorectal cancer. However, there is no study of PINCH in gastric cancer, therefore, the aim of this project was to investigate PINCH expression and its clinicopathological significance in gastric adenocarcinoma. less thanbrgreater than less thanbrgreater thanPatients and methods: PINCH expression was immunohistochemically examined in normal gastric mucous (n = 30) and gastric adenocarcinoma (n = 73), from gastric cancer patients. less thanbrgreater than less thanbrgreater thanResults: PINCH expression in the associated-stroma of gastric cancers was heterogeneous, and its positive rate (75%) was higher than that of normal gastric mucosa (43%, X-2 = 9.711, p = 0.002). The stronger staining was observed at the invasive edge of tumour when compared to the inner area of tumour. The rate of positive PINCH (88%) in the cases with lymph node metastasis was higher than that (52%) in the cases without metastasis (X-2 = 11.151, p = 0.001). PINCH expression was not correlated with patients gender, age, tumour size, differentiation and invasion depth (p andgt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: PINCH protein might play an important role in the tumourigenesis and metastasis of gastric adenocarcinoma.
  •  
38.
  • Bruhn, Sören, et al. (författare)
  • A Generally Applicable Translational Strategy Identifies S100A4 as a Candidate Gene in Allergy
  • 2014
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:218
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification of diagnostic markers and therapeutic candidate genes in common diseases is complicated by the involvement of thousands of genes. We hypothesized that genes co-regulated with a key gene in allergy, IL13, would form a module that could help to identify candidate genes. We identified a T helper 2 (T(H)2) cell module by small interfering RNA-mediated knockdown of 25 putative IL13-regulating transcription factors followed by expression profiling. The module contained candidate genes whose diagnostic potential was supported by clinical studies. Functional studies of human TH2 cells as well as mouse models of allergy showed that deletion of one of the genes, S100A4, resulted in decreased signs of allergy including TH2 cell activation, humoral immunity, and infiltration of effector cells. Specifically, dendritic cells required S100A4 for activating T cells. Treatment with an anti-S100A4 antibody resulted in decreased signs of allergy in the mouse model as well as in allergen-challenged T cells from allergic patients. This strategy, which may be generally applicable to complex diseases, identified and validated an important diagnostic and therapeutic candidate gene in allergy.
  •  
39.
  • Figueroa, Jonine D., et al. (författare)
  • Genome-wide association study identifies multiple loci associated with bladder cancer risk
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 23:5, s. 1387-1398
  • Tidskriftsartikel (refereegranskat)abstract
    • andidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
  •  
40.
  • Fu, Yi-Ping, et al. (författare)
  • The 19q12 Bladder Cancer GWAS Signal : Association with Cyclin E Function and Aggressive Disease
  • 2014
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:20, s. 5808-5818
  • Tidskriftsartikel (refereegranskat)abstract
    • A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) >= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P-trend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.
  •  
41.
  • Gao, Xiang, et al. (författare)
  • On RF implementation of WINNER II channel model for MIMO OTA performance evaluations
  • 2010
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The development of MIMO over-the-air (OTA) test methodology is an ongoing activity in 3GPP RAN4, CTIA and EU COST Action 2100. In this paper, the focus is on the anechoic chamber approach, which uses a uniform circular array of probe antennas to replicate directional channels for the device under test (DUT) at the array center. In particular, we study in simulation the complexity requirements of implementing the WINNER II clustered delay line (CDL) model in RF using off-the-shelf RF components. Our results reveal that a significant reduction in complexity of the CDL model can be achieved while keeping both ergodic and outage capacity to within 10% of the full model. This suggests that it is both feasible and cost effective in implementing state-of-the-art directional channel models in RF for MIMO OTA tests.
  •  
42.
  • Gao, Xiang, et al. (författare)
  • On simplifying WINNER II channel model for MIMO OTA performance evaluation
  • 2011
  • Ingår i: Proceedings of the 5th European Conference on Antennas and Propagation (EUCAP). - 9781457702501 - 9788882020743
  • Konferensbidrag (refereegranskat)abstract
    • The development of MIMO over-the-air (OTA) test methodology is an ongoing activity in 3GPP RAN4, CTIA and EU COST Action 2100. In this paper, the focus is on the anechoic chamber approach, which uses a uniform circular array of probe antennas to replicate directional channels for the device-under- test at the array center. In particular, we study in simulation the complexity requirements of implementing the WINNER II clustered delay line (CDL) model in RF using off-the-shelf RF components. Our results reveal that a significant reduction in complexity of the CDL model can be achieved, while keeping the change in both ergodic and outage capacities under 10% relative to the full model. This suggests that it is both feasible and cost effective in implementing state-of-the-art directional channel models in RF for MIMO OTA performance evaluations.
  •  
43.
  • Hammarberg, Peter, et al. (författare)
  • Coded IDMA system performance with parallel interleavers
  • 2010
  • Ingår i: [Host publication title missing]. - 9781424470693 ; , s. 1-4
  • Konferensbidrag (refereegranskat)abstract
    • In this paper we evaluate the use of parallel interleavers for user separation in coded IDMA systems. The parallel interleavers have previously been evaluated for uncoded systems, and we here present extended results for the coded case. The new results are important for real systems, as they will most likely use performance enhancing channel coding. The parallel interleavers are designed to remove the risk of memory access collision during interleaving. These problems may occur when the interleaving process is being parallelized in order to support parallel processing at the decoder. The results show that the degree of parallelization in the interleaver design has an insignificant effect on the considered coded system performance. Furthermore, our results also show that the use of parallel interleavers gives a performance that is similar to that obtained when using random interleavers.
  •  
44.
  • Hu, Ning, et al. (författare)
  • Energy-Efficient Relaying Strategy with Network Coding in Two-Way Parallel Channels
  • 2011
  • Ingår i: ISRN Communications and Networking. - : Hindawi Limited. - 2090-4355 .- 2090-4363. ; 2011
  • Tidskriftsartikel (refereegranskat)abstract
    • We consider a two-way communication assisted by parallel regenerative decode-and-forward relays operating in orthogonal channels. In a system with limited channel state information at each source and relay node, an optimum distributed power allocation strategy is proposed to minimize the total transmit power, providing a target signal-to-noise ratio at each destination with a target outage probability. Moreover, combined with opportunistic relaying and network coding, a distributed decision mechanism is proposed for the relay node to decide whether to help the transmission or not. In this proposal, each source works out the transmit power and the decision threshold then broadcasts them. The selected relay compares the decision threshold with the channel gain of its weaker relay-to-destination link, then determines whether to forward the networkcoded data or not. Simulation results show the advantage of this strategy in terms of energy efficiency for a two-hop two-way communication scenario. The proposed strategy is very flexible as it can trade outage to power consumption and vice versa.
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45.
  • Hu, Y., et al. (författare)
  • Antagonistic Effects of a Mixture of Low-Dose Nonylphenol and Di-N-Butyl Phthalate (Monobutyl Phthalate) on the Sertoli Cells and Serum Reproductive Hormones in Prepubertal Male Rats In Vitro and In Vivo
  • 2014
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The estrogenic chemical nonylphenol (NP) and the antiandrogenic agent di-n-butyl phthalate (DBP) are regarded as widespread environmental endocrine disruptors (EDCs) which at high doses in some species of laboratory animals, such as mice and rats, have adverse effects on male reproduction and development. Given the ubiquitous coexistence of various classes of EDCs in the environment, their combined effects warrant clarification. In this study, we attempted to determine the mixture effects of NP and DBP on the testicular Sertoli cells and reproductive endocrine hormones in serum in male rats based on quantitative data analysis by a mathematical model. In the in vitro experiment, monobutyl phthalate (MBP), the active metabolite of DBP, was used instead of DBP. Sertoli cells were isolated from 9-day-old Sprague-Dawley rats followed by treatment with NP and MBP, singly or combined. Cell viability, apoptosis, necrosis, membrane integrity and inhibin-B concentration were tested. In the in vivo experiment, rats were gavaged on postnatal days 23-35 with a single or combined NP and DBP treatment. Serum reproductive hormone levels were recorded. Next, Bliss Independence model was employed to analyze the quantitative data obtained from the in vitro and in vivo investigation. Antagonism was identified as the mixture effects of NP and DBP (MBP). In this study, we demonstrate the potential of Bliss Independence model for the prediction of interactions between estrogenic and antiandrogenic agents.
  •  
46.
  • Hu, Y., et al. (författare)
  • Mixture effects of nonylphenol and di-n-butyl phthalate (monobutyl phthalate) on the tight junctions between Sertoli cells in male rats in vitro and in vivo
  • 2014
  • Ingår i: Experimental and Toxicologic Pathology. - : Elsevier BV. - 0940-2993. ; 66:9-10, s. 445-454
  • Tidskriftsartikel (refereegranskat)abstract
    • The estrogenic chemical nonylphenol (NP) and the antiandrogenic agent di-n-butyl phthalate (DBP) are regarded as widespread environmental endocrine disruptors (EEDs) which at high doses in some species of laboratory animals have adverse effects on male reproduction and development. Given the ubiquitous coexistence of various classes of EEDs in the environment, their combined effects warrant investigation. In this study, we attempted to clarify the interactions of NP and DBP on tight junctions (TJs) between rat Sertoli cells. In the in vitro experiment, monobutyl phthalate (MBP), the active metabolite of DBP, was used instead of DBP. Sertoli cells were isolated from Sprague-Dawley rats, and treated with NP and MBP, singly or combined. The morphology of Sertoli cells, and structure and functionality of TJs were measured. In the in vivo experiment, rats were gavaged on postnatal day 23-35 with a single or combined NP and DBP treatment. Testicular weight and morphology of TJs were recorded. These data indicated that NP and DBP/MBP, either in single or in combination, induced the structural and function changes of Sertoli cell tight junctions, both in vivo and in vitro. The combined effect on the regulation of TJ proteins at both the protein and gene levels was correlated to the effect exerted by NP, suggesting that the structure and function of Sertoli cells were more sensitive to exposure to NP than MBP. (C) 2014 Elsevier GmbH. All rights reserved.
  •  
47.
  •  
48.
  • Liu, Ning, et al. (författare)
  • Transcriptional regulation mechanisms of hypoxia-induced neuroglobin gene expression.
  • 2012
  • Ingår i: The Biochemical journal. - 1470-8728 .- 0264-6021. ; 443:1, s. 153-164
  • Tidskriftsartikel (refereegranskat)abstract
    • Ngb (neuroglobin) has been identified as a novel endogenous neuroprotectant. However, little is known about the regulatory mechanisms of Ngb expression, especially under conditions of hypoxia. In the present study, we located the core proximal promoter of the mouse Ngb gene to a 554bp segment, which harbours putative conserved NF-κB (nuclear factor κB)- and Egr1 (early growth-response factor 1) -binding sites. Overexpression and knockdown of transcription factors p65, p50, Egr1 or Sp1 (specificity protein 1) increased and decreased Ngb expression respectively. Experimental assessments with transfections of mutational Ngb gene promoter constructs, as well as EMSA (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation) assays, demonstrated that NF-κB family members (p65, p50 and cRel), Egr1 and Sp1 bound in vitro and in vivo to the proximal promoter region of the Ngb gene. Moreover, a κB3 site was found as a pivotal cis-element responsible for hypoxia-induced Ngb promoter activity. NF-κB (p65) and Sp1 were also responsible for hypoxia-induced up-regulation of Ngb expression. Although there are no conserved HREs (hypoxia-response elements) in the promoter of the mouse Ngb gene, the results of the present study suggest that HIF-1α (hypoxia-inducible factor-1α) is also involved in hypoxia-induced Ngb up-regulation. In conclusion, we have identified that NF-κB, Egr1 and Sp1 played important roles in the regulation of basal Ngb expression via specific interactions with the mouse Ngb promoter. NF-κB, Sp1 and HIF-1α contributed to the up-regulation of mouse Ngb gene expression under hypoxic conditions.
  •  
49.
  • Medeiros, Eduardo, et al. (författare)
  • Modeling Alien-Line Impedance Mismatch in Wideband Vectored Wireline Systems
  • 2014
  • Ingår i: IEEE Communications Letters. - 1089-7798. ; 18:9, s. 1527-1530
  • Tidskriftsartikel (refereegranskat)abstract
    • Sudden changes of channel coefficients in a wideband vectored wireline system (such as G.fast) due to changes in the terminating impedance of lines outside the vectored group can seriously degrade stability and throughput. This letter presents a model that predicts the impact of termination mismatch based exclusively on crosstalk data for the properly-terminated state. Experimental results confirm a tight fit between model and mea- surements. The model allows analysis of system performance and stability without dedicated crosstalk measurements for mismatch cases.
  •  
50.
  • Meng, Wen-Jian, et al. (författare)
  • Correlation of SATB1 overexpression with the progression of human rectal cancer
  • 2012
  • Ingår i: International Journal of Colorectal Disease. - : Springer Verlag (Germany). - 0179-1958 .- 1432-1262. ; 27:2, s. 143-150
  • Tidskriftsartikel (refereegranskat)abstract
    • To date, the association between special AT-rich sequence-binding protein 1 (SATB1) and colorectal cancer (CRC) has not been reported. This study was aimed at investigating the expression and potential role of SATB1 in human rectal cancers. less thanbrgreater than less thanbrgreater thanNinety-three paired samples of rectal cancer and distant normal rectal tissue were analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), and the correlations between SATB1 expression and clinicopathological parameters were evaluated. The expression profiles of SATB1 were also investigated in a panel of five human colon carcinoma cell lines. less thanbrgreater than less thanbrgreater thanThe general level of SATB1 mRNA in rectal cancer tissues was statistically significantly higher than that in normal mucosa (P = 0.043). The rate of positive SATB1 protein expression in rectal cancers (44.1%) was significantly higher than that in normal tissues (25.8%) by IHC analysis (P = 0.009). Overexpression of SATB1 mRNA was more predominant in patients with earlier onset of rectal cancer (P = 0.033). SATB1 expression correlated with invasive depth and tumor node metastasis (TNM) stage at both protein and mRNA levels (P andlt; 0.05). Furthermore, SATB1 expression in the poorly metastatic KM12C cells was significantly lower than the highly metastatic KM12SM and KM12L4A cells and higher than the HCT116 and SW480 cells (P = 0.001). These results were further confirmed by Western blotting. less thanbrgreater than less thanbrgreater thanOur results indicate that SATB1 may play an important role in the progression of human rectal cancer, which represents a possible new mechanism underlying CRC.
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