| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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
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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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| 5. |
- 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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| 6. |
- Abelev, B., et al.
(författare)
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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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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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| 11. |
- 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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| 12. |
- 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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| 13. |
- 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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| 14. |
- 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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| 15. |
- Abelev, B., et al.
(författare)
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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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| 16. |
- Abelev, B., et al.
(författare)
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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
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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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| 17. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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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| 18. |
- Abdoullaye, Doukary, et al.
(författare)
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Permanent genetic resources added to molecular ecology resources database 1 August 2009 - 30 September 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:1, s. 232-236
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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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| 19. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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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.
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| 20. |
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| 21. |
- Wang, Zhaoming, et al.
(författare)
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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
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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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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| 22. |
- Figueroa, Jonine D., et al.
(författare)
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Genome-wide association study identifies multiple loci associated with bladder cancer risk
- 2014
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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.
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| 23. |
- Holmfeldt, Linda, et al.
(författare)
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The genomic landscape of hypodiploid acute lymphoblastic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:3, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
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| 24. |
- Qi, Qibin, et al.
(författare)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
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Tidskriftsartikel (refereegranskat)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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| 25. |
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| 26. |
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| 27. |
- Argiropoulos, Bob, et al.
(författare)
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Linkage of the potent leukemogenic activity of Meis1 to cell-cycle entry and transcriptional regulation of cyclin D3.
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 115:20, s. 4071-82
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Tidskriftsartikel (refereegranskat)abstract
- MEIS1 is a three-amino acid loop extension class homeodomain-containing homeobox (HOX) cofactor that plays key roles in normal hematopoiesis and leukemogenesis. Expression of Meis1 is rate-limiting in MLL-associated leukemias and potently interacts with Hox and NUP98-HOX genes in leukemic transformation to promote self-renewal and proliferation of hematopoietic progenitors. The oncogenicity of MEIS1 has been linked to its transcriptional activation properties. To further reveal the pathways triggered by Meis1, we assessed the function of a novel engineered fusion form of Meis1, M33-MEIS1, designed to confer transcriptional repression to Meis1 target genes that are otherwise up-regulated in normal and malignant hematopoiesis. Retroviral overexpression of M33-Meis1 resulted in the rapid and complete eradication of M33-Meis1-transduced normal and leukemic cells in vivo. Cell-cycle analysis showed that M33-Meis1 impeded the progression of cells from G(1)-to-S phase, which correlated with significant reduction of cyclin D3 levels and the inhibition of retinoblastoma (pRb) hyperphosphorylation. We identified cyclin D3 as a direct downstream target of MEIS1 and M33-MEIS1 and showed that the G(1)-phase accumulation and growth suppression induced by M33-Meis1 was partially relieved by overexpression of cyclin D3. This study provides strong evidence linking the growth-promoting activities of Meis1 to the cyclin D-pRb cell-cycle control pathway.
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| 28. |
- Fu, Yi-Ping, et al.
(författare)
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The 19q12 Bladder Cancer GWAS Signal : Association with Cyclin E Function and Aggressive Disease
- 2014
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:20, s. 5808-5818
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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.
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| 29. |
- Hu, Y., et al.
(författare)
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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
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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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.
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| 30. |
- Hu, Y., et al.
(författare)
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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
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Ingår i: Experimental and Toxicologic Pathology. - : Elsevier BV. - 0940-2993. ; 66:9-10, s. 445-454
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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.
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| 31. |
- Lammer, H., et al.
(författare)
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Exoplanet status report: Observation, characterization and evolution of exoplanets and their host stars
- 2010
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Ingår i: Solar System Research. - 1608-3423 .- 0038-0946. ; 44:4, s. 290-310
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Tidskriftsartikel (refereegranskat)abstract
- After the discovery of more than 400 planets beyond our Solar System, the characterization of exoplanets as well as their host stars can be considered as one of the fastest growing fields in space science during the past decade. The characterization of exoplanets can only be carried out in a well coordinated interdisciplinary way which connects planetary science, solar/stellar physics and astrophysics. We present a status report on the characterization of exoplanets and their host stars by reviewing the relevant space- and ground-based projects. One finds that the previous strategy changed from space mission concepts which were designed to search, find and characterize Earth-like rocky exoplanets to: A statistical study of planetary objects in order to get information about their abundance, an identification of potential target and finally its analysis. Spectral analysis of exoplanets is mandatory, particularly to identify bio-signatures on Earth-like planets. Direct characterization of exoplanets should be done by spectroscopy, both in the visible and in the infrared spectral range. The way leading to the direct detection and characterization of exoplanets is then paved by several questions, either concerning the pre-required science or the associated observational strategy.
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| 32. |
- Moretti, Rocco, et al.
(författare)
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Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions
- 2013
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Ingår i: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 81:11, s. 1980-1987
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Tidskriftsartikel (refereegranskat)abstract
- Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state of predictive methodology. Here we describe a community-wide assessment of methods to predict the effects of mutations on protein-protein interactions. Twenty-two groups predicted the effects of comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders and the results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful methods explicitly considered the effects of mutation on monomer stability in addition to binding affinity, carried out explicit side-chain sampling and backbone relaxation, evaluated packing, electrostatic, and solvation effects, and correctly identified around a third of the beneficial mutations. Much room for improvement remains for even the best techniques, and large-scale fitness landscapes should continue to provide an excellent test bed for continued evaluation of both existing and new prediction methodologies. Proteins 2013; 81:1980-1987.
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| 33. |
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| 34. |
- Qi, Chong, et al.
(författare)
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Alternate proof of the Rowe-Rosensteel proposition and seniority conservation
- 2010
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 82:1, s. 014304-
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Tidskriftsartikel (refereegranskat)abstract
- For a system with three identical nucleons in a single-j shell, the states can be written as the angular-momentum coupling of a nucleon pair and the odd nucleon. The overlaps between these nonorthonormal states form a matrix that coincides with the one derived by Rowe and Rosensteel [Phys. Rev. Lett. 87, 172501 ( 2001)]. The propositions they state are related to the eigenvalue problems of the matrix and dimensions of the associated subspaces. In this work, the propositions are proven from the symmetric properties of the 6j symbols. Algebraic expressions for the dimension of the states, eigenenergies, as well as conditions for conservation of seniority can be derived from the matrix.
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| 35. |
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| 36. |
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| 37. |
- Wang, Cong, et al.
(författare)
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Inhibition of Wnt/beta-catenin signaling promotes epithelial differentiation of mesenchymal stem cells and repairs bleomycin-induced lung injury
- 2014
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Ingår i: American Journal of Physiology-Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 307:3
-
Tidskriftsartikel (refereegranskat)abstract
- Idiopathic pulmonary fibrosis is a progressive lung disorder of unknown etiology. Previous studies have shown that aberrant activation of the Wnt/beta-catenin signaling cascade occurs in lungs of patients with idiopathic pulmonary fibrosis. Given the important roles of the Wnt/beta-catenin signaling pathway in the development of pulmonary fibrosis, we targeted this pathway for the intervention of pulmonary fibrosis with XAV939, a small molecule that specifically inhibits Tankyrase 1/2, eventually leading to the degradation of beta-catenin and suppression of the Wnt/beta-catenin signaling pathway. Our results demonstrated that XAV939 significantly inhibited the activation of Wnt/beta-catenin signaling and attenuated bleomycin-induced lung fibrosis in mice, and thus improved the survival of mice with lung injury. Interestingly, previous investigations have confirmed that endogenous and exogenous mesenchymal stem cells could be recruited to the injured lung, although the exact effects of these cells are debatable. To determine the effect of Wnt/beta-catenin signaling in the epithelial differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs), we established a coculture system that contains BM-MSCs and alveolar type II epithelial cells. The in vitro experiments demonstrated that XAV939 could promote the differentiation of BM-MSCs into an epithelium-like phenotype in the coculture system. We also found that XAV939 could inhibit the proliferation and myofibroblast differentiation of NIH/3T3 fibroblasts. This work supports that inhibition of the Wnt/beta-catenin signaling pathway may be exploited for the treatment of idiopathic pulmonary fibrosis for which effective treatment strategies are still lacking.
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| 38. |
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