| 1. |
- Abelev, B., et al.
(författare)
-
Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at root s(NN)=2.76 TeV
- 2013
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 720:1-3, s. 52-62
-
Tidskriftsartikel (refereegranskat)abstract
- The inclusive transverse momentum (p(T)) distributions of primary charged particles are measured in the pseudo-rapidity range vertical bar eta vertical bar <0.8 as a function of event centrality in Pb-Pb collisions at root S-NN = 2.76 TeV with ALICE at the LHC. The data are presented in the p(T) range 0.15 < p(T) <50 GeV/c for nine centrality intervals from 70-80% to 0-5%. The results in Pb-Pb are presented in terms of the nuclear modification factor R-AA using a pp reference spectrum measured at the same collision energy. We observe that the suppression of high-p(T) particles strongly depends on event centrality. The yield is most suppressed in central collisions (0-5%) with R-AA approximate to 0.13 at p(T) = 6-7 GeV/c. Above p(T) = 7 GeV/c, there is a significant rise in the nuclear modification factor, which reaches R-AA approximate to 0.4 for p(T) > 30 GeV/c. In peripheral collisions (70-80%), only moderate suppression (R-AA approximate to 0.6-0.7) and a weak p(T) dependence is observed. The measured nuclear modification factors are compared to other measurements and model calculations. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 2. |
- Abelev, B., et al.
(författare)
-
Charged kaon femtoscopic correlations in pp collisions at root s=7 TeV
- 2013
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:5
-
Tidskriftsartikel (refereegranskat)abstract
- Correlations of two charged identical kaons (KchKch) are measured in pp collisions at root s = 7 TeV by the ALICE experiment at the Large Hadron Collider (LHC). One-dimensional (KKch)-K-ch correlation functions are constructed in three multiplicity and four transverse momentum ranges. The (KKch)-K-ch femtoscopic source parameters R and lambda are extracted. The (KKch)-K-ch correlations show a slight increase of femtoscopic radii with increasing multiplicity and a slight decrease of radii with increasing transverse momentum. These trends are similar to the ones observed for pi pi and K-s(0) K-s(0) correlations in pp and heavy-ion collisions. However at high multiplicities, there is an indication that the one-dimensional correlation radii for charged kaons are larger than those for pions in contrast to what was observed in heavy-ion collisions at the Relativistic Heavy-Ion Collider. DOI:10.1103/PhysRevD.87.052016
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| 3. |
- Abelev, B., et al.
(författare)
-
Coherent J/psi photoproduction in ultra-peripheral Pb-Pb collisions at root s(NN)=2.76 TeV
- 2013
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 718:4-5, s. 1273-1283
-
Tidskriftsartikel (refereegranskat)abstract
- The ALICE Collaboration has made the first measurement at the LHC of J/psi photoproduction in ultra-peripheral Pb-Pb collisions at root s(NN) = 2.76 TeV. The J/psi is identified via its dimuon decay in the forward rapidity region with the muon spectrometer for events where the hadronic activity is required to be minimal. The analysis is based on an event sample corresponding to an integrated luminosity of about 55 mu b(-1). The cross section for coherent J/psi production in the rapidity interval -3.6 < y < -2.6 is measured to be d sigma(coh)(J/psi)/dy = 1.00 +/- 0.18(stat)(-0.26)(+0.24)(syst) mb. The result is compared to theoretical models for coherent J/psi production and found to be in good agreement with those models which include nuclear gluon shadowing. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved.
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| 4. |
- Abelev, B., et al.
(författare)
-
Pseudorapidity Density of Charged Particles in p plus Pb Collisions at root s(NN)=5.02 TeV
- 2013
-
Ingår i: Physical Review Letters. - 1079-7114. ; 110:3
-
Tidskriftsartikel (refereegranskat)abstract
- The charged-particle pseudorapidity density measured over four units of pseudorapidity in nonsingle-diffractive p + Pb collisions at a center-of-mass energy per nucleon pair root s(NN) = 5.02 TeV is presented. The average value at midrapidity is measured to be 16.81 +/- 0.71 (syst), which corresponds to 2.14 +/- 0.17 (syst) per participating nucleon, calculated with the Glauber model. This is 16% lower than in nonsingle-diffractive pp collisions interpolated to the same collision energy and 84% higher than in d + Au collisions at root s(NN) = 0.2 TeV. The measured pseudorapidity density in p + Pb collisions is compared to model predictions and provides new constraints on the description of particle production in high-energy nuclear collisions. DOI: 10.1103/PhysRevLett.110.032301
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| 5. |
- Abelev, B., et al.
(författare)
-
Transverse Momentum Distribution and Nuclear Modification Factor of Charged Particles in p plus Pb Collisions at root(NN)-N-s=5.02 TeV
- 2013
-
Ingår i: Physical Review Letters. - 1079-7114. ; 110:8
-
Tidskriftsartikel (refereegranskat)abstract
- The transverse momentum (pT) distribution of primary charged particles is measured in minimum bias (non-single-diffractive) p + Pb collisions at root(NN)-N-s = 5.02 TeV with the ALICE detector at the LHC. The pT spectra measured near central rapidity in the range 0.5< p(T) < 20 GeV/c exhibit a weak pseudorapidity dependence. The nuclear modification factor R-pPb is consistent with unity for p(T) above 2 GeV/c. This measurement indicates that the strong suppression of hadron production at high p(T) observed in Pb + Pb collisions at the LHC is not due to an initial-state effect. The measurement is compared to theoretical calculations. DOI: 10.1103/PhysRevLett.110.082302
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| 6. |
- Abelev, B., et al.
(författare)
-
Upgrade of the ALICE Experiment Letter Of Intent
- 2014
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 41:8
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Tidskriftsartikel (refereegranskat)abstract
- ALICE (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. These plans are presented in the ALICE Upgrade Letter of Intent, submitted to the LHCC (LHC experiments Committee) in September 2012. In order to fully exploit the physics reach of the LHC in this field, high-precision measurements of the heavy-flavour production, quarkonia, direct real and virtual photons, and jets are necessary. This will be achieved by an increase of the LHC Pb–Pb instant luminosity up to 6×1027 cm−2s−1 and running the ALICE detector with the continuous readout at the 50 kHz event rate. The physics performance accessible with the upgraded detector, together with the main detector modifications, are presented.
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| 7. |
- Abbas, E., et al.
(författare)
-
J/psi Elliptic Flow in Pb-Pb Collisions at root s(NN)=2.76 TeV
- 2013
-
Ingår i: Physical Review Letters. - 1079-7114. ; 111:16
-
Tidskriftsartikel (refereegranskat)abstract
- We report on the first measurement of inclusive J/psi elliptic flow v(2) in heavy-ion collisions at the LHC. The measurement is performed with the ALICE detector in Pb-Pb collisions at root s(NN) = 2.76 TeV in the rapidity range 2.5 < y < 4.0. The dependence of the J/psi v(2) on the collision centrality and on the J/psi transverse momentum is studied in the range 0 <= p(T) < 10 GeV/c. For semicentral Pb-Pb collisions at root s(NN) = 2.76 TeV, an indication of nonzero v(2) is observed with a largest measured value of v(2) = 0.116 +/-0.046(stat) +/- 0.029(syst) for J/psi in the transverse momentum range 2 <= p(T) < 4 GeV/c. The elliptic flow measurement complements the previously reported ALICE results on the inclusive J/psi nuclear modification factor and favors the scenario of a significant fraction of J/psi production from charm quarks in a deconfined partonic phase.
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| 8. |
- Abelev, B., et al.
(författare)
-
Centrality dependence of pi, K, and p production in Pb-Pb collisions at root s(NN)=2.76 TeV
- 2013
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:4
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Tidskriftsartikel (refereegranskat)abstract
- In this paper measurements are presented of pi(+/-), K-+/-, p, and (p) over bar production at midrapidity (vertical bar y vertical bar < 0.5), in Pb-Pb collisions at root s(NN) = 2.76 TeV as a function of centrality. The measurement covers the transverse-momentum (p(T)) range from 100, 200, and 300 MeV/c up to 3, 3, and 4.6 GeV/c for pi, K, and p, respectively. The measured p(T) distributions and yields are compared to expectations based on hydrodynamic, thermal and recombination models. The spectral shapes of central collisions show a stronger radial flow than measured at lower energies, which can be described in hydrodynamic models. In peripheral collisions, the p(T) distributions are not well reproduced by hydrodynamic models. Ratios of integrated particle yields are found to be nearly independent of centrality. The yield of protons normalized to pions is a factor similar to 1.5 lower than the expectation from thermal models.
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| 9. |
- Abelev, B., et al.
(författare)
-
Centrality determination of Pb-Pb collisions at root s(NN)=2.76 TeV with ALICE
- 2013
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:4
-
Tidskriftsartikel (refereegranskat)abstract
- This publication describes the methods used to measure the centrality of inelastic Pb-Pb collisions at a center-of-mass energy of 2.76 TeV per colliding nucleon pair with ALICE. The centrality is a key parameter in the study of the properties of QCD matter at extreme temperature and energy density, because it is directly related to the initial overlap region of the colliding nuclei. Geometrical properties of the collision, such as the number of participating nucleons and the number of binary nucleon-nucleon collisions, are deduced from a Glauber model with a sharp impact parameter selection and shown to be consistent with those extracted from the data. The centrality determination provides a tool to compare ALICE measurements with those of other experiments and with theoretical calculations.
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| 10. |
- Abelev, B., et al.
(författare)
-
Charge correlations using the balance function in Pb-Pb collisions at root s(NN)=2.76 TeV
- 2013
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 723:4-5, s. 267-279
-
Tidskriftsartikel (refereegranskat)abstract
- In high-energy heavy-ion collisions, the correlations between the emitted particles can be used as a probe to gain insight into the charge creation mechanisms. In this Letter, we report the first results of such studies using the electric charge balance function in the relative pseudorapidity (Delta eta) and azimuthal angle (Delta phi) in Pb-Pb collisions at root s(NN) = 2.76 TeV with the ALICE detector at the Large Hadron Collider. The width of the balance function decreases with growing centrality (i.e. for more central collisions) in both projections. This centrality dependence is not reproduced by HIJING, while AMPT, a model which incorporates strings and parton rescattering, exhibits qualitative agreement with the measured correlations in Delta phi but fails to describe the correlations in Delta eta. A thermal blast-wave model incorporating local charge conservation and tuned to describe the p(T) spectra and v(2) measurements reported by ALICE, is used to fit the centrality dependence of the width of the balance function and to extract the average separation of balancing charges at freeze-out. The comparison of our results with measurements at lower energies reveals an ordering with root s(NN): the balance functions become narrower with increasing energy for all centralities. This is consistent with the effect of larger radial flow at the LHC energies but also with the late stage creation scenario of balancing charges. However, the relative decrease of the balance function widths in Delta eta and Delta phi, with centrality from the highest SPS to the LHC energy exhibits only small differences. This observation cannot be interpreted solely within the framework where the majority of the charge is produced at a later stage in the evolution of the heavy-ion collision. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 11. |
- 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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| 12. |
- Abelev, B., et al.
(författare)
-
Measurement of the inclusive differential jet cross section in pp collisions at root s=2.76 TeV
- 2013
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 722:4-5, s. 262-272
-
Tidskriftsartikel (refereegranskat)abstract
- The ALICE Collaboration at the CERN Large Hadron Collider reports the first measurement of the inclusive differential jet cross section at mid-rapidity in pp collisions at root s = 2.76 TeV, with integrated luminosity of 13.6 nb(-1). Jets are measured over the transverse momentum range 20 to 125 GeV/c and are corrected to the particle level. Calculations based on Next-to-Leading Order perturbative QCD are in good agreement with the measurements. The ratio of inclusive jet cross sections for jet radii R = 0.2 and R = 0.4 is reported, and is also well reproduced by a Next-to-Leading Order perturbative QCD calculation when hadronization effects are included. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 13. |
- Abelev, B., et al.
(författare)
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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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| 14. |
- Abbas, E., et al.
(författare)
-
Centrality dependence of the pseudorapidity density distribution for charged particles in Pb-Pb collisions at root s(NN)=2.76 TeV
- 2013
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 726:4-5, s. 610-622
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first wide-range measurement of the charged-particle pseudorapidity density distribution, for different centralities (the 0-5%, 5-10%, 10-20%, and 20-30% most central events) in Pb-Pb collisions at root s(NN) = 2.76 TeV at the LHC. The measurement is performed using the full coverage of the ALICE detectors, -5.0 < eta < 5.5, and employing a special analysis technique based on collisions arising from LHC 'satellite' bunches. We present the pseudorapidity density as a function of the number of participating nucleons as well as an extrapolation to the total number of produced charged particles (N-ch = 17165 +/- 772 for the 0-5% most central collisions). From the measured dN(ch)/d eta distribution we derive the rapidity density distribution, dN(ch)/dy, under simple assumptions. The rapidity density distribution is found to be significantly wider than the predictions of the Landau model. We assess the validity of longitudinal scaling by comparing to lower energy results from RHIC. Finally the mechanisms of the underlying particle production are discussed based on a comparison with various theoretical models. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 15. |
- Abbas, E., et al.
(författare)
-
Charmonium and e(+)e(-) pair photoproduction at mid-rapidity in ultra-peripheral Pb-Pb collisions at root s(NN)=2.76 TeV
- 2013
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:11
-
Tidskriftsartikel (refereegranskat)abstract
- The ALICE Collaboration at the LHC has measured the J/psi and psi' photoproduction at mid-rapidity in ultra-peripheral Pb-Pb collisions at root s(NN) = 2.76 TeV. The charmonium is identified via its leptonic decay for events where the hadronic activity is required to be minimal. The analysis is based on an event sample corresponding to an integrated luminosity of about 23 mu b(-1). The cross section for coherent and incoherent J/psi production in the rapidity interval -0.9 < y < 0.9, are d sigma(coh)(J/psi)/dy = 2.38(-0.24)(+0.34)(sta + sys) mb and d sigma(inc)(J/psi)/dy = 0.98(-0.17)(+0.19)(sta + sys) mb and , respectively. The results are compared to theoretical models for J/psi production and the coherent cross section is found to be in good agreement with those models incorporating moderate nuclear gluon shadowing at Bjorken-x around 10(-3), such as EPS09 parametrization. In addition the cross section for the process gamma gamma -> e(+)e(-) has been measured and found to be in agreement with models implementing QED at leading order.
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| 16. |
- Abbas, E., et al.
(författare)
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Mid-rapidity anti-baryon to baryon ratios in pp collisions at root s=0.9, 2.76 and 7 TeV measured by ALICE
- 2013
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:7
-
Tidskriftsartikel (refereegranskat)abstract
- The ratios of yields of anti-baryons to baryons probes the mechanisms of baryon-number transport. Results for (p) over bar /p, (Lambda) over bar/Lambda, (Xi) over bar (+)/(Xi) over bar (-) and (Omega) over bar (+)/(Omega) over bar (-) in pp collisions at root s = 0.9, 2.76 and 7 TeV, measured with the ALICE detector at the LHC, are reported. Within the experimental uncertainties and ranges covered by our measurement, these ratios are independent of rapidity, transverse momentum and multiplicity for all measured energies. The results are compared to expectations from event generators, such as PYTHIA and HIJING/B, that are used to model the particle production in pp collisions. The energy dependence of (p) over bar /p, (Lambda) over bar/(Lambda) over bar, (Xi) over bar (+)/(Xi) over bar (-) and (Omega) over bar (+)/(Omega) over bar (-), reaching values compatible with unity for root s = 7 TeV, complement the earlier (p) over bar /p measurement of ALICE. These dependencies can be described by exchanges with the Regge-trajectory intercept of alpha(J) approximate to 0.5, which are suppressed with increasing rapidity interval Delta y. Any significant contribution of an exchange not suppressed at large Delta y (reached at LHC energies) is disfavoured.
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| 17. |
- Abbas, E., et al.
(författare)
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Performance of the ALICE VZERO system
- 2013
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- ALICE is an LHC experiment devoted to the study of strongly interacting matter in proton-proton, proton-nucleus and nucleus-nucleus collisions at ultra-relativistic energies. The ALICE VZERO system, made of two scintillator arrays at asymmetric positions, one on each side of the interaction point, plays a central role in ALICE. In addition to its core function as a trigger source, the VZERO system is used to monitor LHC beam conditions, to reject beam-induced backgrounds and to measure basic physics quantities such as luminosity, particle multiplicity, centrality and event plane direction in nucleus-nucleus collisions. After describing the VZERO system, this publication presents its performance over more than four years of operation at the LHC.
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| 18. |
- Abelev, B., et al.
(författare)
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D Meson Elliptic Flow in Noncentral Pb-Pb Collisions at root(S)(NN)=2.76 TeV
- 2013
-
Ingår i: Physical Review Letters. - 1079-7114. ; 111:10
-
Tidskriftsartikel (refereegranskat)abstract
- Azimuthally anisotropic distributions of D-0, D+, and D*+ mesons were studied in the central rapidity region (vertical bar y vertical bar < 0.8) in Pb-Pb collisions at a center-of-mass energy root(S)(NN) = 2.76 TeV per nucleon-nucleon collision, with the ALICE detector at the LHC. The second Fourier coefficient upsilon(2) (commonly denoted elliptic flow) was measured in the centrality class 30%-50% as a function of the D meson transverse momentum p(T), in the range 2-16 GeV/c. The measured upsilon(2) of D mesons is comparable in magnitude to that of light-flavor hadrons. It is positive in the range 2 < p(T) < 6 GeV/c with 5.7 sigma significance, based on the combination of statistical and systematic uncertainties.
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| 19. |
- Abelev, B., et al.
(författare)
-
Multiplicity dependence of the average transverse momentum in pp, p-Pb, and Pb-Pb collisions at the LHC
- 2013
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 727:4-5, s. 371-380
-
Tidskriftsartikel (refereegranskat)abstract
- The average transverse momentum (p(T)) versus the charged-particle multiplicity N-ch was measured in p-Pb collisions at a collision energy per nucleon-nucleon root S-NN = 5.02 TeV and in pp collisions at collision energies of root s = 0.9, 2.76, and 7 TeV in the kinematic range 0.15 < p(T) < 10.0 GeV/c and vertical bar eta vertical bar < 0.3 with the ALICE apparatus at the LHC. These data are compared to results in Pb-Pb collisions at root S-NN = 2.76 TeV at similar charged-particle multiplicities. In pp and p-Pb collisions, a strong increase of (p(T)) with N-ch is observed, which is much stronger than that measured in Pb-Pb collisions. For pp collisions, this could be attributed, within a model of hadronizing strings, to multiple-parton interactions and to a final-state color reconnection mechanism. The data in p-Pb and Pb-Pb collisions cannot be described by an incoherent superposition of nucleon-nucleon collisions and pose a challenge to most of the event generators. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 20. |
- Fredholm, Simon, et al.
(författare)
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SATB1 in Malignant T Cells
- 2018
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Ingår i: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 138:8, s. 1805-1815
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Tidskriftsartikel (refereegranskat)abstract
- Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.
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| 21. |
- Lindahl, Lise M., et al.
(författare)
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STAT5 induces miR-21 expression in cutaneous T cell lymphoma
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:29, s. 45730-45744
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Tidskriftsartikel (refereegranskat)abstract
- In cutaneous T cell lymphomas (CTCL), miR-21 is aberrantly expressed in skin and peripheral blood and displays anti-apoptotic properties in malignant T cells. It is, however, unclear exactly which cells express miR-21 and what mechanisms regulate miR-21. Here, we demonstrate miR-21 expression in situ in both malignant and reactive lymphocytes as well as stromal cells. qRT-PCR analysis of 47 patients with mycosis fungoides (MF) and Sezary Syndrome (SS) confirmed an increased miR- 21 expression that correlated with progressive disease. In cultured malignant T cells miR-21 expression was inhibited by Tofacitinib (CP-690550), a clinical-grade JAK3 inhibitor. Chromatin immunoprecipitation (ChIP) analysis showed direct binding of STAT5 to the miR-21 promoter. Cytokine starvation ex vivo triggered a decrease in miR-21 expression, whereas IL-2 induced an increased miR-21 expression in primary SS T cells and cultured cytokine-dependent SS cells (SeAx). siRNA-mediated depletion of STAT5 inhibited constitutive- and IL-2- induced miR-21 expression in cytokine- independent and dependent T cell lines, respectively. IL-15 and IL-2 were more potent than IL-21 in inducing miR-21 expression in the cytokine-dependent T cells. In conclusion, we provide first evidence that miR-21 is expressed in situ in CTCL skin lesions, induced by IL-2 and IL-15 cytokines, and is regulated by STAT5 in malignant T cells. Thus, our data provide novel evidence for a pathological role of IL-2Rg cytokines in promoting expression of the oncogenic miR-21 in CTCL.
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| 22. |
- Blumel, Edda, et al.
(författare)
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Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
- 2019
-
Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.
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| 23. |
- Buus, Terkild Brink, et al.
(författare)
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Single-cell heterogeneity in Sézary syndrome
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:16, s. 2115-2126
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Tidskriftsartikel (refereegranskat)abstract
- Sezary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with a median life expectancy of less than 4 years. Although initial treatment responses are often good, the vast majority of patients with SS fail to respond to ongoing therapy. We hypothesize that malignant T cells are highly heterogeneous and harbor subpopulations of SS cells that are both sensitive and resistant to treatment. Here, we investigate the presence of single-cell heterogeneity and resistance to histone deacetylase inhibitors (HDACi) within primary malignant T cells from patients with SS. Using single-cell RNA sequencing and flow cytometry, we find that malignant T cells from all investigated patients with SS display a high degree of single-cell heterogeneity at both the mRNA and protein levels. We show that this heterogeneity divides the malignant cells into distinct subpopulations that can be isolated by their expression of different surface antigens. Finally, we show that treatment with HDACi (suberanilohydroxamic acid and romidepsin) selectively eliminates some subpopulations while leaving other subpopulations largely unaffected. In conclusion, we show that patients with SS display a high degree of single-cell heterogeneity within the malignant T-cell population, and that distinct subpopulations of malignant T cells carry HDACi resistance. Our data point to the importance of understanding the heterogeneous nature of malignant SS cells in each individual patient to design combinational and new therapies to counter drug resistance and treatment failure.
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| 24. |
- Christensen, Lise Lotte, et al.
(författare)
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The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population
- 2008
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 9, s. 52-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mutations in the mismatch repair genes hMLH1 and hMSH2 predispose to hereditary non-polyposis colorectal cancer (HNPCC). Genetic screening of more than 350 Danish patients with colorectal cancer (CRC) has led to the identification of several new genetic variants (e.g. missense, silent and non-coding) in hMLH1 and hMSH2. The aim of the present study was to investigate the frequency of these variants in hMLH1 and hMSH2 in Danish patients with sporadic colorectal cancer and in the healthy background population. The purpose was to reveal if any of the common variants lead to increased susceptibility to colorectal cancer. METHODS: Associations between genetic variants in hMLH1 and hMSH2 and sporadic colorectal cancer were evaluated using a case-cohort design. The genotyping was performed on DNA isolated from blood from the 380 cases with sporadic colorectal cancer and a sub-cohort of 770 individuals. The DNA samples were analyzed using Single Base Extension (SBE) Tag-arrays. A Bonferroni corrected Fisher exact test was used to test for association between the genotypes of each variant and colorectal cancer. Linkage disequilibrium (LD) was investigated using HaploView (v3.31). RESULTS: Heterozygous and homozygous changes were detected in 13 of 35 analyzed variants. Two variants showed a borderline association with colorectal cancer, whereas the remaining variants demonstrated no association. Furthermore, the genomic regions covering hMLH1 and hMSH2 displayed high linkage disequilibrium in the Danish population. Twenty-two variants were neither detected in the cases with sporadic colorectal cancer nor in the sub-cohort. Some of these rare variants have been classified either as pathogenic mutations or as neutral variants in other populations and some are unclassified Danish variants. CONCLUSION: None of the variants in hMLH1 and hMSH2 analyzed in the present study were highly associated with colorectal cancer in the Danish population. High linkage disequilibrium in the genomic regions covering hMLH1 and hMSH2, indicate that common genetic variants in the two genes in general are not involved in the development of sporadic colorectal cancer. Nevertheless, some of the rare unclassified variants in hMLH1 and hMSH2 might be involved in the development of colorectal cancer in the families where they were originally identified.
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| 25. |
- Dengler, Juergen, et al.
(författare)
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GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands
- 2018
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Ingår i: Phytocoenologia. - : Schweizerbart. - 0340-269X. ; 48:3, s. 331-347
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Tidskriftsartikel (refereegranskat)abstract
- GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
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| 26. |
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| 27. |
- Gluud, Maria, et al.
(författare)
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MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas
- 2020
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 12:5
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Forskningsöversikt (refereegranskat)abstract
- Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL.
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| 28. |
- Krogh, Kristian B. R. M., et al.
(författare)
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Characterization and kinetic analysis of a thermostable GH3 beta-glucosidase from Penicillium brasilianum
- 2010
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Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 86:1, s. 143-154
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Tidskriftsartikel (refereegranskat)abstract
- A GH3 beta-glucosidase (BGL) from Penicillium brasilianum was purified to homogeneity after cultivation on a cellulose and xylan rich medium. The BGL was identified in a genomic library, and it was successfully expressed in Aspergillus oryzae. The BGL had excellent stability at elevated temperatures with no loss in activity after 24 h of incubation at 60A degrees C at pH 4-6, and the BGL was shown to have significantly higher stability at these conditions in comparison to Novozym 188 and to other fungal GH3 BGLs reported in the literature. The BGL had significant lower affinity for cellobiose compared with the artificial substrate para-nitrophenyl-beta-d-glucopyranoside (pNP-Glc) and further, pronounced substrate inhibition using pNP-Glc. Kinetic studies demonstrated the high importance of using cellobiose as substrate and glucose as inhibitor to describe the inhibition kinetics of BGL taking place during cellulose hydrolysis. A novel assay was developed to characterize this glucose inhibition on cellobiose hydrolysis. The assay uses labelled glucose-C-13(6) as inhibitor and subsequent mass spectrometry analysis to quantify the hydrolysis rates.
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| 29. |
- Krogh, K.B.R.M., et al.
(författare)
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Characterization and kinetic analysis of a thermostable GH3 β-glucosidase from Penicillum brasilianum
- 2010
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Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 86:86, s. 143-154
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Tidskriftsartikel (refereegranskat)abstract
- A GH3 β-glucosidase (BGL) from Penicillum brasilianum was purified to homogeneity after cultivation on a cellulose and xylan rich medium. The BGL was identified in a genomic library, and it was successfully expressed in Aspergillus oryzae. The BGL had excellent stability at elevated temperatures with no loss in activity after 24 h of incubation at 60°C at pH 4-6, and the BGL was shown to have significantly higher stability at these conditions in comparison to Novozym 188 and to other fungal GH3 BGLs reported in the literature. The BGL had significant lower afinity for cellobiose compared with the artificial substrate para-nitrophenyl-β-D-glucopyranoside (pNP-Glc)and further, pronounced substrate inhibition using p-NP-Glc. Kinetic studies demonstrated the high importance of using cellbiose as substrate and glucose as inhibitor to describe the inhibition kinetics of BGL taking place during cellulose hydrolysis. A novel assay was developed to characterize this glucose inhibition on cellobiose hydrolosis. The assay uses labelled glucose-13C6 as inhibitor and subsequent mass spectrometry analysis to quantify the hydrolysis rates
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| 30. |
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| 31. |
- Munk-Olsen, Trine, et al.
(författare)
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Postpartum depression : a developed and validated model predicting individual risk in new mothers
- 2022
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Postpartum depression (PPD) is a serious condition associated with potentially tragic outcomes, and in an ideal world PPDs should be prevented. Risk prediction models have been developed in psychiatry estimating an individual's probability of developing a specific condition, and recently a few models have also emerged within the field of PPD research, although none are implemented in clinical care. For the present study we aimed to develop and validate a prediction model to assess individualized risk of PPD and provide a tentative template for individualized risk calculation offering opportunities for additional external validation of this tool. Danish population registers served as our data sources and PPD was defined as recorded contact to a psychiatric treatment facility (ICD-10 code DF32-33) or redeemed antidepressant prescriptions (ATC code N06A), resulting in a sample of 6,402 PPD cases (development sample) and 2,379 (validation sample). Candidate predictors covered background information including cohabitating status, age, education, and previous psychiatric episodes in index mother (Core model), additional variables related to pregnancy and childbirth (Extended model), and further health information about the mother and her family (Extended+ model). Results indicated our recalibrated Extended model with 14 variables achieved highest performance with satisfying calibration and discrimination. Previous psychiatric history, maternal age, low education, and hyperemesis gravidarum were the most important predictors. Moving forward, external validation of the model represents the next step, while considering who will benefit from preventive PPD interventions, as well as considering potential consequences from false positive and negative test results, defined through different threshold values.
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| 32. |
- Vadivel, Chella Krishna, et al.
(författare)
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JAK3 Is Expressed in the Nucleus of Malignant T Cells in Cutaneous T Cell Lymphoma (CTCL).
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Perturbation in JAK-STAT signaling has been reported in the pathogenesis of cutaneous T cell lymphoma (CTCL). JAK3 is predominantly associated with the intra-cytoplasmic part of IL-2Rγc located in the plasma membrane of hematopoietic cells. Here we demonstrate that JAK3 is also ectopically expressed in the nucleus of malignant T cells. We detected nuclear JAK3 in various CTCL cell lines and primary malignant T cells from patients with Sézary syndrome, a leukemic variant of CTCL. Nuclear localization of JAK3 was independent of its kinase activity whereas STAT3 had a modest effect on nuclear JAK3 expression. Moreover, JAK3 nuclear localization was only weakly affected by blockage of nuclear export. An inhibitor of the nuclear export protein CRM1, Leptomycin B, induced an increased expression of SOCS3 in the nucleus, but only a weak increase in nuclear JAK3. Importantly, immunoprecipitation experiments indicated that JAK3 interacts with the nuclear protein POLR2A, the catalytic subunit of RNA Polymerase II. Kinase assays showed tyrosine phosphorylation of recombinant human Histone H3 by JAK3 in vitro-an effect which was blocked by the JAK inhibitor (Tofacitinib citrate). In conclusion, we provide the first evidence of nuclear localization of JAK3 in malignant T cells. Our findings suggest that JAK3 may have a cytokine-receptor independent function in the nucleus of malignant T cells, and thus a novel non-canonical role in CTCL.
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