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Density fluctuations near the QCD critical point can be probed via an intermittency analysis in relativistic heavy-ion collisions. We report the first measurement of intermittency in Au+Au collisions at sNN−−−√ = 7.7-200 GeV measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The scaled factorial moments of identified charged hadrons are analyzed at mid-rapidity and within the transverse momentum phase space. We observe a power-law behavior of scaled factorial moments in Au+Au collisions and a decrease in the extracted scaling exponent (ν) from peripheral to central collisions. The ν is consistent with a constant for different collisions energies in the mid-central (10-40\%) collisions. Moreover, the ν in the 0-5\% most central Au+Au collisions exhibits a non-monotonic energy dependence that reaches a possible minimum around sNN−−−√ = 27 GeV. The physics implications on the QCD phase structure are discussed.
Density fluctuations near the QCD critical point can be probed via an intermittency analysis in relativistic heavy-ion collisions. We report the first measurement of intermittency in Au+Au collisions at √sNN = 7.7-200 GeV measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The scaled factorial moments of identified charged hadrons are analyzed at mid-rapidity and within the transverse momentum phase space. We observe a power-law behavior of scaled factorial moments in Au+Au collisions and a decrease in the extracted scaling exponent (ν) from peripheral to central collisions. The ν is consistent with a constant for different collisions energies in the mid-central (10-40%) collisions. Moreover, the ν in the 0-5% most central Au+Au collisions exhibits a non-monotonic energy dependence that reaches a minimum around √sNN = 27 GeV. The physics implications on the QCD phase structure are discussed.
Observation of directed flow of hypernuclei Λ³H and Λ⁴H in √sNN = 3 GeV Au+Au collisions at RHIC
(2023)
We report here the first observation of directed flow (v1) of the hypernuclei 3ΛH and 4ΛH in mid-central Au+Au collisions at sNN−−−√ = 3 GeV at RHIC. These data are taken as part of the beam energy scan program carried out by the STAR experiment. From 165 × 106 events in 5%-40% centrality, about 8400 3ΛH and 5200 4ΛH candidates are reconstructed through two- and three-body decay channels. We observe that these hypernuclei exhibit significant directed flow. Comparing to that of light nuclei, it is found that the midrapidity v1 slopes of 3ΛH and 4ΛH follow baryon number scaling, implying that the coalescence is the dominant mechanism for these hypernuclei production in such collisions.
The linear and mode-coupled contributions to higher-order anisotropic flow are presented for Au+Au collisions at √sN N = 27, 39, 54.4, and 200 GeV and compared to similar measurements for Pb+Pb collisions at the Large Hadron Collider (LHC). The coefficients and the flow harmonics’ correlations, which characterize the linear and mode-coupled response to the lower-order anisotropies, indicate a beam energy dependence consistent with an influence from the specific shear viscosity (η/s). In contrast, the dimensionless coefficients, mode-coupled response coefficients, and normalized symmetric cumulants are approximately beam-energy independent, consistent with a significant role from initialstate effects. These measurements could provide unique supplemental constraints to (i) distinguish between different initial-state models and (ii) delineate the temperature (T ) and baryon chemical potential (μB ) dependence of the specific shear viscosity η s (T ,μB ).
The linear and mode-coupled contributions to higher-order anisotropic flow are presented for Au+Au collisions at sNN−−−√ = 27, 39, 54.4, and 200 GeV and compared to similar measurements for Pb+Pb collisions at the Large Hadron Collider (LHC). The coefficients and the flow harmonics' correlations, which characterize the linear and mode-coupled response to the lower-order anisotropies, indicate a beam energy dependence consistent with an influence from the specific shear viscosity (η/s). In contrast, the dimensionless coefficients, mode-coupled response coefficients, and normalized symmetric cumulants are approximately beam-energy independent, consistent with a significant role from initial-state effects. These measurements could provide unique supplemental constraints to (i) distinguish between different initial-state models and (ii) delineate the temperature (T) and baryon chemical potential (μB) dependence of the specific shear viscosity ηs(T,μB).
Effect of event selection on jetlike correlation measurement in d+Au collisions at √sNN = 200 GeV
(2015)
Dihadron correlations are analyzed in √sNN = 200 GeV d + Au collisions classified by forward charged particle multiplicity and zero-degree neutral energy in the Au-beam direction. It is found that the jetlike correlated yield increases with the event multiplicity. After taking into account this dependence, the non-jet contribution on the away side is minimal, leaving little room for a back-to-back ridge in these collisions.
We report high-precision measurements of the longitudinal double-spin asymmetry, 𝐴𝐿𝐿, for midrapidity inclusive jet and dijet production in polarized 𝑝𝑝 collisions at a center-of-mass energy of √𝑠=200 GeV. The new inclusive jet data are sensitive to the gluon helicity distribution, Δ𝑔(𝑥,𝑄2), for gluon momentum fractions in the range from 𝑥≃0.05 to 𝑥≃0.5, while the new dijet data provide further constraints on the 𝑥 dependence of Δ𝑔(𝑥,𝑄2). The results are in good agreement with previous measurements at √𝑠=200 GeV and with recent theoretical evaluations of prior world data. Our new results have better precision and thus strengthen the evidence that Δ𝑔(𝑥,𝑄2) is positive for 𝑥>0.05.
Measurement of inclusive J/ψ polarization in p + p collisions at √s=200 GeV by the STAR experiment
(2020)
We report on new measurements of inclusive 𝐽/𝜓 polarization at midrapidity in 𝑝+𝑝 collisions at √𝑠=200 GeV by the STAR experiment at the Relativistic Heavy Ion Collider. The polarization parameters, 𝜆𝜃, 𝜆𝜙, and 𝜆𝜃𝜙, are measured as a function of transverse momentum (𝑝T) in both the helicity and Collins-Soper (CS) reference frames within 𝑝T<10 GeV/𝑐. Except for 𝜆𝜃 in the CS frame at the highest measured 𝑝T, all three polarization parameters are consistent with 0 in both reference frames without any strong 𝑝T dependence. Several model calculations are compared with data, and the one using the Color Glass Condensate effective field theory coupled with nonrelativistic QCD gives the best overall description of the experimental results, even though other models cannot be ruled out due to experimental uncertainties.
We report the measurement of K∗0 meson at midrapidity (|y|< 1.0) in Au+Au collisions at sNN−−−√~=~7.7, 11.5, 14.5, 19.6, 27 and 39 GeV collected by the STAR experiment during the RHIC beam energy scan (BES) program. The transverse momentum spectra, yield, and average transverse momentum of K∗0 are presented as functions of collision centrality and beam energy. The K∗0/K yield ratios are presented for different collision centrality intervals and beam energies. The K∗0/K ratio in heavy-ion collisions are observed to be smaller than that in small system collisions (e+e and p+p). The K∗0/K ratio follows a similar centrality dependence to that observed in previous RHIC and LHC measurements. The data favor the scenario of the dominance of hadronic re-scattering over regeneration for K∗0 production in the hadronic phase of the medium.
Elliptic flow measurements from two-, four- and six-particle correlations are used to investigate flow fluctuations in collisions of U+U at sNN−−−√= 193 GeV, Cu+Au at sNN−−−√= 200 GeV and Au+Au spanning the range sNN−−−√= 11.5 - 200 GeV. The measurements show a strong dependence of the flow fluctuations on collision centrality, a modest dependence on system size, and very little if any, dependence on particle species and beam energy. The results, when compared to similar LHC measurements, viscous hydrodynamic calculations, and T$\mathrel{\protect\raisebox{-2.1pt}{R}}$ENTo model eccentricities, indicate that initial-state-driven fluctuations predominate the flow fluctuations generated in the collisions studied.
Elliptic flow measurements from two-, four- and six-particle correlations are used to investigate flow fluctuations in collisions of U+U at sNN−−−√ = 193 GeV, Cu+Au at sNN−−−√ = 200 GeV and Au+Au spanning the range sNN−−−√ = 11.5 - 200 GeV. The measurements show a strong dependence of the flow fluctuations on collision centrality, a modest dependence on system size, and very little if any, dependence on particle species and beam energy. The results, when compared to similar LHC measurements, viscous hydrodynamic calculations, and Glauber model eccentricities, indicate that initial-state-driven fluctuations predominate the flow fluctuations generated in the collisions studied.
Azimuthal anisotropy measurement of (multi-)strange hadrons in Au+Au collisions at √sNN = 54.4 GeV
(2023)
Azimuthal anisotropy of produced particles is one of the most important observables used to access the collective properties of the expanding medium created in relativistic heavy-ion collisions. In this paper, we present second (v2) and third (v3) order azimuthal anisotropies of K0S, ϕ, Λ, Ξ and Ω at mid-rapidity (|y|<1) in Au+Au collisions at sNN−−−√ = 54.4 GeV measured by the STAR detector. The v2 and v3 are measured as a function of transverse momentum and centrality. Their energy dependence is also studied. v3 is found to be more sensitive to the change in the center-of-mass energy than v2. Scaling by constituent quark number is found to hold for v2 within 10%. This observation could be evidence for the development of partonic collectivity in 54.4 GeV Au+Au collisions. Differences in v2 and v3 between baryons and anti-baryons are presented, and ratios of v3/v3/22 are studied and motivated by hydrodynamical calculations. The ratio of v2 of ϕ mesons to that of anti-protons (v2(ϕ)/v2(p¯)) shows centrality dependence at low transverse momentum, presumably resulting from the larger effects from hadronic interactions on anti-proton v2.
The polarization of Λ and Λ¯ hyperons along the beam direction has been measured relative to the second and third harmonic event planes in isobar Ru+Ru and Zr+Zr collisions at √sNN = 200 GeV. This is the first experimental evidence of the hyperon polarization by the triangular flow originating from the initial density fluctuations. The amplitudes of the sine modulation for the second and third harmonic results are comparable in magnitude, increase from central to peripheral collisions, and show a mild pT dependence. The azimuthal angle dependence of the polarization follows the vorticity pattern expected due to elliptic and triangular anisotropic flow, and qualitatively disagree with most hydrodynamic model calculations based on thermal vorticity and shear induced contributions. The model results based on one of existing implementations of the shear contribution lead to a correct azimuthal angle dependence, but predict centrality and pT dependence that still disagree with experimental measurements. Thus, our results provide stringent constraints on the thermal vorticity and shear-induced contributions to hyperon polarization. Comparison to previous measurements at RHIC and the LHC for the second-order harmonic results shows little dependence on the collision system size and collision energy.
We report new STAR measurements of the single-spin asymmetries 𝐴𝐿 for 𝑊+ and 𝑊− bosons produced in polarized proton-proton collisions at √𝑠=510 GeV as a function of the decay-positron and decay-electron pseudorapidity. The data were obtained in 2013 and correspond to an integrated luminosity of 250 pb−1. The results are combined with previous results obtained with 86 pb−1. A comparison with theoretical expectations based on polarized lepton-nucleon deep-inelastic scattering and prior polarized proton-proton data suggests a difference between the ¯𝑢 and ¯𝑑 quark helicity distributions for 0.05<𝑥<0.25. In addition, we report new results for the double-spin asymmetries 𝐴𝐿𝐿 for 𝑊±, as well as 𝐴𝐿 for 𝑍/𝛾* production and subsequent decay into electron-positron pairs.
The elliptic (v2) and triangular (v3) azimuthal anisotropy coefficients in central 3He+Au, d+Au, and p+Au collisions at sNN−−−√ = 200 GeV are measured as a function of transverse momentum (pT) at mid-rapidity (|η|<0.9), via the azimuthal angular correlation between two particles both at |η|<0.9. While the v2(pT) values depend on the colliding systems, the v3(pT) values are system-independent within the uncertainties, suggesting an influence on eccentricity from sub-nucleonic fluctuations in these small-sized systems. These results also provide stringent constraints for the hydrodynamic modeling of these systems.
Measurement of inclusive charged-particle jet production in Au+Au collisions at √sNN = 200 GeV
(2021)
The STAR Collaboration at the Relativistic Heavy Ion Collider reports the first measurement of inclusive jet production in peripheral and central Au+Au collisions at sNN−−−−√=200 GeV. Jets are reconstructed with the anti-kT algorithm using charged tracks with pseudorapidity |η|<1.0 and transverse momentum 0.2<pchT,jet<30 GeV/c, with jet resolution parameter R=0.2, 0.3, and 0.4. The large background yield uncorrelated with the jet signal is observed to be dominated by statistical phase space, consistent with a previous coincidence measurement. This background is suppressed by requiring a high-transverse-momentum (high-pT) leading hadron in accepted jet candidates. The bias imposed by this requirement is assessed, and the pT region in which the bias is small is identified. Inclusive charged-particle jet distributions are reported in peripheral and central Au+Au collisions for 5<pchT,jet<25 GeV/c and 5<pchT,jet<30 GeV/c, respectively. The charged-particle jet inclusive yield is suppressed for central Au+Au collisions, compared to both the peripheral Au+Au yield from this measurement and to the pp yield calculated using the PYTHIA event generator. The magnitude of the suppression is consistent with that of inclusive hadron production at high pT, and that of semi-inclusive recoil jet yield when expressed in terms of energy loss due to medium-induced energy transport. Comparison of inclusive charged-particle jet yields for different values of R exhibits no significant evidence for medium-induced broadening of the transverse jet profile for R<0.4 in central Au+Au collisions. The measured distributions are consistent with theoretical model calculations that incorporate jet quenching.
Measurement of inclusive charged-particle jet production in Au + Au collisions at √sNN=200 GeV
(2020)
The STAR Collaboration at the Relativistic Heavy Ion Collider reports the first measurement of inclusive jet production in peripheral and central Au+Au collisions at √𝑠𝑁𝑁=200 GeV. Jets are reconstructed with the anti-𝑘𝑇 algorithm using charged tracks with pseudorapidity |𝜂|<1.0 and transverse momentum 0.2<𝑝ch
𝑇,jet<30 GeV/𝑐, with jet resolution parameter 𝑅=0.2, 0.3, and 0.4. The large background yield uncorrelated with the jet signal is observed to be dominated by statistical phase space, consistent with a previous coincidence measurement. This background is suppressed by requiring a high-transverse-momentum (high-𝑝𝑇) leading hadron in accepted jet candidates. The bias imposed by this requirement is assessed, and the 𝑝𝑇 region in which the bias is small is identified. Inclusive charged-particle jet distributions are reported in peripheral and central Au+Au collisions for 5<𝑝ch
𝑇,jet<25 GeV/𝑐 and 5<𝑝ch
𝑇,jet<30 GeV/𝑐, respectively. The charged-particle jet inclusive yield is suppressed for central Au+Au collisions, compared to both the peripheral Au+Au yield from this measurement and to the 𝑝𝑝 yield calculated using the PYTHIA event generator. The magnitude of the suppression is consistent with that of inclusive hadron production at high 𝑝𝑇 and that of semi-inclusive recoil jet yield when expressed in terms of energy loss due to medium-induced energy transport. Comparison of inclusive charged-particle jet yields for different values of 𝑅 exhibits no significant evidence for medium-induced broadening of the transverse jet profile for 𝑅 <0.4 in central Au+Au collisions. The measured distributions are consistent with theoretical model calculations that incorporate jet quenching.
The STAR Collaboration reports measurements of the transverse single-spin asymmetry (TSSA) of inclusive 𝜋0 at center-of-mass energies (√𝑠) of 200 GeV and 500 GeV in transversely polarized proton-proton collisions in the pseudo-rapidity region 2.7 to 4.0. The results at the two different energies show a continuous increase of the TSSA with Feynman-𝑥, and, when compared to previous measurements, no dependence on √𝑠 from 19.4 GeV to 500 GeV is found. To investigate the underlying physics leading to this large TSSA, different topologies have been studied. 𝜋0 with no nearby particles tend to have a higher TSSA than inclusive 𝜋0. The TSSA for inclusive electromagnetic jets, sensitive to the Sivers effect in the initial state, is substantially smaller, but shows the same behavior as the inclusive 𝜋0 asymmetry as a function of Feynman-𝑥. To investigate final-state effects, the Collins asymmetry of 𝜋0 inside electromagnetic jets has been measured. The Collins asymmetry is analyzed for its dependence on the 𝜋0 momentum transverse to the jet thrust axis and its dependence on the fraction of jet energy carried by the 𝜋0. The asymmetry was found to be small in each case for both center-of-mass energies. All the measurements are compared to QCD-based theoretical calculations for transverse-momentum-dependent parton distribution functions and fragmentation functions. Some discrepancies are found, which indicates new mechanisms might be involved.
The longitudinal and transverse spin transfers to Λ (Λ¯¯¯¯) hyperons in polarized proton-proton collisions are expected to be sensitive to the helicity and transversity distributions, respectively, of (anti-)strange quarks in the proton, and to the corresponding polarized fragmentation functions. We report improved measurements of the longitudinal spin transfer coefficient, DLL, and the transverse spin transfer coefficient, DTT, to Λ and Λ¯¯¯¯ in polarized proton-proton collisions at s√ = 200 GeV by the STAR experiment at RHIC. The data set includes longitudinally polarized proton-proton collisions with an integrated luminosity of 52 pb−1, and transversely polarized proton-proton collisions with a similar integrated luminosity. Both data sets have about twice the statistics of previous results and cover a kinematic range of |ηΛ(Λ¯¯¯¯)| < 1.2 and transverse momentum pT,Λ(Λ¯¯¯¯) up to 8 GeV/c. We also report the first measurements of the hyperon spin transfer coefficients DLL and DTT as a function of the fractional jet momentum z carried by the hyperon, which can provide more direct constraints on the polarized fragmentation functions.
The longitudinal and transverse spin transfers to Λ (Λ¯¯¯¯) hyperons in polarized proton-proton collisions are expected to be sensitive to the helicity and transversity distributions, respectively, of (anti-)strange quarks in the proton, and to the corresponding polarized fragmentation functions. We report improved measurements of the longitudinal spin transfer coefficient, DLL, and the transverse spin transfer coefficient, DTT, to Λ and Λ¯¯¯¯ in polarized proton-proton collisions at s√ = 200 GeV by the STAR experiment at RHIC. The data set includes longitudinally polarized proton-proton collisions with an integrated luminosity of 52 pb−1, and transversely polarized proton-proton collisions with a similar integrated luminosity. Both data sets have about twice the statistics of previous results and cover a kinematic range of |ηΛ(Λ¯¯¯¯)| < 1.2 and transverse momentum pT,Λ(Λ¯¯¯¯) up to 8 GeV/c. We also report the first measurements of the hyperon spin transfer coefficients DLL and DTT as a function of the fractional jet momentum z carried by the hyperon, which can provide more direct constraints on the
We report results on an elastic cross section measurement in proton–proton collisions at a center-of-mass energy √𝑠 = 510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23 ≤ −𝑡 ≤ 0.67 GeV2. This is the only measurement of the proton-proton elastic cross section in this 𝑡 range for collision energies above the Intersecting Storage Rings (ISR) and below the Large Hadron Collider (LHC) colliders. We find that a constant slope 𝐵 does not fit the data in the aforementioned 𝑡 range, and we obtain a much better fit using a second-order polynomial for 𝐵(𝑡). This is the first measurement below the LHC energies for which the non-constant behavior 𝐵(𝑡) is observed. The 𝑡 dependence of 𝐵 is also determined using six subintervals of 𝑡 in the STAR measured 𝑡 range, and is in good agreement with the phenomenological models. The measured elastic differential cross section d𝜎∕dt agrees well with the results obtained at √𝑠 = 540 GeV for proton–antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR 𝑡-range is 𝜎f id el = 462.1 ± 0.9(stat.) ± 1.1(syst.) ± 11.6(scale) 𝜇b.
The differential cross section for 𝑍0 production, measured as a function of the boson’s transverse momentum (𝑝T), provides important constraints on the evolution of the transverse momentum dependent parton distribution functions (TMDs). The transverse single spin asymmetry (TSSA) of the 𝑍0 is sensitive to one of the polarized TMDs, the Sivers function, which is predicted to have the opposite sign in 𝑝 + 𝑝 → 𝑊 ∕𝑍 + 𝑋 from that which enters in semi-inclusive deep inelastic scattering. In this Letter, the STAR Collaboration reports the first measurement of the 𝑍0∕𝛾∗ differential cross section as a function of its 𝑝T in 𝑝+𝑝 collisions at a center-of-mass energy of 510 GeV, together with the 𝑍0∕𝛾∗ total cross section. We also report the measurement of 𝑍0∕𝛾∗ TSSA in transversely polarized 𝑝+𝑝 collisions at 510 GeV.
We report a new measurement of the production of electrons from open heavy-flavor hadron decays (HFEs) at mid-rapidity (|y|< 0.7) in Au+Au collisions at sNN−−−√=200 GeV. Invariant yields of HFEs are measured for the transverse momentum range of 3.5<pT<9 GeV/c in various configurations of the collision geometry. The HFE yields in head-on Au+Au collisions are suppressed by approximately a factor of 2 compared to that in p+p collisions scaled by the average number of binary collisions, indicating strong interactions between heavy quarks and the hot and dense medium created in heavy-ion collisions. Comparison of these results with models provides additional tests of theoretical calculations of heavy quark energy loss in the quark-gluon plasma.
We report results on an elastic cross section measurement in proton-proton collisions at a center-of-mass energy s√=510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23≤−t≤0.67 GeV2. We find that a constant slope B does not fit the data in the aforementioned t range, and we obtain a much better fit using a second-order polynomial for B(t). The t dependence of B is determined using six subintervals of t in the STAR measured t range, and is in good agreement with the phenomenological models. The measured elastic differential cross section dσ/dt agrees well with the results obtained at s√=546 GeV for proton--antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR t-range is σfidel=462.1±0.9(stat.)±1.1(syst.)±11.6(scale) μb.
We report results on an elastic cross section measurement in proton-proton collisions at a center-of-mass energy s√=510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23≤−t≤0.67 GeV2. We find that a constant slope B does not fit the data in the aforementioned t range, and we obtain a much better fit using a second-order polynomial for B(t). The t dependence of B is determined using six subintervals of t in the STAR measured t range, and is in good agreement with the phenomenological models. The measured elastic differential cross section dσ/dt agrees well with the results obtained at s√=546 GeV for proton--antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR t-range is σfidel=462.1±0.9(stat.)±1.1(syst.)±11.6(scale) μb.
We report results on an elastic cross section measurement in proton-proton collisions at a center-of-mass energy s√=510 GeV, obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section is measured in the four-momentum transfer squared range 0.23≤−t≤0.67 GeV2. We find that a constant slope B does not fit the data in the aforementioned t range, and we obtain a much better fit using a second-order polynomial for B(t). The t dependence of B is determined using six subintervals of t in the STAR measured t range, and is in good agreement with the phenomenological models. The measured elastic differential cross section dσ/dt agrees well with the results obtained at s√=546~GeV for proton--antiproton collisions by the UA4 experiment. We also determine that the integrated elastic cross section within the STAR t-range is σfidel=462.1±0.9(stat.)±1.1(syst.)±11.6(scale) μb.
We measure triangular flow relative to the reaction plane at 3 GeV center-of-mass energy in Au+Au collisions at the BNL Relativistic Heavy Ion Collider. A significant v3 signal for protons is observed, which increases for higher rapidity, higher transverse momentum, and more peripheral collisions. The triangular flow is essentially rapidity-odd with a slope at mid-rapidity, dv3/dy|(y=0), opposite in sign compared to the slope for directed flow. No significant v3 signal is observed for charged pions and kaons. Comparisons with models suggest that a mean field potential is required to describe these results, and that the triangular shape of the participant nucleons is the result of stopping and nuclear geometry.
We report the first measurements of cumulants, up to 4th order, of deuteron number distributions and proton-deuteron correlations in Au+Au collisions recorded by the STAR experiment in phase-I of Beam Energy Scan (BES) program at the Relativistic Heavy Ion Collider. Deuteron cumulants, their ratios, and proton-deuteron mixed cumulants are presented for different collision centralities covering a range of center-of-mass energy per nucleon pair sNN−−−−√~=~7.7 to 200~GeV. It is found that the cumulant ratios at lower collision energies favor a canonical ensemble over a grand canonical ensemble in thermal models. An anti-correlation between proton and deuteron multiplicity is observed across all collision energies and centralities, consistent with the expectation from global baryon number conservation. The UrQMD model coupled with a phase-space coalescence mechanism qualitatively reproduces the collision-energy dependence of cumulant ratios and proton-deuteron correlations.
We report a new measurement of the production of electrons from open heavy-flavor hadron decays (HFEs) at mid-rapidity (|y| < 0.7) in Au+Au collisions at √sNN = 200 GeV. Invariant yields of HFEs are measured for the transverse momentum range of 3.5 < pT < 9 GeV/c in various configurations of the collision geometry. The HFE yields in head-on Au+Au collisions are suppressed by approximately a factor of 2 compared to that in p + p collisions scaled by the average number of binary collisions, indicating strong interactions between heavy quarks and the hot and dense medium created in heavy-ion collisions. Comparison of these results with models provides additional tests of theoretical calculations of heavy quark energy loss in the quark-gluon plasma.
We report a new measurement of the production of electrons from open heavy-flavor hadron decays (HFEs) at mid-rapidity (|y|< 0.7) in Au+Au collisions at sNN−−−√=200 GeV. Invariant yields of HFEs are measured for the transverse momentum range of 3.5<pT<9 GeV/c in various configurations of the collision geometry. The HFE yields in head-on Au+Au collisions are suppressed by approximately a factor of 2 compared to that in p+p collisions scaled by the average number of binary collisions, indicating strong interactions between heavy quarks and the hot and dense medium created in heavy-ion collisions. Comparison of these results with models provides additional tests of theoretical calculations of heavy quark energy loss in the quark-gluon plasma.
We report the first measurements of cumulants, up to 4𝑡ℎ order, of deuteron number distributions and protondeuteron correlations in Au+Au collisions recorded by the STAR experiment in phase-I of Beam Energy Scan (BES) program at the Relativistic Heavy Ion Collider. Deuteron cumulants, their ratios, and proton-deuteron mixed cumulants are presented for different collision centralities covering a range of center-of-mass energy per nucleon pair √𝑠NN = 7.7 to 200 GeV. It is found that the cumulant ratios at lower collision energies favor a canonical ensemble over a grand canonical ensemble in thermal models. An anti-correlation between proton and deuteron multiplicity is observed across all collision energies and centralities, consistent with the expectation from global baryon number conservation. The UrQMD model coupled with a phase-space coalescence mechanism qualitatively reproduces the collision-energy dependence of cumulant ratios and proton-deuteron correlations.
Natural Killer (NK) cells are involved in the host immune response against infections due to viral, bacterial and fungal pathogens, all of which are a significant cause of morbidity and mortality in immunocompromised patients. Since the recovery of the immune system has a major impact on the outcome of an infectious complication, there is major interest in strengthening the host response in immunocompromised patients, either by using cytokines or growth factors or by adoptive cellular therapies transfusing immune cells such as granulocytes or pathogen-specific T-cells. To date, relatively little is known about the potential of adoptively transferring NK cells in immunocompromised patients with infectious complications, although the anti-cancer property of NK cells is already being investigated in the clinical setting. This review will focus on the antimicrobial properties of NK cells and the current standing and future perspectives of generating and using NK cells as immunotherapy in patients with infectious complications, an approach which is promising and might have an important clinical impact in the future.
Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers.
Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment.
Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects.
Rhabdomyosarcoma (RMS), the most common cancer of connective tissues in pediatrics, is often resistant to conventional therapies. One underlying mechanism of this resistance is the overexpression of Inhibitor of Apoptosis (IAP) proteins, leading to a dysfunctional cell death program within tumor cells. Smac mimetics (SM) are small molecules that can reactivate the cell death program by antagonizing IAP proteins and thereby compensating their overexpression. Here, we report that SM sensitize two RMS cell lines (RD and RH30) toward natural killer (NK) cell-mediated killing on the one hand, and increase the cytotoxic potential of NK cells on the other. The SM-induced sensitization of RH30 cells toward NK cell-mediated killing is significantly reduced through blocking tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on NK cells prior to coculture. In addition, the presence of zVAD.fmk, a pancaspase inhibitor, rescues tumor cells from the increase in killing, indicating an apoptosis-dependent cell death. On the NK cell side, the presence of SM in addition to IL-2 during the ex vivo expansion leads to an increase in their cytotoxic activity against RH30 cells. This effect is mainly TNFα-dependent and partially mediated by NK cell activation, which is associated with transcriptional upregulation of NF-κB target genes such as IκBα and RelB. Taken together, our findings implicate that SM represent a novel double-hit strategy, sensitizing tumor and activating NK cells with one single drug.
Neuroblastoma (NB) is the most common solid extracranial tumor in childhood. Despite therapeutic progress, prognosis in high-risk NB is poor and innovative therapies are urgently needed. Therefore, we addressed the potential cytotoxic capacity of interleukin (IL)-activated natural killer (NK) cells compared to cytokine-induced killer (CIK) cells for the treatment of NB. NK cells were isolated from peripheral blood mononuclear cells (PBMCs) by indirect CD56-enrichment or CD3/CD19-depletion and expanded with different cytokine combinations, such as IL-2, IL-15, and/or IL-21 under feeder-cell free conditions. CIK cells were generated from PBMCs by ex vivo stimulation with interferon-γ, IL-2, OKT-3, and IL-15. Comparative analysis of expansion rate, purity, phenotype and cytotoxicity was performed. CD56-enriched NK cells showed a median expansion rate of 4.3-fold with up to 99% NK cell content. The cell product after CD3/CD19-depletion consisted of a median 43.5% NK cells that expanded significantly faster reaching also 99% of NK cell purity. After 10–12 days of expansion, both NK cell preparations showed a significantly higher median cytotoxic capacity against NB cells relative to CIK cells. Remarkably, these NK cells were also capable of efficiently killing NB spheroidal 3D culture in long-term cytotoxicity assays. Further optimization using a novel NK cell culture medium and a prolonged culturing procedure after CD3/CD19-depletion for up to 15 days enhanced the expansion rate up to 24.4-fold by maintaining the cytotoxic potential. Addition of an IL-21 boost prior to harvesting significantly increased the cytotoxicity. The final cell product consisted for the major part of CD16−, NCR-expressing, poly-functional NK cells with regard to cytokine production, CD107a degranulation and antitumor capacity. In summary, our study revealed that NK cells have a significantly higher cytotoxic potential to combat NB than CIK cell products, especially following the synergistic use of IL-15 and IL-21 for NK cell activation. Therefore, the use of IL-15+IL-21 expanded NK cells generated from CD3/CD19-depleted apheresis products seems to be highly promising as an immunotherapy in combination with haploidentical stem cell transplantation (SCT) for high-risk NB patients.
Natural killer (NK) cells play an important role following allogeneic hematopoietic stem cell transplantation (HSCT) exerting graft-versus-leukemia/tumor effect and mediating pathogen-specific immunity. Although NK cells are the first donor-derived lymphocytes reconstituting post-HSCT, their distribution of CD56++CD16− (CD56bright), CD56++CD16+ (CD56intermediate=int), and CD56+CD16++ (CD56dim) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood. The proportion of CD56bright/CD56int/CD56dim changed from 15/8/78% in early childhood to 6/4/90% in adults, respectively. Within this study, we first compared the NK cell reconstitution post-HSCT to reference values of NK cell subpopulations of healthy children. Afterward, we investigated the reconstitution of NK cell subpopulations post-HSCT in correlation to acute graft versus host disease (aGvHD) and chronic graft versus host disease (cGvHD) as well as to viral infections. Interestingly, after a HSCT follow-up phase of 12 months, the distribution of NK cell subpopulations largely matched the 50th percentile of the reference range for healthy individuals. Patients suffering from aGvHD and cGvHD showed a delayed reconstitution of NK cells. Remarkably, within the first 2 months post-HSCT, patients suffering from aGvHD had significantly lower levels of CD56bright NK cells compared to patients without viral infection or without graft versus host disease (GvHD). Therefore, the amount of CD56bright NK cells might serve as an early prognostic factor for GvHD development. Furthermore, a prolonged and elevated peak in CD56int NK cells seemed to be characteristic for the chronification of GvHD. In context of viral infection, a slightly lower CD56 and CD16 receptor expression followed by a considerable reduction in the absolute CD56dim NK cell numbers combined with reoccurrence of CD56int NK cells was observed. Our results suggest that a precise analysis of the reconstitution of NK cell subpopulations post-HSCT might indicate the occurrence of undesired events post-HSCT such as severe aGvHD.values
Background: Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients.
Methods/Design: ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and - in absence of available stem cells from earlier harvesting - undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3rd (arm A + B) and the 5th lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS.
Discussion: This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. Trial registration: ISRCTN16345835 (date of registration 2010-08-24).
BACKGROUND: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks.
RESULTS: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired.
CONCLUSIONS: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.
High-risk rhabdomyosarcoma (RMS) occurring in childhood to young adulthood is associated with a poor prognosis; especially children above the age of 10 with advanced stage alveolar RMS still succumb to the disease within a median of 2 years. The advent of chimeric antigen receptor (CAR)-engineered T cells marked significant progress in the treatment of refractory B cell malignancies, but experience for solid tumors has proven challenging. We speculate that this is at least in part due to the poor quality of the patient's own T cells and therefore propose using CAR-modified cytokine-induced killer (CIK) cells as effector cells. CIK cells are a heterogeneous population of polyclonal T cells that acquire phenotypic and cytotoxic properties of natural killer (NK) cells through the cultivation process, becoming so-called T-NK cells. CIK cells can be genetically modified to express CARs. They are minimally alloreactive and can therefore be acquired from haploidentical first-degree relatives. Here, we explored the potential of ERBB2-CAR-modified random-donor CIK cells as a treatment for RMS in xenotolerant mice bearing disseminated high-risk RMS tumors. In otherwise untreated mice, RMS tumors engrafted 13–35 days after intravenous tumor cell injection, as shown by in vivo bioluminescence imaging, immunohistochemistry, and polymerase chain reaction for human gDNA, and mice died shortly thereafter (median/range: 62/56–66 days, n = 5). Wild-type (WT) CIK cells given at an early stage delayed and eliminated RMS engraftment in 4 of 6 (67%) mice, while ERBB2-CAR CIK cells inhibited initial tumor load in 8 of 8 (100%) mice. WT CIK cells were detectable but not as active as CAR CIK cells at distant tumor sites. CIK cell therapies during advanced RMS delayed but did not inhibit tumor progression compared to untreated controls. ERBB2-CAR CIK cell therapy also supported innate immunity as evidenced by selective accumulation of NK and T-NK cell subpopulations in disseminated RMS tumors, which was not observed for WT CIK cells. Our data underscore the power of heterogenous immune cell populations (T, NK, and T-NK cells) to control solid tumors, which can be further enhanced with CARs, suggesting ERBB2-CAR CIK cells as a potential treatment for high-risk RMS.
No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors
(2019)
Background: IgG-class autoantibodies to N-Methyl-D-Aspartate (NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis. Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results. We measured NMDA antibodies in a large, well phenotyped sample of Parkinson patients without and with cognitive impairment (n = 296) and controls (n = 295) free of neuropsychiatric disease. Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.
Methods: NMDA antibodies were analysed in the serum of patients and controls using well established validated assays. We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.
Results: The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients (13%) than in controls (22%) and higher than in previous studies in both groups. NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment, nor with quantitative indicators of disease severity and cognitive impairment. A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.
Conclusion: It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g. to Parkinson disease with dementia, while NMDA IgG antibodies define a separate disease of its own.