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Measurements of anisotropic flow coefficients (vn) and their cross-correlations using two- and multi-particle cumulant methods are reported in collisions of pp at s√=13 TeV, p-Pb at sNN−−−√=5.02 TeV, Xe-Xe at sNN−−−√=5.44 TeV, and Pb-Pb at sNN−−−√=5.02 TeV recorded with the ALICE detector. The multiplicity dependence of vn is studied in a very wide range from 20 to 3000 particles produced in the mid-rapidity region |η|<0.8 for the transverse momentum range 0.2<pT<3.0 GeV/c. An ordering of the coefficients v2>v3>v4 is found in pp and p-Pb collisions, similar to that seen in large collision systems, while a weak v2 multiplicity dependence is observed relative to nucleus-nucleus collisions in the same multiplicity range. Using a novel subevent method, v2 measured with four-particle cumulants is found to be compatible with that from six-particle cumulants in pp and p-Pb collisions. The magnitude of the correlation between v2n and v2m, evaluated with the symmetric cumulants SC(m,n) is observed to be positive at all multiplicities for v2 and v4, while for v2 and v3 it is negative and changes sign for multiplicities below 100, which may indicate a different vn fluctuation pattern in this multiplicity range. The observed long-range multi-particle azimuthal correlations in high multiplicity pp and p-Pb collisions can neither be described by PYTHIA 8 nor by IP-Glasma+MUSIC+UrQMD model calculations, and hence provide new insights into the understanding of collective effects in small collision systems.
Measurements of anisotropic flow coefficients (vn) and their cross-correlations using two- and multi-particle cumulant methods are reported in collisions of pp at s√=13 TeV, p-Pb at sNN−−−√=5.02 TeV, Xe-Xe at sNN−−−√=5.44 TeV, and Pb-Pb at sNN−−−√=5.02 TeV recorded with the ALICE detector. These measurements are performed as a function of multiplicity in the mid-rapidity region |η|<0.8 for the transverse momentum range 0.2<pT<3.0 GeV/c. An ordering of the coefficients v2>v3>v4 is found in pp and p-Pb collisions, similar to that seen in large collision systems, while a weak v2 multiplicity dependence is observed relative to nucleus--nucleus collisions in the same multiplicity range. Using the novel subevent method, v2 measured in pp and p-Pb collisions with four-particle cumulants is found to be compatible with that from six-particle cumulants. The symmetric cumulants SC(m,n) calculated with the subevent method which evaluate the correlation strength between v2n and v2m are also presented. The presented data, which add further support to the existence of long-range multi-particle azimuthal correlations in high multiplicity pp and p-Pb collisions, can neither be described by PYTHIA8 nor by IP-Glasma+MUSIC+UrQMD model calculations, and hence provide new insights into the understanding of collective effects in small collision systems.
We present the first measurements of femtoscopic correlations between the K0 S and K± particles in pp collisions at √s = 7 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding solely via the a0(980) resonance. The extracted kaon source radius and correlation strength parameters for K0 SK− are found to be equal within the experimental uncertainties to those for K0 SK+. Results of the present study are compared with those from identical-kaon femtoscopic studies also performed with pp collisions at √s = 7 TeV by ALICE andwith a K0 SK± measurement in Pb–Pb collisions at √sNN = 2.76 TeV. Combined with the Pb–Pb results, our pp analysis is found to be compatible with th e interpretation of the a0(980) having a tetraquark structure instead of that of a diquark.
The procedure for the energy calibration of the high granularity electromagnetic calorimeter PHOS of the ALICE experiment is presented. The methods used to perform the relative gain calibration, to evaluate the geometrical alignment and the corresponding correction of the absolute energy scale, to obtain the nonlinearity correction coefficients and finally, to calculate the time-dependent calibration corrections, are discussed and illustrated by the PHOS performance in proton-proton (pp) collisions at s√=13 TeV. After applying all corrections, the achieved mass resolution of π0 and η mesons for pT>1.7 GeV/c is σπ0m=4.56±0.03 MeV/c2 and σηm=15.3±1.0 MeV/c2.
The procedure for the energy calibration of the high granularity electromagnetic calorimeter PHOS of the ALICE experiment is presented. The methods used to perform the relative gain calibration, to evaluate the geometrical alignment and the corresponding correction of the absolute energy scale, to obtain the nonlinearity correction coefficients and finally, to calculate the time-dependent calibration corrections, are discussed and illustrated by the PHOS performance in proton-proton (pp) collisions at s√ = 13 TeV. After applying all corrections, the achieved mass resolutions for π0 and η mesons for pT>1.7 GeV/c are σπ0m=4.56±0.03 MeV/c2 and σηm=15.3±1.0 MeV/c2, respectively.
The procedure for the energy calibration of the high granularity electromagnetic calorimeter PHOS of the ALICE experiment is presented. The methods used to perform the relative gain calibration, to evaluate the geometrical alignment and the corresponding correction of the absolute energy scale, to obtain the nonlinearity correction coefficients and finally, to calculate the time-dependent calibration corrections, are discussed and illustrated by the PHOS performance in proton-proton (pp) collisions at √s=13 TeV. After applying all corrections, the achieved mass resolutions for π0 and η mesons for pT > 1.7 GeV/c are σmπ0 = 4.56 ± 0.03 MeV/c2 and σmη = 15.3 ± 1.0 MeV/c2, respectively.
Background and Aim: Genome-wide association studies revealed a strong association between cardiovascular diseases (CVD) and clonal hematopoiesis of indeterminate potential (CHIP), highlighting one of its most common CHIP-driving mutations-TET2 (ten-eleven translocation 2), as a target for CHIP related CVD research. Our lab has established the generation of self-organizing cardiac organoids (SCO), which demonstrate the cellular composition and organization of the native human heart, and mimics human myocardial responses to stress stimulation. This project aims to examine whether SCOs would be an appropriate CHIP model and decipher promising drugs for cardiovascular CHIP treatment.
Methods: To study TET2-mutant cardiovascular CHIP, we set up the TET2 cardiac-CHIP model through a knockdown (KD) of TET2 in myeloid cells that infiltrated our lab-made SCO. Immunofluorescence and qPCR were performed to ascertain TET2-KD myeloid cell infiltration, SCO fibrosis, and apoptosis assessments. SCO fibrosis was further analyzed by immunofluorescence staining, and cardiac contractile frequency and amplitude were determined by calcium flux analysis. Finally, RNAseq was performed to analyze transcriptomic changes in drug/vehicle-treated TET2-KD myeloid cells and the TET2 cardiac-CHIP model.
Results: The TET2 cardiac-CHIP model resulted in significantly increased inflammation in SCO, accompanied by fibrosis and more cleaved Caspase-3, causing cardiomyocytes apoptosis and promoting the release of cTNT. The shortlisted drugs revealed a reduction of proliferation in TET2-KD myeloid cells, decreased pro-inflammatory cytokines, and a higher apoptosis level. Furthermore, the TET2 cardiac-CHIP model treated with selected drugs showed a remarkable decline in TET2-KD myeloid cell infiltration and pro-inflammation cytokines, cardiomyocyte apoptosis, fibrosis, and lowered cTNT levels, while drug control groups were not affected. Moreover, the drug treatment groups improved the heartbeat frequency and amplitude accessed by the calcium transient assay. RNAseq data also validated the above findings.
Conclusions & Discussion: Our results indicate that SCOs are an efficient pre-clinical model for studying and validating CHIP genes and drug interactions. Our data revealed that TET2-KD myeloid cells invade SCO and secrete pro-inflammatory cytokines, which promote apoptosis of cardiomyocytes and the release of cTNT. In this regard, our TET2 cardiac-CHIP model matches the inflammatory phenotype previously characterized in CHIP patients. Nevertheless, this phenotype could be rescued using positive drug candidates (Clopidogrel, R406, and Lanatoside C) selected by this project, emphasizing the significant value of our TET2 cardiac-CHIP model for drug screens and pre-clinical validation studies. Furthermore, among these three drug candidates, we found Lancatoside C, as proved by FDA/EMA, showed an unmet possibility for clinical therapeutic demand, insinuating potential benefit in repurposing Lanatoside C for the treatment of TET2-mutant cardiovascular CHIP.