Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a severe disorder of lung vasculature that causes right heart failure. Homeostatic effects of flow-activated transcription factor Krüppel-like factor 2 (KLF2) are compromised in PAH. Here we show that KLF2-induced exosomal microRNAs, miR-181a-5p and miR-324-5p act together to attenuate pulmonary vascular remodeling and that their actions are mediated by Notch4 and ETS1 and other key regulators of vascular homeostasis. Expressions of KLF2, miR-181a-5p and miR-324-5p are reduced, while levels of their target genes are elevated in pre-clinical PAH, idiopathic PAH and heritable PAH with missense p.H288Y KLF2 mutation. Therapeutic supplementation of miR-181a-5p and miR-324-5p reduces proliferative and angiogenic responses in patient-derived cells and attenuates disease progression in PAH mice. This study shows that reduced KLF2 signaling is a common feature of human PAH and highlights the potential therapeutic role of KLF2-regulated exosomal miRNAs in PAH and other diseases associated with vascular remodelling

Photoproduction of low-pT J/ψ from peripheral to central Pb–Pb collisions at 5.02 TeV

An excess of J/ψ yield at very low transverse momentum (pT < 0.3 GeV/c), originating from coherent photoproduction, is observed in peripheral and semicentral hadronic Pb–Pb collisions at a center-of-mass energy per nucleon pair of sqrt(sNN) = 5.02 TeV. The measurement is performed with the ALICE detector via the dimuon decay channel at forward rapidity (2.5 < y <4). The nuclear modification factor at very low pT and the coherent photoproduction cross section are measured as a function of centrality down to the 10% most central collisions. These results extend the previous study at sqrt(sNN) = 2.76 TeV, confirming the clear excess over hadronic production in the pT range 0-0.3 GeV/c and the centrality range 70–90%, and establishing an excess with a significance greater than 5σ also in the 50–70% and 30–50% centrality ranges. The results are compared with earlier measurements at sqrt(sNN) = 2.76 TeV and with different theoretical predictions aiming at describing how coherent photoproduction occurs in hadronic interactions with nuclear overlap

Observation of flow angle and flow magnitude fluctuations in Pb-Pb collisions at sNN=5.02TeV at the CERN Large Hadron Collider

This Letter reports on the first measurements of transverse momentum dependent flow angle n and flow magnitude vn fluctuations determined using new four-particle correlators. The measurements are performed for various centralities in Pb–Pb collisions at a center-of-mass energy per nucleon pair of √s NN = 5.02 TeV with ALICE at the CERN Large Hadron Collider. Both flow angle and flow magnitude fluctuations are observed in the presented centrality ranges and are strongest in the most central collisions and for a transverse momentum pT > 2 GeV/c. Comparison with theoretical models, including iEBE-VISHNU, MUSIC, and AMPT, show that the measurements exhibit unique sensitivities to the initial state of heavy-ion collisions

First measurement of Ωc 0 production in pp collisions at s=13 TeV

The inclusive production of the charm–strange baryon Omega_c^0 is measured for the first time via its hadronic decay into Omega-pi+ at midrapidity (|y|<0.5) in proton–proton (pp) collisions at the centre-of-mass energy sqrt(s) = 13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 < pT < 12 GeV/c . The pT dependence of the Omega_C^0-baryon production relative to the prompt D^0-meson and to the prompt Csi_C^0-baryon production is compared to various models that take different hadronisation mechanisms into consideration. In the measured pT interval, the ratio of the pT-integrated cross sections of Omega_c^0 and prompt Lambda_c^+ baryons multiplied by the Omega- pi+ branching ratio is found to be larger by a factor of about 20 with a significance of about 4σ when compared to e+e- collisions

f0(980) production in inelastic pp collisions at s = 5.02 TeV

The measurement of the production of f0(980) in inelastic pp collisions at sqrt(s) = 5.02 TeV is presented. This is the first reported measurement of inclusive f0(980) yield at LHC energies. The production is measured at midrapidity, |y| pi+pi- hadronic decay channel using the ALICE detector. The pT-differential yields are compared to those of pions, protons and ϕ mesons as well as to predictions from the HERWIG 7.2 QCD-inspired Monte Carlo event generator and calculations from a coalescence model that uses the AMPT model as an input. The ratio of the pT-integrated yield of f0(980) relative to pions is compared to measurements in e+e- and pp collisions at lower energies and predictions from statistical hadronisation models and HERWIG 7.2. A mild collision energy dependence of the f0(980) to pion production is observed in pp collisions from SPS to LHC energies. All considered models underpredict the pT-integrated 2f0(980)/(pi+ + pi-) ratio. The prediction from the canonical statistical hadronisation model assuming a zero total strangeness content of f0(980) is consistent with the data within 1.9σ and is the closest to the data. The results provide an essential reference for future measurements of the particle yield and nuclear modification in p–Pb and Pb–Pb collisions, which have been proposed to be instrumental to probe the elusive nature and quark composition of the f0(980) scalar meson

Measurement of the production of (anti)nuclei in p–Pb collisions at sNN=8.16TeV

Measurements of (anti)proton, (anti)deuteron, and (anti)3He production in the rapidity range -1 > y > 0 as a function of the transverse momentum and event multiplicity in p–Pb collisions at a center-of-mass energy per nucleon–nucleon pair sqrt(sNN) = 8.16 TeV are presented. The coalescence parameters B2 and B3, measured as a function of the transverse momentum per nucleon and of the mean charged-particle multiplicity density, confirm a smooth evolution from low to high multiplicity across different collision systems and energies. The ratios between (anti)deuteron and (anti)3He yields and those of (anti)protons are also reported as a function of the mean charged-particle multiplicity density. A comparison with the predictions of the statistical hadronization and coalescence models for different collision systems and center-of-mass energies favors the coalescence description for the deuteron-to-proton yield ratio with respect to the canonical statistical model

Measurement of beauty-strange meson production in Pb–Pb collisions at sNN=5.02TeV via non-prompt Ds + mesons

The production yields of non-prompt D_s^+ mesons, namely D_s^+ mesons from beauty-hadron decays, were measured for the first time as a function of the transverse momentum (pT) at midrapidity (|y| phi pi+, with phi -> K+ K-, in the 4 < pT < 36 GeV/c and 2 < pT < 24 GeV/c intervals for the 0–10% and 30–50% centrality classes, respectively. The measured yields of non-prompt D_S^+ mesons are compared to those of prompt D_s^+ and non-prompt D0 mesons by calculating the ratios of the production yields in Pb–Pb collisions and the nuclear modification factor RAA. The ratio between the RAA of non-prompt D_s^+ and prompt D_s^+ mesons, and that between the RAA of non-prompt D_s^+ and non-prompt D0 mesons in central Pb–Pb collisions are found to be on average higher than unity in the 4 < pT < 12 GeV/c interval with a statistical significance of about 1.6 sigma and 1.7 sigma, respectively. The measured RAA ratios are compared with the predictions of theoretical models of heavy-quark transport in a hydrodynamically expanding QGP that incorporate hadronisation via quark recombination

Investigation of K+K- interactions via femtoscopy in Pb-Pb collisions at sNN =2.76 TeV at the CERN Large Hadron Collider

Femtoscopic correlations of nonidentical charged kaons (K+K-) are studied in Pb-Pb collisions at a center-of-mass energy per nucleon-nucleon collision sNN=2.76 TeV by ALICE at the CERN Large Hadron Collider. One-dimensional K+K- correlation functions are analyzed in three centrality classes and eight intervals of particle-pair transverse momentum. The Lednický and Luboshitz interaction model used in the K+K- analysis includes the final-state Coulomb interactions between kaons and the final-state interaction through a0(980) and f0(980) resonances. The mass of f0(980) and coupling were extracted from the fit to K+K- correlation functions using the femtoscopic technique. The measured mass and width of the f0(980) resonance are consistent with other published measurements. The height of the φ(1020) meson peak present in the K+K- correlation function rapidly decreases with increasing source radius, qualitatively in agreement with an inverse volume dependence. A phenomenological fit to this trend suggests that the φ(1020) meson yield is dominated by particles produced directly from the hadronization of the system. The small fraction subsequently produced by final-state interactions could not be precisely quantified with data presented in this paper and will be assessed in future work

Measurement of the Lifetime and Λ Separation Energy of _{Λ}^{3}H

The most precise measurements to date of the _{Λ}^{3}H lifetime τ and Λ separation energy B_{Λ} are obtained using the data sample of Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV collected by ALICE at the LHC. The _{Λ}^{3}H is reconstructed via its charged two-body mesonic decay channel (_{Λ}^{3}H→^{3}He+π^{-} and the charge-conjugate process). The measured values τ=[253±11(stat)±6(syst)]  ps and B_{Λ}=[102±63(stat)±67(syst)]  keV are compatible with predictions from effective field theories and confirm that the _{Λ}^{3}H structure is consistent with a weakly bound system

Towards the understanding of the genuine three-body interaction for p–p–p and p–p–Λ\Lambda

Three-body nuclear forces play an important role in the structure of nuclei and hypernuclei and are also incor- porated in models to describe the dynamics of dense baryonic matter, such as in neutron stars. So far, only indirect mea- surements anchored to the binding energies of nuclei can be used to constrain the three-nucleon force, and if hyperons are considered, the scarce data on hypernuclei impose only weak constraints on the three-body forces. In this work, we present the first direct measurement of the p–p–p and p–p–Lambda systems in terms of three-particle correlation functions car- ried out for pp collisions at √s = 13 TeV. Three-particle cumulants are extracted from the correlation functions by applying the Kubo formalism, where the three-particle inter- action contribution to these correlations can be isolated after subtracting the known two-body interaction terms. A nega- tive cumulant is found for the p–p–p system, hinting to the presence of a residual three-body effect while for p–p–Lambda the cumulant is consistent with zero. This measurement demon- strates the accessibility of three-baryon correlations at the LHC