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In the very heavy collision system 197Au+197Au the K+ production process was studied as a function of impact parameter at 1 GeV/nucleon, a beam energy well below the free N-N threshold. The K+ multiplicity increases more than linearly with the number of participant nucleons and the K+/ pi + ratio rises significantly when going from peripheral to central collisions. The measured K+ double differential cross section is enhanced by a factor of 6 compared to microscopic transport calculations if secondary processes (Delta N-->K Lambda N and Delta Delta -->K Lambda N) are ignored.
Despite the recent availability of vaccines against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an urgent need for specific anti-SARS-CoV-2 drugs. Monoclonal neutralizing antibodies are an important drug class in the global fight against the SARS-CoV-2 pandemic due to their ability to convey immediate protection and their potential to be used as both prophylactic and therapeutic drugs. Clinically used neutralizing antibodies against respiratory viruses are currently injected intravenously, which can lead to suboptimal pulmonary bioavailability and thus to a lower effectiveness. Here we describe DZIF-10c, a fully human monoclonal neutralizing antibody that binds the receptor-binding domain of the SARS-CoV-2 spike protein. DZIF-10c displays an exceptionally high neutralizing potency against SARS-CoV-2, retains full activity against the variant of concern (VOC) B.1.1.7 and still neutralizes the VOC B.1.351, although with reduced potency. Importantly, not only systemic but also intranasal application of DZIF-10c abolished the presence of infectious particles in the lungs of SARS-CoV-2 infected mice and mitigated lung pathology when administered prophylactically. Along with a favorable pharmacokinetic profile, these results highlight DZIF-10c as a novel human SARS-CoV-2 neutralizing antibody with high in vitro and in vivo antiviral potency. The successful intranasal application of DZIF-10c paves the way for clinical trials investigating topical delivery of anti-SARS-CoV-2 antibodies.
Background: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.
Objective: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).
Methods: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period.
Results: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred.
Conclusion: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.
The production cross section of prompt Λ+c charm baryons was measured with the ALICE detector at the LHC at midrapidity in proton-proton (pp) and proton-lead (p-Pb) collisions at a centre-of-mass energy per nucleon pair of sNN−−−√=5.02 TeV. The Λ+c and Λ¯¯¯¯−c baryons were reconstructed in the hadronic decay channels Λ+c→pK−π+ and Λ+c→pK0S and respective charge conjugates. The measured differential cross sections as a function of transverse momentum (pT) and the pT-integrated Λ+c production cross section in pp and in p-Pb collisions are presented. The Λ+c nuclear modification factor (RpPb), calculated from the cross sections in pp and in p-Pb collisions, is presented and compared with the RpPb of D mesons. The Λ+c/D0 ratio is also presented and compared with the light-flavour baryon-to-meson ratios p/π and Λ/K0S, and measurements from other LHC experiments. The results are compared to predictions from model calculations and Monte Carlo event generators.
The production cross section of prompt Λ+c charm baryons was measured with the ALICE detector at the LHC at midrapidity in proton-proton (pp) and proton-lead (p-Pb) collisions at a centre-of-mass energy per nucleon pair of sNN−−−√=5.02 TeV. The Λ+c and Λ¯¯¯¯−c baryons were reconstructed in the hadronic decay channels Λ+c→pK−π+ and Λ+c→pK0S and respective charge conjugates. The measured differential cross sections as a function of transverse momentum (pT) and the pT-integrated Λ+c production cross section in pp and in p-Pb collisions are presented. The Λ+c nuclear modification factor (RpPb), calculated from the cross sections in pp and in p-Pb collisions, is presented and compared with the RpPb of D mesons. The Λ+c/D0 ratio is also presented and compared with the light-flavour baryon-to-meson ratios p/π and Λ/K0S, and measurements from other LHC experiments. The results are compared to predictions from model calculations and Monte Carlo event generators.
The production cross section of prompt Λ+c charmed baryons was measured with the ALICE detector at the LHC at midrapidity in proton-proton (pp) and proton-lead (p-Pb) collisions at a centre-of-mass energy per nucleon pair of sNN−−−√=5.02 TeV. The Λ+c and Λ¯¯¯¯−c baryons were reconstructed in the hadronic decay channels Λ+c→pK−π+ and Λ+c→pK0S and respective charge conjugates. The measured differential cross sections as a function of transverse momentum (pT) and the pT-integrated Λ+c production cross section in pp and in p-Pb collisions are presented. The Λ+c nuclear modification factor (RpPb), calculated from the cross sections in pp and in p-Pb collisions, is presented and compared with the RpPb of D mesons. The Λ+c/D0 ratio is also presented and compared with the light-flavour baryon-to-meson ratios p/π and Λ/K0S, and measurements from other LHC experiments. The results are compared to predictions from model calculations and Monte Carlo event generators.
Jet fragmentation transverse momentum distributions in pp and p–Pb collisions at √s, √sNN = 5.02 TeV
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Jet fragmentation transverse momentum (jT) distributions are measured in proton-proton (pp) and proton-lead (p-Pb) collisions at sNN−−−√ = 5.02 TeV with the ALICE experiment at the LHC. Jets are reconstructed with the ALICE tracking detectors and electromagnetic calorimeter using the anti-kT algorithm with resolution parameter R=0.4 in the pseudorapidity range |η|<0.25. The jT values are calculated for charged particles inside a fixed cone with a radius R=0.4 around the reconstructed jet axis. The measured jT distributions are compared with a variety of parton-shower models. Herwig and PYTHIA 8 based models describe the data well for the higher jT region, while they underestimate the lower jT region. The jT distributions are further characterised by fitting them with a function composed of an inverse gamma function for higher jT values (called the "wide component"), related to the perturbative component of the fragmentation process, and with a Gaussian for lower jT values (called the "narrow component"), predominantly connected to the hadronisation process. The width of the Gaussian has only a weak dependence on jet transverse momentum, while that of the inverse gamma function increases with increasing jet transverse momentum. For the narrow component, the measured trends are successfully described by all models except for Herwig. For the wide component, Herwig and PYTHIA 8 based models slightly underestimate the data for the higher jet transverse momentum region. These measurements set constraints on models of jet fragmentation and hadronisation.
Long- and short-range correlations for pairs of charged particles are studied via two-particle angular correlations in pp collisions at s√=13 TeV and p−Pb collisions at sNN−−−√=5.02 TeV. The correlation functions are measured as a function of relative azimuthal angle Δφ and pseudorapidity separation Δη for pairs of primary charged particles within the pseudorapidity interval |η|<0.9 and the transverse-momentum interval 1<pT<4 GeV/c. Flow coefficients are extracted for the long-range correlations (1.6<|Δη|<1.8) in various high-multiplicity event classes using the low-multiplicity template fit method. The method is used to subtract the enhanced yield of away-side jet fragments in high-multiplicity events. These results show decreasing flow signals toward lower multiplicity events. Furthermore, the flow coefficients for events with hard probes, such as jets or leading particles, do not exhibit any significant changes compared to those obtained from high-multiplicity events without any specific event selection criteria. The results are compared with hydrodynamic-model calculations, and it is found that a better understanding of the initial conditions is necessary to describe the results, particularly for low-multiplicity events.
Long- and short-range correlations for pairs of charged particles are studied via two-particle angular correlations in pp collisions at √sNN = 13 TeV and p–Pb collisions at √s = 5.02 TeV. The correlation functions are measured as a function of relative azimuthal angle ∆φ and pseudorapidity separation ∆η for pairs of primary charged particles within the pseudorapidity interval |η| < 0.9 and the transverse-momentum interval 1 < pT < 4 GeV/c. Flow coefficients are extracted for the long-range correlations (1.6 < |∆η| < 1.8) in various high-multiplicity event classes using the low-multiplicity template fit method. The method is used to subtract the enhanced yield of away-side jet fragments in high-multiplicity events. These results show decreasing flow signals toward lower multiplicity events. Furthermore, the flow coefficients for events with hard probes, such as jets or leading particles, do not exhibit any significant changes compared to those obtained from high-multiplicity events without any specific event selection criteria. The results are compared with hydrodynamic-model calculations, and it is found that a better understanding of the initial conditions is necessary to describe the results, particularly for low-multiplicity events.