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The effect of nuclear interactions on measurable net-proton number fluctuations in heavy ion collisions at the SIS18/GSI accelerator is investigated. The state of the art UrQMD model including interaction potentials is employed. It is found that the nuclear forces enhance the baryon number cumulants, as predicted from grand canonical thermodynamical models. The effect however is smeared out for proton number fluctuations due to iso-spin randomization and global baryon number conservation, which decreases the cumulant ratios. For a rapidity acceptance window larger than Δy > 0.4 the effects of global baryon number conservation dominate and all cumulant ratios are significantly smaller than 1.
It is proposed to install an experimental setup in the fixed-target hall of the Nuclotron with the final goal to perform a research program focused on the production of strange matter in heavyion collisions at beam energies between 2 and 6 A GeV. The basic setup will comprise a large acceptance dipole magnet with inner tracking detector modules based on double-sided Silicon micro-strip sensors and GEMs. The outer tracking will be based on the drift chambers and straw tube detector. Particle identification will be based on the time-of-flight measurements. This setup will be sufficient perform a comprehensive study of strangeness production in heavy-ion collisions, including multi-strange hyperons, multi-strange hypernuclei, and exotic multi-strange heavy objects. These pioneering measurements would provide the first data on the production of these particles in heavy-ion collisions at Nuclotron beam energies, and would open an avenue to explore the third (strangeness) axis of the nuclear chart. The extension of the experimental program is related with the study of in-medium effects for vector mesons decaying in hadronic modes. The studies of the NN and NA reactions for the reference is assumed.
Background: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1‐INH‐HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS‐2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo.
Methods: OPuS‐2 was a Phase 3, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator‐confirmed attacks.
Results: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack‐free during the 84‐day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE‐QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated.
Conclusions: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1‐INH‐HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.
Background: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA®, CSL Behring) was established in the 16-week COMPACT trial.
Objective: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC).
Methods: Open-label, randomised, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naïve or who had completed the COMPACT trial, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional up-titration to optimise prophylaxis. ClinicalTrials.gov registration: NCT02316353.
Results: 126 patients with a monthly attack rate of 4.3 in 3 months prior to entry in the COMPACT program were enrolled and treated for a mean of 1·5 years; 44 patients (34·9%) had >2 years exposure. Median steady-state C1-INH functional activity increased to a maximum of 73.0% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11·3 and 8·5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualised attack rates were 1·3 and 1·0, respectively and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for >2 years, 19 (83%) were attack-free during months 25–30 of treatment.
Conclusion: In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms.
Sepsis is generally considered as a severe condition of inflammation that leads to lymphocyte apoptosis and multiple organ dysfunction. Hydroxysafflor yellow A (HSYA) exerts anti-inflammatory and anti-apoptotic effects in infectious diseases. However, the therapeutic effect of HSYA on polymicrobial sepsis remains unknown. This study was undertaken to investigate the therapeutic effects and the mechanisms of action of HSYA on immunosuppression in a murine model of sepsis induced by cecal ligation and puncture (CLP). NIH mice were randomly divided into four groups: control group, sham group, CLP group, and CLP+HSYA group. HSYA (120 mg/kg) was intravenously injected into experimental mice at 12 h before CLP, concurrent with CLP and 12 h after CLP. The levels of circulating inflammatory cytokines, the apoptosis of CD4+ and CD8+ T lymphocytes, and protein expression of cytochrome C (Cytc), Bax, Bcl-2, cleaved caspase-9, and cleaved caspase-3 were examined. Plasma levels of IL-6, IL-10 and TNF-alpha as well as the apoptosis of CD4+ T lymphocytes were increased compared with sham group. These changes were accompanied by increases of pro-apoptotic proteins including Cytc, Bax, cleaved caspase-9, and cleaved caspase-3 and decreases of anti-apoptotic protein Bcl-2 in CD4+ T lymphocytes from mice undergoing CLP. In contrast, we fail to observe significant effect of HSYA on the apoptosis of CD8+ T lymphocytes in CLP-treated group. Of note, HSYA treatment reversed all above changes observed in CD4+ T lymphocytes, and significantly increased the ratio of CD4+:CD8+ T lymphocytes in CLP-treated mice. In conclusion, HSYA was an effective therapeutic agent in ameliorating sepsis-induced apoptosis of CD4+ T lymphocytes probably through its anti-inflammatory and anti-apoptotic effects.
48Si: An atypical nucleus?
(2019)
Using the relativistic Hartree–Fock Lagrangian PKA1, we investigate the properties of the exotic nucleus 48Si, which is predicted to be an atypical nucleus characterized by i) the onset of doubly magicity, ii) its location at the drip line, iii) the presence of dual semi-bubble structure (distinct central depletion in both of neutron and proton density profiles) in the ground state, and iv) the occurrence of pairing reentrance at finite temperature. While not being new for each, these phenomena are found to simultaneously occur in 48Si. For instance, the dual semi-bubble structure reduces the spin–orbit splitting of low-ℓ orbitals and upraises the s orbitals, leading therefore to distinct N=34 and Z=14 magic shells in 48Si. Consequently, the doubly magicities provide extra stability for such extreme neutron-rich system at the drip line. Associating with the neutron shell N=34 and continuum above, the pairing correlations are reengaged interestingly at finite temperature. Theoretical nuclear modelings are known to be poorly predictive in general, and we asset our confidence in the prediction of our modeling on the fact that the predictions of PKA1 in various regions of the nuclear chart have systematically been found correct and more specifically in the region of pf shell. Whether our predictions are confirmed or not, 48Si provides a concrete benchmark for the understanding of the nature of nuclear force.
Two species of Xorides Latreille, 1809 are reported parasitizing wood-boring insects in trunks and relatively larger twigs of Juglans mandshurica Maxim. in Kuandian Manzu Autonomous County, Liaoning, in the Palaearctic part of China. Two new species are described: X. juglanse Sheng, Broad & Sun sp. nov. and X. kuandianense Sheng, Broad & Sun sp. nov. One species, X. sapporensis (Uchida, 1928), was associated with wood-borers in J. mandshurica Maxim. for the first time. A key to the 46 species of Xorides Latreille known from China is provided.
We construct a new equation of state for the baryonic matter under an intense magnetic field within the framework of covariant density functional theory. The composition of matter includes hyperons as well as Δ-resonances. The extension of the nucleonic functional to the hypernuclear sector is constrained by the experimental data on Λ and Ξ-hypernuclei. We find that the equation of state stiffens with the inclusion of the magnetic field, which increases the maximum mass of neutron star compared to the non-magnetic case. In addition, the strangeness fraction in the matter is enhanced. Several observables, like the Dirac effective mass, particle abundances, etc. show typical oscillatory behavior as a function of the magnetic field and/or density which is traced back to the occupation pattern of Landau levels.
In the last decade, the Climate Limited-area Modeling Community (CLM-Community) has contributed to the Coordinated Regional Climate Downscaling Experiment (CORDEX) with an extensive set of regional climate simulations. Using several versions of the COSMO-CLM-Community model, ERA-Interim reanalysis and eight global climate models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) were dynamically downscaled with horizontal grid spacings of 0.44∘ (∼ 50 km), 0.22∘ (∼ 25 km), and 0.11∘ (∼ 12 km) over the CORDEX domains Europe, South Asia, East Asia, Australasia, and Africa. This major effort resulted in 80 regional climate simulations publicly available through the Earth System Grid Federation (ESGF) web portals for use in impact studies and climate scenario assessments. Here we review the production of these simulations and assess their results in terms of mean near-surface temperature and precipitation to aid the future design of the COSMO-CLM model simulations. It is found that a domain-specific parameter tuning is beneficial, while increasing horizontal model resolution (from 50 to 25 or 12 km grid spacing) alone does not always improve the performance of the simulation. Moreover, the COSMO-CLM performance depends on the driving data. This is generally more important than the dependence on horizontal resolution, model version, and configuration. Our results emphasize the importance of performing regional climate projections in a coordinated way, where guidance from both the global (GCM) and regional (RCM) climate modeling communities is needed to increase the reliability of the GCM–RCM modeling chain.
In the last decade, the Climate Limited-area Modeling (CLM) Community has contributed to the Coordinated Regional Climate Downscaling Experiment (CORDEX) with an extensive set of regional climate simulations. Using several versions of the COSMO-CLM community model, ERA-Interim reanalysis and eight Global Climate Models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) were dynamically downscaled with horizontal grid spacings of 0.44◦(∼50 km), 0.22◦ (∼25 km) and 0.11◦ (∼12 km) over the CORDEX domains Europe, South Asia, East Asia, Australasia and Africa. This major effort resulted in 80 regional climate simulations publicly available through the Earth System Grid Federation (ESGF) web portals for use in impact studies and climate scenario assessments. Here we review the production of these simulations and assess their results in terms of mean near-surface temperature and precipitation to aid the future design of the COSMO-CLM model simulations. It is found that a domain-specific parameter tuning is beneficial, while increasing horizontal model resolution (from 50 to 25 or 12 km grid spacing) alone does not always improve the performance of the simulation. Moreover, the COSMO-CLM performance depends on the driving data. This is generally more important than the dependence on horizontal resolution, model version and configuration. Our results emphasize the importance of performing regional climate projections in a coordinated way, where guidance from both the global (GCM) and regional (RCM) climate modelling communities is needed to increase the reliability of the GCM-RCM modelling chain.
In this study, we use simulations from seven global vegetation models to provide the first multi‐model estimate of fire impacts on global tree cover and the carbon cycle under current climate and anthropogenic land use conditions, averaged for the years 2001–2012. Fire globally reduces the tree covered area and vegetation carbon storage by 10%. Regionally, the effects are much stronger, up to 20% for certain latitudinal bands, and 17% in savanna regions. Global fire effects on total carbon storage and carbon turnover times are lower with the effect on gross primary productivity (GPP) close to 0. We find the strongest impacts of fire in savanna regions. Climatic conditions in regions with the highest burned area differ from regions with highest absolute fire impact, which are characterized by higher precipitation. Our estimates of fire‐induced vegetation change are lower than previous studies. We attribute these differences to different definitions of vegetation change and effects of anthropogenic land use, which were not considered in previous studies and decreases the impact of fire on tree cover. Accounting for fires significantly improves the spatial patterns of simulated tree cover, which demonstrates the need to represent fire in dynamic vegetation models. Based upon comparisons between models and observations, process understanding and representation in models, we assess a higher confidence in the fire impact on tree cover and vegetation carbon compared to GPP, total carbon storage and turnover times. We have higher confidence in the spatial patterns compared to the global totals of the simulated fire impact. As we used an ensemble of state‐of‐the‐art fire models, including effects of land use and the ensemble median or mean compares better to observational datasets than any individual model, we consider the here presented results to be the current best estimate of global fire effects on ecosystems.
Chronic inflammation is characterized by persisting leukocyte infiltration of the affected tissue, which is enabled by activated endothelial cells (ECs). Chronic inflammatory diseases remain a major pharmacotherapeutic challenge, and thus the search for novel drugs and drug targets is an ongoing demand. We have identified the natural product vioprolide A (vioA) to exert anti-inflammatory actions in vivo and in ECs in vitro through inhibition of its cellular target nucleolar protein 14 (NOP14). VioA attenuated the infiltration of microglia and macrophages during laser-induced murine choroidal neovascularization and the leukocyte trafficking through the vascular endothelium in the murine cremaster muscle. Mechanistic studies revealed that vioA downregulates EC adhesion molecules and the tumor necrosis factor receptor (TNFR) 1 by decreasing the de novo protein synthesis in ECs. Most importantly, we found that inhibition of importin-dependent NF-ĸB p65 nuclear translocation is a crucial part of the action of vioA leading to reduced NF-ĸB promotor activity and inflammatory gene expression. Knockdown experiments revealed a causal link between the cellular target NOP14 and the anti-inflammatory action of vioA, classifying the natural product as unique drug lead for anti-inflammatory therapeutics.
The nuclear stopping, the elliptic flow, and the HBT interferometry are calculated by the UrQMD transport model, in which potentials for “pre-formed” particles (string fragments) from color fluxtube fragmentation as well as for confined particles are considered. This description provides stronger pressure at the early stage and describes these observables better than the default cascade mode (where the “pre-formed” particles from string fragmentation are treated to be free-streaming). It should be stressed that the inclusion of potential interactions pushes down the calculated HBT radius RO and pulls up the RS so that the HBT time-related puzzle disappears throughout the energies from AGS, SPS, to RHIC.
Based on the microscopic transport model UrQMD in which hadronic and string degrees of freedom are employed, the HBT parameters in the longitudinal co-moving system are investigated for charged pion and kaon, and Λ sources in heavy ion collisions (HICs) at SPS and RHIC energies. In the Cascade mode, RO and the RL at high SPS and RHIC energies do not follow the mT-scaling, however, after considering a soft equation of state with momentum dependence (SM-EoS) for formed baryons and a density-dependent Skyrme-like potential for “pre-formed” particles, the HBT radii of pions and kaons and even those of Λs with large transverse momenta follow the mT-scaling function R=3/mT fairly well.
We construct a set of hyperonic equations of state (EoS) by assuming SU(3) symmetry within the baryon octet and by using a covariant density functional (CDF) theory approach. The low-density regions of our EoS are constrained by terrestrial experiments, while the high-density regime is modeled by systematically varying the nuclear matter skewness coefficient Qsat and the symmetry energy slope Lsym. The sensitivity of the EoS predictions is explored in terms of z parameter of the SU(3) symmetric model that modifies the meson-hyperon coupling constants away from their SU(6) symmetric values. Our results show that model EoS based on our approach can support static Tolman-Oppenheimer-Volkof (TOV) masses in the range 2.3-2.5M⊙ in the large-Qsat and small-z regime, however, such stars contain only a trace amount of hyperons compared to SU(6) models. We also construct uniformly rotating Keplerian configurations for our model EoS for which the masses of stellar sequences may reach up to 3.0M⊙. These results are used to explore the systematic dependence of the ratio of maximum masses of rotating and static stars, the lower bound on the rotational frequency of the models that will allow secondary masses in the gravitational waves events to be compact stars with M2≲3.0M⊙ and the strangeness fraction on the model parameters. We conclude that very massive stellar models can be, in principle, constructed within the SU(3) symmetric model, however, they are nucleonic-like as their strangeness fraction drops below 3%.
Effects of a phase transition on HBT correlations in an integrated Boltzmann+hydrodynamics approach
(2009)
A systematic study of HBT radii of pions, produced in heavy ion collisions in the intermediate energy regime (SPS), from an integrated (3+1)d Boltzmann+hydrodynamics approach is presented. The calculations in this hybrid approach, incorporating an hydrodynamic stage into the Ultra-relativistic Quantum Molecular Dynamics transport model, allow for a comparison of different equations of state retaining the same initial conditions and final freeze-out. The results are also compared to the pure cascade transport model calculations in the context of the available data. Furthermore, the effect of different treatments of the hydrodynamic freeze-out procedure on the HBT radii are investigated. It is found that the HBT radii are essentially insensitive to the details of the freeze-out prescription as long as the final hadronic interactions in the cascade are taken into account. The HBT radii RL and RO and the RO/RS ratio are sensitive to the EoS that is employed during the hydrodynamic evolution. We conclude that the increased lifetime in case of a phase transition to a QGP (via a Bag Model equation of state) is not supported by the available data.
The ALICE Collaboration at the LHC reports measurement of the inclusive production cross section of electrons from semi-leptonic decays of beauty hadrons with rapidity |y| < 0.8 and transverse momentum 1 < pT < 10 GeV/c, in pp collisions at √s = 2.76 TeV. Electrons not originating from semi-electronic decay of beauty hadrons are suppressed using the impact parameter of the corresponding tracks. The production cross section of beauty decay electrons is compared to the result obtained with an alternative method which uses the distribution of the azimuthal angle between heavy-flavour decay electrons and charged hadrons. Perturbative QCD predictions agree with the measured cross section within the experimental and theoretical uncertainties. The integrated visible cross section, σb→e = 3.47 ± 0.40(stat) +1.12 −1.33(sys) ± 0.07(norm) μb, was extrapolated to full phase space using Fixed Order plus Next-to-Leading Log (FONLL) calculations to obtain the total bb production ¯ cross section, σbb¯ = 130 ± 15.1(stat) +42.1 −49.8(sys) +3.4 −3.1(extr) ± 2.5(norm) ± 4.4(BR) μb.
An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.
Transverse momentum spectra of π±, K± and p(p¯) up to pT = 20 GeV/c at mid-rapidity in pp, peripheral (60–80%) and central (0–5%) Pb–Pb collisions at √sNN = 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pion ratios both show a distinct peak at pT ≈ 3 GeV/c in central Pb–Pb collisions. Below the peak, pT < 3 GeV/c, both ratios are in good agreement with hydrodynamical calculations, suggesting that the peak itself is dominantly the result of radial flow rather than anomalous hadronization processes. For pT > 10 GeV/c particle ratios in pp and Pb–Pb collisions are in agreement and the nuclear modification factors for π±, K± and p(p¯) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets.