Rigidity-dependent cosmic ray energy spectra in the knee region obtained with the GAMMA experiment

On the basis of the extensive air shower (EAS) data obtained by the GAMMA experiment, the energy spectra and elemental composition of the primary cosmic rays are derived in the 1-100 PeV energy range. The reconstruction of the primary energy spectra is carried out using an EAS inverse approach in the framework of the SIBYLL2.1 and QGSJET01 interaction models and the hypothesis of power-law primary energy spectra with rigidity-dependent knees. The energy spectra of primary H, He, O-like and Fe-like nuclei obtained with the SIBYLL interaction model agree with corresponding extrapolations of the balloon and satellite data to ~1 PeV energies. The energy spectra obtained from the QGSJET model show a predominantly proton composition in the knee region. The rigidity-dependent knee feature of the primary energy spectra for each interaction model is displayed at the following rigidities: ~2.5+/-0.2 PV (SIBYLL) and ~3.1-4.2 PV (QGSJET). All the results presented are derived taking into account the detector response, the reconstruction uncertainties of the EAS parameters, and fluctuations in the EAS development.Comment: 28 pages, 18 figures, accepted for publication in Astroparticle Physic

Gamma-Ray Bursts: The Underlying Model

A pedagogical derivation is presented of the ``fireball'' model of gamma-ray bursts, according to which the observable effects are due to the dissipation of the kinetic energy of a relativistically expanding wind, a ``fireball.'' The main open questions are emphasized, and key afterglow observations, that provide support for this model, are briefly discussed. The relativistic outflow is, most likely, driven by the accretion of a fraction of a solar mass onto a newly born (few) solar mass black hole. The observed radiation is produced once the plasma has expanded to a scale much larger than that of the underlying ``engine,'' and is therefore largely independent of the details of the progenitor, whose gravitational collapse leads to fireball formation. Several progenitor scenarios, and the prospects for discrimination among them using future observations, are discussed. The production in gamma- ray burst fireballs of high energy protons and neutrinos, and the implications of burst neutrino detection by kilometer-scale telescopes under construction, are briefly discussed.Comment: In "Supernovae and Gamma Ray Bursters", ed. K. W. Weiler, Lecture Notes in Physics, Springer-Verlag (in press); 26 pages, 2 figure

Fermi acceleration in astrophysical jets

We consider the acceleration of energetic particles by Fermi processes (i.e., diffusive shock acceleration, second order Fermi acceleration, and gradual shear acceleration) in relativistic astrophysical jets, with particular attention given to recent progress in the field of viscous shear acceleration. We analyze the associated acceleration timescales and the resulting particle distributions, and discuss the relevance of these processes for the acceleration of charged particles in the jets of AGNs, GRBs and microquasars, showing that multi-component powerlaw-type particle distributions are likely to occur.Comment: 6 pages, one figure; based on talk at "The multimessenger approach to unidentified gamma-ray sources", Barcelona/Spain, July 2006; accepted for publication in Astrophysics and Space Scienc

Host range, transmissibility and antigenicity of a pangolin coronavirus

The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. In primary human cells, PgCoV replicated efficiently but with reduced fitness and showed less efficient transmission via airborne route compared with SARS-CoV-2 in hamsters. PgCoV was potently inhibited by US Food and Drug Administration approved drugs, and neutralized by COVID-19 patient sera and SARS-CoV-2 therapeutic antibodies in vitro. A pan-Sarbecovirus antibody and SARS-CoV-2 S2P recombinant protein vaccine protected BALB/c mice from PgCoV infection. In K18-hACE2 mice, PgCoV infection caused severe clinical disease, but mice were protected by a SARS-CoV-2 human antibody. Efficient PgCoV replication in primary human cells and hACE2 mice, coupled with a capacity for airborne spread, highlights an emergence potential. However, low competitive fitness, pre-immune humans and the benefit of COVID-19 countermeasures should impede its ability to spread globally in human populations

SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia

The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3′ end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence

Unexpected distribution of ν1f7/2 strength in Ca 49

The calcium isotopes have emerged as a critical testing ground for new microscopically derived shell-model interactions, and a great deal of experimental and theoretical focus has been directed toward this region. We investigate the relative spectroscopic strengths associated with 1f7/2 neutron hole states in Ca47,49 following one-neutron knockout reactions from Ca48,50. The observed reduction of strength populating the 7/21- state in Ca49, as compared to Ca47, is inconsistent with shell-model calculations using both phenomenological interactions such as GXPF1, and interactions derived from microscopically based two- and three-nucleon forces. The result suggests a fragmentation of the l=3 strength to higher-lying states as suggested by the microscopic calculations, but the observed magnitude of the reduction is not reproduced in any shell-model description

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136