Abstract
At redshift
z
= 4.618, GRB 220101A is the most distant gamma-ray burst (GRB) detected by Fermi/LAT to date. It is also a very energetic event, with an equivalent isotropic energy of 3.6 × 10
...54
erg. We jointly analyzed the Fermi/GBM and LAT observations of GRB 220101A with two independent approaches and found a significant spectral break at sub-100 MeV energies during the prompt emission. The fast variability of the emission suggests that this spectral attenuation is caused by internal opacity to pair creation. Regardless of the nature of the emission processes assumed in the spectral analysis, we infer a moderate value for the jet Lorentz factor, Γ ∼ 110, and find that all of the high-energy emission was produced above and near the photosphere, at a distance of ∼10
14
cm from the central engine. We compare these results with the four other LAT-detected GRBs with similar properties.
At redshift z = 4.618, GRB 220101A is the most distant gamma-ray burst (GRB) detected by Fermi/LAT to date. It is also a very energetic event, with an equivalent isotropic energy of ...\(3.6\times10^{54}\) erg. We jointly analyzed the Fermi/GBM and LAT observations of GRB 220101A with two independent approaches and found a significant spectral break at sub-100 MeV energies during the prompt emission. The fast variability of the emission suggests that this spectral attenuation is caused by internal opacity to pair creation. Regardless of the nature of the emission processes assumed in the spectral analysis, we infer a moderate value for the jet Lorentz factor, \(\Gamma\sim110\), and find that all of the high-energy emission was produced above and near the photosphere, at a distance of \(\sim10^{14}\) cm from the central engine. We compare these results with the four other LAT-detected GRBs with similar properties.
We present 294 pulsars found in GeV data from the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope. Another 33 millisecond pulsars (MSPs) discovered in deep radio searches of LAT ...sources will likely reveal pulsations once phase-connected rotation ephemerides are achieved. A further dozen optical and/or X-ray binary systems co-located with LAT sources also likely harbor gamma-ray MSPs. This catalog thus reports roughly 340 gamma-ray pulsars and candidates, 10% of all known pulsars, compared to \(\leq 11\) known before Fermi. Half of the gamma-ray pulsars are young. Of these, the half that are undetected in radio have a broader Galactic latitude distribution than the young radio-loud pulsars. The others are MSPs, with 6 undetected in radio. Overall, >235 are bright enough above 50 MeV to fit the pulse profile, the energy spectrum, or both. For the common two-peaked profiles, the gamma-ray peak closest to the magnetic pole crossing generally has a softer spectrum. The spectral energy distributions tend to narrow as the spindown power \(\dot E\) decreases to its observed minimum near \(10^{33}\) erg s\(^{-1}\), approaching the shape for synchrotron radiation from monoenergetic electrons. We calculate gamma-ray luminosities when distances are available. Our all-sky gamma-ray sensitivity map is useful for population syntheses. The electronic catalog version provides gamma-ray pulsar ephemerides, properties and fit results to guide and be compared with modeling results.
An incremental version of the fourth catalog of active galactic nuclei (AGNs) detected by the Fermi-Large Area Telescope is presented. This version (4LAC-DR3) derives from the third data release of ...the 4FGL catalog based on 12 years of E>50 MeV gamma-ray data, where the spectral parameters, spectral energy distributions (SEDs), yearly light curves, and associations have been updated for all sources. The new reported AGNs include 587 blazar candidates and four radio galaxies. We describe the properties of the new sample and outline changes affecting the previously published one. We also introduce two new parameters in this release, namely the peak energy of the SED high-energy component and the corresponding flux. These parameters allow an assessment of the Compton dominance, the ratio of the Inverse-Compton to the synchrotron peak luminosities, without relying on X-ray data.
We present an incremental version (4FGL-DR3, for Data Release 3) of the fourth Fermi-LAT catalog of gamma-ray sources. Based on the first twelve years of science data in the energy range from 50 MeV ...to 1 TeV, it contains 6658 sources. The analysis improves on that used for the 4FGL catalog over eight years of data: more sources are fit with curved spectra, we introduce a more robust spectral parameterization for pulsars, and we extend the spectral points to 1 TeV. The spectral parameters, spectral energy distributions, and associations are updated for all sources. Light curves are rebuilt for all sources with 1 yr intervals (not 2 month intervals). Among the 5064 original 4FGL sources, 16 were deleted, 112 are formally below the detection threshold over 12 yr (but are kept in the list), while 74 are newly associated, 10 have an improved association, and seven associations were withdrawn. Pulsars are split explicitly between young and millisecond pulsars. Pulsars and binaries newly detected in LAT sources, as well as more than 100 newly classified blazars, are reported. We add three extended sources and 1607 new point sources, mostly just above the detection threshold, among which eight are considered identified, and 699 have a plausible counterpart at other wavelengths. We discuss degree-scale residuals to the global sky model and clusters of soft unassociated point sources close to the Galactic plane, which are possibly related to limitations of the interstellar emission model and missing extended sources.
IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 ...pneumonia with a good safety profile. OBJECTIVE: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. INTERVENTIONS: Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy. MAIN OUTCOME AND MEASURES: The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2 ratio less than 150 mm Hg, whichever came first. RESULTS: A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37
1. Several recent studies have considered the relative effects of local vs. landscape factors on diversity of several animal taxa in grasslands. However, very few have considered vascular plant or ...Orthoptera species, both of which are important biotic components of grassland ecosystems. The general aim of this study was to determine the effect of grassland management and landscape composition, and their potential interactions, on diversity patterns of vascular plants and Orthoptera in Alpine hay meadows. 2. We considered three groups of management regimes defined by different amounts of fertilizer nitrogen applied and cutting frequency: (i) extensive, (ii) low intensive and (iii) intensive meadows situated in different landscape contexts. To evaluate the relative importance of meadow management and landscape composition on diversity patterns, we applied analysis of covariance and variation partitioning analyses. 3. Diversity patterns of both taxonomic groups were affected primarily by grassland management. The extensive management regime was most suitable for conserving high species richness of both taxonomic groups. The intensive meadows were characterized by plant communities dominated by a few ruderal and competitor species, and by Orthoptera communities composed of only a few abundant Caelifera species (e.g. Chorthippus parallelus), while Ensifera species had very low individual densities. 4. Regarding the landscape determinants, plant diversity patterns were not significantly related to any landscape composition variables. In contrast, a high proportion of urban elements and grassland in the surrounding landscape (radius 500 m) affected Orthoptera species richness negatively. 5. Synthesis and applications. The implementation of well-targeted agri-environment schemes for compensation payments against intensification and abandonment of extensive hay meadows seems to be a promising tool to protect both taxonomic groups. In this context, we suggest that the existing Swiss ecological compensation area (ECA) hay meadow agri-environment scheme, which requires at least one cut every year and no fertilizer application, might also be suitable for the Italian Alps. Moreover, the significant influence of landscape composition on Orthoptera diversity suggests that the effectiveness of measures applied at a field scale may be improved by integration of protected area schemes, promoting extensive management at a farm scale.
The determinants of plant species richness and composition of meadows are often mutually related, showing joint effects on plant diversity. Thus, the specific objective of this paper was to evaluate ...the relative importance of soil, topography, and field management explanatory variables on plant species richness and composition of mown meadows in an area of the Southern Alps. The data consisted of 159
taxa sampled during the summer of 2003 in 56 10
×
10
m
2 sampling plots. For each plot, 25 explanatory variables were recorded. The variation in species richness and composition was divided into the three sets of explanatory variables using a variation partitioning method. Species richness was mostly controlled both by the short-term effect of nitrogen fertilisation, and, as stressed by studies in other landscape contexts in Europe, by the long-term effect of soil phosphorus accumulation. The decrease of plant species number on the most fertile meadows was the consequence of the dominance of few competitors or ruderals, which prevented the establishment of small stress-tolerant species. In contrast to species richness, plant species composition presented an important pure effect of topography (altitude and slope). Species composition depended on several topography, soil, and field management factors. Thus, for both conservation and restoration of species-rich hay meadows, it is necessary to maintain a low level of soil P content, and to prevent the abandonment of parcels on steep slopes and in marginal areas, because these hosted the highest level of plant diversity.
The dystrophin gene (DMD) is the largest gene in the human genome, mapping on the Xp21 chromosome locus. It spans 2.2Mb and accounts for approximately 0,1% of the entire human genome. Mutations in ...this gene cause Duchenne and Becker Muscular Dystrophy, X-linked Dilated Cardiomyopathy, and other milder muscle phenotypes. Beside the remarkable number of reports describing dystrophin gene expression and the pathogenic consequences of the gene mutations in dystrophinopathies, the full scenario of the DMD transcription dynamics remains however, poorly understood. Considering that the full transcription of the DMD gene requires about 16h, we have investigated the activity of RNA Polymerase II along the entire DMD locus within the context of specific chromatin modifications using a variety of chromatin-based techniques.
Our results unveil a surprisingly powerful processivity of the RNA polymerase II along the entire 2.2Mb of the DMD locus with just one site of pausing around intron 52. We also discovered epigenetic marks highlighting the existence of four novel cis‑DNA elements, two of which, located within intron 34 and exon 45, appear to govern the architecture of the DMD chromatin with implications on the expression levels of the muscle dystrophin mRNA.
Overall, our findings provide a global view on how the entire DMD locus is dynamically transcribed by the RNA pol II and shed light on the mechanisms involved in dystrophin gene expression control, which can positively impact on the optimization of the novel ongoing therapeutic strategies for dystrophinopathies.
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