438 research outputs found
Detection of variable VHE gamma-ray emission from the extra-galactic gamma-ray binary LMC P3
Context. Recently, the high-energy (HE, 0.1-100 GeV) -ray emission
from the object LMC P3 in the Large Magellanic Cloud (LMC) has been discovered
to be modulated with a 10.3-day period, making it the first extra-galactic
-ray binary.
Aims. This work aims at the detection of very-high-energy (VHE, >100 GeV)
-ray emission and the search for modulation of the VHE signal with the
orbital period of the binary system.
Methods. LMC P3 has been observed with the High Energy Stereoscopic System
(H.E.S.S.); the acceptance-corrected exposure time is 100 h. The data set has
been folded with the known orbital period of the system in order to test for
variability of the emission. Energy spectra are obtained for the orbit-averaged
data set, and for the orbital phase bin around the VHE maximum.
Results. VHE -ray emission is detected with a statistical
significance of 6.4 . The data clearly show variability which is
phase-locked to the orbital period of the system. Periodicity cannot be deduced
from the H.E.S.S. data set alone. The orbit-averaged luminosity in the
TeV energy range is erg/s. A luminosity of erg/s is reached during 20% of the orbit. HE and VHE
-ray emissions are anti-correlated. LMC P3 is the most luminous
-ray binary known so far.Comment: 5 pages, 3 figures, 1 table, accepted for publication in A&
Detailed spectral and morphological analysis of the shell type SNR RCW 86
Aims: We aim for an understanding of the morphological and spectral
properties of the supernova remnant RCW~86 and for insights into the production
mechanism leading to the RCW~86 very high-energy gamma-ray emission. Methods:
We analyzed High Energy Spectroscopic System data that had increased
sensitivity compared to the observations presented in the RCW~86 H.E.S.S.
discovery publication. Studies of the morphological correlation between the
0.5-1~keV X-ray band, the 2-5~keV X-ray band, radio, and gamma-ray emissions
have been performed as well as broadband modeling of the spectral energy
distribution with two different emission models. Results:We present the first
conclusive evidence that the TeV gamma-ray emission region is shell-like based
on our morphological studies. The comparison with 2-5~keV X-ray data reveals a
correlation with the 0.4-50~TeV gamma-ray emission.The spectrum of RCW~86 is
best described by a power law with an exponential cutoff at TeV and a spectral index of ~. A static
leptonic one-zone model adequately describes the measured spectral energy
distribution of RCW~86, with the resultant total kinetic energy of the
electrons above 1 GeV being equivalent to 0.1\% of the initial kinetic
energy of a Type I a supernova explosion. When using a hadronic model, a
magnetic field of ~100G is needed to represent the measured data.
Although this is comparable to formerly published estimates, a standard
E spectrum for the proton distribution cannot describe the gamma-ray
data. Instead, a spectral index of ~1.7 would be required, which
implies that ~erg has been transferred into
high-energy protons with the effective density cm^-3. This
is about 10\% of the kinetic energy of a typical Type Ia supernova under the
assumption of a density of 1~cm^-3.Comment: accepted for publication by A&
Characterizing the gamma-ray long-term variability of PKS 2155-304 with H.E.S.S. and Fermi-LAT
Studying the temporal variability of BL Lac objects at the highest energies
provides unique insights into the extreme physical processes occurring in
relativistic jets and in the vicinity of super-massive black holes. To this
end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in
the high (HE, 100 MeV 200 GeV)
gamma-ray domain. Over the course of ~9 yr of H.E.S.S observations the VHE
light curve in the quiescent state is consistent with a log-normal behavior.
The VHE variability in this state is well described by flicker noise
(power-spectral-density index {\ss}_VHE = 1.10 +0.10 -0.13) on time scales
larger than one day. An analysis of 5.5 yr of HE Fermi LAT data gives
consistent results ({\ss}_HE = 1.20 +0.21 -0.23, on time scales larger than 10
days) compatible with the VHE findings. The HE and VHE power spectral densities
show a scale invariance across the probed time ranges. A direct linear
correlation between the VHE and HE fluxes could neither be excluded nor firmly
established. These long-term-variability properties are discussed and compared
to the red noise behavior ({\ss} ~ 2) seen on shorter time scales during
VHE-flaring states. The difference in power spectral noise behavior at VHE
energies during quiescent and flaring states provides evidence that these
states are influenced by different physical processes, while the compatibility
of the HE and VHE long-term results is suggestive of a common physical link as
it might be introduced by an underlying jet-disk connection.Comment: 11 pages, 16 figure
Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee
These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments
The exceptionally powerful TeV gamma-ray emitters in the Large Magellanic Cloud
The Large Magellanic Cloud, a satellite galaxy of the Milky Way, has been
observed with the High Energy Stereoscopic System (H.E.S.S.) above an energy of
100 billion electron volts for a deep exposure of 210 hours. Three sources of
different types were detected: the pulsar wind nebula of the most energetic
pulsar known N 157B, the radio-loud supernova remnant N 132D and the largest
non-thermal X-ray shell - the superbubble 30 Dor C. The unique object SN 1987A
is, surprisingly, not detected, which constrains the theoretical framework of
particle acceleration in very young supernova remnants. These detections reveal
the most energetic tip of a gamma-ray source population in an external galaxy,
and provide via 30 Dor C the unambiguous detection of gamma-ray emission from a
superbubble.Comment: Published in Science Magazine (Jan. 23, 2015). This ArXiv version has
the supplementary online material incorporated as an appendix to the main
pape
Deletion of Nlrp3 protects from inflammation-induced skeletal muscle atrophy
BACKGROUND: Critically ill patients develop atrophic muscle failure, which increases morbidity and mortality. Interleukin-1ÎČ (IL-1ÎČ) is activated early in sepsis. Whether IL-1ÎČ acts directly on muscle cells and whether its inhibition prevents atrophy is unknown. We aimed to investigate if IL-1ÎČ activation via the Nlrp3 inflammasome is involved in inflammation-induced atrophy. METHODS: We performed an experimental study and prospective animal trial. The effect of IL-1ÎČ on differentiated C2C12 muscle cells was investigated by analyzing gene-and-protein expression, and atrophy response. Polymicrobial sepsis was induced by cecum ligation and puncture surgery in Nlrp3 knockout and wild type mice. Skeletal muscle morphology, gene and protein expression, and atrophy markers were used to analyze the atrophy response. Immunostaining and reporter-gene assays showed that IL-1ÎČ signaling is contained and active in myocytes. RESULTS: Immunostaining and reporter gene assays showed that IL-1ÎČ signaling is contained and active in myocytes. IL-1ÎČ increased Il6 and atrogene gene expression resulting in myocyte atrophy. Nlrp3 knockout mice showed reduced IL-1ÎČ serum levels in sepsis. As determined by muscle morphology, organ weights, gene expression, and protein content, muscle atrophy was attenuated in septic Nlrp3 knockout mice, compared to septic wild-type mice 96Â h after surgery. CONCLUSIONS:
IL-1ÎČ directly acts on myocytes to cause atrophy in sepsis. Inhibition of IL-1ÎČ activation by targeting Nlrp3 could be useful to prevent inflammation-induced muscle failure in critically ill patients
Glucocorticoid-Treated Mice Are an Inappropriate Positive Control for Long-Term Preclinical Studies in the mdx Mouse
Dmd(mdx) (mdx) mice are used as a genetic and biochemical model of dystrophin deficiency. The long-term consequences of glucocorticoid (GC) treatment on dystrophin-deficient skeletal and heart muscle are not yet known. Here we used systematic phenotyping to assess the long-term consequences of GC treatment in mdx mice. Our investigation addressed not only the effects of GC on the disease phenotype but also the question of whether GCs can be used as a positive control for preclinical drug evaluations.We performed nine pre-clinical efficacy trials (treated Nâ=â129, untreated Nâ=â106) of different durations in 9-to-50-week-old dystrophic mdx mice over a 3-year time period using standardized methods. In all these trials, we used either 1 mg/kg body weight of prednisone or 5 mg/kg body weight of prednisolone as positive controls to compare the efficacy of various test drugs. Data from untreated controls and GC-treated mice in the various trials have been pooled and analyzed to assess the effects of GCs on dystrophin-deficient skeletal and cardiac muscles of mdx mice. Our results indicate that continuous GC treatment results in early (e.g., at 50 days) improvements in normalized parameters such as grip strength, motor coordination and maximal in vitro force contractions on isolated EDL muscle, but these initial benefits are followed by a progressive loss of muscle strength after 100 days. We also found a significant increase in heart fibrosis that is reflected in a significant deterioration in cardiac systolic function after 100 days of treatment.Continuous administration of prednisone to mdx mice initially improves skeletal muscle strength, but further therapy result in deterioration of muscle strength and cardiac function associated with enhanced cardiac fibrosis. These results suggest that GCs may not serve as an appropriate positive control for long-term mdx mouse preclinical trials
Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies
Introduction: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. Methods: A total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the KaplanâMeier estimator. Results: Of 65 patients tested, 32 (49%) and 23 (35%) tested positive for C1q and C3d fixing, respectively. Of the 32 C1q-positive (c1q+) patients, 13 (41%) did not show concomitant C3d fixing. The mean fluorescence intensity values of the original immunoglobulin G DSA correlated poorly with complement-fixing positivity (C1q: adjusted R2 0.072; C3d: adjusted R2 0.11; p < 0.05). C1q+ antibodies were associated with acute tubulitis [0.75 ± 0.18 (C1q+) vs. 0.25 ± 0.08 (C1qâ) episodes per patient (mean ± standard error of the mean; p < 0.05] but not with worse long-term renal allograft dysfunction (median time to primary event 5.9 (C1q+) vs. 6.4 (C1qâ) years; hazard ratio (HR) 0.74; 95% confidence ratio (CI) 0.30â1.81; p = 0.58]. C3d-positive (C3d+) antibodies were associated with positive C4d histological staining [47% (C3d+) vs. 20% (C3dâ); p = 0.04] and with significantly worse long-term allograft dysfunction [median time to primary event: 5.6 (C3d+) vs. 6.5 (C3dâ) years; HR 0.38; 95% CI 0.15â0.97; p = 0.04]. Conclusion: Assessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at the highest risk of long-term renal allograft dysfunction
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