114 research outputs found
Efficacy of Continuous Interleukin 1 Blockade in Mevalonate Kinase Deficiency: A Multicenter Retrospective Study in 13 Adult Patients and Literature Review
OBJECTIVE: To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD).
METHODS: We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7).
RESULTS: Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively.
CONCLUSION: These data support frequent partial responses, showing a better response with canakinumab. The genotype and therapeutic outcomes correlation should help in the personalization of treatment
Discovery of the Binary Pulsar PSR B1259-63 in Very-High-Energy Gamma Rays around Periastron with H.E.S.S
We report the discovery of very-high-energy (VHE) gamma-ray emission of the
binary system PSR B1259-63/SS 2883 of a radio pulsar orbiting a massive,
luminous Be star in a highly eccentric orbit. The observations around the 2004
periastron passage of the pulsar were performed with the four 13 m Cherenkov
telescopes of the H.E.S.S. experiment, recently installed in Namibia and in
full operation since December 2003. Between February and June 2004, a gamma-ray
signal from the binary system was detected with a total significance above 13
sigma. The flux was found to vary significantly on timescales of days which
makes PSR B1259-63 the first variable galactic source of VHE gamma-rays
observed so far. Strong emission signals were observed in pre- and
post-periastron phases with a flux minimum around periastron, followed by a
gradual flux decrease in the months after. The measured time-averaged energy
spectrum above a mean threshold energy of 380 GeV can be fitted by a simple
power law F_0(E/1 TeV)^-Gamma with a photon index Gamma =
2.7+-0.2_stat+-0.2_sys and flux normalisation F_0 = (1.3+-0.1_stat+-0.3_sys)
10^-12 TeV^-1 cm^-2 s^-1. This detection of VHE gamma-rays provides unambiguous
evidence for particle acceleration to multi-TeV energies in the binary system.
In combination with coeval observations of the X-ray synchrotron emission by
the RXTE and INTEGRAL instruments, and assuming the VHE gamma-ray emission to
be produced by the inverse Compton mechanism, the magnetic field strength can
be directly estimated to be of the order of 1 G.Comment: 10 pages, 8 figures, accepted in Astronomy and Astrophysics on 2 June
2005, replace: document unchanged, replaced author field in astro-ph entry -
authors are all members of the H.E.S.S. collaboration and three additional
authors (99+3, see document
Observations of Mkn 421 in 2004 with H.E.S.S. at large zenith angles
Mkn 421 was observed during a high flux state for nine nights in April and
May 2004 with the fully operational High Energy Stereoscopic System (H.E.S.S.)
in Namibia. The observations were carried out at zenith angles of
60--65, which result in an average energy threshold of 1.5 TeV
and a collection area reaching 2~km at 10~TeV. Roughly 7000 photons from
Mkn~421 were accumulated with an average gamma-ray rate of 8 photons/min. The
overall significance of the detection exceeds 100 standard deviations. The
light-curve of integrated fluxes above 2~TeV shows changes of the diurnal flux
up to a factor of 4.3. For nights of high flux, intra-night variability is
detected with a decay time of less than 1 hour. The time averaged energy
spectrum is curved and is well described by a power-law with a photon index
\egamm and an exponential cutoff at \ecut~TeV and an average integral flux
above 2~TeV of 3 Crab flux units. Significant variations of the spectral shape
are detected with a spectral hardening as the flux increases. Contemporaneous
multi-wavelength observations at lower energies (X-rays and gamma-rays above
~GeV) indicate smaller relative variability amplitudes than seen
above 2~TeV during high flux state observed in April 2004.Comment: 5 pages, 4 figures, published in A&
Very high energy gamma rays from the direction of Sagittarius A*.
We report the detection of a point-like source of very high energy (VHE) -rays coincident within 1' of Sgr A *, obtained with the HESS array of Cherenkov telescopes. The -rays exhibit a power-law energy spectrum with a spectral index of and a flux above the 165 GeV threshold of m -2 s -1. The measured flux and spectrum differ substantially from recent results reported in particular by the CANGAROO collaboration
A possible association of the new VHE gamma-ray source HESS J1825--137 with the pulsar wind nebula G18.0--0.7
We report on a possible association of the recently discovered very
high-energy -ray source HESS J1825--137 with the pulsar wind nebula
(commonly referred to as G 18.0--0.7) of the year old
Vela-like pulsar PSR B1823--13. HESS J1825--137 was detected with a
significance of 8.1 in the Galactic Plane survey conducted with the
H.E.S.S. instrument in 2004. The centroid position of HESS J1825--137 is offset
by 11\arcmin south of the pulsar position. \emph{XMM-Newton} observations have
revealed X-ray synchrotron emission of an asymmetric pulsar wind nebula
extending to the south of the pulsar. We argue that the observed morphology and
TeV spectral index suggest that HESS J1825--137 and G 18.0--0.7 may be
associated: the lifetime of TeV emitting electrons is expected to be longer
compared to the {\it XMM-Newton} X-ray emitting electrons, resulting in
electrons from earlier epochs (when the spin-down power was larger)
contributing to the present TeV flux. These electrons are expected to be
synchrotron cooled, which explains the observed photon index of , and
the longer lifetime of TeV emitting electrons naturally explains why the TeV
nebula is larger than the X-ray size. Finally, supernova remnant expansion into
an inhomogeneous medium is expected to create reverse shocks interacting at
different times with the pulsar wind nebula, resulting in the offset X-ray and
TeV -ray morphology.Comment: 5 pages, 3 figures, to appear in Astronomy and Astrophysics Letter
Fasting and High-Fat Diet Alter Histone Deacetylase Expression in the Medial Hypothalamus
Increasing attention is now being given to the epigenetic regulation of animal and human behaviors including the stress response and drug addiction. Epigenetic factors also influence feeding behavior and metabolic phenotypes, such as obesity and insulin sensitivity. In response to fasting and high-fat diets, the medial hypothalamus changes the expression of neuropeptides regulating feeding, metabolism, and reproductive behaviors. Histone deacetylases (HDACs) are involved in the epigenetic control of gene expression and alter behavior in response to a variety of environmental factors. Here, we examined the expression of HDAC family members in the medial hypothalamus of mice in response to either fasting or a high-fat diet. In response to fasting, HDAC3 and â4 expression levels increased while HDAC10 and â11 levels decreased. Four weeks on a high-fat diet resulted in the increased expression of HDAC5 and â8. Moreover, fasting decreased the number of acetylated histone H3- and acetylated histone H4-positive cells in the ventrolateral subdivision of the ventromedial hypothalamus. Therefore, HDACs may be implicated in altered gene expression profiles in the medial hypothalamus under different metabolic states
Measurement of the Crab Flux Above 60 GeV with the CELESTE Cherenkov Telescope
We have converted the former solar electrical plant THEMIS (French Pyrenees)
into an atmospheric Cherenkov detector called CELESTE, which records gamma rays
above 30 GeV (7E24 Hz). Here we present the first sub-100 GeV detection by a
ground based telescope of a gamma ray source, the Crab nebula, in the energy
region between satellite measurements and imaging atmospheric Cherenkov
telescopes. At our analysis threshold energy of 60 +/- 20 GeV we measure a
gamma ray rate of 6.1 +/- 0.8 per minute. Allowing for 30% systematic
uncertainties and a 30% error on the energy scale yields an integral gamma ray
flux of I(E>60 GeV) = 6.2^{+5.3}_{-2.3} E-6 photons m^-2 s^-1. The analysis
methods used to obtain the gamma ray signal from the raw data are detailed. In
addition, we determine the upper limit for pulsed emission to be <12% of the
Crab flux at the 99% confidence level, in the same energy range. Our result
indicates that if the power law observed by EGRET is attenuated by a cutoff of
form e^{-E/E_0} then E_0 < 26 GeV. This is the lowest energy probed by a
Cherenkov detector and leaves only a narrow range unexplored beyond the energy
range studied by EGRET.Comment: 34 pages, accepted by the Astrophysical Journa
A low level of extragalactic background light as revealed by big gamma-rays from blazars
The diffuse extragalactic background light consists of the sum of the starlight emitted by galaxies through the history of the Universe, and it could also have an important contribution from the 'first stars', which may have formed before galaxy formation began. Direct measurements are difficult and not yet conclusive, owing to the large uncertainties caused by the bright foreground emission associated with zodiacal light1. An alternative approach2, 3, 4, 5 is to study the absorption features imprinted on the -ray spectra of distant extragalactic objects by interactions of those photons with the background light photons6. Here we report the discovery of -ray emission from the blazars7 H 2356 - 309 and 1ES 1101 - 232, at redshifts z = 0.165 and z = 0.186, respectively. Their unexpectedly hard spectra provide an upper limit on the background light at optical/near-infrared wavelengths that appears to be very close to the lower limit given by the integrated light of resolved galaxies8. The background flux at these wavelengths accordingly seems to be strongly dominated by the direct starlight from galaxies, thus excluding a large contribution from other sourcesâin particular from the first stars formed9. This result also indicates that intergalactic space is more transparent to -rays than previously thought
Discovery of extended VHE gamma-ray emission from the asymmetric pulsar wind nebula in MSH 15-52 with H.E.S.S
The Supernova Remnant MSH 15-52 has been observed in very high energy (VHE)
gamma-rays using the H.E.S.S. 4-telescope array located in Namibia. A gamma-ray
signal is detected at the 25 sigma level during an exposure of 22.1 hours live
time. The image reveals an elliptically shaped emission region around the
pulsar PSR B1509-58, with semi-major axis 6' in the NW-SE direction and
semi-minor axis 2' approximately. This morphology coincides with the diffuse
pulsar wind nebula as observed at X-ray energies by ROSAT. The overall energy
spectrum from 280 GeV up to 40 TeV can be fitted by a power law with photon
index Gamma = 2.27 +/- 0.03(stat.) +/- 0.20(syst.). The detected emission can
be plausibly explained by inverse Compton scattering of accelerated
relativistic electrons with soft photons.Comment: 5 pages, 3 figures, accepted by A&A letter
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