361 research outputs found
Evaluation of clinical and genetic factors in the population pharmacokinetics of carbamazepine
Associahedra via spines
An associahedron is a polytope whose vertices correspond to triangulations of
a convex polygon and whose edges correspond to flips between them. Using
labeled polygons, C. Hohlweg and C. Lange constructed various realizations of
the associahedron with relevant properties related to the symmetric group and
the classical permutahedron. We introduce the spine of a triangulation as its
dual tree together with a labeling and an orientation. This notion extends the
classical understanding of the associahedron via binary trees, introduces a new
perspective on C. Hohlweg and C. Lange's construction closer to J.-L. Loday's
original approach, and sheds light upon the combinatorial and geometric
properties of the resulting realizations of the associahedron. It also leads to
noteworthy proofs which shorten and simplify previous approaches.Comment: 27 pages, 11 figures. Version 5: minor correction
Cosmic structure formation in Hybrid Inflation models
A wide class of inflationary models, known as Hybrid Inflation models, may
produce topological defects during a phase transition at the end of the
inflationary epoch. We point out that, if the energy scale of these defects is
close to that of Grand Unification, then their effect on cosmic structure
formation and the generation of microwave background anisotropies cannot be
ignored. Therefore, it is possible for structure to be seeded by a combination
of the adiabatic perturbations produced during inflation and active
isocurvature perturbations produced by defects. Since the two mechanisms are
uncorrelated the power spectra can be computed by a weighted average of the
individual contributions. We investigate the possible observational
consequences of this with reference to general Hybrid Inflation models and also
a specific model based on Supergravity. These mixed perturbation scenarios have
some novel observational consequences and these are discussed qualitatively.Comment: 22 Page
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&
Orbital effects of a monochromatic plane gravitational wave with ultra-low frequency incident on a gravitationally bound two-body system
We analytically compute the long-term orbital variations of a test particle
orbiting a central body acted upon by an incident monochromatic plane
gravitational wave. We assume that the characteristic size of the perturbed
two-body system is much smaller than the wavelength of the wave. Moreover, we
also suppose that the wave's frequency is much smaller than the particle's
orbital one. We make neither a priori assumptions about the direction of the
wavevector nor on the orbital geometry of the planet. We find that, while the
semi-major axis is left unaffected, the eccentricity, the inclination, the
longitude of the ascending node, the longitude of pericenter and the mean
anomaly undergo non-vanishing long-term changes. They are not secular trends
because of the slow modulation introduced by the tidal matrix coefficients and
by the orbital elements themselves. They could be useful to indepenedently
constrain the ultra-low frequency waves which may have been indirectly detected
in the BICEP2 experiment. Our calculation holds, in general, for any
gravitationally bound two-body system whose characteristic frequency is much
larger than the frequency of the external wave. It is also valid for a generic
perturbation of tidal type with constant coefficients over timescales of the
order of the orbital period of the perturbed particle.Comment: LaTex2e, 24 pages, no figures, no tables. Changes suggested by the
referees include
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
Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives
PFS (Prime Focus Spectrograph), a next generation facility instrument on the
8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed,
optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394
reconfigurable fibers will be distributed over the 1.3 deg field of view. The
spectrograph has been designed with 3 arms of blue, red, and near-infrared
cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure
at a resolution of ~1.6-2.7A. An international collaboration is developing this
instrument under the initiative of Kavli IPMU. The project is now going into
the construction phase aiming at undertaking system integration in 2017-2018
and subsequently carrying out engineering operations in 2018-2019. This article
gives an overview of the instrument, current project status and future paths
forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and
Instrumentation 201
Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population
BACKGROUND: Acquired myasthenia gravis (MG) is a rare antibody-mediated autoimmune disease caused by impaired neuromuscular transmission, leading to abnormal muscle fatigability. The aetiology is complex, including genetic risk factors of the human leukocyte antigen (HLA) complex and unknown environmental factors. Although associations between the HLA complex and MG are well established, not all involved components of the HLA predisposition to this heterogeneous disease have been revealed. Well-powered and comprehensive HLA analyses of subgroups in MG are warranted, especially in late onset MG. METHODOLOGY/PRINCIPAL FINDINGS: This case-control association study is of a large population-based Norwegian cohort of 369 MG patients and 651 healthy controls. We performed comprehensive genotyping of four classical HLA loci (HLA-A, -B, -C and -DRB1) and showed that the DRB1*15:01 allele conferred the strongest risk in late onset MG (LOMG; onset ≥ 60 years) (OR 2.38, p(c)7.4 × 10(-5)). DRB1*13:01 was found to be a protective allele for both early onset MG (EOMG) and LOMG (OR 0.31, p(c) 4.71 × 10(-4)), a finding not previously described. No significant association was found to the DRB1*07:01 allele (p(nc) = 0.18) in a subset of nonthymomatous anti-titin antibody positive LOMG as reported by others. HLA-B*08 was mapped to give the strongest contribution to EOMG, supporting previous studies. CONCLUSION: The results from this study provide important new information concerning the susceptibility of HLA alleles in Caucasian MG, with highlights on DRB1*15:01 as being a major risk allele in LOMG
TNF-α mediated keratinocyte expression and release of matrix metalloproteinase 9: putative mechanism of pathogenesis in Stevens-Johnson syndrome/ toxic epidermal necrolysis.
Stevens Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse drug reactions (ADRs) characterised by widespread keratinocyte cell-death and epidermal detachment. At present, there is little understanding of how the detachment occurs or how it is abrogated by the TNF-α inhibitor etanercept, an effective SJS/TEN treatment. RNA-sequencing was used to identify upregulated transcripts in formalin-fixed paraffin-embedded SJS/TEN skin biopsies. Epidermal matrix metalloproteinase 9 (MMP9) expression was assessed by immunohistochemistry in skin biopsies and cultured human skin explants exposed to serum from cutaneous ADRs patients. TNF-α-induced MMP9 expression and activity, and its abrogation by etanercept was determined using the HaCaT immortalised keratinocyte cell-line. Epidermal MMP9 expression was significantly higher in SJS/TEN skin (70.6%) vs. healthy control skin (0%, p=0.0098) and non-bullous skin reactions (10.7%, p=0.0002). SJS/TEN serum induced significant MMP9 expression and collagenase activity in healthy skin explants, which was reduced by etanercept. Etanercept was also able negate the TNF-α induced MMP9 expression in the HaCaT cell line. Data suggest that elevated epidermal MMP9 expression and collagenase activity is a putative pathogenic mechanism in SJS/TEN, which is limited by etanercept. Modulation of MMP9 expression and activity represents to our knowledge a previously unreported therapeutic target for the treatment of SJS/TEN
2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease
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