3,575 research outputs found
Identification of the major adducts formed by reaction of benzo(a)pyrene diol epoxide with DNA in vitro.
Revertant fibres and dystrophin traces in Duchenne muscular dystrophy: Implication for clinical trials
Duchenne muscular dystrophy (DMD) is characterised by the absence of dystrophin in muscle biopsies, although residual dystrophin can be present, either as dystrophin-positive (revertant) fibres or traces. As restoration of dystrophin expression is the end point of clinical trials, such residual dystrophin is a key factor in recruitment of patients and may also confound the analysis of dystrophin restoration in treated patients, if, as previously observed in the mdx mouse, revertant fibres increase with age. In 62% of the diagnostic biopsies reports of 65 DMD patients studied, traces or revertants were recorded with no correlation between traces or revertants, the patients' performance, or corticosteroids response. In nine of these patients, there was no increase in traces or revertants in biopsies taken a mean of 8.23 years (5.8-10.4 years) after the original diagnostic biopsy. This information should help in the design and execution of clinical trials focused on dystrophin restoration strategies. (C) 2010 Elsevier B.V. All rights reserved
Multisystem proteinopathy due to a homozygous p.Arg159His VCP mutation : a tale of the unexpected
ObjectiveTo assess the clinical, radiologic, myopathologic, and proteomic findings in a patient manifesting a multisystem proteinopathy due to a homozygous valosin-containing protein gene (VCP) mutation previously reported to be pathogenic in the heterozygous state.MethodsWe studied a 36-year-old male index patient and his father, both presenting with progressive limb-girdle weakness. Muscle involvement was assessed by MRI and muscle biopsies. We performed whole-exome sequencing and Sanger sequencing for segregation analysis of the identified p.Arg159His VCP mutation. To dissect biological disease signatures, we applied state-of-the-art quantitative proteomics on muscle tissue of the index case, his father, 3 additional patients with VCP-related myopathy, and 3 control individuals.ResultsThe index patient, homozygous for the known p.Arg159His mutation in VCP, manifested a typical VCP-related myopathy phenotype, although with a markedly high creatine kinase value and a relatively early disease onset, and Paget disease of bone. The father exhibited a myopathy phenotype and discrete parkinsonism, and multiple deceased family members on the maternal side of the pedigree displayed a dementia, parkinsonism, or myopathy phenotype. Bioinformatic analysis of quantitative proteomic data revealed the degenerative nature of the disease, with evidence suggesting selective failure of muscle regeneration and stress granule dyshomeostasis.ConclusionWe report a patient showing a multisystem proteinopathy due to a homozygous VCP mutation. The patient manifests a severe phenotype, yet fundamental disease characteristics are preserved. Proteomic findings provide further insights into VCP-related pathomechanisms
Neutron and proton spectra from the decay of hypernuclei
We have determined the spectra of neutrons and protons following the decay of
hypernuclei through the one- and two-nucleon induced mechanisms. The
momentum distributions of the primary nucleons are calculated and a Monte Carlo
simulation is used to account for final state interactions. From the spectra we
calculate the number of neutrons () and protons () per
decay and show how the measurement of these quantities, particularly , can
lead to a determination of , the ratio of neutron to
proton induced decay. We also show that the consideration of the
two-nucleon induced channel has a repercussion in the results, widening the
band of allowed values of with respect to what is
obtained neglecting this channel.Comment: 30 pages, 12 Postscript figures, uuencoded file, ReVTeX, epsf.st
Image resonance in the many-body density of states at a metal surface
The electronic properties of a semi-infinite metal surface without a bulk gap are studied by a formalism that is able to account for the continuous spectrum of the system. The density of states at the surface is calculated within the GW approximation of many-body perturbation theory. We demonstrate the presence of an unoccupied surface resonance peaked at the position of the first image state. The resonance encompasses the whole Rydberg series of image states and cannot be resolved into individual peaks. Its origin is the shift in spectral weight when many-body correlation effects are taken into account
FroDO: From Detections to 3D Objects
Object-oriented maps are important for scene understanding since they jointly capture geometry and semantics, allow individual instantiation and meaningful reasoning about objects. We introduce FroDO, a method for accurate 3D reconstruction of object instances from RGB video that infers their location, pose and shape in a coarse to fine manner. Key to FroDO is to embed object shapes in a novel learnt shape space that allows seamless switching between sparse point cloud and dense DeepSDF decoding. Given an input sequence of localized RGB frames, FroDO first aggregates 2D detections to instantiate a 3D bounding box per object. A shape code is regressed using an encoder network before optimizing shape and pose further under the learnt shape priors using sparse or dense shape representations. The optimization uses multi-view geometric, photometric and silhouette losses. We evaluate on real-world datasets, including Pix3D, Redwood-OS, and ScanNet, for single-view, multi-view, and multi-object reconstruction
CDW, Superconductivity and Anomalous Metallic Behavior in 2D Transition Metal Dichalcogenides
We propose a theory for quasi-two-dimensional transition metal
dichalcogenides that provides a unified microscopic picture of the charge
density wave (CDW) and superconducting phases. We show, based on the
electron-phonon coupling and Fermi surface topology, that a CDW order parameter
with six-fold symmetry and nodes (f-wave) gives a consistent description of the
available experimental data. The elementary excitations in the CDW phase are
Dirac electrons. The superconducting state has its origin on the attractive
interaction mediated by phonons. The theory predicts strong deviations from
Fermi liquid theory in the CDW phase.Comment: 4 pages, 3 figure
Lifetimes of image-potential states on copper surfaces
The lifetime of image states, which represent a key quantity to probe the
coupling of surface electronic states with the solid substrate, have been
recently determined for quantum numbers on Cu(100) by using
time-resolved two-photon photoemission in combination with the coherent
excitation of several states (U. H\"ofer et al, Science 277, 1480 (1997)). We
here report theoretical investigations of the lifetime of image states on
copper surfaces. We evaluate the lifetimes from the knowledge of the
self-energy of the excited quasiparticle, which we compute within the GW
approximation of many-body theory. Single-particle wave functions are obtained
by solving the Schr\"odinger equation with a realistic one-dimensional model
potential, and the screened interaction is evaluated in the random-phase
approximation (RPA). Our results are in good agreement with the experimentally
determined decay times.Comment: 4 pages, 1 figure, to appear in Phys. Rev. Let
Bayesian Network Enhanced with Structural Reliability Methods: Methodology
We combine Bayesian networks (BNs) and structural reliability methods (SRMs)
to create a new computational framework, termed enhanced Bayesian network
(eBN), for reliability and risk analysis of engineering structures and
infrastructure. BNs are efficient in representing and evaluating complex
probabilistic dependence structures, as present in infrastructure and
structural systems, and they facilitate Bayesian updating of the model when new
information becomes available. On the other hand, SRMs enable accurate
assessment of probabilities of rare events represented by computationally
demanding, physically-based models. By combining the two methods, the eBN
framework provides a unified and powerful tool for efficiently computing
probabilities of rare events in complex structural and infrastructure systems
in which information evolves in time. Strategies for modeling and efficiently
analyzing the eBN are described by way of several conceptual examples. The
companion paper applies the eBN methodology to example structural and
infrastructure systems
FOC5-2PRIMARY HEPATOCELLULAR DAMAGE AND SUPPRESSED FAT MOBILIZATION IN HEAVY DRINKERS WITH PNPLA3 G GENOTYPE
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