88 research outputs found
Deformation of polymer films by bending forces
We study the deformation of nano--scale polymer films which are subject to
external bending forces by means of computer simulation. The polymer is
represented by a generalized bead--spring--model, intended to reproduce
characteristic features of n--alkanes. The film is loaded by the action of a
prismatic blade which is pressed into the polymer bulk from above and a pair of
columns which support the film from below. The interaction between blade and
support columns and the polymer is modelled by the repulsive part of a
Lennard-Jones potential. For different system sizes as well as for different
chainlengths, this nano--scale experiment is simulated by molecular dynamics
methods. Our results allow us to give a first characterization of deformed
states for such films. We resolve the kinetic and the dynamic stage of the
deformation process in time and access the length scale between discrete
particle and continuum mechanics behaviour. For the chainlengths considered
here, we find that the deformation process is dominated by shear. We observe
strangling effects for the film and deformation fluctuations in the steady
state.Comment: 15 pages, 8 figure
Modelling of amorphous polymer surfaces in computer simulation
We study surface effects in amorphous polymer systems by means of computer
simulation. In the framework of molecular dynamics, we present two different
methods to prepare such surfaces. {\em Free} surfaces are stabilized solely by
van--der--Waals interactions whereas {\em confined} surfaces emerge in the
presence of repelling plates. The two models are compared in various computer
simulations. For free surfaces, we analyze the migration of end--monomers to
the surface. The buildup of density and pressure profiles from zero to their
bulk values depends on the surface preparation method. In the case of confined
surfaces, we find density and pressure oszillations next to the repelling
plates. We investigate the influence of surfaces on the coordination number, on
the orientation of single bonds, and on polymer end--to--end vectors.
Furthermore, different statistical methods to determine location and width of
the surface region for systems of various chain lengths are discussed and
applied. We introduce a ``height function'' and show that this method allows to
determine average surface profiles only by scanning the outermost layer of
monomers.Comment: 23 pages, 12 figure
Clinical Outcomes With a Repositionable Self-Expanding Transcatheter Aortic Valve Prosthesis: The International FORWARD Study
Background Clinical outcomes in large patient populations from real-world clinical practice with a next-generation self-expanding transcatheter aortic valve are lacking. Objectives This study sought to document the clinical and device performance outcomes of transcatheter aortic valve replacement (TAVR) with a next-generation, self-expanding transcatheter heart valve (THV) system in patients with severe symptomatic aortic stenosis (AS) in routine clinical practice. Methods The FORWARD (CoreValve Evolut R FORWARD) study is a prospective, single-arm, multinational, multicenter, observational study. An independent clinical events committee adjudicated safety endpoints based on Valve Academic Research Consortium-2 definitions. An independent echocardiographic core laboratory evaluated all echocardiograms. From January 2016 to December 2016, TAVR with the next-generation self-expanding THV was attempted in 1,038 patients with symptomatic, severe AS at 53 centers on 4 continents. Results Mean age was 81.8 ± 6.2 years, 64.9% were women, the mean Society of Thoracic Surgeons Predicted Risk of Mortality was 5.5 ± 4.5%, and 33.9% of patients were deemed frail. The repositioning feature of the THV was applied in 25.8% of patients. A single valve was implanted in the proper anatomic location in 98.9% of patients. The mean aortic valve gradient was 8.5 ± 5.6 mm Hg, and moderate or severe aortic regurgitation was 1.9% at discharge. All-cause mortality was 1.9%, and disabling stroke occurred in 1.8% at 30 days. The expected-to-observed early surgical mortality ratio was 0.35. A pacemaker was implanted in 17.5% of patients. Conclusions TAVR using the next-generation THV is clinically safe and effective for treating older patients with severe AS at increased operative risk. (CoreValve Evolut R FORWARD Study [FORWARD]; NCT02592369
Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition
SummarySmoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant
Genetic effects on gene expression across human tissues
Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas
Genetic effects on gene expression across human tissues
Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease
Recrystallised Tungsten Exposed to Simultaneous Steady State and High Pulse Number Transient Heat Loads
Recrystallised adn ITER Grade Oriented Tungsten Exposed to High Pulse Number Transient Heat Loads at Elevated Temperatures
Thermal Shock Response of Tungsten Grades at High of Tungsten rades at High Base Temperatures
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