487 research outputs found
Defects in SiO2 as the possible origin of near interface traps in the SiC∕SiO2 system: A systematic theoretical study
A systematic study of the level positions of intrinsic and carbon defects in SiO2 is presented, based on density functional calculations with a hybrid functional in an alpha-quartz supercell. The results are analyzed from the point of view of the near interface traps (NIT), observed in both SiC/SiO2 and Si/SiO2 systems, and assumed to have their origins in the oxide. It is shown that the vacancies and the oxygen interstitial can be excluded as the origin of such NIT, while the silicon interstitial and carbon dimers give rise to gap levels in the energy range inferred from experiments. The properties of these defects are discussed in light of the knowledge about the SiC/SiO2 interface
Chondrogenic differentiation of growth factor-stimulated precursor cells in cartilage repair tissue is associated with increased HIF-1α activity
SummaryObjectiveTo investigate the chondrogenic potential of growth factor-stimulated periosteal cells with respect to the activity of Hypoxia-inducible Factor 1α (HIF-1α).MethodsScaffold-bound autologous periosteal cells, which had been activated by Insulin-like Growth Factor 1 (IGF-1) or Bone Morphogenetic Protein 2 (BMP-2) gene transfer using both adeno-associated virus (AAV) and adenoviral (Ad) vectors, were applied to chondral lesions in the knee joints of miniature pigs. Six weeks after transplantation, the repair tissues were investigated for collagen type I and type II content as well as for HIF-1α expression. The functional role of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling on BMP-2/IGF-1-induced HIF-1α expression was assessed in vitro by employing specific inhibitors.ResultsUnstimulated periosteal cells formed a fibrous extracellular matrix in the superficial zone and a fibrocartilaginous matrix in deep zones of the repair tissue. This zonal difference was reflected by the absence of HIF-1α staining in superficial areas, but moderate HIF-1α expression in deep zones. In contrast, Ad/AAVBMP-2-stimulated periosteal cells, and to a lesser degree Ad/AAVIGF-1-infected cells, adopted a chondrocyte-like phenotype with strong intracellular HIF-1α staining throughout all zones of the repair tissue and formed a hyaline-like matrix. In vitro, BMP-2 and IGF-1 supplementation increased HIF-1α protein levels in periosteal cells, which was based on posttranscriptional mechanisms rather than de novo mRNA synthesis, involving predominantly the MEK/ERK pathway.ConclusionThis pilot experimental study on a relatively small number of animals indicated that chondrogenesis by precursor cells is facilitated in deeper hypoxic zones of cartilage repair tissue and is stimulated by growth factors which enhance HIF-1α activity
Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental Arthritis
Insulin like growth factor (IGF)-I can act on a variety of cells involved in cartilage and bone repair, yet IGF-I has not been studied extensively in the context of inflammatory arthritis. The objective of this study was to investigate whether IGF-I overexpression in the osteoblast lineage could lead to increased reparative or pathological bone formation in rheumatoid arthritis and/or spondyloarthritis respectively.status: publishe
Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients
CDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and a novel frameshift variant (c.1041dup, p.Ser348Glnfs*2) in the gene CDC14A, respectively. To evaluate the pathogenicity of both loss-of-function variants, we analyzed the effects of both variants on the RNA-level. The splice variant was characterized using a minigene assay. Altered expression levels due to the c.1041dup variant were assessed using RT-qPCR. In summary, cDNA analysis confirmed that the c.1421+2T>C variant activates a cryptic splice site, resulting in a truncated transcript (c.1414_1421del, p.Val472Leufs*20) and the c.1041dup variant results in a defective transcript that is likely degraded by nonsense-mediated mRNA decay. The present study functionally characterizes two variants and provides further confirmatory evidence that CDC14A is associated with a rare form of hereditary hearing loss
Variational Density Matrix Method for Warm Condensed Matter and Application to Dense Hydrogen
A new variational principle for optimizing thermal density matrices is
introduced. As a first application, the variational many body density matrix is
written as a determinant of one body density matrices, which are approximated
by Gaussians with the mean, width and amplitude as variational parameters. The
method is illustrated for the particle in an external field problem, the
hydrogen molecule and dense hydrogen where the molecular, the dissociated and
the plasma regime are described. Structural and thermodynamic properties
(energy, equation of state and shock Hugoniot) are presented.Comment: 26 pages, 13 figures. submitted to Phys. Rev. E, October 199
Association between High Levels of Blood Macrophage Migration Inhibitory Factor, Inappropriate Adrenal Response, and Early Death in Patients with Severe Sepsis
Background.Identification of new therapeutic targets remains an imperative goal to improve the morbidity and mortality associated with severe sepsis and septic shock. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, has recently emerged as a critical mediator of innate immunity and experimental sepsis, and it is an attractive new target for the treatment of sepsis. Methods.Circulating concentrations of MIF were measured in 2 clinical trial cohorts of 145 pediatric and adult patients who had severe sepsis or septic shock caused predominantly by infection with Neisseria meningitidis or other gram-negative bacteria, to study the kinetics of MIF during sepsis, to analyze the interplay between MIF and other mediators of sepsis or stress hormones (adrenocorticotropic hormone and cortisol), and to determine whether MIF is associated with patient outcome. Results.Circulating concentrations of MIF were markedly elevated in 96% of children and adults who had severe sepsis or septic shock, and they remained elevated for several days. MIF levels were correlated with sepsis severity scores, presence of shock, disseminated intravascular coagulation, urine output, blood pH, and lactate and cytokine levels. High levels of MIF were associated with a rapidly fatal outcome. Moreover, in meningococcal sepsis, concentrations of MIF were positively correlated with adrenocorticotropic hormone levels and negatively correlated with cortisol levels and the cortisol : adrenocorticotropic hormone ratio, suggesting an inappropriate adrenal response to sepsis. Conclusions.MIF is markedly and persistently up-regulated in children and adults with gram-negative sepsis and is associated with parameters of disease severity, with dysregulated pituitary-adrenal function in meningococcal sepsis, and with early deat
Molecular dynamics simulation for modeling plasma spectroscopy
The ion-electron coupling properties for a ion impurity in an electron gas
and for a two component plasma are carried out on the basis of a regularized
electron-ion potential removing the short-range Coulomb divergence. This work
is largely motivated by the study of radiator dipole relaxation in plasmas
which makes a real link between models and experiments. Current radiative
property models for plasmas include single electron collisions neglecting
charge-charge correlations within the classical quasi-particle approach
commonly used in this field. The dipole relaxation simulation based on
electron-ion molecular dynamics proposed here will provide means to benchmark
and improve model developments. Benefiting from a detailed study of a single
ion imbedded in an electron plasma, the challenging two-component ion-electron
molecular dynamics simulations are proven accurate. They open new possibilities
to obtain reference lineshape data.Comment: submitted for publication in the proceedings of the International
Conference on Strongly Coupled Coulomb Systems, Journal of Physics
Thermodynamics of hot dense H-plasmas: Path integral Monte Carlo simulations and analytical approximations
This work is devoted to the thermodynamics of high-temperature dense hydrogen
plasmas in the pressure region between and Mbar. In particular
we present for this region results of extensive calculations based on a
recently developed path integral Monte Carlo scheme (direct PIMC). This method
allows for a correct treatment of the thermodynamic properties of hot dense
Coulomb systems. Calculations were performed in a broad region of the
nonideality parameter and degeneracy parameter . We give a comparison with a few available results from
other path integral calculations (restricted PIMC) and with analytical
calculations based on Pade approximations for strongly ionized plasmas. Good
agreement between the results obtained from the three independent methods is
found.Comment: RevTex file, 21 pages, 5 ps-figures include
Molecular Dynamics for Fermions
The time-dependent variational principle for many-body trial states is used
to discuss the relation between the approaches of different molecular dynamics
models to describe indistinguishable fermions. Early attempts to include
effects of the Pauli principle by means of nonlocal potentials as well as more
recent models which work with antisymmetrized many-body states are reviewed
under these premises.
Keywords: Many-body theory; Fermion system; Molecular dynamics; Wave-packet
dynamics; Time-dependent variational principle; Statistical properties;
Canonical ensemble; Ergodicity; Time averagingComment: 97 pages, 13 postscript figures. To be published in July 2000 issue
of Reviews of Modern Physics. More information at http://www-aix.gsi.de/~fmd
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