Hydrogen-induced rupture of strained Si─O bonds in amorphous silicon dioxide

Using ab initio modeling we demonstrate that H atoms can break strained Si─O bonds in continuous amorphous silicon dioxide (a−SiO2) networks, resulting in a new defect consisting of a threefold-coordinated Si atom with an unpaired electron facing a hydroxyl group, adding to the density of dangling bond defects, such as E′ centers. The energy barriers to form this defect from interstitial H atoms range between 0.5 and 1.3 eV. This discovery of unexpected reactivity of atomic hydrogen may have significant implications for our understanding of processes in silica glass and nanoscaled silica, e.g., in porous low-permittivity insulators, and strained variants of a−SiO2

Schneditz D. Reactive hyperemia in the human liver

We tested whether hepatic blood flow is altered following central hypovolemia caused by simulated orthostatic stress. After 30 min of supine rest, hemodynamic, plasma density, and indocyanine green (ICG) clearance responses were determined during and after release of a 15-min 40 mmHg lower body negative pressure (LBNP) stimulus. Plasma density shifts and the time course of plasma ICG concentration were used to assess intravascular volume and hepatic perfusion changes. Plasma volume decreased during LBNP (Ϫ10%) as did cardiac output (Ϫ15%), whereas heart rate (ϩ14%) and peripheral resistance (ϩ17%) increased, as expected. On the basis of ICG elimination, hepatic perfusion decreased from 1.67 Ϯ 0.32 (pre-LBNP control) to 1.29 Ϯ 0.26 l/min (Ϫ22%) during LBNP. Immediately after LBNP release, we found hepatic perfusion 25% above control levels (to 2.08 Ϯ 0.48 l/min, P ϭ 0.0001). Hepatic vascular conductance after LBNP was also significantly higher than during pre-LBNP control (21.4 Ϯ 5.4 vs. 17.1 Ϯ 3.1 ml ⅐ min Ϫ1 ⅐ mmHg Ϫ1 , P Ͻ 0.0001). This indicates autoregulatory vasodilatation in response to relative ischemia during a stimulus that has cardiovascular effects similar to normal orthostasis. We present evidence for physiological post-LBNP reactive hyperemia in the human liver. Further studies are needed to quantify the intensity of this response in relation to stimulus duration and magnitude, and clarify its mechanism. hepatic; indocyanine green; orthostasis; splanchnic blood flow; autoregulation; lower body negative pressure CENTRAL HYPOVOLEMIA, AS CAUSED by blood redistribution (e.g., orthostasis) or blood loss (e.g., trauma) can be simulated by application of negative pressure to the body from the iliac crest downward (lower body "negative" pressure, LBNP), as this leads to peripheral blood pooling while avoiding additional hydrostatic effects of upright posture (14). Driven by decreased load on cardiopulmonary and eventually arterial baroreceptors, neurohumoral readjustments occur. The splanchnic vascular bed is a major regulatory target because it represents a large regional vascular conductance and constitutes the primary blood reserve in cardiovascular "emergency" situations (11) Even low (Յ20 mmHg) levels of LBNP suffice to induce sympathetic activation and reduce splanchnic perfusion (17), whereas higher stimulus levels (e.g., 50 mmHg) lower splanchnic vascular conductance as well, by as much as Ϸ30% (6, 33). Reduced perfusion has local metabolic consequences. Vascular "escape" from sympathetic influence (9, 34) and the general concept of "reactive hyperemia" (20, 31) and autoregulation (38) are well established, but hepatic reactive hyperemia as such has not yet been reported. Splanchnic ischemia is connected to hypotensive episodes especially under prolonged hypovolemic stress such as hemodialysis and ultrafiltration of excess body fluid (12, 36). We speculated whether a much shorter perturbation such as standard LBNP would also induce ischemia. We measured hepatic clearance of ICG as a surrogate for splanchnic perfusion before, during, and after LBNP and hypothesized that after LBNP-induced vasoconstriction, hepatic perfusion would not only return to but also actually exceed pre-LBNP control levels, owing to local effects of relative hypoperfusion induced metabolite accumulation that occurred during LBNP. METHODS The study was done in 14 healthy, male volunteers of moderate physical fitness, free from cardiovascular, renal, hepatic, and pulmonary diseases and not on any medication. The subjects abstained from use of tobacco, caffeine, alcohol, and heavy exercise for at least 48 h preceding each investigation and the subjects were their own controls. The Graz Medical University Research Ethics Committee approved the study protocol, and written, informed consent was obtained from each subject. Before the study, LBNP sham runs without blood sampling were carried out for familiarization to the study (24). Protocols were conducted between 9 and 12 AM to minimize circadian influences on hemodynamic variables (29). The subjects were fasting and emptied the bladder before each study. An antecubital vein was cannulated, for blood sampling and administration of ICG. Experiments were carried out in a semidark, quiet room maintained at 24°C and humidity at 55%. A padded pair of tightly connected chains was used to stabilize and maintain an exact sealing position at the exact level of the iliac crest within the LBNP box (14). The box was equipped with a footrest that was individually adjusted before LBNP was commenced. A pillow supported the head to avoid stimulation of the otolith organs, which has been reported to increase muscle sympathetic nerve activity and calf vascular resistance (21). Baseline data were collected for 30 min in the supine position, with the seal in place, before LBNP to allow for reequilibration of gravityrelated fluid shifts (16). Pressure within the box was lowered electronically by a pump within 10 s and monitored by an electronic gauge (24). LBNP (Ϫ40 mmHg) lasted for 15 min because any longer period affects LBNP tolerance (15). During LBNP the subjects were instructed to avoid movements of the lower limbs and to breathe normally. The post-LBNP observation period lasted another 15 min. The time course of the experimental protocol is shown in Blood volume and hepatic perfusion. ICG (25 mg) was injected at two times, 20 min before and 7 min into LBNP, with sufficient time between injections for ICG to be completely cleared from the blood stream. Whereas the ICG disappearance following the first injectio

Temperature and voltage dependences of the capture and emission times of individual traps in high-k dielectrics

a b s t r a c t Quantized threshold voltage (VTH) relaxation transients are observed in nano-scaled field effect transistors (FETs) after bias temperature stress. The abrupt steps are due to trapping/detrapping of individual defects in the gate oxide and indicate their characteristic emission/capture times. Individual traps are studied in n-channel SiO 2 /HfSiO FETs after positive gate stress to complement previous studies performed on SiO(N). Similarly to single SiO(N) traps, strong thermal and bias dependences of the emission and capture times are demonstrated. The high-k traps have a higher density but a reduced impact on VTH due to their separation from the channel

Chiral Quark Model with Configuration Mixing

The implications of one gluon exchange generated configuration mixing in the Chiral Quark Model ($\chi$QM$_{gcm}$) with SU(3) and axial U(1) symmetry breakings are discussed in the context of proton flavor and spin structure as well as the hyperon $\beta$-decay parameters. We find that $\chi$QM$_{gcm}$ with SU(3) symmetry breaking is able to give a satisfactory unified fit for spin and quark distribution functions, with the symmetry breaking parameters $\alpha=.4$, $\beta=.7$ and the mixing angle $\phi=20^o$, both for NMC and the most recent E866 data. In particular, the agreement with data, in the case of $G_A/G_V, \Delta_8$, F, D, $f_s$ and $f_3/f_8$, is quite striking.Comment: 16 pages, LaTex, Table and Appendix adde

SU(4) Chiral Quark Model with Configuration Mixing

Chiral quark model with configuration mixing and broken SU(3)\times U(1) symmetry has been extended to include the contribution from c\bar c fluctuations by considering broken SU(4) instead of SU(3). The implications of such a model have been studied for quark flavor and spin distribution functions corresponding to E866 and the NMC data. The predicted parameters regarding the charm spin distribution functions, for example, \Delta c, \frac{\Delta c}{{\Delta \Sigma}}, \frac{\Delta c}{c} as well as the charm quark distribution functions, for example, \bar c, \frac{2\bar c}{(\bar u+\bar d)}, \frac{2 \bar c}{(u+d)} and \frac{(c+ \bar c)}{\sum (q+\bar q)} are in agreement with other similar calculations. Specifically, we find \Delta c=-0.009, \frac{\Delta c}{{\Delta \Sigma}}=-0.02, \bar c=0.03 and \frac{(c+ \bar c)}{\sum (q+\bar q)}=0.02 for the \chiQM parameters a=0.1, \alpha=0.4, \beta=0.7, \zeta_{E866}=-1-2 \beta, \zeta_{NMC}=-2-2 \beta and \gamma=0.3, the latter appears due to the extension of SU(3) to SU(4).Comment: 10 RevTeX pages. Accepted for publication in Phys. Rev.

Presence of Epstein-Barr virus latency type III at the single cell level in post- transplantation lymphoproliferative disorders and AIDS related lymphomas

AIMS: To investigate the expression pattern of Epstein-Barr virus (EBV) latent genes at the single cell level in post-transplantation lymphoproliferative disorders and acquired immunodefiency syndrome (AIDS) related lymphomas, in relation to cellular morphology. METHODS: Nine post-transplantation lymphoproliferative disorders and three AIDS related lymphomas were subjected to immunohistochemistry using monoclonal antibodies specific for EBV nuclear antigen 1 (EBNA1) (2H4), EBNA2 (PE2 and the new rat anti-EBNA2 monoclonal antibodies 1E6, R3, and 3E9), and LMP1 (CS1-4 and S12). Double staining was performed combining R3 or 3E9 with S12. RESULTS: R3 and 3E9 anti-EBNA2 monoclonal antibodies were more sensitive than PE2, enabling the detection of more EBNA2 positive lymphoma cells. Both in post-transplantation lymphoproliferative disorders and AIDS related lymphomas, different expression patterns were detected at the single cell level. Smaller neoplastic cells were positive for EBNA2 but negative for LMP1. Larger and more blastic neoplastic cells, sometimes resembling Reed-Sternberg cells, were LMP1 positive but EBNA2 negative (EBV latency type II). Morphologically intermediate neoplastic cells coexpressing EBNA2 and LMP1 (EBV latency type III), were detected using R3 and 3E9, and formed a considerable part of the neoplastic population in four of nine post-transplantation lymphoproliferative disorders and two of three AIDS related lymphomas. All samples contained a subpopulation of small tumour cells positive exclusively for Epstein-Barr early RNA and EBNA1. The relation between cellular morphology and EBV expression patterns in this study was less pronounced in AIDS related lymphomas than in post-transplantation lymphoproliferative disorders, because the AIDS related lymphomas were less polymorphic than the post-transplantation lymphoproliferative disorders. CONCLUSIONS: In post-transplantation lymphoproliferative disorders and AIDS related lymphomas, EBV latency type III can be detected by immunohistochemistry in a subpopulation of tumour cells using sensitive monoclonal antibodies R3 and 3E9. Our data suggest that EBV infected tumour cells in these lymphomas undergo gradual changes in the expression of EBV latent genes, and that these changes are associated with changes in cellular morphology

The Influence of cis-Regulatory Elements on DNA Methylation Fidelity

It is now established that, as compared to normal cells, the cancer cell genome has an overall inverse distribution of DNA methylation (“methylome”), i.e., predominant hypomethylation and localized hypermethylation, within “CpG islands” (CGIs). Moreover, although cancer cells have reduced methylation “fidelity” and genomic instability, accurate maintenance of aberrant methylomes that underlie malignant phenotypes remains necessary. However, the mechanism(s) of cancer methylome maintenance remains largely unknown. Here, we assessed CGI methylation patterns propagated over 1, 3, and 5 divisions of A2780 ovarian cancer cells, concurrent with exposure to the DNA cross-linking chemotherapeutic cisplatin, and observed cell generation-successive increases in total hyper- and hypo-methylated CGIs. Empirical Bayesian modeling revealed five distinct modes of methylation propagation: (1) heritable (i.e., unchanged) high- methylation (1186 probe loci in CGI microarray); (2) heritable (i.e., unchanged) low-methylation (286 loci); (3) stochastic hypermethylation (i.e., progressively increased, 243 loci); (4) stochastic hypomethylation (i.e., progressively decreased, 247 loci); and (5) considerable “random” methylation (582 loci). These results support a “stochastic model” of DNA methylation equilibrium deriving from the efficiency of two distinct processes, methylation maintenance and de novo methylation. A role for cis-regulatory elements in methylation fidelity was also demonstrated by highly significant (p<2.2×10−5) enrichment of transcription factor binding sites in CGI probe loci showing heritably high (118 elements) and low (47 elements) methylation, and also in loci demonstrating stochastic hyper-(30 elements) and hypo-(31 elements) methylation. Notably, loci having “random” methylation heritability displayed nearly no enrichment. These results demonstrate an influence of cis-regulatory elements on the nonrandom propagation of both strictly heritable and stochastically heritable CGIs

Remodeling of the chromatin structure of the facioscapulohumeral muscular dystrophy (FSHD) locus and upregulation of FSHD-related gene 1 (FRG1) expression during human myogenic differentiation

<p>Abstract</p> <p>Background</p> <p>Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder associated with the partial deletion of integral numbers of 3.3 kb D4Z4 DNA repeats within the subtelomere of chromosome 4q. A number of candidate FSHD genes, adenine nucleotide translocator 1 gene (<it>ANT1</it>), FSHD-related gene 1 (<it>FRG1</it>), <it>FRG2 </it>and <it>DUX4c</it>, upstream of the D4Z4 array (FSHD locus), and double homeobox chromosome 4 (<it>DUX4</it>) within the repeat itself, are upregulated in some patients, thus suggesting an underlying perturbation of the chromatin structure. Furthermore, a mouse model overexpressing <it>FRG1 </it>has been generated, displaying skeletal muscle defects.</p> <p>Results</p> <p>In the context of myogenic differentiation, we compared the chromatin structure and tridimensional interaction of the D4Z4 array and <it>FRG1 </it>gene promoter, and <it>FRG1 </it>expression, in control and FSHD cells. The <it>FRG1 </it>gene was prematurely expressed during FSHD myoblast differentiation, thus suggesting that the number of D4Z4 repeats in the array may affect the correct timing of <it>FRG1 </it>expression. Using chromosome conformation capture (3C) technology, we revealed that the <it>FRG1 </it>promoter and D4Z4 array physically interacted. Furthermore, this chromatin structure underwent dynamic changes during myogenic differentiation that led to the loosening of the <it>FRG1</it>/4q-D4Z4 array loop in myotubes. The <it>FRG1 </it>promoter in both normal and FSHD myoblasts was characterized by H3K27 trimethylation and Polycomb repressor complex binding, but these repression signs were replaced by H3K4 trimethylation during differentiation. The D4Z4 sequences behaved similarly, with H3K27 trimethylation and Polycomb binding being lost upon myogenic differentiation.</p> <p>Conclusion</p> <p>We propose a model in which the D4Z4 array may play a critical chromatin function as an orchestrator of <it>in cis </it>chromatin loops, thus suggesting that this repeat may play a role in coordinating gene expression.</p

Use and efficacy of bone morphogenetic proteins in fracture healing

Signal transduction in aging related disease