Origin of trap assisted tunnelling in ammonia annealed SiC trench MOSFETs

The interface between silicon carbide (SiC) and silicon dioxide (SiO2) is of considerable importance for the performance and reliability of 4H-SiC (trench) metal oxide semiconductor field effect transistors (MOSFETs) and various different post oxidation anneals (POAs) have been used to optimize its quality. Whereas nitric oxide (NO) POA leads to very reliable and well performing MOSFETs, ammonia (NH3) can further improve the device performance, however, at the cost of the gate oxide (GOX) reliability, e.g. leading to trap assisted tunneling (TAT). We investigate the origin of TAT and GOX leakage in differently annealed gate oxides experimentally, using 4H-SiC trench MOSFETs, and theoretically, using Density Functional Theory (DFT) simulations. Our findings reinforce the view that the NO anneal for SiC devices results in the best overall quality as devices annealed in NH3 and nitrogen N2 show higher oxide charge density and leakage currents. DFT simulations demonstrate that, contrary to what has often been assumed so far, NH3 annealing leads to the formation of additional hydrogen related defects, which open leakage paths in the oxide otherwise not present in NO treated oxides

The Glass Transition Temperature of Water: A Simulation Study

We report a computer simulation study of the glass transition for water. To mimic the difference between standard and hyperquenched glass, we generate glassy configurations with different cooling rates and calculate the $T$ dependence of the specific heat on heating. The absence of crystallization phenomena allows us, for properly annealed samples, to detect in the specific heat the simultaneous presence of a weak pre-peak (``shadow transition''), and an intense glass transition peak at higher temperature. We discuss the implications for the currently debated value of the glass transition temperature of water. We also compare our simulation results with the Tool-Narayanaswamy-Moynihan phenomenological model.Comment: submitted to Phys. Re

Design of small molecule-responsive microRNAs based on structural requirements for Drosha processing

MicroRNAs (miRNAs) are prevalent regulatory RNAs that mediate gene silencing and play key roles in diverse cellular processes. While synthetic RNA-based regulatory systems that integrate regulatory and sensing functions have been demonstrated, the lack of detail on miRNA structure–function relationships has limited the development of integrated control systems based on miRNA silencing. Using an elucidated relationship between Drosha processing and the single-stranded nature of the miRNA basal segments, we developed a strategy for designing ligand-responsive miRNAs. We demonstrate that ligand binding to an aptamer integrated into the miRNA basal segments inhibits Drosha processing, resulting in titratable control over gene silencing. The generality of this control strategy was shown for three aptamer–small molecule ligand pairs. The platform can be extended to the design of synthetic miRNAs clusters, cis-acting miRNAs and self-targeting miRNAs that act both in cis and trans, enabling fine-tuning of the regulatory strength and dynamics. The ability of our ligand-responsive miRNA platform to respond to user-defined inputs, undergo regulatory performance tuning and display scalable combinatorial control schemes will help advance applications in biological research and applied medicine

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

Productive osseous changes about the wrist in rheumatoid arthritis

Radiographs of 225 consecutive patients with adult-form rheumatoid arthritis were examined for evidence of productive osseous changes about the wrist. The prevalence of new bone on the ulnar styloid was 10%. This form of new bone is probably due to overlying chronic tenosynovitis. A collar of new bone around the ulnar head is a result of degenerative change in the distal radioulnar joint. In general, productive osseous changes in rheumatoid arthritis may represent inflammatory periosteal bone formation, osteophytosis, or contact remodeling. We found no evidence of an association between diffuse idiopathic skeletal hyperostosis and extensive productive osseous changes in patients with rheumatoid arthritis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46784/1/256_2004_Article_BF00350967.pd

Gastric Emphysema: An Etiologic Classification

I Gas within the wall of the stomach is a rare radiologic finding. The stomach has been the least often reported site of intramural gas in the hollow viscera. Based on etiology, gas in the wall of the stomach can be classified as either gastric emphysema or emphysematous gastritis. Gastric emphysema may be classified into traumatic, pulmonary or obstructive types depending upon the mechanism and pathogenesis. Three cases of gastric emphysema, each of different etiology, are presented to emphasize the subclassification of gastric emphysema. The clinical and prognostic significance of this classification is emphasized.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72543/1/j.1440-1673.1984.tb02363.x.pd

Characterisation of development and electrophysiological mechanisms underlying rhythmicity of the avian lymph heart

Despite significant advances in tissue engineering such as the use of scaffolds, bioreactors and pluripotent stem cells, effective cardiac tissue engineering for therapeutic purposes has remained a largely intractable challenge. For this area to capitalise on such advances, a novel approach may be to unravel the physiological mechanisms underlying the development of tissues that exhibit rhythmic contraction yet do not originate from the cardiac lineage. Considerable attention has been focused on the physiology of the avian lymph heart, a discrete organ with skeletal muscle origins yet which displays pacemaker properties normally only found in the heart. A functional lymph heart is essential for avian survival and growth in ovo. The histological nature of the lymph heart is similar to skeletal muscle although molecular and bioelectrical characterisation during development to assess mechanisms that contribute towards lymph heart contractile rhythmicity have not been undertaken. A better understanding of these processes may provide exploitable insights for therapeutic rhythmically contractile tissue engineering approaches in this area of significant unmet clinical need. Here, using molecular and electrophysiological approaches, we describe the molecular development of the lymph heart to understand how this skeletal muscle becomes fully functional during discrete in ovo stages of development. Our results show that the lymph heart does not follow the normal transitional programme of myogenesis as documented in most skeletal muscle, but instead develops through a concurrent programme of precursor expansion, commitment to myogenesis and functional differentiation which offers a mechanistic explanation for its rapid development. Extracellular electrophysiological field potential recordings revealed that the peak-to-peak amplitude of electrically evoked local field potentials elicited from isolated lymph heart were significantly reduced by treatment with carbachol; an effect that could be fully reversed by atropine. Moreover, nifedipine and cyclopiazonic acid both significantly reduced peak-to-peak local field potential amplitude. Optical recordings of lymph heart showed that the organ’s rhythmicity can be blocked by the HCN channel blocker, ZD7288; an effect also associated with a significant reduction in peak-to-peak local field potential amplitude. Additionally, we also show that isoforms of HCN channels are expressed in avian lymph heart. These results demonstrate that cholinergic signalling and L-type Ca2+ channels are important in excitation and contraction coupling, while HCN channels contribute to maintenance of lymph heart rhythmicity