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

Biological embedding of childhood adversity: from physiological mechanisms to clinical implications

Background: Adverse psychosocial exposures in early life, namely experiences such as child maltreatment, caregiver stress or depression, and domestic or community violence, have been associated in epidemiological studies with increased lifetime risk of adverse outcomes, including diabetes, heart disease, cancers, and psychiatric illnesses. Additional work has shed light on the potential molecular mechanisms by which early adversity becomes “biologically embedded” in altered physiology across body systems. This review surveys evidence on such mechanisms and calls on researchers, clinicians, policymakers, and other practitioners to act upon evidence. Observations Childhood psychosocial adversity has wide-ranging effects on neural, endocrine, immune, and metabolic physiology. Molecular mechanisms broadly implicate disruption of central neural networks, neuroendocrine stress dysregulation, and chronic inflammation, among other changes. Physiological disruption predisposes individuals to common diseases across the life course. Conclusions: Reviewed evidence has important implications for clinical practice, biomedical research, and work across other sectors relevant to public health and child wellbeing. Warranted changes include increased clinical screening for exposures among children and adults, scale-up of effective interventions, policy advocacy, and ongoing research to develop new evidence-based response strategies

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

A Phenomenological Description of (\pi^{-}\Delta^{++}) Photo- and Electroproduction in Nucleon Resonance Region

The (\pi^{-}\Delta^{++}) production on the nucleon by real and virtual photons is discussed as initial step in a simple model approach for the two pion photo- and electroproduction on the nucleon, with emphasis on nucleon resonance excitation which is of interest for new facilities like TJNAF. A calculation for (\pi^{-}\Delta^{++}) channel in resonance excitation region is presented and compared to existing experimental data along with a discussion of physical effects that we find to be of relevance. The calculation is proposed as a starting basis for the investigation of (N^{*}) electromagnetic form factors using experimental data about two pion production by real and virtual photons.Comment: 36 pages, 14 figures, to be published in Nucl. Phys.

Glycogene Expression Alterations Associated with Pancreatic Cancer Epithelial-Mesenchymal Transition in Complementary Model Systems

The ability to selectively detect and target cancer cells that have undergone an epithelial-mesenchymal transition (EMT) may lead to improved methods to treat cancers such as pancreatic cancer. The remodeling of cellular glycosylation previously has been associated with cell differentiation and may represent a valuable class of molecular targets for EMT.As a first step toward investigating the nature of glycosylation alterations in EMT, we characterized the expression of glycan-related genes in three in-vitro model systems that each represented a complementary aspect of pancreatic cancer EMT. These models included: 1) TGFβ-induced EMT, which provided a look at the active transition between states; 2) a panel of 22 pancreatic cancer cell lines, which represented terminal differentiation states of either epithelial-like or mesenchymal-like; and 3) actively-migrating and stationary cells, which provided a look at the mechanism of migration. We analyzed expression data from a list of 587 genes involved in glycosylation (biosynthesis, sugar transport, glycan-binding, etc.) or EMT. Glycogenes were altered at a higher prevalence than all other genes in the first two models (p<0.05 and <0.005, respectively) but not in the migration model. Several functional themes were shared between the induced-EMT model and the cell line panel, including alterations to matrix components and proteoglycans, the sulfation of glycosaminoglycans; mannose receptor family members; initiation of O-glycosylation; and certain forms of sialylation. Protein-level changes were confirmed by Western blot for the mannose receptor MRC2 and the O-glycosylation enzyme GALNT3, and cell-surface sulfation changes were confirmed using Alcian Blue staining.Alterations to glycogenes are a major component of cancer EMT and are characterized by changes to matrix components, the sulfation of GAGs, mannose receptors, O-glycosylation, and specific sialylated structures. These results provide leads for targeting aggressive and drug resistant forms of pancreatic cancer cells

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

Effects of nitridation on SiC/SiO2 structures studied by hard X-ray photoelectron spectroscopy

SiC is set to enable a new era in power electronics impacting a wide range of energy technologies, from electric vehicles to renewable energy. Its physical characteristics outperform silicon in many aspects, including band gap, breakdown field, and thermal conductivity. The main challenge for further development of SiC-based power semiconductor devices is the quality of the interface between SiC and its native dielectric SiO$_2$. High temperature nitridation processes can improve the interface quality and ultimately the device performance immensely, but the underlying chemical processes are still poorly understood. Here, we present an energy-dependent hard X-ray photoelectron spectroscopy (HAXPES) study probing non-destructively SiC and SiO$_2$ and their interface in device stacks treated in varying atmospheres. We successfully combine laboratory- and synchrotron-based HAXPES to provide unique insights into the chemistry of interface defects and their passivation through nitridation processes

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