Non-destructive imaging of buried electronic interfaces using a decelerated scanning electron beam

Recent progress in nanotechnology enables the production of atomically abrupt interfaces in multilayered junctions, allowing to increase the number of transistors in a processor, as known as Moore’s law, for example. However, uniform electron transport has never been achieved across the entire interfacial area in junctions due to the existence of local defects, causing local heating and reduction in transport efficiency. To date, junction uniformity has been predominantly assessed by cross-sectional transmission electron microscopy, which requires slicing and milling processes with potentially introducing additional damage and deformation. It is therefore essential to develop an alternative non-destructive method. Here we show a non-destructive technique using scanning electron microscopy to map buried junction properties. By controlling the electron-beam energy, we demonstrate the contrast imaging of local junction resistances at a controlled depth. This technique can be applied to any buried junctions, from conventional semiconductor and metal devices to organic devices

Sensitization of catastrophic cognition in cognitive-behavioral therapy for panic disorder

<p>Abstract</p> <p>Background</p> <p>Cognitive model of panic disorder have proposed that panic attacks result from the catastrophic misinterpretation of certain bodily sensations. Cognitive-Behavioral Therapy (CBT) for panic disorder aims to change these catastrophic cognitions. CBT intervention successfully caused reduction of catastrophic cognitions and symptomatic improvement in the majority of cases. However there are some patients who fail to modify their catastrophic cognitions or rather experience an increase in them during CBT treatment. It is clinically and theoretically important to understand about cognitive sensitization of panic disorder during CBT sessions. The purpose of the present study is 1) to clarify the baseline characteristics of panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment, and 2) to examine the course of symptomatic changes for them.</p> <p>Methods</p> <p>Of ninety-five outpatients with panic disorder started the group CBT program for treatment of panic disorder, seventy-nine completer were classified as "cognitively sensitized (CS)" or "cognitive responding (CR)" or "no-responder" according to the difference of the Agoraphobic Cognitions Questionnaire score across treatment. We compared the CS and CR patients in terms of their baseline clinical characteristics. Then we assessed the symptomatic and functional changes for both groups.</p> <p>Results</p> <p>At the start of the CBT program, despite of the same degree of panic disorder severity, CS scored significantly lower on ACQ score than CR. CS also showed significantly lower score on anticipatory anxiety compared to CR. At the end of treatment CS showed significant improvement in severity of panic disorder, although the degree of improvement was smaller than that for CR. Then CS would progressively reduce their agoraphobic fear and avoidance, and would improve their functional impairment up to three month of follow-up.</p> <p>Conclusion</p> <p>Panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment could nonetheless gradually improve. They showed a relatively low level of catastrophic cognition and anticipatory anxiety before starting the CBT program. We might conclude that temporary sensitization of catastrophic cognition may be necessary before improvement especially among those with initially low catastrophic body sensation fears and that we need not be concerned too much with temporary increase in catastrophic cognition in the process of CBT for panic disorder.</p

Ectopic PDX-1 Expression Directly Reprograms Human Keratinocytes along Pancreatic Insulin-Producing Cells Fate

BACKGROUND: Cellular differentiation and lineage commitment have previously been considered irreversible processes. However, recent studies have indicated that differentiated adult cells can be reprogrammed to pluripotency and, in some cases, directly into alternate committed lineages. However, although pluripotent cells can be induced in numerous somatic cell sources, it was thought that inducing alternate committed lineages is primarily only possible in cells of developmentally related tissues. Here, we challenge this view and analyze whether direct adult cell reprogramming to alternate committed lineages can cross the boundaries of distinct developmental germ layers. METHODOLOGY/PRINCIPAL FINDINGS: We ectopically expressed non-integrating pancreatic differentiation factors in ectoderm-derived human keratinocytes to determine whether these factors could directly induce endoderm-derived pancreatic lineage and β-cell-like function. We found that PDX-1 and to a lesser extent other pancreatic transcription factors, could rapidly and specifically activate pancreatic lineage and β-cell-like functional characteristics in ectoderm-derived human keratinocytes. Human keratinocytes transdifferentiated along the β cell lineage produced processed and secreted insulin in response to elevated glucose concentrations. Using irreversible lineage tracing for KRT-5 promoter activity, we present supporting evidence that insulin-positive cells induced by ectopic PDX-1 expression are generated in ectoderm derived keratinocytes. CONCLUSIONS/SIGNIFICANCE: These findings constitute the first demonstration of human ectoderm cells to endoderm derived pancreatic cells transdifferentiation. The study represents a proof of concept which suggests that transcription factors induced reprogramming is wider and more general developmental process than initially considered. These results expanded the arsenal of adult cells that can be used as a cell source for generating functional endocrine pancreatic cells. Directly reprogramming somatic cells into alternate desired tissues has important implications in developing patient-specific, regenerative medicine approaches

The roles of static stability and tropical – extratropical interactions in the summer interannual variability of the North Atlantic sector

Summer seasonal forecast skill in the North Atlantic sector is lower than winter skill. To identify potential controls on predictability, the sensitivity of North Atlantic baroclinicity to atmospheric drivers is quantified. Using ERA-INTERIM reanalysis data, North Atlantic storm-track baroclinicity is shown to be less sensitive to meridional temperature-gradient variability in summer. Static stability shapes the sector’s interannual variability by modulating the sensitivity of baroclinicity to variations in meridional temperature gradients and tropopause height and by modifying the baroclinicity itself. High static stability anomalies at upper levels result in more zonal extratropical cyclone tracks and higher eddy kinetic energy over the British Isles in the summertime. These static stability anomalies are not strongly related to the summer NAO; but they are correlated with the suppression of convection over the tropical Atlantic and with a poleward-shifted subtropical jet. These results suggest a non-local driver of North Atlantic variability. Furthermore, they imply that improved representations of convection over the south-eastern part of North America and the tropical Atlantic might improve summer seasonal forecast skill

The effects of juvenile stress on anxiety, cognitive bias and decision making in adulthood:a rat model

Stress experienced in childhood is associated with an increased risk of developing psychiatric disorders in adulthood. These disorders are particularly characterized by disturbances to emotional and cognitive processes, which are not currently fully modeled in animals. Assays of cognitive bias have recently been used with animals to give an indication of their emotional/cognitive state. We used a cognitive bias test, alongside a traditional measure of anxiety (elevated plus maze), to investigate the effects of juvenile stress (JS) on adulthood behaviour using a rodent model. During the cognitive bias test, animals were trained to discriminate between two reward bowls based on a stimulus (rough/smooth sandpaper) encountered before they reached the bowls. One stimulus (e.g. rough) was associated with a lower value reward than the other (e.g. smooth). Once rats were trained, their cognitive bias was explored through the presentation of an ambiguous stimulus (intermediate grade sandpaper): a rat was classed as optimistic if it chose the bowl ordinarily associated with the high value reward. JS animals were lighter than controls, exhibited increased anxiety-like behaviour in the elevated plus maze and were more optimistic in the cognitive bias test. This increased optimism may represent an optimal foraging strategy for these underweight animals. JS animals were also faster than controls to make a decision when presented with an ambiguous stimulus, suggesting altered decision making. These results demonstrate that stress in the juvenile phase can increase anxiety-like behaviour and alter cognitive bias and decision making in adulthood in a rat model

Regulation of p73 activity by post-translational modifications

The transcription factor p73 is a member of the p53 family that can be expressed as at least 24 different isoforms with pro- or anti-apoptotic attributes. The TAp73 isoforms are expressed from an upstream promoter and are regarded as bona fide tumor suppressors; they can induce cell cycle arrest/apoptosis and protect against genomic instability. On the other hand, ΔNp73 isoforms lack the N-terminus transactivation domain; hence, cannot induce the expression of pro-apoptotic genes, but still can oligomerize with TAp73 or p53 to block their transcriptional activities. Therefore, the ratio of TAp73 isoforms to ΔNp73 isoforms is critical for the quality of the response to a genomic insult and needs to be delicately regulated at both transcriptional and post-translational level. In this review, we will summarize the current knowledge on the post-translational regulatory pathways involved to keep p73 protein under control. A comprehensive understanding of p73 post-translational modifications will be extremely useful for the development of new strategies for treating and preventing cancer

Intronic Cis-Regulatory Modules Mediate Tissue-Specific and Microbial Control of angptl4/fiaf Transcription

The intestinal microbiota enhances dietary energy harvest leading to increased fat storage in adipose tissues. This effect is caused in part by the microbial suppression of intestinal epithelial expression of a circulating inhibitor of lipoprotein lipase called Angiopoietin-like 4 (Angptl4/Fiaf). To define the cis-regulatory mechanisms underlying intestine-specific and microbial control of Angptl4 transcription, we utilized the zebrafish system in which host regulatory DNA can be rapidly analyzed in a live, transparent, and gnotobiotic vertebrate. We found that zebrafish angptl4 is transcribed in multiple tissues including the liver, pancreatic islet, and intestinal epithelium, which is similar to its mammalian homologs. Zebrafish angptl4 is also specifically suppressed in the intestinal epithelium upon colonization with a microbiota. In vivo transgenic reporter assays identified discrete tissue-specific regulatory modules within angptl4 intron 3 sufficient to drive expression in the liver, pancreatic islet β-cells, or intestinal enterocytes. Comparative sequence analyses and heterologous functional assays of angptl4 intron 3 sequences from 12 teleost fish species revealed differential evolution of the islet and intestinal regulatory modules. High-resolution functional mapping and site-directed mutagenesis defined the minimal set of regulatory sequences required for intestinal activity. Strikingly, the microbiota suppressed the transcriptional activity of the intestine-specific regulatory module similar to the endogenous angptl4 gene. These results suggest that the microbiota might regulate host intestinal Angptl4 protein expression and peripheral fat storage by suppressing the activity of an intestine-specific transcriptional enhancer. This study provides a useful paradigm for understanding how microbial signals interact with tissue-specific regulatory networks to control the activity and evolution of host gene transcription

Detecting macroecological patterns in bacterial communities across independent studies of global soils

This study and participants were funded in part by ERC Adv grant 26055290 (KSR, WHvdP); BBSRC David Phillips Fellowship (BB/L02456X/1) (FTDV); ERC Grant Agreements 242658 [BIOCOM] and 647038 [BIODESERT] (FTM); the European Regional Development Fund (Centre of Excellence EcolChange) (JD); Yorkshire Agricultural Society, Nafferton Ecological Farming Group, and the Northumbria University Research Development Fund (CHO); BBSRC Training Grant (BB/K501943/1) (CH); Wallenberg Academy Fellowship (KAW 2012.0152), Formas (214-2011-788) and Vetenskapsrådet (612-2011-5444) (ED); the Glastir Monitoring & Evaluation Programme (Contract reference: C147/2010/11) and the full support of the GMEP team on the Glastir project (DLJ, SC, DAR)