142 research outputs found

    Assessment of Durable SiC JFET Technology for +600 C to -125 C Integrated Circuit Operation

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    Electrical characteristics and circuit design considerations for prototype 6H-SiC JFET integrated circuits (ICs) operating over the broad temperature range of -125 C to +600 C are described. Strategic implementation of circuits with transistors and resistors in the same 6H-SiC n-channel layer enabled ICs with nearly temperature-independent functionality to be achieved. The frequency performance of the circuits declined at temperatures increasingly below or above room temperature, roughly corresponding to the change in 6H-SiC n-channel resistance arising from incomplete carrier ionization at low temperature and decreased electron mobility at high temperature. In addition to very broad temperature functionality, these simple digital and analog demonstration integrated circuits successfully operated with little change in functional characteristics over the course of thousands of hours at 500 C before experiencing interconnect-related failures. With appropriate further development, these initial results establish a new technology foundation for realizing durable 500 C ICs for combustion engine sensing and control, deep-well drilling, and other harsh-environment applications

    Learning to Segment Microscopy Images with Lazy Labels

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    The need for labour intensive pixel-wise annotation is a major limitation of many fully supervised learning methods for segmenting bioimages that can contain numerous object instances with thin separations. In this paper, we introduce a deep convolutional neural network for microscopy image segmentation. Annotation issues are circumvented by letting the network being trainable on coarse labels combined with only a very small number of images with pixel-wise annotations. We call this new labelling strategy `lazy' labels. Image segmentation is stratified into three connected tasks: rough inner region detection, object separation and pixel-wise segmentation. These tasks are learned in an end-to-end multi-task learning framework. The method is demonstrated on two microscopy datasets, where we show that the model gives accurate segmentation results even if exact boundary labels are missing for a majority of annotated data. It brings more flexibility and efficiency for training deep neural networks that are data hungry and is applicable to biomedical images with poor contrast at the object boundaries or with diverse textures and repeated patterns

    Novel High Temperature Capacitive Pressure Sensor Utilizing SiC Integrated Circuit Twin Ring Oscillators

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    This paper describes initial development and testing of a novel high temperature capacitive pressure sensor system. The pressure sensor system consists of two 4H-SiC 11-stage ring oscillators and a SiCN capacitive pressure sensor. One oscillator has the capacitive pressure sensor fixed at one node in its feedback loop and varies as a function of pressure and temperature while the other provides a pressure-independent reference frequency which can be used to temperature compensate the output of the first oscillator. A two-day repeatability test was performed up to 500C on the oscillators and the oscillator fundamental frequency changed by only 1. The SiCN capacitive pressure sensor was characterized at room temperature from 0 to 300 psi. The sensor had an initial capacitance of 3.76 pF at 0 psi and 1.75 pF at 300 psi corresponding to a 54 change in capacitance. The integrated pressure sensor system was characterized from 0 to 300 psi in steps of 50 psi over a temperature range of 25 to 500C. The pressure sensor system sensitivity was 0.113 kHzpsi at 25C and 0.026 kHzpsi at 500C

    Forward Technology Solar Cell Experiment First On-Orbit Data

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    This paper presents first on orbit measured data from the Forward Technology Solar Cell Experiment (FTSCE). FTSCE is a space experiment housed within the 5th Materials on the International Space Station Experiment (MISSE-5). MISSE-5 was launched aboard the Shuttle return to flight mission (STS-114) on July 26, 2005 and deployed on the exterior of the International Space Station (ISS). The experiment will remain in orbit for nominally one year, after which it will be returned to Earth for post-flight testing and analysis. While on orbit, the experiment is designed to measure a 36 point current vs. voltage (IV) curve on each of the experimental solar cells, and the data is continuously telemetered to Earth. The experiment also measures the solar cell temperature and the orientation of the solar cells to the sun. A range of solar cell technologies are included in the experiment including state-of-the-art triple junction InGaP/GaAs/Ge solar cells from several vendors, thin film amorphous Si and CuIn(Ga)Se2 cells, and next-generation technologies like single-junction GaAs cells grown on Si wafers and metamorphic InGaP/InGaAs/Ge triple-junction cells. In addition to FTSCE, MISSE-5 also contains a Thin-Film Materials experiment. This is a passive experiment that will provide data on the effect of the space environment on more than 200 different materials. FTSCE was initially conceived in response to various on-orbit and ground test anomalies associated with space power systems. The Department of Defense (DoD) required a method of rapidly obtaining on orbit validation data for new space solar cell technologies, and NRL was tasked to devise an experiment to meet this requirement. Rapid access to space was provided by the MISSE Program which is a NASA Langley Research Center program. MISSE-5 is a completely self-contained experiment system with its own power generation and storage system and communications system. The communications system, referred to as PCSat, transmits and receives in the Amateur Radio band providing a node on the Amateur Radio Satellite Service. This paper presents an overview of the various aspects of MISSE-5 and a sample of the first measured on orbit data

    The influence of anesthetics, neurotransmitters and antibiotics on the relaxation processes in lipid membranes

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    In the proximity of melting transitions of artificial and biological membranes fluctuations in enthalpy, area, volume and concentration are enhanced. This results in domain formation, changes of the elastic constants, changes in permeability and slowing down of relaxation processes. In this study we used pressure perturbation calorimetry to investigate the relaxation time scale after a jump into the melting transition regime of artificial lipid membranes. This time corresponds to the characteristic rate of domain growth. The studies were performed on single-component large unilamellar and multilamellar vesicle systems with and without the addition of small molecules such as general anesthetics, neurotransmitters and antibiotics. These drugs interact with membranes and affect melting points and profiles. In all systems we found that heat capacity and relaxation times are related to each other in a simple manner. The maximum relaxation time depends on the cooperativity of the heat capacity profile and decreases with a broadening of the transition. For this reason the influence of a drug on the time scale of domain formation processes can be understood on the basis of their influence on the heat capacity profile. This allows estimations of the time scale of domain formation processes in biological membranes.Comment: 12 pages, 6 figure

    Recognition of Anesthetic Barbiturates by a Protein Binding Site: A High Resolution Structural Analysis

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    Barbiturates potentiate GABA actions at the GABAA receptor and act as central nervous system depressants that can induce effects ranging from sedation to general anesthesia. No structural information has been available about how barbiturates are recognized by their protein targets. For this reason, we tested whether these drugs were able to bind specifically to horse spleen apoferritin, a model protein that has previously been shown to bind many anesthetic agents with affinities that are closely correlated with anesthetic potency. Thiopental, pentobarbital, and phenobarbital were all found to bind to apoferritin with affinities ranging from 10–500 µM, approximately matching the concentrations required to produce anesthetic and GABAergic responses. X-ray crystal structures were determined for the complexes of apoferritin with thiopental and pentobarbital at resolutions of 1.9 and 2.0 Å, respectively. These structures reveal that the barbiturates bind to a cavity in the apoferritin shell that also binds haloalkanes, halogenated ethers, and propofol. Unlike these other general anesthetics, however, which rely entirely upon van der Waals interactions and the hydrophobic effect for recognition, the barbiturates are recognized in the apoferritin site using a mixture of both polar and nonpolar interactions. These results suggest that any protein binding site that is able to recognize and respond to the chemically and structurally diverse set of compounds used as general anesthetics is likely to include a versatile mixture of both polar and hydrophobic elements

    To hit or not to hit, that is the question -genome-wide structure-based druggability predictions for <i>pseudomonas aeruginosa </i>proteins

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    Pseudomonas aeruginosa is a Gram-negative bacterium known to cause opportunistic infections in immune-compromised or immunosuppressed individuals that often prove fatal. New drugs to combat this organism are therefore sought after. To this end, we subjected the gene products of predicted perturbative genes to structure-based druggability predictions using DrugPred. Making this approach suitable for large-scale predictions required the introduction of new methods for calculation of descriptors, development of a workflow to identify suitable pockets in homologous proteins and establishment of criteria to obtain valid druggability predictions based on homologs. We were able to identify 29 perturbative proteins of P. aeruginosa that may contain druggable pockets, including some of them with no or no drug-like inhibitors deposited in ChEMBL. These proteins form promising novel targets for drug discovery against P. aeruginosa

    Anaesthetic Impairment of Immune Function Is Mediated via GABAA Receptors

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    GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients.We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin.Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem

    General Anesthetics Predicted to Block the GLIC Pore with Micromolar Affinity

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    Although general anesthetics are known to modulate the activity of ligand-gated ion channels in the Cys-loop superfamily, there is at present neither consensus on the underlying mechanisms, nor predictive models of this modulation. Viable models need to offer quantitative assessment of the relative importance of several identified anesthetic binding sites. However, to date, precise affinity data for individual sites has been challenging to obtain by biophysical means. Here, the likely role of pore block inhibition by the general anesthetics isoflurane and propofol of the prokaryotic pentameric channel GLIC is investigated by molecular simulations. Microscopic affinities are calculated for both single and double occupancy binding of isoflurane and propofol to the GLIC pore. Computations are carried out for an open-pore conformation in which the pore is restrained to crystallographic radius, and a closed-pore conformation that results from unrestrained molecular dynamics equilibration of the structure. The GLIC pore is predicted to be blocked at the micromolar concentrations for which inhibition by isofluorane and propofol is observed experimentally. Calculated affinities suggest that pore block by propofol occurs at signifcantly lower concentrations than those for which inhibition is observed: we argue that this discrepancy may result from binding of propofol to an allosteric site recently identified by X-ray crystallography, which may cause a competing gain-of-function effect. Affinities of isoflurane and propofol to the allosteric site are also calculated, and shown to be 3 mM for isoflurane and for propofol; both anesthetics have a lower affinity for the allosteric site than for the unoccupied pore

    Early above- and below-ground responses of subboreal conifer seedlings to various levels of deciduous canopy removal

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    We examined the growth of understory conifers, following partial or complete deciduous canopy removal, in a field study established in two regions in Canada. In central British Columbia, we studied the responses of three species (Pseudotsuga menziesii var. glauca (Beissn.) Franco, Picea glauca (Moench) Voss x Picea engelmannii Parry ex Engelm., and Abies lasiocarpa (Hook.) Nutt.), and in northwestern Quebec, we studied one species (Abies balsamea (L.) Mill.). Stem and root diameter and height growth were measured 5 years before and 3 years after harvesting. Both root and stem diameter growth increased sharply following release but seedlings showed greater root growth, suggesting that in the short term, improvement in soil resource capture and transport, and presumably stability, may be more important than an increase in stem diameter and height growth. Response was strongly size dependent, which appears to reflect greater demand for soil resources as well as higher light levels and greater tree vigour before release for taller individuals. Growth ratios could not explain the faster response generally attributed to true fir species or the unusual swift response of spruces. Good prerelease vigour of spruces, presumably favoured by deciduous canopies, could explain their rapid response to release
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