Primary vertex reconstruction

This report reviews the improved method of primary vertex off-line reconstruction. The new method for primary vertex seed finding as well as modified procedure for vertex fit have been briefly described. Results of the primary vertex reconstruction performance are presented and compared to the previous version of the package. Improvement in the primary vertex reconstruction efficiencies is observed. Small but statistically significant bias, coming mostly from the long-living tracks as well as from a bias of the Velo measurements present in the DC06 simulation, affects the determination of the primary vertex position along the beam direction

The evolution of farnesoid X, vitamin D, and pregnane X receptors: insights from the green-spotted pufferfish (Tetraodon nigriviridis) and other non-mammalian species

<p>Abstract</p> <p>Background</p> <p>The farnesoid X receptor (FXR), pregnane X receptor (PXR), and vitamin D receptor (VDR) are three closely related nuclear hormone receptors in the NR1H and 1I subfamilies that share the property of being activated by bile salts. Bile salts vary significantly in structure across vertebrate species, suggesting that receptors binding these molecules may show adaptive evolutionary changes in response. We have previously shown that FXRs from the sea lamprey (<it>Petromyzon marinus</it>) and zebrafish (<it>Danio rerio</it>) are activated by planar bile alcohols found in these two species. In this report, we characterize FXR, PXR, and VDR from the green-spotted pufferfish (<it>Tetraodon nigriviridis</it>), an actinopterygian fish that unlike the zebrafish has a bile salt profile similar to humans. We utilize homology modelling, docking, and pharmacophore studies to understand the structural features of the <it>Tetraodon </it>receptors.</p> <p>Results</p> <p><it>Tetraodon </it>FXR has a ligand selectivity profile very similar to human FXR, with strong activation by the synthetic ligand GW4064 and by the primary bile acid chenodeoxycholic acid. Homology modelling and docking studies suggest a ligand-binding pocket architecture more similar to human and rat FXRs than to lamprey or zebrafish FXRs. <it>Tetraodon </it>PXR was activated by a variety of bile acids and steroids, although not by the larger synthetic ligands that activate human PXR such as rifampicin. Homology modelling predicts a larger ligand-binding cavity than zebrafish PXR. We also demonstrate that VDRs from the pufferfish and Japanese medaka were activated by small secondary bile acids such as lithocholic acid, whereas the African clawed frog VDR was not.</p> <p>Conclusions</p> <p>Our studies provide further evidence of the relationship between both FXR, PXR, and VDR ligand selectivity and cross-species variation in bile salt profiles. Zebrafish and green-spotted pufferfish provide a clear contrast in having markedly different primary bile salt profiles (planar bile alcohols for zebrafish and sterically bent bile acids for the pufferfish) and receptor selectivity that matches these differences in endogenous ligands. Our observations to date present an integrated picture of the co-evolution of bile salt structure and changes in the binding pockets of three nuclear hormone receptors across the species studied.</p

Microsystems, Space Qualified Electronics and Mobile Sensor Platforms for Harsh Environment Applications and Planetary Exploration

NASA Glenn Research Center is presently developing and applying a range of sensor and electronic technologies that can enable future planetary missions. These include space qualified instruments and electronics, high temperature sensors for Venus missions, mobile sensor platforms, and Microsystems for detection of a range of chemical species and particulates. A discussion of each technology area and its level of maturity is given. It is concluded that there is a strong need for low power devices which can be mobile and provide substantial characterization of the planetary environment where and when needed. While a given mission will require tailoring of the technology for the application, basic tools which can enable new planetary missions are being developed

Yearlong 500 C Operational Demonstration of Up-Scaled 4H-SiC JFET Integrated Circuits

This work describes recent progress in the design, processing, and testing of significantly up-scaled 500 C durable 4H-SiC junction field effect transistor (JFET) integrated circuit (IC) technology with two-level interconnect undergoing development at NASA Glenn Research Center. For the first time, stable electrical operation of semiconductor ICs for over one year at 500 C in air atmosphere is reported. These groundbreaking durability results were attained on two-level interconnect JFET demonstration ICs with 175 or more transistors on each chip. This corresponds to a more than 7-fold increase in 500 C-durable circuit complexity from the 24 transistor ring oscillator ICs reported at HiTEC 2016. These results advance the technology foundation for realizing long-term durable 500 C ICs with increased functional capability for combustion engine sensing and control, planetary exploration, deep-well drilling monitoring, and other harsh-environment applications

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

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

6H-SiC Transistor Integrated Circuits Demonstrating Prolonged Operation at 500 C

The NASA Glenn Research Center is developing very high temperature semiconductor integrated circuits (ICs) for use in the hot sections of aircraft engines and for Venus exploration where ambient temperatures are well above the approximately 300 degrees Centigrade effective limit of silicon-on-insulator IC technology. In order for beneficial technology insertion to occur, such transistor ICs must be capable of prolonged operation in such harsh environments. This paper reports on the fabrication and long-term 500 degrees Centigrade operation of 6H-SiC integrated circuits based on epitaxial 6H-SiC junction field effect transistors (JFETs). Simple analog amplifier and digital logic gate ICs have now demonstrated thousands of hours of continuous 500 degrees Centigrade operation in oxidizing air atmosphere with minimal changes in relevant electrical parameters. Electrical characterization and modeling of transistors and circuits at temperatures from 24 degrees Centigrade to 500 degrees Centigrade is also described. Desired analog and digital IC functionality spanning this temperature range was demonstrated without changing the input signals or power supply voltages

Long-Term Characterization of 6H-SiC Transistor Integrated Circuit Technology Operating at 500 C

NASA has been developing very high temperature semiconductor integrated circuits for use in the hot sections of aircraft engines and for Venus exploration. This paper reports on long-term 500 C electrical operation of prototype 6H-SiC integrated circuits based on epitaxial 6H-SiC junction field effect transistors (JFETs). As of this writing, some devices have surpassed 4000 hours of continuous 500 C electrical operation in oxidizing air atmosphere with minimal change in relevant electrical parameters

Stable Electrical Operation of 6H-SiC JFETs and ICs for Thousands of Hours at 500 C

The fabrication and testing of the first semiconductor transistors and small-scale integrated circuits (ICs) to achieve up to 3000 h of stable electrical operation at 500 C in air ambient is reported. These devices are based on an epitaxial 6H-SiC junction field-effect transistor process that successfully integrated high temperature ohmic contacts, dielectric passivation, and ceramic packaging. Important device and circuit parameters exhibited less than 10% of change over the course of the 500 C operational testing. These 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

Challenges Predicting Ligand-Receptor Interactions of Promiscuous Proteins: The Nuclear Receptor PXR

Transcriptional regulation of some genes involved in xenobiotic detoxification and apoptosis is performed via the human pregnane X receptor (PXR) which in turn is activated by structurally diverse agonists including steroid hormones. Activation of PXR has the potential to initiate adverse effects, altering drug pharmacokinetics or perturbing physiological processes. Reliable computational prediction of PXR agonists would be valuable for pharmaceutical and toxicological research. There has been limited success with structure-based modeling approaches to predict human PXR activators. Slightly better success has been achieved with ligand-based modeling methods including quantitative structure-activity relationship (QSAR) analysis, pharmacophore modeling and machine learning. In this study, we present a comprehensive analysis focused on prediction of 115 steroids for ligand binding activity towards human PXR. Six crystal structures were used as templates for docking and ligand-based modeling approaches (two-, three-, four- and five-dimensional analyses). The best success at external prediction was achieved with 5D-QSAR. Bayesian models with FCFP_6 descriptors were validated after leaving a large percentage of the dataset out and using an external test set. Docking of ligands to the PXR structure co-crystallized with hyperforin had the best statistics for this method. Sulfated steroids (which are activators) were consistently predicted as non-activators while, poorly predicted steroids were docked in a reverse mode compared to 5α-androstan-3β-ol. Modeling of human PXR represents a complex challenge by virtue of the large, flexible ligand-binding cavity. This study emphasizes this aspect, illustrating modest success using the largest quantitative data set to date and multiple modeling approaches

Yearlong 500 C Operational Demonstration of Up-Scaled 4H-SiC JFET Integrated Circuits

This work describes recent progress in the design, processing, upscaling, and testing of 500C durable two-level interconnect 4H-SiC JFET IC technology undergoing development at NASA Glenn Research Center. For the first time, stable electrical operation of semiconductor ICs for 1 year (8760 hours) at 500C in air atmosphere is reported. These groundbreaking durability results were attained on two-level interconnect JFET demonstration ICs with 175 or more transistors on each chip. This corresponds to a more than 7-fold increase in 500C-durable circuit complexity from the 24 transistor ring oscillator ICs reported at HiTEC 2016