1,847 research outputs found

    A disorder to order transition accompanies catalysis in retinaldehyde dehydrogenase type II

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    Retinaldehyde dehydrogenase II (RalDH2) converts retinal to the transcriptional regulator retinoic acid in the developing embryo. The x-ray structure of the enzyme revealed an important structural difference between this protein and other aldehyde dehydrogenases of the same enzyme superfamily; a 20-amino acid span in the substrate access channel in retinaldehyde dehydrogenase II is disordered, whereas in other aldehyde dehydrogenases this region forms a well defined wall of the substrate access channel. We asked whether this disordered loop might order during the course of catalysis and provide a means for an enzyme that requires a large substrate access channel to restrict access to the catalytic machinery by smaller compounds that might potentially enter the active site and be metabolized. Our experiments, a combination of kinetic, spectroscopic, and crystallographic techniques, suggest that a disorder to order transition is linked to catalytic activity

    Performance of the ABCN-25 readout chip for the ATLAS Inner Detector Upgrade

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    We present the test results of the ABCN-25 front end chip implemented in CMOS 0.25 μm technology and optimised for the short, 2.5 cm, silicon strips intended to be used in the upgrade of the ATLAS Inner Detector. We have obtained the full functionality of the readout part, the expected performance of the analogue front-end and the operation of the power control circuits. The performance is evaluated in view of the minimization of the power consumption, as the upgrade detector may contain up to 70 million of channels. System tests with different power distribution schemes proposed for the future tracker detectors are possible with this chip. The ABCN-25 ASIC is now serving as the prototype readout chip in the developments of the modules and staves for the upgrade of the ATLAS Inner Detector

    Histidine switch controlling pH-dependent protein folding and DNA binding in a transcription factor at the core of synthetic network devices

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    © 2016 The Royal Society of Chemistry. Therapeutic strategies have been reported that depend on synthetic network devices in which a urate-sensing transcriptional regulator detects pathological levels of urate and triggers production or release of urate oxidase. The transcription factor involved, HucR, is a member of the multiple antibiotic resistance (MarR) protein family. We show that protonation of stacked histidine residues at the pivot point of long helices that form the scaffold of the dimer interface leads to reversible formation of a molten globule state and significantly attenuated DNA binding at physiological temperatures. We also show that binding of urate to symmetrical sites in each protein lobe is communicated via the dimer interface. This is the first demonstration of regulation of a MarR family transcription factor by pH-dependent interconversion between a molten globule and a compact folded state. Our data further suggest that HucR may be utilized in synthetic devices that depend on detection of pH changes

    Attitudes Towards and Limitations to ICT Use in Assisted and Independent Living Communities: Findings from a Specially-Designed Technological Intervention

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    Much literature has been devoted to theoretical explanations of the learning processes of older adults and to the methods of teaching best utilized in older populations. However, there has been less focus on the education of older adults who reside in assisted and independent living communities (AICs), especially with regards to information and communication technology (ICT) education. The purpose of this study is to determine whether participants\u27 attitudes and views towards computers and the Internet are affected as a result of participating in an eight-week training program designed to enhance computer and Internet use among older adults in such communities. Specifically, we examine if ICT education specially designed for AIC residents results in more positive attitudes towards ICTs and a perceived decrease in factors that may limit or prevent computer and Internet use. We discuss the implications of these results for enhancing the quality of life for older adults in AICs and make recommendations for those seeking to decrease digital inequality among older adults in these communities through their own ICT classes

    The HADES Tracking System

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    The tracking system of the dielectron spectrometer HADES at GSI Darmstadt is formed out of 24 low-mass, trapezoidal multi-layer drift chambers providing in total about 30 square meter of active area. Low multiple scattering in the in total four planes of drift chambers before and after the magnetic field is ensured by using helium-based gas mixtures and aluminum cathode and field wires. First in-beam performance results are contrasted with expectations from simulations. Emphasis is placed on the energy loss information, exploring its relevance regarding track recognition.Comment: 6 pages, 4 figures, presented at the 10th Vienna Conference on Instrumentation, Vienna, February 2004, to be published in NIM A (special issue

    Structure and tissue distribution of some retinoid-binding proteins

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    Vitamin A has, apart from its function in the visual pigments, general effects on several organs. Early signs of vitamin A deficiency include keratinization of epithelia and hyperkeratosis of the skin. To elucidate a generalized function for vitamin A, we have taken the approach of tracing the vitamin from its storage site in the liver via its blood transport by the retinol-binding protein (RBP) to its uptake by susceptible cells. We have also examined the intracellular occurrence of vitamin A as regards its binding to specific receptor proteins. Here we summarize data on the amino acid sequences of several vitamin A-binding proteins. The finding that CRBP and CRABP, the two intracellular proteins, are homologous to each other, to a myelin protein, and to a fatty acid-binding protein may shed light on the functions of these proteins. Retinoic acid, which binds to CRABP but not CRBP, induces differentiation of teratocarcinoma cells. This is accompanied by a lowering of the CRABP concentration, an increase of the CRBP level, and an increase in the uptake of retinol from RBP. The epidermis contains both CRBP and CRABP, and their distributions are rather similar. However, in contrast to CRBP, CRABP is most abundant in cells lining the hair follicles. CRBP occurs in greatest relative amounts in the outer layers of the epidermis. Since techniques have been developed to measure CRBP and CRABP, normal and disease-affected skin may now be explored as to quantity and cellular distribution of the retinoid-binding proteins

    Isometric force production parameters during normal and experimental low back pain conditions

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    BACKGROUND: The control of force and its between-trial variability are often taken as critical determinants of motor performance. Subjects performed isometric trunk flexion and extension forces without and with experiment pain to examine if pain yields changes in the control of trunk forces. The objective of this study is to determine if experimental low back pain modifies trunk isometric force production. METHODS: Ten control subjects participated in this study. They were required to exert 50 and 75% of their isometric maximal trunk flexion and extension torque. In a learning phase preceding the non painful and painful trials, visual and verbal feedbacks were provided. Then, subjects were asked to perform 10 trials without any feedback. Time to peak torque, time to peak torque variability, peak torque variability as well as constant and absolute error in peak torque were calculated. Time to peak and peak dF/dt were computed to determine if the first peak of dF/dt could predict the peak torque achieved. RESULTS: Absolute and constant errors were higher in the presence of a painful electrical stimulation. Furthermore, peak torque variability for the higher level of force was increased with in the presence of experimental pain. The linear regressions between peak dF/dt, time to peak dF/dt and peak torque were similar for both conditions. Experimental low back pain yielded increased absolute and constant errors as well as a greater peak torque variability for the higher levels of force. The control strategy, however, remained the same between the non painful and painful condition. Cutaneous pain affects some isometric force production parameters but modifications of motor control strategies are not implemented spontaneously. CONCLUSIONS: It is hypothesized that adaptation of motor strategies to low back pain is implemented gradually over time. This would enable LBP patients to perform their daily tasks with presumably less pain and more accuracy

    The HERA-B Ring Imaging Cherenkov Counter

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    The HERA-B RICH uses a radiation path length of 2.8 m in C_4F_10 gas and a large 24 square meters spherical mirror for imaging Cherenkov rings. The photon detector consists of 2240 Hamamatsu multi-anode photomultipliers with about 27000 channels. A 2:1 reducing two-lens telescope in front of each PMT increases the sensitive area at the expense of increased pixel size, resulting in a contribution to the resolution which roughly matches that of dispersion. The counter was completed in January of 1999, and its performance has been steady and reliable over the years it has been in operation. The design performance of the RICH was fully reached: the average number of detected photons in the RICH for a beta=1 particle was found to be 33 with a single hit resolution of 0.7 mrad and 1 mrad in the fine and coarse granularity regions, respectively.Comment: 29 pages, 23 figure
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