142 research outputs found

    Academic leadership: changing conceptions, identities and experiences in UK Higher Education

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    © Leadership Foundation for Higher EducationThis report presents the findings from a research project on academic leadership in UK higher education. The overall aim of this project was to explore and understand ‘academic leadership’ that relates directly to the core academic functions of teaching, research and service (including academic administration and outreach), as distinct from managerial aspects of leading higher education institutions (HEIs) such as financial and strategic planning, marketing and human resource management (HRM).Leadership Foundation for Higher Educatio

    The FIREBIRD Instrument for Relativistic Electrons: Enabling Technologies for a Fast High-Sensitivity, Low-Power Space Weather Radiation Payload

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    Miniaturized instrument payloads on small satellite and nanosatellite platforms that are deployed in low Earth orbit are demonstrating cost effective weather monitoring platforms with increased temporal and spatial resolution compared to larger weather satellites. The NASA Earth Decadal Survey [1] states that improving the revisit time of microwave radiometers would significantly improve weather forecasting. Radiometers such as the Advanced Technology Microwave Sounder (ATMS) on Suomi National Polar-orbiting Partnership (Suomi-NPP) and the Joint Polar Satellite System-1 (JPSS-1), now NOAA-20, provide an average revisit rate of 7.6 hours; however, a constellation of six CubeSats in three orbital Low Earth Orbit (LEO) planes with microwave radiometers such as the Time-Resolved Observations of Precipitations structure and storm Intensity with a Constellation of Smallsats (TROPICS) mission would provide a refresh rate of better than 60 minutes. In order to effectively use CubeSats in a constellation as a weather monitoring platform, calibration must be used to provide measurements consistent with state of the art measurements, such as ATMS that has a NeDT at 300K of 0.5-3.0K [2]. In this work, we use the Joint Center for Satellite Data Assimilation (JCSDA) Community Radiative Transfer Model (CRTM) to simulate brightness temperatures (https://www.jcsda.noaa.gov/projects_crtm.php), which are used to assess miniaturized microwave radiometer radiometric biases. CRTM is a fast radiative transfer model that uses Fortran functions, structure variables, and coefficient data of the modeled sensor to simulate radiances. The user inputs surface characteristics, scan angles, and atmospheric profiles from sources such as radiosondes, Numerical Weather Prediction (NWP) models, and Global Positioning System Radio Occultation (GPSRO) measurements. The output of CRTM is a simulated brightness temperature that is used to correct radiometric biases in order to meet required instrument NeDT performance. We use radiosonde, GPSRO, and NWP ERA-5 atmospheric profiles in CRTM and compare the results to ATMS brightness temperatures and find an average difference in brightness temperature of 1.95 K, which is comparable to ATMS Integrated Calibration/Validation System (https://www.star.nesdis.noaa.gov/icvs/status_NPP_ATMS.php) reports which show channel bias variations of up to 2 K. We take a similar approach to provide calibration for the Micro-sized Microwave Atmospheric Satellite-2A (MicroMAS-2A), a 3U CubeSat that was launched on January 11th, 2018. MicroMAS-2A carries a 1U 10-channel passive microwave radiometer that provides imagery near 90 and 206 GHz, temperature sounding near 118 GHz, and moisture sounding near 183 GHz. We develop an approach for comparing MicroMas-2A brightness temperatures to radiosonde, GPSRO, and NWP ERA5 atmospheric profiles. Due to the scarcity of GPSRO and radiosonde profiles near the MicroMAS-2A data segments, we determine that NWP models will be the best option for radiance validation. After the next stage of calibration of MicroMAS-2A is completed, we will compare CRTM simulated radiances from ERA profiles to the initial sensor data, with expected results of channel bias variations of \u3c 2 K

    Temperature and electrolyte optimization of the α-hemolysin latch sensing zone for detection of base modification in double-stranded DNA

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    The latch region of the wild-type protein pore α-hemolysin (α-HL) constitutes a sensing zone for individual abasic sites (and furan analogs) in double-stranded DNA (dsDNA). The presence of an abasic site or furan within a DNA duplex, electrophoretically captured in the α-HL vestibule and positioned at the latch region, can be detected based on the current blockage prior to duplex unzipping. We investigated variations in blockage current as a function of temperature (12–35°C) and KCl concentration (0.15–1.0 M) to understand the origin of the current signature and to optimize conditions for identifying the base modification. In 1 M KCl solution, substitution of a furan for a cytosine base in the latch region results in an ∼8 kJ mol−1 decrease in the activation energy for ion transport through the protein pore. This corresponds to a readily measured ∼2 pA increase in current at room temperature. Optimal resolution for detecting the presence of a furan in the latch region is achieved at lower KCl concentrations, where the noise in the measured blockage current is significantly lower. The noise associated with the blockage current also depends on the stability of the duplex (as measured from the melting temperature), where a greater noise in the measured blockage current is observed for less stable duplexes

    Determining the neurotransmitter concentration profile at active synapses

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    Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

    Hydrodynamic properties of cyclodextrin molecules in dilute solutions

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    Three well-known representatives of the cyclodextrin family were completely characterized by molecular hydrodynamics methods in three different solvents. For the first time the possibility of an estimation of velocity sedimentation coefficients s between 0.15 and 0.5 S by the numerical solution of the Lamm equation is shown. Comparison of the experimental hydrodynamic characteristics of the cyclodextrins with theoretical calculations for toroidal molecules allows an estimation of the thickness of the solvent layers on the surface of cyclodextrin molecules

    The Effects of NR2 Subunit-Dependent NMDA Receptor Kinetics on Synaptic Transmission and CaMKII Activation

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    N-Methyl-d-aspartic acid (NMDA) receptors are widely expressed in the brain and are critical for many forms of synaptic plasticity. Subtypes of the NMDA receptor NR2 subunit are differentially expressed during development; in the forebrain, the NR2B receptor is dominant early in development, and later both NR2A and NR2B are expressed. In heterologous expression systems, NR2A-containing receptors open more reliably and show much faster opening and closing kinetics than do NR2B-containing receptors. However, conflicting data, showing similar open probabilities, exist for receptors expressed in neurons. Similarly, studies of synaptic plasticity have produced divergent results, with some showing that only NR2A-containing receptors can drive long-term potentiation and others showing that either subtype is capable of driving potentiation. In order to address these conflicting results as well as open questions about the number and location of functional receptors in the synapse, we constructed a Monte Carlo model of glutamate release, diffusion, and binding to NMDA receptors and of receptor opening and closing as well as a model of the activation of calcium-calmodulin kinase II, an enzyme critical for induction of synaptic plasticity, by NMDA receptor-mediated calcium influx. Our results suggest that the conflicting data concerning receptor open probabilities can be resolved, with NR2A- and NR2B-containing receptors having very different opening probabilities. They also support the conclusion that receptors containing either subtype can drive long-term potentiation. We also are able to estimate the number of functional receptors at a synapse from experimental data. Finally, in our models, the opening of NR2B-containing receptors is highly dependent on the location of the receptor relative to the site of glutamate release whereas the opening of NR2A-containing receptors is not. These results help to clarify the previous findings and suggest future experiments to address open questions concerning NMDA receptor function

    The role of neutralizing antibodies in prevention of HIV-1 infection: what can we learn from the mother-to-child transmission context?

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    International audienceIn most viral infections, protection through existing vaccines is linked to the presence of vaccine-induced neutralizing antibodies (NAbs). However, more than 30 years after the identification of AIDS, the design of an immunogen able to induce antibodies that would neutralize the highly diverse HIV-1 variants remains one of the most puzzling challenges of the human microbiology. The role of antibodies in protection against HIV-1 can be studied in a natural situation that is the mother-to-child transmission (MTCT) context. Indeed, at least at the end of pregnancy, maternal antibodies of the IgG class are passively transferred to the fetus protecting the neonate from new infections during the first weeks or months of life. During the last few years, strong data, presented in this review, have suggested that some NAbs might confer protection toward neonatal HIV-1 infection. In cases of transmission, it has been shown that the viral population that is transmitted from the mother to the infant is usually homogeneous, genetically restricted and resistant to the maternal HIV-1-specific antibodies. Although the breath of neutralization was not associated with protection, it has not been excluded that NAbs toward specific HIV-1 strains might be associated with a lower rate of MTCT. A better identification of the antibody specificities that could mediate protection toward MTCT of HIV-1 would provide important insights into the antibody responses that would be useful for vaccine development. The most convincing data suggesting that NAbs migh confer protection against HIV-1 infection have been obtained by experiments of passive immunization of newborn macaques with the first generation of human monoclonal broadly neutralizing antibodies (HuMoNAbs). However, these studies, which included only a few selected subtype B challenge viruses, provide data limited to protection against a very restricted number of isolates and therefore have limitations in addressing the hypervariability of HIV-1. The recent identification of highly potent second-generation cross-clade HuMoNAbs provides a new opportunity to evaluate the efficacy of passive immunization to prevent MTCT of HIV-1

    The costs and effects of introducing selectively trained radiographers to an A&E reporting service: a retrospective controlled before and after study

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    The costs and effects of introducing selectively trained radiographers reporting accident and emergency (A&E) radiographs of the appendicular skeleton in a district general hospital were assessed using a retrospective controlled before and after design. Reference standard reports were compared with a random stratified sample of 200 A&E and 200 general practitioner (GP) reports before and after the intervention. GP reports were used as a non-intervention, non-equivalent control group. An A&E specialist registrar judged whether incorrect A&E reports might have a clinically important effect on patient management. The effect of incorrect A&E reports on outcome was assessed by patient re-attendance to the hospital because of missed abnormalities. The annual, average and incremental costs of radiographers and radiologists reporting A&E radiographs were calculated and a sensitivity analysis was undertaken. The introduction of the radiographers resulted in a 1% (95% CI –7.9 to 5.9) fall in A&E radiograph reporting accuracy and 11% (95% CI –33.7 to 11.3) reduction of cases in which incorrect A&E reports might have a clinically important effect on patient management. Only two A&E reports (one before and one after the intervention) affected patient outcome in that a fracture missed at the first visit resulted in patient re-attendance to the X-ray Department. There was a saving of £361 per annum to the X-ray Department. In conclusion this study provides further evidence that selectively trained radiographers can accurately report A&E plain radiographs and at no additional cost
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