5,265 research outputs found

    A novel laser ranging system for measurement of ground-to-satellite distances

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    A technique was developed for improving the precision of laser ranging measurements of ground-to-satellite distances. The method employs a mode-locked laser transmitter and utilizes an image converter tube equipped with deflection plates in measuring the time of flight of the laser pulse to a distant retroreflector and back. Samples of the outgoing and returning light pulses are focussed on the photocathode of the image converter tube, whose deflection plates are driven by a high-voltage 120 MHz sine wave derived from a very stable oscillator. From the relative positions of the images produced at the output phosphor by the two light pulses, it is possible to make a precise determination of the fractional amount by which the time of flight exceeds some large integral multiple of the period of the deflection sinusoid

    A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency

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    SynGAP is a postsynaptic density (PSD) protein that binds to PDZ domains of the scaffold protein PSD-95. We previously reported that heterozygous deletion of Syngap1 in mice is correlated with increased steady-state levels of other key PSD proteins that bind PSD-95, although the level of PSD-95 remains constant (Walkup et al., 2016). For example, the ratio to PSD-95 of Transmembrane AMPA-Receptor-associated Proteins (TARPs), which mediate binding of AMPA-type glutamate receptors to PSD-95, was increased in young Syngap1+/- mice. Here we show that only females and not males show a highly significant correlation between an increase in TARP and a decrease in synGAP in the PSDs of Syngap1+/- rodents. The data reveal a sex difference in the adaptation of the PSD scaffold to synGAP haploinsufficiency

    The development of a new measure of quality of life for children with congenital cardiac disease

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    The purpose of the study was to develop a questionnaire measuring health-related R1 quality of life for children and adolescents with congenital heart disease, the ConQol, that would have both clinical and research applications. We describe here the process of construction of a questionnaire, the piloting and the development of a weighted scoring system, and data on the psychometric performance of the measure in a sample of 640 children and young people recruited via 6 regional centres for paediatric cardiology from across the United Kingdom. The ConQol has two versions, one designed for children aged from 8 to 11 years, and the other for young people aged from 12 to 16 years. Initial findings suggest that it is a valid and reliable instrument, is acceptable to respondents, and is simple to administer in both a research and clinical context

    Lifting the Mood on Treating Fragile X

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    Only a decade ago, it was believed that a genetic diagnosis of intellectual disability and autism offered little in the way of hope for a medical treatment to lessen the burden on the affected individuals and their families. However, recent research aimed at understanding the cellular and molecular mechanisms that underlie the pathogenesis of ASD has ushered in a new era of targeted treatment strategies. Studies in fragile X syndrome (FXS) have been at the forefront of this revolution, and they are forging a path that could define future approaches to the treatment of ASD

    Kaposi's sarcoma in a patient with erythroblastopenia and thymoma: Reactivation after topical corticosteroids

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    We report a 69-year-old female with erythroblastopenia and thymoma who developed lesions of Kaposi's sarcoma (KS) after thymectomy, 2 months after the initiation of therapy with methylprednisolone. Control of mucocutaneous KS lesions was obtained with radiotherapy, interferon alfa-2b and withdrawal of systemic immunosuppressive therapy. Erosive oral lichen planus appeared later, and after therapy with topical corticosteroids a new lesion of KS developed that regressed after withdrawal of topical corticosteroids. The detection of HHV-8 only in lesional skin supports the hypothesis that this virus can trigger the development of KS lesions

    FMRP sustains presynaptic function via control of activity-dependent bulk endocytosis

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    Synaptic vesicle (SV) recycling is essential for the maintenance of neurotransmission, with a number of neurodevelopmental disorders linked to defects in this process. Fragile X syndrome (FXS) results from a loss of fragile X mental retardation protein (FMRP) encoded by the FMR1 gene. Hyperexcitability of neuronal circuits is a key feature of FXS, therefore we investigated whether SV recycling was affected by the absence of FMRP during increased neuronal activity. We revealed that primary neuronal cultures from male Fmr1 knock-out (KO) rats display a specific defect in activity-dependent bulk endocytosis (ADBE). ADBE is dominant during intense neuronal activity, and this defect resulted in an inability of Fmr1 KO neurons to sustain SV recycling during trains of high-frequency stimulation. Using a molecular replacement strategy, we also revealed that a human FMRP mutant that cannot bind BK channels failed to correct ADBE dysfunction in KO neurons, however this dysfunction was corrected by BK channel agonists. Therefore, FMRP performs a key role in sustaining neurotransmitter release via selective control of ADBE, suggesting intervention via this endocytosis mode may correct the hyperexcitability observed in FXS. SIGNIFICANCE STATEMENT Loss of fragile X mental retardation protein (FMRP) results in fragile X syndrome (FXS), however whether its loss has a direct role in neurotransmitter release remains a matter of debate. We demonstrate that neurons lacking FMRP display a specific defect in a mechanism that sustains neurotransmitter release during intense neuronal firing, called activity-dependent bulk endocytosis (ADBE). This discovery provides key insights into mechanisms of brain communication that occur because of loss of FMRP function. Importantly it also reveals ADBE as a potential therapeutic target to correct the circuit hyperexcitability observed in FXS

    A New E-Professionalism/Social Media Course: Student Reflections and Impact

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    This poster provides a review of interim results from a qualitative study on first-year medical students\u27 attitudes and perceptions of their definition of medical professionalism in social media. Included in the study is an evaluation of changes in perspective since becoming a medical student and after participating in an E-Professionalism and Social Media instructional session

    Sensitive Detection and Early Prognostic Significance of p24 Antigen in Heat-Denatured Plasma of Human Immunodeficiency Virus Type 1-Infected Infants

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    Immune complex formation causes underdetection of p24 antigen in human immunodeficiencyvirus(HIV)infection.Brieflyboilingdilutedplasma releasesallcomplexedantigen, which can then be measured by some commercial assays. In a retrospective pediatric cohort study, the specificity of this procedure in 390 uninfected samples was 96.9% after initial testing and 100% after neutralization. Sensitivity among 125 postnatal infected samples was, at a detection of 2 pg/ml., 96.0% (97% neutralizable) compared with 47.7% for regular antigen (76% neutralizable), 96% for polymerase chain reaction, and 77% for viral culture. The high sensitivity and specificity of heat-denatured antigen was confirmed by prospectively testing 113 additional samples.Quantitativeanalysisofsamplesfrominfectedinfants showedlowlevelsofp24 antigen in 29% of cord blood sera, a postnatal increase to levels that were during the first 6 months of life inversely associated with survival, and persistence of antigenemia thereafter independent of clinical status. Prevalence and antigen levels were significantly lower in mothers. The persistent antigenemia in children indicates that their immune systems cannot restrict HIV expression as efficiently as those of adult
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