165 research outputs found

    Selective Visualization of Fluorescent Sterols in Caenorhabditis elegans by Bleach-Rate-Based Image Segmentation

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    The nematode Caenorhabditis elegans is a genetically tractable model organism to investigate sterol transport. In vivo imaging of the fluorescent sterol, dehydroergosterol (DHE), is challenged by C. elegans' high autofluorescence in the same spectral region as emission of DHE. We present a method to detect DHE selectively, based on its rapid bleaching kinetics compared to cellular autofluorescence. Worms were repeatedly imaged on an ultraviolet-sensitive wide field (UV-WF) microscope, and bleaching kinetics of DHE were fitted on a pixel-basis to mathematical models describing the intensity decay. Bleach-rate constants were determined for DHE in vivo and confirmed in model membranes. Using this method, we could detect enrichment of DHE in specific tissues like the nerve ring, the spermateca and oocytes. We confirm these results in C. elegans gut-granule-loss (glo) mutants with reduced autofluorescence and compare our method with three-photon excitation microscopy of sterol in selected tissues. Bleach-rate-based UV-WF imaging is a useful tool for genetic screening experiments on sterol transport, as exemplified by RNA interference against the rme-2 gene coding for the yolk receptor and for worm homologues of Niemann-Pick C disease proteins. Our approach is generally useful for identifying fluorescent probes in the presence of high cellular autofluorescence

    Terahertz emission by diffusion of carriers and metal-mask dipole inhibition of radiation

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    Terahertz (THz) radiation can be generated by ultrafast photo-excitation of carriers in a semiconductor partly masked by a gold surface. A simulation of the effect taking into account the diffusion of carriers and the electric field shows that the total net current is approximately zero and cannot account for the THz radiation. Finite element modelling and analytic calculations indicate that the THz emission arises because the metal inhibits the radiation from part of the dipole population, thus creating an asymmetry and therefore a net current. Experimental investigations confirm the simulations and show that metal-mask dipole inhibition can be used to create THz emitters.Comment: 9 pages, 5 figures; Fixed figure

    Projection Postulate and Atomic Quantum Zeno Effect

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    The projection postulate has been used to predict a slow-down of the time evolution of the state of a system under rapidly repeated measurements, and ultimately a freezing of the state. To test this so-called quantum Zeno effect an experiment was performed by Itano et al. (Phys. Rev. A 41, 2295 (1990)) in which an atomic-level measurement was realized by means of a short laser pulse. The relevance of the results has given rise to controversies in the literature. In particular the projection postulate and its applicability in this experiment have been cast into doubt. In this paper we show analytically that for a wide range of parameters such a short laser pulse acts as an effective level measurement to which the usual projection postulate applies with high accuracy. The corrections to the ideal reductions and their accumulation over n pulses are calculated. Our conclusion is that the projection postulate is an excellent pragmatic tool for a quick and simple understanding of the slow-down of time evolution in experiments of this type. However, corrections have to be included, and an actual freezing does not seem possible because of the finite duration of measurements.Comment: 25 pages, LaTeX, no figures; to appear in Phys. Rev.

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    'Biomedical nemesis? Critical deliberations with regard health and social care integration for social work with older people’

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    This document is the Accepted Manuscript version of a published work that appeared in final form in International Social Work. To access the final edited and published work see http://dx.doi.org/10.1177/0020872816651698.This paper questions ongoing moves towards integration into health care for social work with older people in the UK. Whilst potentially constructing clearer pathways to support integration risks reducing welfare provisions for a traditional low priority user group, while further extending privatisation. Integration models also understate the ideological impact of biomedical perspectives within health and social care domains, conflate roles and undermine the potential positive role of ‘holistic’ multi-agency care. Constructive social work for older people is likely to further dilute within aggressive integrated models of welfare: which will be detrimental for meeting many of the complex needs of ageing populations

    Bio-analytical Assay Methods used in Therapeutic Drug Monitoring of Antiretroviral Drugs-A Review

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