160 research outputs found

    In vitro biosynthesis of ring-extended cyclosporins

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    Cytotoxicity Effects of Different Surfactant Molecules Conjugated to Carbon Nanotubes on Human Astrocytoma Cells

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    Phase contrast and epifluorescence microscopy were utilized to monitor morphological changes in human astrocytoma cells during a time-course exposure to single-walled carbon nanotube (SWCNT) conjugates with different surfactants and to investigate sub-cellular distribution of the nanotube conjugates, respectively. Experimental results demonstrate that cytotoxicity of the nanotube/surfactant conjugates is related to the toxicity of surfactant molecules attached on the nanotube surfaces. Both sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) are toxic to cells. Exposure to CNT/SDS conjugates (0.5 mg/mL) for less than 5 min caused changes in cell morphology resulting in a distinctly spherical shape compared to untreated cells. In contrast, sodium cholate (SC) and CNT/SC did not affect cell morphology, proliferation, or growth. These data indicate that SC is an environmentally friendly surfactant for the purification and dispersion of SWCNTs. Epifluorescence microscopy analysis of CNT/DNA conjugates revealed distribution in the cytoplasm of cells and did not show adverse effects on cell morphology, proliferation, or viability during a 72-h incubation. These observations suggest that the SWCNTs could be used as non-viral vectors for diagnostic and therapeutic molecules across the blood–brain barrier to the brain and the central nervous system

    The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

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    Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

    Multi-Band Bathymetry Mapping with Spiking Neuron Anomaly Detection

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    The developed method extracts bathymetry distributions from multiple satellite image bands. The automated remote sensing function is sparsely coded and combines spiking neural net anomaly filtration, spline, and multi-band fittings. Survey data were used to identify an activation threshold, decay rate, spline fittings, and multi-band weighting factors. Errors were computed for remotely sensed Landsat satellite images. Multi-band fittings achieved an average error of 25.3 cm. This proved sufficiently accurate to automatically extract shorelines to eliminate land areas in bathymetry mapping

    Multi-Band Bathymetry Mapping with Spiking Neuron Anomaly Detection

    No full text
    The developed method extracts bathymetry distributions from multiple satellite image bands. The automated remote sensing function is sparsely coded and combines spiking neural net anomaly filtration, spline, and multi-band fittings. Survey data were used to identify an activation threshold, decay rate, spline fittings, and multi-band weighting factors. Errors were computed for remotely sensed Landsat satellite images. Multi-band fittings achieved an average error of 25.3 cm. This proved sufficiently accurate to automatically extract shorelines to eliminate land areas in bathymetry mapping

    Didemnin-B Induces Cell-Death by Apoptosis - the Fastest Induction of Apoptosis Ever Described

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    Didemnin B, a cyclic N-methylated peptolide induces apoptosis in human HL-60 cells. When incubated with 1 mu M didemnin B, unsynchronized HL-60 cultures undergo apoptosis to 100% within 140 minutes. Apoptosis has been assessed by the typical apoptotic morphology, the presence of double-stranded DNA fragments within the cytosol and the generation of DNA ladders. None of these characteristics of apoptosis are seen when HL-60 cells are pretreated with 1 mM Zn2+ immediately before treatment with didemnin B. (C) 1995 Academic Press, Inc

    Neurones express glutamine synthetase when deprived of glutamine or interaction with astrocytes

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    P>Glutamine synthetase (GS) forms glutamine by catalyzing the ATP-dependent amidation of glutamate. In healthy brains, GS is restricted to astrocytes but in Alzheimer's disease and cell culture, GS has been detected in neurones

    Apoptosis induced by inhibitors of the plasma membrane NADH-oxidase involves Bcl-2 and calcineurin

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    Activation of the plasma membrane NADH-oxidoreductase (PMOR) system by addition of growth factors or extracellular electron accepters stimulates cellular proliferation, We now show that the vanilloids capsaicin, dihydrocapsaicin, and resiniferatoxin are inhibitors of the NADH-oxidase activity of the PMOR system and that both these and two previously identified PMOR inhibitors (chloroquine and retinoic acid) induce apoptosis in human B-cell and mouse myeloid cell lines. At the optimal concentration, PMOR inhibitors can induce between 50 and 70% of apoptosis in mouse myeloid and human B-cell lines within 8-12 h, provided these cell lines do not express Bcl-2. The immunosuppressants cyclosporin A and fujimycin (tacrolimus) inhibit PMOR inhibitor-induced apoptosis. By using combinations of these immunosuppressants and excess amounts of their nonimmunosuppressive analogues, we demonstrate that in human B-cell lines the Bcl-2-sensitive apoptotic pathway triggered by PMOR inhibitors involves signaling through the protein phosphatase calcineurin. We suggest that the PMOR system is a redox sensor that can, depending on the ambient redox environment and the availability of growth factors, regulate plasma membrane calcium fluxes and signal for apoptosis through calcineurin. Bcl-2, a protein that is thought to inhibit apoptosis by regulating reactive oxygen species and calcium fluxes in the cell, inhibits this apoptotic pathway
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