3,680 research outputs found

    Pharmacokinetics and antinociceptive effects of tramadol and its metabolite O-desmethyltramadol following intravenous administration in sheep

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    Although sheep are widely used as an experimental model for various surgical procedures there is a paucity of data on the pharmacokinetics and efficacy of analgesic drugs in this species. The aims of this study were to investigate the pharmacokinetics of intravenously (IV) administered tramadol and its active metabolite O-desmethyltramadol (M1) and to assess the mechanical antinociceptive effects in sheep. In a prospective, randomized, blinded study, six healthy adult sheep were given 4 and 6\u2009mg/kg tramadol and saline IV in a cross-over design with a 2-week wash-out period. At predetermined time points blood samples were collected and physiological parameters and mechanical nociceptive threshold (MNT) values were recorded. The analytical determination of tramadol and M1 was performed using high performance liquid chromatography. Pharmacokinetic parameters fitted a two- and a non-compartmental model for tramadol and M1, respectively. Normally distributed data were analysed by a repeated mixed linear model. Plasma concentration vs. time profiles of tramadol and M1 were similar after the two doses. Tramadol and M1 plasma levels decreased rapidly in the systemic circulation, with both undetectable after 6\u2009h following drug administration. Physiological parameters did not differ between groups; MNT values were not statistically significant between groups at any time point. It was concluded that although tramadol and M1 concentrations in plasma were above the human minimum analgesic concentration after both treatments, no mechanical antinociceptive effects of tramadol were reported. Further studies are warranted to assess the analgesic efficacy of tramadol in sheep

    Segmentation-Free Korean Handwriting Recognition Using Neural Network Training

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    The idea of segmentation-free handwriting recognition has been introduced within the rise of deep learning. This technique is designed to recognize any script language/symbols as long as feedable training image set exists. The VGG-16 convolutional neural network model is used as a character spotting network using Faster R-CNN. Through the process of manual tagging, the location, size, and types of recognizable symbols are provided to train the network. This approach has been tested previously on text written in the Bangla script, where it has shown over 90% of accuracy overall. For Bangla, the network is trained and tested on Boise State Bangla Handwriting dataset. For Korean, the network is trained using the PE_92 Handwritten Korean character image database and shows promising results

    Variable Intrinsic Absorption in Mrk 279

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    We examine the variability in the intrinsic absorption in the Seyfert 1 galaxy Mrk 279 using three epochs of observations from the Far Ultraviolet Spectroscopic Explorer (FUSE) and two epochs of observations with the Space Telescope Imaging Spectrograph on the Hubble Space Telescope. Rather than finding simple photoionization responses of the absorbing gas to changes in the underlying continuum, the observed changes in the absorption profiles can be understood more clearly if the effective covering fraction of the gas in all emission components, continuum and broad and intermediate velocity width emission lines, is accounted for. While we do not uniquely solve for all of these separate covering fractions and the ionic column densities using the spectral data, we examine the parameter space using previously well-constrained solutions for continuum and single emission component covering fractions. Assuming full coverage of the continuum, we find that of the two velocity components of the Mrk 279 absorption most likely associated with its outflow, one likely has zero coverage of the intermediate line region while the other does not. For each component, however, the broad line region is more fully covered than the intermediate line region. Changes in the O VI column densities are unconstrained due to saturation, but we show that small changes in the nonsaturated C IV and N V column densities are consistent with the outflow gas having zero or partial covering of the intermediate line region and an ionization parameter changing from ~0.01 to ~0.1 from 2002 to 2003 as the UV continuum flux increased by a factor of ~8. The absence of a change in the C III absorbing column density is attributed to this species arising outside the Mrk 279 outflow.Comment: 36 pages, 18 figures, accepted to Ap

    Cell-Free Synthetic Biology Platform for Engineering Synthetic Biological Circuits and Systems

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    Synthetic biology brings engineering disciplines to create novel biological systems for biomedical and technological applications. The substantial growth of the synthetic biology field in the past decade is poised to transform biotechnology and medicine. To streamline design processes and facilitate debugging of complex synthetic circuits, cell-free synthetic biology approaches has reached broad research communities both in academia and industry. By recapitulating gene expression systems in vitro, cell-free expression systems offer flexibility to explore beyond the confines of living cells and allow networking of synthetic and natural systems. Here, we review the capabilities of the current cell-free platforms, focusing on nucleic acid-based molecular programs and circuit construction. We survey the recent developments including cell-free transcription– translation platforms, DNA nanostructures and circuits, and novel classes of riboregulators. The links to mathematical models and the prospects of cell-free synthetic biology platforms will also be discussed.11Yscopu

    Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator

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    In vitro compartmentalization of biochemical reaction networks is a crucial step towards engineering artificial cell-scale devices and systems. At this scale the dynamics of molecular systems becomes stochastic, which introduces several engineering challenges and opportunities. Here we study a programmable transcriptional oscillator system that is compartmentalized into microemulsion droplets with volumes between 33 fl and 16 pl. Simultaneous measurement of large populations of droplets reveals major variations in the amplitude, frequency and damping of the oscillations. Variability increases for smaller droplets and depends on the operating point of the oscillator. Rather than reflecting the stochastic kinetics of the chemical reaction network itself, the variability can be attributed to the statistical variation of reactant concentrations created during their partitioning into droplets. We anticipate that robustness to partitioning variability will be a critical challenge for engineering cell-scale systems, and that highly parallel time-series acquisition from microemulsion droplets will become a key tool for characterization of stochastic circuit function.1172sciescopu
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