Human-Robot Control Strategies for the NASA/DARPA Robonaut

The Robotic Systems Technology Branch at the NASA Johnson Space Center (JSC) is currently developing robot systems to reduce the Extra-Vehicular Activity (EVA) and planetary exploration burden on astronauts. One such system, Robonaut, is capable of interfacing with external Space Station systems that currently have only human interfaces. Robonaut is human scale, anthropomorphic, and designed to approach the dexterity of a space-suited astronaut. Robonaut can perform numerous human rated tasks, including actuating tether hooks, manipulating flexible materials, soldering wires, grasping handrails to move along space station mockups, and mating connectors. More recently, developments in autonomous control and perception for Robonaut have enabled dexterous, real-time man-machine interaction. Robonaut is now capable of acting as a practical autonomous assistant to the human, providing and accepting tools by reacting to body language. A versatile, vision-based algorithm for matching range silhouettes is used for monitoring human activity as well as estimating tool pose

Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription

AbstractBackground: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion. Consequently, inhibition of GSK-3 activity has been proposed to play a role in the regulation of numerous signalling pathways that elicit pleiotropic cellular responses. This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3.Results: SB-216763 and SB-415286 are structurally distinct maleimides that inhibit GSK-3α in vitro, with Kis of 9 nM and 31 nM respectively, in an ATP competitive manner. These compounds inhibited GSK-3β with similar potency. However, neither compound significantly inhibited any member of a panel of 24 other protein kinases. Furthermore, treatment of cells with either compound stimulated responses characteristic of extracellular stimuli that are known to inhibit GSK-3 activity. Thus, SB-216763 and SB-415286 stimulated glycogen synthesis in human liver cells and induced expression of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells. In both cases, compound treatment was demonstrated to inhibit cellular GSK-3 activity as assessed by activation of glycogen synthase, which is a direct target of this kinase.Conclusions: SB-216763 and SB-415286 are novel, potent and selective cell permeable inhibitors of GSK-3. Therefore, these compounds represent valuable pharmacological tools with which the role of GSK-3 in cellular signalling can be further elucidated. Furthermore, development of similar compounds may be of use therapeutically in disease states associated with elevated GSK-3 activity such as non-insulin dependent diabetes mellitus and neurodegenerative disease

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Enantioselective assay for the determination of perhexiline enantiomers in human plasma by liquid chromatography

Copyright © Elsevier B.V. All rights reserved.Effective use of the antianginal agent perhexiline is difficult because saturable metabolism by the polymorphic cytochrome P450 2D6 (CYP2D6) isoform produces elevated plasma perhexiline concentrations that have been associated with serious hepatic and neurological toxicity. Perhexiline is marketed for therapeutic use as a racemate and there is evidence for differences in the disposition of its enantiomers. The current study describes an enantioselective HPLC-fluorescent method utilising pre-column derivatization with (R)-(−)-1-(1-napthyl)ethyl isocyanate. Following derivatization, the enantiomers are resolved on a C18 column with gradient elution using a mobile phase composed of methanol and water. The method described is suitable for the quantification of (+)- and (−)-perhexiline in human plasma following clinical doses and demonstrates sufficient sensitivity, accuracy and precision between 0.01 and 2.00 mg/l for each enantiomer, with intra-assay coefficients of variation and bias <20% at 0.01 mg/l and <10% at 2.00 mg/l, and inter-assay coefficients of variation and biases <15% at 0.03 mg/l and <10% at 0.40 and 0.75 mg/l. The application of this method to plasma samples collected from a patient treated with perhexiline revealed that (+)-perhexiline concentrations were higher than (−)-perhexiline concentrations, confirming the stereoselective disposition of perhexiline. The current study describes an enantioselective method that utilises pre-column formation of fluorescent diastereomers that are resolved on a C18 HPLC column using a gradient of methanol and water.Benjamin J. Davies, Megan K. Herbert, Julie A. Culbert, Simon M. Pyke, Janet K. Coller, Andrew A. Somogyi, Robert W. Milne and Benedetta C. Sallustiohttp://www.elsevier.com/wps/find/journaldescription.cws_home/643040/description#descriptio