1,754 research outputs found

    An Efficient, Green Chemical Synthesis of the Malaria\ud Drug, Piperaquine

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    To provide a robust, efficient synthesis of the malaria drug piperaquine for potential use in resource-poor settings. We used in-process analytical technologies (IPAT; HPLC) and a program of experiments to develop a synthesis of piperaquine that avoids the presence of a toxic impurity in the API and is optimized for overall yield and operational simplicity. A green-chemical synthesis of piperaquine is described that proceeds in 92 – 93 % overall yield. The chemistry is robust and provides very pure piperaquine tetraphosphate salt (> 99.5 %). The overall process utilizes modest amounts (about 8 kg/kg) of 2-propanol and ethyl acetate as the only organic materials not incorporated into the API; roughly 60 % of this waste can be recycled into the production process. This process also completely avoids the formation of a toxic impurity commonly seen in piperaquine that is otherwise difficult to remove. An efficient synthesis of piperaquine is described that may be useful for application in resource-poor settings as a means of expanding access to and reducing the cost of ACTs

    Long-term outcomes of patients undergoing endovascular infrainguinal interventions with single-vessel peroneal artery runoff

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    ObjectivesRecent reports have shown promising early results after endovascular revascularization (percutaneous transluminal angioplasty [PTA]/stent) of patients with peroneal artery-only runoff (PAOR), although the long-term durability is unclear. This study evaluated long-term primary patency and limb salvage of PTA/stent in patients with single-vessel runoff and critical limb ischemia to determine if the peroneal artery yields inferior results.MethodsFrom January 2002 to December 2007, 1075 infrainguinal PTA/stent procedures were performed in 920 patients. The study cohort comprised 201 limbs in 187 patients with single-vessel runoff and critical limb ischemia. End points included primary patency, assisted patency, limb salvage, and survival. Long-term outcomes were determined by Kaplan-Meier life-table and multivariate Cox regression analyses.ResultsThere were 104 PAOR and 97 limbs with single-vessel posterior or anterior tibial artery runoff (non-PAOR). Median follow-up was 25 months (range, 0-75 months). PAOR patients tended to be older (77.36 ± 0.92 vs 72.65 ± 1.18 years, P = .002) and were more likely to be taking clopidogrel at presentation (88% vs 76%; P = .04). There were no statistically significant differences in 5-year primary patency (26% ± 6.8% vs 30% ± 7.6%; P = .79), assisted patency (75% ± 8.8% vs 81% ± 7.0%; P = .77), limb salvage (74% ± 8.0% vs 75% ± 7.1%; P = .47), and survival (38% ± 7.7% vs 47% ± 6.6%; P = .99) between the PAOR and the non-PAOR groups, respectively. On Cox regression multivariate analysis, total occlusions predicted decreased assisted patency (hazard ratio, 2.99; 95% confidence interval, 1.21-7.41; P = .02), whereas younger age predicted poor limb salvage (hazard ratio, 0.97; 95% confidence interval, 0.94-0.99; P = .04). PAOR was not an independent predictor of any outcome on multivariate analysis.ConclusionsPatients with PAOR have similar long-term outcomes to patients with non-PAOR. Thus, infrainguinal endovascular revascularization can be considered a first-line therapy for patients with PAOR and critical limb ischemia

    Performance of the Center-Of-Curvature Optical Assembly During Cryogenic Testing of the James Webb Space Telescope

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    The James Webb Space Telescope (JWST) primary mirror (PM) is 6.6 meters in diameter and consists of 18 hexagonal segments, each 1.5 meters point-to-point. Each segment has a 6 degree-of-freedom hexapod actuation system and a radius-of-curvature (ROC) actuation system. The full telescope was tested at its cryogenic operating temperature at Johnson Space Center (JSC) in 2017. This testing included center-of-curvature measurements of the PM wavefront error using the Center-of-Curvature Optical Assembly (COCOA), along with the Absolute Distance Meter Assembly (ADMA). The COCOA included an interferometer, a reflective null, an interferometer-null calibration system, coarse and fine alignment systems, and two displacement measuring interferometer systems. A multiple-wavelength interferometer was used to enable alignment and phasing of the PM segments. By combining measurements at two laser wavelengths, synthetic wavelengths up to 15 millimeters could be achieved, allowing mirror segments with millimeter-level piston errors to be phased to the nanometer level. The ADMA was used to measure and set the spacing between the PM and the focus of the COCOA null (i.e., the PM center-of-curvature) for determination of the ROC. This paper describes the COCOA, the PM test setup, the testing performed, the test results, and the performance of the COCOA in aligning & phasing the PM segments and measuring the final PM wavefront error

    The CMS Integration Grid Testbed

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    The CMS Integration Grid Testbed (IGT) comprises USCMS Tier-1 and Tier-2 hardware at the following sites: the California Institute of Technology, Fermi National Accelerator Laboratory, the University of California at San Diego, and the University of Florida at Gainesville. The IGT runs jobs using the Globus Toolkit with a DAGMan and Condor-G front end. The virtual organization (VO) is managed using VO management scripts from the European Data Grid (EDG). Gridwide monitoring is accomplished using local tools such as Ganglia interfaced into the Globus Metadata Directory Service (MDS) and the agent based Mona Lisa. Domain specific software is packaged and installed using the Distrib ution After Release (DAR) tool of CMS, while middleware under the auspices of the Virtual Data Toolkit (VDT) is distributed using Pacman. During a continuo us two month span in Fall of 2002, over 1 million official CMS GEANT based Monte Carlo events were generated and returned to CERN for analysis while being demonstrated at SC2002. In this paper, we describe the process that led to one of the world's first continuously available, functioning grids.Comment: CHEP 2003 MOCT01

    Intermediate filaments of zebrafish retinal and optic nerve astrocytes and Müller glia: differential distribution of cytokeratin and GFAP

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    <p>Abstract</p> <p>Background</p> <p>Optic nerve regeneration (ONR) following injury is a model for central nervous system regeneration. In zebrafish, ONR is rapid - neurites cross the lesion and enter the optic tectum within 7 days; in mammals regeneration does not take place unless astrocytic reactivity is suppressed. Glial fibrillary acidic protein (GFAP) is used as a marker for retinal and optic nerve astrocytes in both fish and mammals, even though it has long been known that astrocytes of optic nerves in many fish, including zebrafish, express cytokeratins and not GFAP. We used immunofluorescence to localize GFAP and cytokeratin in wild-type zebrafish and transgenic zebrafish expressing green fluorescent protein (GFP) under control of a GFAP promoter to determine the pattern of expression of intermediate filaments in retina and optic nerve.</p> <p>Findings</p> <p>GFAP labeling and GFAP gene expression as indicated by GFP fluorescence was found only in the Müller glial cells of the retina. Within Müller cells, GFP fluorescence filled the entire cell while GFAP labelling was more restricted in distribution. No GFAP expression was observed in optic nerves. Cytokeratin labeling of astrocytes was observed throughout the optic nerve and less intensely in cells in the retinal inner plexiform layer. The retinal inner limiting membrane was strongly labeled by anti-cytokeratin.</p> <p>Conclusions</p> <p>Studies of astrocyte function during ONR in zebrafish cannot solely rely on GFAP as an astrocyte marker or indicator of reactivity. Future studies of ONR in zebrafish should include evaluation of changes in cytokeratin expression and localization in the optic nerve.</p
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