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Bharathi Avula Babu L. Tekwani Narayan D. Chaurasiya NP Dhammika Nanayakkara Yan‐Hong Wang Shabana I. Khan Vijender R. Adelli Rajnish Sahu Mahmoud A. Elsohly James D. McChesney Ikhlas A. Khan Larry A. Walker 《Journal of mass spectrometry : JMS》2013,48(2):276-285
Therapeutic efficiency and hemolytic toxicity of primaquine (PQ), the only drug available for radical cure of relapsing vivax malaria are believed to be mediated by its metabolites. However, identification of these metabolites has remained a major challenge apparently due to low quantities and their reactive nature. Drug candidates labeled with stable isotopes afford convenient tools for tracking drug‐derived metabolites in complex matrices by liquid chromatography‐tandem mass spectrometry (LC‐MS‐MS) and filtering for masses with twin peaks attributable to the label. This study was undertaken to identify metabolites of PQ from an in vitro incubation of a 1:1 w/w mixture of 13C6‐PQ/PQ with primary human hepatocytes. Acquity ultra‐performance LC (UHPLC) was integrated with QTOF‐MS to combine the efficiency of separation with high sensitivity, selectivity of detection and accurate mass determination. UHPLC retention time, twin mass peaks with difference of 6 (originating from 13C6‐PQ/PQ), and MS‐MS fragmentation pattern were used for phenotyping. Besides carboxy‐PQ (cPQ), formed by oxidative deamination of PQ to an aldehyde and subsequent oxidation, several other metabolites were identified: including PQ alcohol, predictably generated by oxidative deamination of PQ to an aldehyde and subsequent reduction, its acetate and the alcohol's glucuronide conjugate. Trace amounts of quinone‐imine metabolites of PQ and cPQ were also detected which may be generated by hydroxylation of the PQ/cPQ quinoline ring at the 5‐position and subsequent oxidation. These findings shed additional light on the human hepatic metabolism of PQ, and the method can be applied for identification of reactive PQ metabolites generated in vivo in preclinical and clinical studies. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
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Requejo-Isidro J McGinty J Munro I Elson DS Galletly NP Lever MJ Neil MA Stamp GW French PM Kellett PA Hares JD Dymoke-Bradshaw AK 《Optics letters》2004,29(19):2249-2251
We report the development of a high-speed wide-field fluorescence-lifetime imaging (FLIM) system that provides fluorescence-lifetime images at rates of as many as 29 frames/s. A FLIM multiwell plate reader and a potentially portable FLIM endoscopic system operating at 355-nm excitation have been demonstrated. 相似文献
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John Galletly J. Fletcher und A. Percy Smith 《Fresenius' Journal of Analytical Chemistry》1881,20(1):267-268
Ohne Zusammenfassung 相似文献
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David Bushnell Gerard D. Galletly 《International Journal of Solids and Structures》1974,10(11):1271-1286
Experimental and analytical buckling pressures are presented for very carefully fabricated thin cylindrical shells with 45, 60 and 75° conical heads and for cylindrical shells with torispherical heads pierced by axisymmetric cylindrical nozzles of various thicknesses and diameters. Nonsymmetric buckling occurs at pressures for which some of the material is loading plastically in the neighborhoods of stress concentrations caused by meridional slope discontinuities. The buckling pressures for the cone-cylinder vessels are predicted within 2.6 per cent and for the pierced torispherical vessels within 4.4 per cent with use of BOSOR5, a computer program based on the finite difference energy method in which axisymmetric large deflections, nonlinear material properties and nonsymmetric bifurcation buckling are accounted for. The predicted buckling pressures of the pierced torispherical specimens are rather sensitive to details of the analytical model in the neighborhood of the juncture between the nozzle and the head. The buckling pressures of the cone-cylinder vessels can be accurately predicted by treatment of the wall material as elastic, enforcement of the full compatibility conditions at the juncture in the prebuckling analysis, and release of the rotation compatibility condition in the bifurcation (eigenvalue) analysis. 相似文献
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F. Willy Hinrichsen Erich Kindscher J. Marcusson Fendler Schneider Spence Budde Kuhn Harries C. R. Boggs S. Axelrod Hinrichsen Manasse Gasparini Frank Marckwald W. A. Ducca Gerhard Hübener Memmler Werner Esch Jules Bock Galletly Scott F. Kirchhof A. Tschirch W. Schmitz W. J. Britland H. E. Potts Weber Ditmar Paul Goldberg Frank Birkner Coolbaugb Betterton D. Spence J. Young John A. Schaeffer 《Analytical and bioanalytical chemistry》1919,58(10-11):490-504
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John Galletly 《Fresenius' Journal of Analytical Chemistry》1872,11(1):307
Ohne Zusammenfassung 相似文献
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Arnold tongues are phase-locking regions in parameter space, originally studied in circle-map models of cardiac arrhythmias. They show where a periodic system responds by synchronizing to an external stimulus. Clinical studies of resting or anesthetized patients exhibit synchronization between heart-beats and respiration. Here we show that these results are successfully modeled by a circle-map, neatly combining the phenomena of respiratory sinus arrhythmia (RSA, where inspiration modulates heart-rate) and cardioventilatory coupling (CVC, where the heart is a pacemaker for respiration). Examination of the Arnold tongues reveals that while RSA can cause synchronization, the strongest mechanism for synchronization is CVC, so that the heart is acting as a pacemaker for respiration. 相似文献
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Unsteady flow in a semi-infinite contracting or expanding pipeis reinvestigated using long series analysis. The proposed seriesmethod is useful in analysing the problem for a moderately largeconstant ( = aa/, where a = a(t), the radius of the pipe isa function of time, a(t) is the velocity of the wall, and iskinematic viscosity). For positive values of (expansion ofthe pipe) accuracy of the series representing shear stress andpressure gradient is increased from = 2.89 to = 6.0 by extractingthe singularity followed by completion of the series. For negativevalues of (contraction of the pipe), we revert the series whichresults into the increase of the region of validity of the transposedseries from = -25.0 to = -2.89. Later we use Padé approximantsfor summing them. Also, the asymptotic solution for large valuesof is obtained and it agrees closely with pure numerical valuesof shear stress at the wall and pressure gradient. 相似文献
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