High-performance liquid chromatography and preliminary pharmacokinetics of rufloxacin and its metabolites, N-desmethylrufloxacin and rufloxacinsulfoxide, in urine of rhesus monkey Macaca mulatta.

A gradient high-performance liquid chromatographic method for the quantification of rufloxacin and two of its metabolites in urine, N-desmethylrufloxacin and rufloxacinsulfoxide, has been developed and validated. Monkey urine samples were diluted ten times with distilled water and 20 microliters were injected onto a Cp Spher 5-ODS column, 5 microns particle size. The mobile phase was a mixture of 4% acetonitrile and 96% buffer at time 0, which changed linearly over 37 min to 26% acetonitrile and 74% buffer. Detection was achieved at 246 nm. The limit of detection of the three compounds was 0.50 microgram/ml. An example of a pharmacokinetic study of rufloxacin and its metabolites in monkeys is shown.     

Viskoelastizität eines Systems mit orientierbaren Körpern

Zusammenfassung Hess (1977) folgend wird eine thermodynamische Beschreibung des viskoelastischen Verhaltens einer Flüssigkeit mit zweierlei orientierbaren, aber starren Teilchen gegeben. Viskose Strömung und Orientierung jedes Teilchentypus bringen in die Entropieproduktion je ein Glied ein, wobei die Orientierungsterme die corotierende oder Jaumannsche Ableitung der Orientationstensoren enthalten. Aus einem System gekoppelter Gleichungen, linear in den spurlosen Tensoren für Spannung, Schergeschwindigkeit und Teilchenorientierung, wurden Formeln für die (komplexe) Viskosität und die (komplexen) Normalspannungskoeffizienten bei stetiger oder periodischer Scherung, für die komplexe Viskosität auch bei paralleler Superposition beider Scherungstypen hergeleitet. Für ein binäres System, sind die Ergebnisse mit denen des corotierenden Jeffreysmodells in Einklang. Der Ausbau der Theorie mit einem Relaxationsmechanismus kann die Einschränkung auf Viskositätsabnahmen mit höchstens einem Faktor 9, welche für das Jeffreysmodell typisch ist, beseitigen. Bei Superposition mit konstanter stetiger Schergeschwindigkeit und abnehmender Frequenz verschwindet die Differenz zwischen dynamischer und nichtnewtonscher Viskosität, und das Maximum der Viskositätskurve liegt, dem Befund an Polymerlösungen widersprechend, rechts zur Kurve für periodische Scherung.Herrn Prof. Dr. F. H. Müller gewidmet.     

Charged pion production in 70 GeV/cK + p interactions

Inclusive charged pion production is studied in an exposure of BEBC, filled with hydrogen, to an incidentK ⁺ beam of 70 GeV/c. Total cross sections for pion production and inclusive longitudinal and transverse momentum distributions of π^?'s and of positive particles are presented and compared with data at lower energies. Earlier evidence for scaling in the fragmentation regions is confirmed. The central region π^? cross section increases proportionally top _LAB ^?1/4 ; positive particles show almost no energy dependence atx=0. Particle ratios π⁺/π^? are studied as a function ofx andy ^* and a comparison with 70 GeV/cK ^? p data is made. Analysis of structure functions for (ππ) pairs and of particle production associated with π^± triggers at large |x| in the context of quark/parton models, provides qualitative evidence for the diquark-quark structure of the proton.     

Conformational analysis of TMC114, a novel HIV-1 protease inhibitor

TMC114, a potent novel HIV-1 protease inhibitor, remains active against a broad spectrum of mutant viruses. In order to bind to a variety of mutants, the compound needs to make strong, preferably backbone, interactions and have enough conformational flexibility to adapt to the changing geometry of the active site. The conformational analysis of TMC114 in the gas phase yielded 43 conformers in which five types of intramolecular H-bond interactions could be observed. All 43 conformers were subject to both rigid and flexible ligand docking in the wild-type and a triple mutant (L63P/V82T/I84V) of HIV-1 protease. The largest binding energy was calculated for the conformations that are close to the conformation observed in the X-ray complexes of TMC114 and HIV-1 protease.     

A Globally Convergent Algorithm to Compute All Nash Equilibria for <Emphasis Type="Italic">n</Emphasis>-Person Games

In this paper we present an algorithm to compute all Nash equilibria for generic finite n-person games in normal form. The algorithm relies on decomposing the game by means of support-sets. For each support-set, the set of totally mixed equilibria of the support-restricted game can be characterized by a system of polynomial equations and inequalities. By finding all the solutions to those systems, all equilibria are found. The algorithm belongs to the class of homotopy-methods and can be easily implemented. Finally, several techniques to speed up computations are proposed.     

Vortex-antivortex nucleation in magnetically nanotextured superconductors: magnetic-field-driven and thermal scenarios

Within the Ginzburg-Landau formalism, we predict two novel mechanisms of vortex-antivortex nucleation in a magnetically nanostructured superconductor. Although counterintuitive, nucleation of vortex-antivortex pairs can be activated in a superconducting (SC) film covered by arrays of submicron ferromagnets (FMs) when exposed to an external homogeneous magnetic field. In another scenario, we predict the thermal induction of vortex-antivortex configurations in SC-FM samples. This phenomenon leads to a new type of Little-Parks oscillations of the FM magnetization-temperature phase boundary of the SC film.     

Crystal and molecular structure ofN-[1-(2-phenylethyl)-4-piperidinylium]-N-phenylpropanamide (fentanyl) citrate-toluene solvate

The crystal structure of fentanyl has been determined as part of a structure-activity relationship study on a congeneric series of 4-anilinopiperidines. The compound crystallizes as a citrate toluene solvate, C₂₂H₂₈N₂O · C₆H₈O₇ · C₇H₈, in the monoclinic space groupP2₁/c witha = 18.292(6),b = 9.825(4),c = 19.479(4) Å, = 107.43(3) °, andZ = 4. The structure was solved by direct methods using the program Simpel, and refined by block-diagonal least squares to anR value of 0.092. The torsion angle that describes the conformation of theN-phenyl ring relative to the piperidine ring is 123 ° and differs from that found in other 4-substituted anilinopiperidines (172–177 °).