Profiling primaquine metabolites in primary human hepatocytes using UHPLC‐QTOF‐MS with 13C stable isotope labeling

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.     

Soliton-sound interactions in quasi-one-dimensional Bose-Einstein condensates

Longitudinal confinement of dark solitons in quasi-one-dimensional Bose-Einstein condensates leads to sound emission and reabsorption. We perform quantitative studies of the dynamics of a soliton oscillating in a tight dimple trap, embedded in a weaker harmonic trap. The dimple depth provides a sensitive handle to control the soliton-sound interaction. In the limit of no reabsorption, the power radiated is found to be proportional to the soliton acceleration squared. An experiment is proposed to detect sound emission as a change in amplitude and frequency of soliton oscillations.     

The stochastic Gross-Pitaevskii equation and some applications

The stochastic Gross-Pitaevskii equation represents a versatile approach for studying the dynamics of trapped degenerate ultracold Bose gases in the presence of large phase and density fluctuations. Following a brief review of the original formulation of Stoof, which highlights the benefits of this approach and its relation to alternative theories, we present selected applications for the dynamics of effectively one-dimensional systems, and briefly discuss the generalization to two-dimensional systems, highlighting certain potential pitfalls in their numerical implementations.     

Basis-dependent dynamics of trapped Bose-Einstein condensates and analogies with semi-classical laser theory

We present a consistent second order perturbation theory for the lowest-lying condensed modes of very small, weakly-interacting Bose-Einstein condensates in terms of bare particle eigenstates in a harmonic trap. After presenting our general approach, we focus on explicit expressions for a simple three-level system, mainly in order to discuss the analogy of a single condensate occupying two modes of a trap with the semi-classical theory for two-mode photon lasers. A subsequent renormalization of the single-particle energies to include the dressing imposed by mean fields demonstrates clearly the consistency of our treatment with other kinetic approaches. Received 14 December 2001     

Controlled vortex-sound interactions in atomic Bose-Einstein condensates

The low temperature dynamics of a vortex in a trapped quasi-two-dimensional Bose-Einstein condensate are studied quantitatively. Precession of an off-centered vortex in a dimple trap, embedded in a weaker harmonic trap, leads to the emission of sound in a dipolar radiation pattern. Sound emission and reabsorption can be controlled by varying the depth of the dimple. In a shallow dimple, the power emitted is proportional to the vortex acceleration-squared over the precession frequency, whereas for a deep dimple, periodic sound reabsorption stabilizes the vortex against radiation-induced decay.     

Computer extended series solution for unsteady flow in a contracting or expanding pipe

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.     

Parametric driving of dark solitons in atomic Bose-Einstein condensates

A dark soliton oscillating in an elongated harmonically confined atomic Bose-Einstein condensate continuously exchanges energy with the sound field. Periodic optical paddles are employed to controllably enhance the sound density and transfer energy to the soliton, analogous to parametric driving. In the absence of damping, the amplitude of the soliton oscillations can be dramatically reduced, whereas with damping, a driven soliton equilibrates as a stable soliton with lower energy, thereby extending the soliton lifetime up to the lifetime of the condensate.