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.     

A direct approach to sojourn times in a busy period of an M/M/1 queue

In this paper we present a direct approach to obtaining joint distributions of various quantities of interest in a busy period in an M/M/1 queue. These quantities are: the sojourn times and waiting times of all the customers in the busy period, the busy period length and the number of customers served in a busy period. Since the evolution of the total workload process between two successive customer arrivals is deterministic, this work gives statistic of the complete evolution of the workload process within a busy period. This work was done when the author was post doctoral fellow with the MAESTRO group at INRIA, Sophia Antipolis, France, and was supported by project no. 2900-IT-1 from the Centre Franco-Indien pour la Promotion de la Recherche Avancee (CEFIPRA).     

Advantages and Limitations of Solid Layer Experiments in Muon Catalyzed Fusion

Since the discovery that muonic deuterium at energies near a few eV could travel distances of the order of 1 mm in condensed hydrogen, and in particular that muonic tritium and muonic deuterium could emerge from the surface of a solid hydrogen layer, the advantages of solid targets have enabled the study of several processes important in muon catalyzed fusion. A review of the results is presented, emphasizing the strengths and limitations of the use of solid hydrogen layer targets. This revised version was published online in August 2006 with corrections to the Cover Date.     

Measurement of absolute photoluminescence quantum yields using integrating spheres – Which way to go?

Two common methods for recording absolute photoluminescence quantum yields using integrating spheres are discussed. These methods are developed from a theoretical standpoint, with a discussion of the assumptions made in each and their principle differences, and practical comparisons between the two are made using a range of different materials and sample types. It is shown that despite the underlying theoretical differences both methods ultimately yield very similar experimental results. Additionally, the concept of a time‐dependent quantum yield is examined and preliminary studies along these lines are presented in the form of an investigation into the photo‐oxidation of a luminescent polymer film.     

Measuring sticking and stripping in muon-catalyzed dt fusion with multilayer thin films

We propose a direct measurement of muon sticking to alpha particles in muon-catalyzed dt fusion at a high density. Exploiting the features of a multilayer thin-film target developed at TRIUMF, the sticking is determined directly by detection of charged fusion products. Experimental separation of initial sticking and stripping may become possible for the first time. Monte Carlo simulations, as well as preliminary results of test measurements are described.     

Sojourn times in (discrete) time shared systems and their continuous time limits

We study the mean sojourn times in two M/G/1 weighted round-robin systems: the weight of a customer at any given point in time in the first system is a function of its age (imparted service), while in the second system the weight is a function of the customer’s remaining processing time (RPT). We provide a sufficient condition under which the sojourn time of a customer with large service requirement (say, x) and that arrives in the steady state is close to that of a customer which starts a busy period and has the same service requirement. A sufficient condition is then provided for continuity of the performance metric (the mean sojourn time) as the quanta size in the discrete time system converges to 0. We then consider a multi-class system and provide relative ordering of the mean sojourn times among the various classes.     

Time-of-flight measurement of resonant molecular formation in muon-catalyzed dt fusion

Preliminary results are reported for an experiment at TRIUMF where a time-of-flight technique was tested for measuring the energy dependence of the rate for muon-catalyzed dt fusion. Muonic tritium atoms were created following transfer of negative muons from muonic protium in a layer of solid hydrogen (protium) containing a small fraction of tritium. The atoms escaped from the solid layer via the Ramsauer-Townsend mechanism, traversed a drift region of 18 mm, and then struck an adjacent layer of deuterium, where the muonic atom could form a molecular system. The time of detection of a fusion product (neutron or alpha) following muon arrival is dependent upon the energy of the muonic tritium atom as it traverses the drift region. By comparison of the time distribution of fusion events with a prediction based on the theoretical energy dependence of the rate, the strength of resonant formation can in principle be determined. The results extracted so far are discussed and the limitations of the method are examined.     

Interface properties of amorphous-crystalline silicon heterojunctions prepared using DC saddle-field PECVD

The planar conductance technique has been previously used in the study of amorphous silicon/crystalline silicon (a-Si:H/c-Si) heterojunctions, grown using conventional Radio Frequency Plasma Enhanced Chemical Vapor Deposition (RF-PECVD), to examine the existence of a strong inversion layer at the c-Si surface. In the present study such measurements were undertaken on a series of heterojunctions in order to provide insight into the nature of the electrical interface between the hydrogenated amorphous silicon, deposited using the DC Saddle Field PECVD system, and the underlying crystalline silicon wafer. The films showed good passivation and a strong inversion layer, indicating their amenability for device applications.