Determination of iphosphamide and seven metabolites in blood plasma,as stable trifluoroacetyl derivatives,by electron capture chemical ionization GC-MS

A method is described for the determination of the antitumor agent iphosphamide and seven of its metabolites in the plasma of cancer patients by multiple ion monitoring (MIM) GC-MS, mainly using the electron capture chemical ionization mode, of stable methyl and/or trifluoroacetyl derivatives. The metabolites determined were 2- and 3-dechloroethyliphosphamide, 4-ketoiphosphamide, carboxyiphosphamide, iphosphamide mustard, and two previously undetected metabolites, chloroethylamine and 1,3-oxazolidine-2-one. The isolation of the acidic and neutral metabolites was performed by solid phase extraction on to C₁₈ adsorbent at pH 4. The weakly acidic iphosphamide mustard, isolated under these conditions with a yield of ca 50%, was measured as a stable methyltrifluoroacetyl derivative, in contrast to the corresponding phosphoramide mustard of the isomer cyclophosphamide which decomposes during derivatization. Chloroethylamine and 1,3-oxazolidine-2-one were isolated with high yield by liquid extraction with ethyl acetate at pH 10. Selective measurement of several metabolite derivatives with similar retention times was performed by multiple ion monitoring MS of specific ion masses, using a methyl phenyl siloxane capillary column previously employed in the study of cyclophosphamide metabolites. Quantitation of metabolites in patient plasma samples could be performed in the concentration range 3 ng to 20 μg per ml of original plasma.     

Sur les valeurs propres d'un oscillateur harmonique perturbé

Sans résumé Dedicated to Professor Shmuel Agmon     

Analysis of plane and axisymmetric flows of incompressible fluids with the stream tube method: Numerical simulation by trust-region optimization algorithm

New concepts for the study of incompressible plane or axisymmetric flows are analysed by the stream tube method. Flows without eddies and pure vortex flows are considered in a transformed domain where the mapped streamlines are rectilinear or circular. The transformation between the physical domain and the computational domain is an unknown of the problem. In order to solve the non-linear set of relevant equations, we present a new algorithm based on a trust region technique which is effective for non-convex optimization problems. Experimental results show that the new algorithm is more robust compared to the Newton-Raphson method.     

Global optimization by random perturbation of the gradient method with a fixed parameter

The paper deals with the global minimization of a differentiable cost function mapping a ball of a finite dimensional Euclidean space into an interval of real numbers. It is established that a suitable random perturbation of the gradient method with a fixed parameter generates a bounded minimizing sequence and leads to a global minimum: the perturbation avoids convergence to local minima. The stated results suggest an algorithm for the numerical approximation of global minima: experiments are performed for the problem of fitting a sum of exponentials to discrete data and to a nonlinear system involving about 5000 variables. The effect of the random perturbation is examined by comparison with the purely deterministic gradient method.     

Mother-to-child transmission of HIV: a simulation-based approach for the evaluation of intervention strategies

Mother-to-child transmission (MTCT) of HIV is the most significant source of HIV infection in children below the age of 15 years. In 2000 alone, about 600 000 new infections occurred, the vast majority from mothers living in developing countries who were not aware of their HIV-positive status. To date, at least 4.3 million children have died from AIDS. In this paper, we discuss the development of an operational model that can be used to evaluate intervention options for the prevention of MTCT of HIV. The problem was approached by defining suitable pregnancy risk groups, prevention options and the required model outputs to evaluate different intervention strategies. The method chosen to approach the problem was a discrete-event, three-phase simulation, built in Visual Basic, with a stochastic semi-Markov structure. The developed model takes individual pregnant women through each stage of their pregnancy, labour and birth. Different intervention strategies may be modelled at any time, including short-course antiretroviral drugs and cessation of breastfeeding. The model is demonstrated with data from Botswana, which has one of the highest HIV-infection rates in the world.     

A kinetic Monte Carlo method on super-lattices for the study of the defect formation in the growth of close packed structures

A modified Kinetic Lattice Monte Carlo model has been developed to predict growth rate regimes and defect formation in the case of the homo-epitaxial growth of close packed crystalline structures. The model is an improvement over standard Monte Carlo algorithms, which usually retain fixed atom positions and bond partners indicative of perfect crystal lattices. Indeed, we extend the concepts of Monte Carlo growth simulations on super-lattices containing additional sites (defect sites) with respect to those of the reference material. This extension implies a reconsideration of the energetic mapping, which is extensively presented, and allows to describe a complex phenomenology that is out of accessibility of standard stochastic approaches. Results obtained using the Kawasaki and the Bond-Counting rules for the transition probability of the Monte Carlo event are discussed in details. These results demonstrate how the defect types (local or extended), the formation mechanisms and the defect generation regimes can be characterized using our approach.     

The synthesis mechanism of Ca3Al2O6 from soft mechanochemically activated precursors studied by time-resolved neutron diffraction up to 1000°C

The reaction pathway for the Ca₃Al₂O₆ formation up to 1300°C, from mechanochemically treated mixtures of amorphous aluminum hydroxide and CaCO₃, was studied in situ by differential thermal analysis, constant heating rate dilatometry and time-resolved neutron powder diffraction. The experiment was carried out, in an open system, on a sample with the nominal Ca₃Al₂O₆ stoichiometry. The results obtained by neutron diffractometry and thermal analysis were in good agreement with the data obtained by scanning electron microscopy and X-ray diffraction on heat-treated and-quenched samples. The synthesis path implied the formation of cryptocrystalline Al₂O₃, crystalline CaO, CaAl₂O₄ and Ca₁₂Al₁₄O₃₃ as transitory phases. Finally the nucleation and growth of the single phase Ca₃Al₂O₆ took place at 1300°C and exhibited porous structure due to CO₂ and H₂O release.