Quantification of mephenytoin and its metabolites 4'-hydroxymephenytoin and nirvanol in human urine using a simple sample processing method

A reliable and easy to use liquid chromatography/tandem mass spectrometry (LC/MS/MS) method without the use of sample extraction was developed for the simultaneous quantification of urinary concentrations of mephenytoin, a standard phenotyping substrate for the cytochrome P450 enzyme CYP2C19, and its phase I metabolites 4'-hydroxymephenytoin and nirvanol. Fifty microL of urine were diluted with a buffered beta-glucuronidase solution and incubated at 37 degrees C for 6 h followed by addition of methanol, containing the internal standard 4'-methoxymephenytoin. The chromatographic separation was achieved using a 100 x 3 mm, 5 micro Thermo Electron Aquasil C18 column with a gradient flow, increasing the organic fraction (acetonitrile/methanol 50:50) of the mobile phase from 10 to 90%. Quantification by triple-stage mass spectrometry (TSQ Quantum, Thermo Electron) was accomplished by negative electrospray ionization in the selected reaction monitoring mode. Linearity was observed for all substances in the concentration range 15-10 000 ng/mL. The lower limit of quantification (LLOQ) was 20 ng/mL for 4'-hydroxymephenytoin and 30 ng/mL for nirvanol and mephenytoin, respectively. Intra- and inter-day inaccuracy did not exceed 9.5% for all substances from LLOQ to 10 000 ng/mL. Intra- and inter-day precision were in the range of 0.8-10.5%. The method was validated according to international ICH and FDA guidelines and successfully applied for phenotyping of Caucasian male volunteers who received an oral dose of 50 mg mephenytoin.     

Use of 19F NMR spectroscopy to screen chemical libraries for ligands that bind to proteins

Identification of compounds from chemical libraries that bind to macromolecules by use of NMR spectroscopy has gained increasing importance during recent years. A simple methodology based on (19)F NMR spectroscopy for the screening of ligands that bind to proteins, which also provides qualitative information about relative binding strengths and the presence of multiple binding sites, is presented here. A library of fluorinated compounds was assembled and investigated for binding to the two bacterial chaperones PapD and FimC, and also to human serum albumin (HSA). It was found that library members which are bound to a target protein could be identified directly from line broadening and/or induced chemical shifts in a single, one-dimensional (19)F NMR spectrum. The results obtained for binding to PapD using (19)F NMR spectroscopy agreed well with independent studies based on surface plasmon resonance, providing support for the versatility and accuracy of the technique. When the library was titrated to a solution of PapD chemical shift and linewidth changes were observed with increasing ligand concentration, which indicated the presence of several binding sites on PapD and enabled the assessment of relative binding strengths for the different ligands. Screening by (19)F NMR spectroscopy should thus be a valuable addition to existing NMR techniques for evaluation of chemical libraries in bioorganic and medicinal chemistry.     

Biharmonic map heat flow into manifolds of nonpositive curvature

Let M ^m and N be two compact Riemannian manifolds without boundary. We consider the L ² gradient flow for the energy . If and N has nonpositive sectional curvature we show that the biharmonic map heat flow exists for all time, and that the solution subconverges to a smooth harmonic map as time goes to infinity. This reproves the celebrated theorem of Eells and Sampson [6] on the existence of harmonic maps in homotopy classes for domain manifolds with dimension less than or equal to 4.Received: 27 March 2003, Accepted: 5 April 2004, Published online: 16 July 2004Mathematics Subject Classification (2000): 58E20, 58J35     

Anomalous spin dephasing in (110) GaAs quantum wells: anisotropy and intersubband effects

A strong anisotropy of electron spin decoherence is observed in GaAs/(AlGa)As quantum wells grown on a (110) oriented substrate. The spin lifetime of spins perpendicular to the growth direction is about one order of magnitude shorter compared to spins along [110]. The spin lifetimes of both spin orientations decrease monotonically above temperatures of 80 and 120 K, respectively. The decrease is very surprising for spins along the [110] direction and cannot be explained by the usual Dyakonov-Perel dephasing mechanism. A novel spin dephasing mechanism is put forward that is based on scattering of electrons between different quantum well subbands.     

Final-state interaction as the origin of the Cronin effect

The Cronin effect that refers to the enhancement of hadron spectra at intermediate p(T) with increasing A in pA collisions is traditionally explained in terms of the broadening of the parton transverse momentum in the initial state. We show that recent data on the nuclear modification factor at eta=0 for d+Au collisions can be understood in terms of the recombination of soft and shower partons in the final state. It is the centrality dependence of the soft parton density that leads to the Cronin effect.     

Non-destructive testing of tubes using a time reverse numerical simulation (TRNS) method

A method for the detection of defects in cylindrical structures and the determination of their positions and orientations is presented in this paper. The scattered field, which is generated by the interaction of excited guided waves with a defect, is evaluated with an approach named time reverse numerical simulation method (TRNS). Since the excited waves and the scattered field propagate along the sample, the time-consuming scanning of the whole tube can be eliminated. The scattered displacement field is measured in three dimensions over time with a laser vibrometer at different locations distributed equally around the circumference at a fixed axial coordinate far away from the defect. Instead of analyzing the complicated time signals directly, they are played back in time. If the recorded displacement histories of the scattered field are reversed in time and played back in an identical structure, the waves travel back the same path and interfere to a maximum at their origin. The result is an amplitude increase at the position of the defect where the scattered field was generated. Instead of playing back the recorded time signals in an experiment, this step is replaced by a numerical simulation. Only this enables the visualization and detection of the amplitude increase. As long as the simulation is of high accuracy, the position of the maximum interference corresponds exactly to the location of the defect in the experiment, although no defect is implemented in the simulation.     

Numerical simulations of pulsed and quasi-cw regimes of synchronously pumped Raman oscillators

Synchronously pumped Raman oscillators allow for an efficient frequency conversion of pump pulses whose power is well below the threshold for extracavity stimulated Raman scattering (SRS). Numerical simulations show that the cavity mismatch of pump laser and Raman oscillator is critical for maximum conversion efficiency and minimum pulse duration for transient and stationary SRS. At a certain mismatch the simulations predict a quasi-cw Raman oscillator output even at moderate cavity quality factors. Optimum operation conditions are discussed for pump pulse trains of finite lengths. The results of the numerical calculations are in qualitative agreement with a simple phenomenological model. PACS 42.55.Ye; 42.65.Dr; 42.55.Lt     

Interaction of C60 with carbon nanotubes and graphite

The interaction of C60 with single-wall carbon nanotubes (SWNTs) and graphite is studied experimentally by thermal desorption spectroscopy and theoretically by molecular-mechanics and molecular-dynamics calculations. The van der Waals parameters and force field for C60-graphene and C60-SWNT interactions are derived from the low-coverage C60 binding energy to the graphite surface. We use these to compare the efficiency of different mechanisms by which C60 can be encapsulated into SWNTs.     

Nearest-neighbor configuration in (GaIn)(NAs) probed by x-ray absorption spectroscopy

Ga(1-x)In(x)N(y)As(1-y) is a promising material system for the fabrication of inexpensive "last-mile" optoelectronic components. However, details of its atomic arrangement and the relationship to observed optical properties is not fully known. Particularly, a blueshift of emission wavelength is observed after annealing. In this work, we use x-ray absorption fine structure to study the chemical environment around N atoms in the material before and after annealing. We find that as-grown molecular beam epitaxy material consists of a nearly random distribution of atoms, while postannealed material shows segregation of In toward N. Ab initio simulations show that this short-range ordering creates a more thermodynamically stable alloy and is responsible for blueshifting the emission.