Sensitive CE-MS method for monitoring of riociguat and desmethylriociguat levels in human serum

Riociguat is novel antihypertensive drug for treatment of pulmonary hypertension. As such, it is still being tested in many clinical and pharmacokinetic trials. Existing methods that determine serum riociguat and desmethylriociguat (DMR) are based solely on liquid chromatography with mass spectrometry. Therefore, we present a novel capillary electrophoresis with mass spectrometry method (CE-MS) for their determination in human serum as alternative method for ongoing trials. Complete resolution of both analytes was achieved by means of pH optimization of ammonium formate background electrolytes that are fully compatible with ESI/MS detection. Simple liquid-liquid extraction was used as sample pretreatment. The calibration dependence of the method was linear (in the range of 10–1000 ng/mL), with adequate accuracy (90.1–114.9%) and precision (13.4%). LOD and LOQ were arbitrarily set at 10 ng/mL for both analytes. Clinical applicability was validated using serum samples from patients treated with riociguat in pharmacokinetic study and the results corresponded with reference HPLC-MS/MS values. Capillary electrophoresis proved to be sensitive and selective tool for the analysis of riociguat and DMR.     

An unstructured mesh finite volume method for modelling saltwater intrusion into coastal aquifers

In this paper, a two-dimensional finite volume unstructured mesh method (FVUM) based on a triangular background interpolation mesh is developed for analysing the evolution of the saltwater intrusion into single and multiple coastal aquifer systems. The model formulation consists of a ground-water flow equation and a salt transport equation. These coupled and non-linear partial differential equations are transformed by FVUM into a system of differential/algebraic equations, which is solved using backward differentiation formulas of order one through five. Simulation results are compared with previously published solutions where good agreement is observed.     

Infrared picosecond absorption spectroscopy of microcrystalline silicon: separation between carrier recombination in crystalline and amorphous fractions

We have studied ultra-fast carrier dynamics of photo-excited carriers in hydrogenated microcrystalline silicon prepared by a very high frequency glow-discharge technique. We report on direct observation of two types of dynamics using selective photo-excitation in picosecond pump and probe measurements. One type of the observed dynamics has been found to be independent of the sample preparation, while the other reflects the relative weights of crystalline and amorphous fractions. We propose a simple rate-equation model that describes the carrier dynamics in microcrystalline silicon in terms of the composition of those in Si microcrystallites and in the a-Si:H tissue which surrounds the microcrystallites. The model without any fitting parameters reproduces the experimental data very well when the dynamics are scaled with relative volume fractions as obtained from Raman spectra. Received: 23 November 2000 / Accepted: 17 March 2001 / Published online: 23 May 2001     

Kinetic Models for Chemotaxis and their Drift-Diffusion Limits

Kinetic models for chemotaxis, nonlinearly coupled to a Poisson equation for the chemo-attractant density, are considered. Under suitable assumptions on the turning kernel (including models introduced by Othmer, Dunbar and Alt), convergence in the macroscopic limit to a drift-diffusion model is proven. The drift-diffusion models derived in this way include the classical Keller-Segel model. Furthermore, sufficient conditions for kinetic models are given such that finite-time-blow-up does not occur. Examples are given satisfying these conditions, whereas the macroscopic limit problem is known to exhibit finite-time-blow-up. The main analytical tools are entropy techniques for the macroscopic limit as well as results from potential theory for the control of the chemo-attractant density.Present address: Centro de Matemática e Aplicações Fundamentais, Universidade de Lisboa, Av. Prof. Gama Pinto 2, 1649-003, Lisboa, Portugal     

The linear polarization constant of R n

Summary He present work deals with estimations of the n-th linear polarization constant c(H)_n of an n-dimensional real Hilbert space H. We provide some new lower bounds on the value of sup_║y║=1 │1,y> ... n,y>│, where x₁, ... ,x_n are unit vectors in H. In particular, the results improve an earlier estimate of Marcus. However, the intriguing conjecture c(H) _n= n^n/2 remains open.     

Random oscillations in the Van der Pol system under the action of a broadband random process

We construct the second approximation for random oscillations described by the Van der Pol equation which are under the action of a broadband random process. Translated from Ukrainskii Matematicheskii Zhurnal, Vol. 50, No. 11, pp. 1517–1521, November, 1998.     

Molecular dynamics simulations of the oligonucleotide with the modified phosphate/phosphonate internucleotide linkage

Impact of the internucleotide linkage modification by inserting a methylene group to the P-O bond (—O—PO ₂ ^— —O— chain changed for —O—PO ₂ ^— —CH₂—O—), on the modified oligonucleotide binding ability to the natural DNA strand was studied by molecular dynamics simulation. Complex of (dT)₁₁ with a deoxyadenosine undecamer containing alternating modified and natural internucleotide linkage was studied as a model system. The Amber force field was completed by a set of new parameters needed to model the modified part of the nucleotide. The simulations confirmed existence of a double-helical complex the melting point of which is considerably higher than 300 K. While the thymidine (unmodified) strand possesses a B-type secondary structure, the conformation of the adenosine (modified) strand is not stable at 300 K. The -ggt conformation of the modified linkages is highly preferred, temporary jumps to the -g-gt and ggt conformations were, however, observed.