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.     

Shock waves in gas flows with nanoparticles

Journal of Thermal Analysis and Calorimetry - The paper focuses on the analytical analysis of the propagation of a normal shock wave in an adiabatic gas flow with nanoparticles. A modified...     

Quantum discreteness effects and flicker fluctuations in tunneling conductivity

An analysis of events in the tunneling junction shows that the interaction of one-electron processes in a many-electron system may be a source of scale-invariant low-frequency fluctuations of conductivity (the interaction consists in that the quantum probability of an electron transition depends on fast random changes in the environment in the course of the transition, including the changes caused by analogous transitions). The theory relates flicker fluctuations in the tunneling conductivity to the discrete character of the spectrum of electron states and explains the nonlinearity of the noise-current characteristic observed in nanocomposites.     

Sur le degré dynamique des transformations de Cremona du plan qui stabilisent une courbe irrationnelle non-elliptique

We show that the first dynamical degree of a Cremona transformation stabilizing an irrational non elliptic curve is 1. Moreover, among these transformations, we characterize those which have finite order. To cite this article: I. Pan, C. R. Acad. Sci. Paris, Ser. I 341 (2005).     

Modulation of the phase difference between polarization modes in single-mode fibers

Mechanisms of polarization modulation in a single-mode fiber that modulate the phase difference between polarization modes without affecting their amplitudes are considered. A coefficient that characterizes the efficiency of cylindrical piezoceramic modulators and is independent of their resonant properties is introduced. Analytical expressions for this coefficient for different modulation mechanisms are derived. The lateral pressure on the fiber is shown to provide the highest efficiency. For isotropic fibers, a modulator with a squeezing covering, which increases significantly its efficiency, is studied. For anisotropic fibers, the most appropriate way of phase difference modulation is longitudinal extension, in which case the birefringence axes do not have to be matched. In most cases, the measured and predicted efficiencies are in good correspondence.     

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.