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...     

Study of radical methyl methacrylate-methacrylic acid copolymerization in isopropyl alcohol by dynamic laser scattering and C-NMR spectroscopy

The copolymerization of methyl methacrylate and methacrylic acid in isopropyl alcohol is studied by kinetic, dynamic laser scattering and ¹³C-NMR methods. Correlations are established between the dependence of the copolymerization rate, the apparent average molecular weight, the diffusion coefficients and the configurational triad composition on the monomer feed. These correlations and the fact that both copolymerization constants are smaller than unity (r_MMA = 0.63 ± 0.03; r_MA = 0.25 ± 0.05) are in good agreement with the assumption that a comonomer complex takes part in the propagation reaction. A new Markov chain method for the estimation of the configurational triad mole fraction which accounts for the complex participation in a macromolecule formation is developed. Qualitative criteria for evidence the participation of the comonomer complex in copolymerization are proposed using experimental and terminal model calculated mole fractions of the compositional triads and diads.     

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).     

Cyclic Hypomonotonicity,Cyclic Submonotonicity,and Integration

Rockafellar has shown that the subdifferentials of convex functions are always cyclically monotone operators. Moreover, maximal cyclically monotone operators are necessarily operators of this type, since one can construct explicitly a convex function, which turns out to be unique up to a constant, whose subdifferential gives back the operator. This result is a cornerstone in convex analysis and relates tightly convexity and monotonicity. In this paper, we establish analogous robust results that relate weak convexity notions to corresponding notions of weak monotonicity, provided one deals with locally Lipschitz functions and locally bounded operators. In particular, the subdifferentials of locally Lipschitz functions that are directionally hypomonotone [respectively, directionally submonotone] enjoy also an additional cyclic strengthening of this notion and in fact are maximal under this new property. Moreover, every maximal cyclically hypomonotone [respectively, maximal cyclically submonotone] operator is always the Clarke subdifferential of some directionally weakly convex [respectively, directionally approximately convex] locally Lipschitz function, unique up to a constant, which in finite dimentions is a lower C² function [respectively, a lower C¹ function].     

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.     

Testing the mechanism of QGP-Induced energy loss

We present an analytic model of jet quenching, based on the (D)GLV energy loss formalism, to describe the system size dependence of QGP-induced parton absorption in relativistic heavy ion collisions. Numerical simulations of the transverse momentum dependence of jet quenching are given for central Au+Au and Cu+Cu reactions. Low p _Tdijet correlations are shown to be sensitive to the reappearance of the lost energy as soft hadrons. At high p _Twe find that the attenuation of dihadrons is similar to that of single inclusive particles. Comparison to recent data from PHENIX and STAR is given as a test of the jet quenching theory.