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.     

Influence of Polarity and Activation Energy in Microwave–Assisted Organic Synthesis (MAOS)

The aim of this work was to determine the parameters that have decisive roles in microwave-assisted reactions and to develop a model, using computational chemistry, to predict a priori the type of reactions that can be improved under microwaves. For this purpose, a computational study was carried out on a variety of reactions, which have been reported to be improved under microwave irradiation. This comprises six types of reactions. The outcomes obtained in this study indicate that the most influential parameters are activation energy, enthalpy, and the polarity of all the species that participate. In addition to this, in most cases, slower reacting systems observe a much greater improvement under microwave irradiation. Furthermore, for these reactions, the presence of a polar component in the reaction (solvent, reagent, susceptor, etc.) is necessary for strong coupling with the electromagnetic radiation. We also quantified that an activation energy of 20–30 kcal mol⁻¹ and a polarity (μ) between 7–20 D of the species involved in the process is required to obtain significant improvements under microwave irradiation.     

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...     

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).     

Kuratowski Convergence of Holomorphic Functions

The notion of Kuratowski convergence is applied to describe a kind of convergence in the context of holomorphic functions. We associate it to a convenient topology, explore its relation with the compact-open topology, thus providing a new set theoretic point of view of this classic topology, and present it in the framework of set-valued mappings.     

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.