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.     

Structure and bonding of lanthanide dinitrogen complexes,Ln(N2)1-8

Lanthanide dinitrogen complexes, Ln(N₂) _x (x = 1-8), were investigated by Density Functional Theory computations using the B3LYP exchange-correlation functional in conjunction with quasirelativistic pseudopotentials for Ln. After a recent study on the lanthanum complexes (A. Kovács, Structural Chemistry 2018 , 29, 1825), the present study aimed to probe the changes upon variously filled 4f subshells of Ln on the structures, stabilities, and bonding properties in related complexes of Nd, Ho, and Lu. The bonding properties were assessed on the basis of natural atomic charges, Ln valence orbital populations, and analysis of bonding molecular orbitals.     

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).     

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.     

Physics, mind, society: Back and forth

The life course of the physicist and biologist George Feher may be seen as an epitome of science of the second half of the 20th century and the beginning of the 21st century. Feher, a native of Slovakia, barely escaped Nazism and communism and became a scientist in the USA. The Nazi concentration camps and the communist gulags have become a symbol of the 20th century. This symbol stands here to pose a question: How the two totalitarian systems, fraught with irrationality, may have arisen and thrived in parallel with an unprecedented expansion of science, the paragon of rationalism? The question has become even more urgent in the 21st century. The Ground Zero, an empty spot left after the collapse of the twin towers of the World Trade Center on 11 September 2001, has become the symbol of the entrance of humankind into the new millennium. We can do much, but we understand too little about who we are and what we are doing — this is a message that the two symbols convey about the precarious stage of our evolution. The second message concerns the role of artifacts, specifically scientific instruments, in the advancement of science. Human cultural evolution has been steadily progressing, in a form of a ratchet, only because artifacts have been continually evolving. Contrary to the common Popperian wisdom, the demarcation in science may not consist in the amenability to theoretical falsification, but rather in the amenability to instrumental grasping. Scientific instruments have empowered humans for impressive feats of manipulation with Nature and themselves. Knowledge arising in the course of autonomous evolution of artifacts may surpass the horizon of human understanding and grasping. New knowledge may still be power, but no longer the power of humans. We may need a revision of some fundamental ideas of European thought. Our understanding of the human mind may entirely reshape our comprehension of the nature of physical knowledge, and vice versa.