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 optodynamic method for the real-time determination of the depth of a laser-drilled hole

An experimental method for determining the real-time depth of laser-drilled holes is presented. The proposed method involves detecting the laser-induced optoacoustic waves generated during the interaction of the laser beam with the material. Our optodynamic study involved measuring the propagation times of these waves as they traveled through the material and analyzing their temporal behavior during the drilling process. The experimental observations revealed an exponential relationship between the propagation time of the longitudinal stress wave and the number of consecutive laser pulses. Received: 25 October 2001 / Accepted: 27 October 2001 / Published online: 20 December 2001     

Fast electrons generation by RF and random fields near the antenna I. One dimensional model and regular fields

Test particle motion and acceleration has been explored in strong radio frequency (RF) fields, for which quasilinear ponderomotive force approximation is not valid. By nonlinear acceleration in spatially varying wave amplitude of RF travelling wave, electrons may be accelerated to time averaged velocities significantly larger than the RF wave phase velocity, and than the boundary plasma thermal velocity, in RF fields of several Volts per centimeter at wave frequency of 7 MHz. It is also demonstrated that even weak spatial gradients, much weaker than those expected in experiments, of the RF wave field amplitude, have significant consequences for the particle motion. Estimates are presented of the total energy transferred from the near antenna RF field to the plasma due to the nonlinear electron acceleration effects.     

Transient binary nucleation from ethanol-hexanol vapour

We study condensation of ethanol-hexanol vapour by numerical solution of kinetic equations. The number of droplets formed in unit volume is computed within self-consistent classical model. It is shown that formation of ethanol-rich droplets prevails at the initial stage of nucleation process, but in the stationary state formation of droplets near the saddle point (on cluster formation energy surface) plays the dominant role. Presented at the 6th Joint Seminar “Development of Materials Science in Research and Education”, Karlštejn, Czech Republic, 17–19 September 1996. This work was supported by Grant No. A1010615 of the Grant Agency of the Academy of Sciences of the Czech Republic.     

Quantum Interference, Quantum Theory of Measurement, and (In)completeness of Quantum Mechanics

The new techniques and ideas in quantum interferometry with neutrons, photons, atoms, electrons, and Bose condensates that fluorished in the last two decades have influenced in a decisive way the thinking and the research in the foundations and interpretation of quantum mechanics. The controversies existing among different schools on the reality of matter waves of quantum theory, the postulates of quantum measurement theory, and the (in)completeness of quantum mechanics have to be approached now in a new way. Our argumentation follows the spirit of the Paris school.     

Fatty acid binding site of mitochondrial uncoupling protein UCP2 as probed by EPR spectroscopy of spin-labeled fatty acids

Electron paramagnetic resonance (EPR) spectroscopy of spin-labeled fatty acids was used to investigate their interaction withEscherichia coli-expressed human mitochondrial uncoupling protein UCP2 refolded from inclusion bodies in nonaethylene glycol monododecyl ether (C₁₂E₉) micelles. 5-DOXYL-stearic acid and 4-PROXYL-palmitic acid bound to UCP2 exhibited additional clearly separated h_+1I, h_?1I “immobile” peaks in the low- and high-field region, respectively, separated by 42 and 44 Gauss, and extensively reduced h_+1M, h_?1M “mobile” peaks, separated by about 30 G, whereas with 7-DOXYL-stearic acid the I and M peaks were smoothed together into one wide peak. Competition of 4-PROXYL-palmitic acid with added palmitic acid, arachidonic acid, and all-cis-8,11,14-eicosatrienoic acid and of 7-DOXYL-stearic acid with arachidonic acid was indicated by the disappearance of the h_+1I, h_?1I “immobile” peaks, whereas redistribution in micelles without protein was indicated by the rising of the h_+1M, h_?1M “mobile” peaks. In conclusion, a competition of palmitic, arachidonic, and eicosatrienoic acid within a putative fatty acid binding site was observed for mitochondrial uncoupling protein UCP2. This finding together with the observation of EPR spectra of highly immobilized probes exclusively in the presence of the recombinant UCP2 suggest the existence of a fatty acid binding site on UCP2 which is a prerequisite of the fatty acid cycling mechanism as previously postulated for UCP1.     

Angular distribution of muon pairs produced by negative pions on deuterium and tungsten in terms of coherent states

Recently published data on thep _T dependence of the angular distributions of muon pairs produced in collisions of negative pions with deuterium and tungsten nuclei reveal an unexpected tendency. We show that the quantum statistical approach involving expansions in terms of coherent states leads in this case to an exact, non-perturbative result which in the lowest order approximation describes the observed trends with sufficient accuracy. In this procedure, the non-vanishing correlations between the coordinates and momenta of dimuons play a decisive role.     

One-Element Extensions in the Variety Generated by Tournaments

We investigate congruences in one-element extensions of algebras in the variety generated by tournaments.     

JET: Preparing the future in fusion

JET (Joint European Torus) is the largest tokamak in the world and the only fusion facility able to operate with Tritium, the fusion fuel, and Beryllium, the ITER first wall material. JET also features the most complete remote handling equipment for invessel maintenance. As a multinational research center, JET provides logistic experience in preparing for operation of the global facility, tokamak ITER.Experiments on JET are focused on ITER-relevant studies, in particular on detailing the operational scenarios (EL My H-modes and advanced regimes), on enhancing the heating systems, on developing diagnostics for burning plasmas etc. Pioneering real-time control techniques have been implemented that maximize performance and minimize internal disturbances of JET plasmas. In helium plasmas, ion cyclotron heating (ICRH) created fast α-particles, mimicking their populations in future burning plasmas. The recent successful Trace Tritium campaign provided important new data on fuel transport. Current enhancements on JET include a new ITER-like ELM-resilient high power ICRH antenna (7 MW) and over twenty new diagnostics that will further extend the JET scientific capabilities and push the facility even closer to the ITER parameters.A special mention is given to the involvement of the fusion experts from Association EURATOM-IPP.CR, who have been actively participating in the collective use of JET facility for more than three years.