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 algebraic characterization ofB-convergent Runge-Kutta methods

Summary In the analysis of discretization methods for stiff intial value problems, stability questions have received most part of the attention in the past.B-stability and the equivalent criterion algebraic stability are well known concepts for Runge-Kutta methods applied to dissipative problems. However, for the derivation ofB-convergence results — error bounds which are not affected by stiffness — it is not sufficient in many cases to requireB-stability alone. In this paper, necessary and sufficient conditions forB-convergence are determined.This paper was written while J. Schneid was visiting the Centre for Mathematics and Computer Science with an Erwin-Schrödinger stipend from the Fonds zur Förderung der wissenschaftlichen Forschung     

Imaging and correlation used for guided laser lithotripsy

High-speed imaging of phenomena akin to laser lithotripsy is performed. A new method for guiding laser light for the stone destruction is proposed. This is based on a combination of signals obtained from the correlation of fluorescent and ballistic images.     

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.     

The synthesis of iron–nickel alloy nanoparticles using a reverse micelle technique

Nanosized Fe_0.2Ni_0.8 particles were prepared by reducing their salts with sodium borohydride (NaBH₄) in cationic water-in-oil (w/o) microemulsions of water/cetyl-trimethyl-amonium bromide (CTAB) and n-butanol/isooctane at 25 °C. According to the TEM and X-ray diffraction analyses, the synthesized particles were around 4–12 nm in size. Due to their nanodimensions, the particles had a primitive cubic (pc) structure rather than the body-centered cubic (BCC) structure of the bulk material. An examination of the synthesis from the reverse micelle reveals that the morphology of the iron–nickel alloy nanoparticles depends mainly on the microemulsion's composition. The magnetization of the nanoparticles was much lower than that of the bulk material, reflecting the influence of the nanodimensions on the particles’ magnetizations.     

On operators and search space topology in multi-objective flow shop scheduling

Multi-objective optimization using evolutionary algorithms identifies Pareto-optimal alternatives or their close approximation by means of a sequence of successive local improvement moves. While several successful applications to combinatorial optimization problems are known, studies of underlying problem structures are still scarce.     

Flips and the Hilbert scheme over an exterior algebra

We study the tangent space at a monomial point M in the Hilbert scheme that parameterizes all ideals with the same Hilbert function as M over an exterior algebra.