Molecular dynamics of 5-HT1A and 5-HT2A serotonin receptors with methylated buspirone analogues

In the present study experimentally determined ligand selectivity of three methylated buspirone analogues (denoted as MM2, MM5 and P55) towards 5-HT_1A and 5-HT_2A serotonin receptors was theoretically investigated on a molecular level. The relationships between the ligand structure and 5-HT_1A and 5-HT_2A receptor affinities were studied and the results were found to be in agreement with the available site-directed mutagenesis and binding affinity data. Molecular dynamics (MD) simulations of ligand-receptor complexes were performed for each investigated analogue, docked twice into the central cavity of 5-HT_1A/5-HT_2A, each time in a different orientation. Present results were compared with our previous theoretical results, obtained for buspirone and its non-methylated analogues. It was found that due to the presence of the methyl group in the piperazine ring the ligand position alters and the structure of the ligand-receptor complex is modified. Further, the positions of derivatives with pyrimidinyl aromatic moiety and quinolinyl moiety are significantly different at the 5-HT_2A receptor. Thus, methylation of such derivatives alters the 3D structures of ligand-receptor complexes in different ways. The ligand-induced changes of the receptor structures were also analysed. The obtained results suggest, that helical domains of both receptors have different dynamical behaviour. Moreover, both location and topography of putative binding sites for buspirone analogues are different at 5-HT_1A and 5-HT_2A receptors.     

Extraction of hysteresis loops from main magnetization curves

In firm catalogues,the basic properties of magnetic materials are often described by their main magnetization curves. Such curves may be used for the first analysis of circuits containing ferromagnetic cores. The analysis will be more accurate, if the curves are transformed into the families of hysteresis loops. To enable the reconstruction of such loops, we formulate a simple model of hysteresis, making main magnetization curve directly dependent on coercivity. In this way we can approximate hysteresis loops of most typical materials in a pretty wide range of magnetization. Application of variable coercivity enables extension of the model to stronger fields.     

The Conley index, cup-length and bifurcation

A module structure of the cohomology Conley index is used to define a relative cup-length. This invariant is applied then to prove a multiplicity theorem for periodic solutions to Hamiltonian systems.     

A practical synthesis and spectroscopic study of new potentially biologically active S-lithocholic acid-substituted derivatives of 2-thiouracil

Five new S-3α-acetoxy-5β-lithocholic acid methyl ester-substituted derivatives of 2-thiouracil and 6-methyl-2-thiouracil have been prepared. 5-Morpholino-methyl-2-thiouracil, 5-piperidinomethyl-2-thiouracil, and 5-(4-methylpiperidino)methyl-2-thiouracil have been obtained via the Mannich reaction between 6-methyl-2-thiouracil, paraformaldehyde, and the cyclic secondary amines morpholine, piperidine, or 4-methylpiperidine in ethanol. The structures of the compounds were confirmed by spectral (¹H NMR, ¹³C NMR, and FT-IR) analyses and mass spectrometry. Estimation of the pharmacotherapeutic potential has been accomplished for the synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS).     

On Hardy?s paradox, weak measurements, and multitasking diagrams

We discuss Hardy?s paradox and weak measurements by using multitasking diagrams, which are introduced to illustrate the progress of quantum probabilities through the double interferometer system. We explain how Hardy?s paradox is avoided and elaborate on the outcome of weak measurements in this context.     

Sparse hamiltonian 2-decompositions together with exact count of numerous Hamilton cycles

We construct multigraphs of any large order with as few as only four 2-decompositions into Hamilton cycles or only two 2-decompositions into Hamilton paths. Nevertheless, some of those multigraphs are proved to have exponentially many Hamilton cycles (Hamilton paths). Two families of large simple graphs are constructed. Members in one class have exactly 16 hamiltonian pairs and in another class exactly four traceable pairs. These graphs also have exponentially many Hamilton cycles and Hamilton paths, respectively. The exact numbers of (Hamilton) cycles and paths are expressed in terms of Lucas- or Fibonacci-like numbers which count 2-independent vertex (or edge) subsets on the n-path or n-cycle. A closed formula which counts Hamilton cycles in the square of the n-cycle is found for n≥5. The presented results complement, improve on, or extend the corresponding well-known Thomason’s results.     

Thiol-functionalized anthraquinones: mass spectrometry and electrochemical studies

Abstract  

In this work, the synthesis of various thiol-functionalized anthraquinone compounds is presented. The studied compounds were characterized by mass spectrometry and the main fragmentation pathways are discussed. The compounds studied formed stable self-assembled monolayers (SAMs) in the gold surface. The parameters for the reduction processes in the gold surface of the studied new anthraquinones were determined by cyclic voltamperometry tests.     

Über eine neue pyknometrische Dichtebestimmungs-Methode der weichen Fette

Ohne Zusammenfassung     

Reaction of some trisubstituted steroid epoxides with triphenylphosphine - iodine complex. Deoxygenation of epoxides

Triphenylphosphine - iodine complex was found to be an effective reagent for deoxygenation of trisubstituted steroidal epoxides. The mechanism of the reaction is proposed.     

Stochastic nonlinear beam equations

An extensible beam equation with a stochastic force of a white noise type is studied, Lyapunov functions techniques being used to prove existence of global mild solutions and asymptotic stability of the zero solution.This research was supported in part by the GA R Grants no. 201/98/1454, 201/01/1197 and by a Royal Society grant