Methodical approaches to bioassay of substances containing unstable functional groups

This article describes the method development approaches for bioassay of substances containing unstable functional groups and forming unstable metabolites using the example of mycophenolic acid, methyldopa and mebeverine metabolite

Formation of "Lightnings" in a Neutron Star Magnetosphere and the Nature of RRATs

The connection between the radio emission from "lightnings" produced by the absorption of high-energy photons from the cosmic gamma-ray background in a neutron star magnetosphere and radio bursts from rotating radio transients (RRATs) is investigated. The lightning length reaches 1000 km; the lightning radius is 100 m and is comparable to the polar cap radius. If a closed magnetosphere is filled with a dense plasma, then lightnings are efficiently formed only in the region of open magnetic field lines. For the radio emission from a separate lightning to be observed, the polar cap of the neutron star must be directed toward the observer and, at the same time, the lightning must be formed. The maximum burst rate is related to the time of the plasma outflow from the polar cap region. The typical interval between two consecutive bursts is ~100 s. The width of a single radio burst can be determined both by the width of the emission cone formed by the lightning emitting regions at some height above the neutron star surface and by a finite lightning lifetime. The width of the phase distribution for radio bursts from RRATs, along with the integrated pulse width, is determined by the width of the bundle of open magnetic field lines at the formation height of the radio emission. The results obtained are consistent with the currently available data and are indicative of a close connection between RRATs, intermittent pulsars, and extreme nullers.Comment: 24 pages, no figures, references update

APPROACHES TO THE DEVELOPMENT OF BIOANALYTICAL METHODS FOR DETERMINATION OF UNSTABLE SUBSTANCES IN BIOLOGICAL FLUIDS

The approaches to bioanalytical method development for determination of substances which contain unstable functional groups in the structure are described. The oxidation and the hydrolysis are main causes of the decomposition of substances in biological fluids. Phenolic hydroxyls contain drugs were selected as examples of oxidable compounds, glucuronides of drugs were selected as examples of hydrolysable compounds. Determination of mycophenolic acid, which contains one phenolic hydroxyl and metabolized by formation of glucuronides, in plasma was performed using high performance liquid chromatography with mass-spectrometry and tandem mass-spectrometry detection. Methyldopa, which contains two phenolic hydroxyls, in stabilized plasma was assayed by high performance liquid chromatography – tandem mass-spectrometry in the range of 0.02–3.00 μg/ml. Concentrations of desmethyl mebeverine acid, which contains in the structure one phenolic hydroxyl and metabolized by formation of phenolic glucuronide, was measured simultaneously with mebeverine acid in the range of 10–2000 ng/ml. The influence of the ion source conversion of glucuronides on the quantitative determination of the substances was studied in the initial part of methods development. The next, selection of anticoagulants based on the study of short-term stability and freeze/thaw stability of the analytes and back conversion of their glucuronides was performed. The combination of anticoagulant K3EDTA and the antioxidant solution containing a mixture of ascorbic acid, sodium sulfite and sodium hydrogen carbonate in the concentrations of 5.0 %, 0.2 % and 2.4 %, respectively, was used to prevent degradation of methyldopa

SoLid : Search for Oscillations with Lithium-6 Detector at the SCK-CEN BR2 reactor

Sterile neutrinos have been considered as a possible explanation for the recent reactor and Gallium anomalies arising from reanalysis of reactor flux and calibration data of previous neutrino experiments. A way to test this hypothesis is to look for distortions of the anti-neutrino energy caused by oscillation from active to sterile neutrino at close stand-off (similar to 6-8m) of a compact reactor core. Due to the low rate of anti-neutrino interactions the main challenge in such measurement is to control the high level of gamma rays and neutron background. The SoLid experiment is a proposal to search for active-to-sterile anti-neutrino oscillation at very short baseline of the SCK center dot CEN BR2 research reactor. This experiment uses a novel approach to detect anti-neutrino with a highly segmented detector based on Lithium-6. With the combination of high granularity, high neutron-gamma discrimination using 6LiF:ZnS(Ag) and precise localization of the Inverse Beta Decay products, a better experimental sensitivity can be achieved compared to other state-of-the-art technology. This compact system requires minimum passive shielding allowing for very close stand off to the reactor. The experimental set up of the SoLid experiment and the BR2 reactor will be presented. The new principle of neutrino detection and the detector design with expected performance will be described. The expected sensitivity to new oscillations of the SoLid detector as well as the first measurements made with the 8 kg prototype detector deployed at the BR2 reactor in 2013-2014 will be reported

SOLID-STATE SYNTHESIS OF TRANSPARENT Lu3Al5O12CERAMICS

In this work, we report on the fabrication of transparent Lu3Al5O12(LuAG) ceramics by the solid-state reaction sintering a mixture of Lu2O3 nanoparticles synthesized by laser ablation and commercially available Al2O3 powder. Microstructure features and optical properties of the obtained LuAG ceramics were investigated

Compaction and flow rule of oxide nanopowders

Transparent Al2O3 ceramics have attracted considerable interest for use in a wide range of optical, electronic and structural applications. The fabrication of these ceramics using powder metallurgy processes requires the development of theoretical approaches to the compaction of nanopowders. In this work, we investigate the compaction processes of two model granular systems imitating Al2O3 nanosized powders. System I is a loosely aggregated powder, and system II is a powder strongly inclined to agglomeration (for instance, calcined powder). The processes of isostatical (uniform), biaxial, and uniaxial compaction as well as uniaxial compaction with simultaneous shear deformation are studied. The energy parameters of compaction such as the energy change of elastic interparticle interactions and dispersion interactions, dissipative energy losses related to the processes of interparticle friction, and the total work of compaction are calculated for all the processes. The nonapplicability of the associated flow rule to the description of deformation processes of oxide nanopowders is shown and an alternative plastic flow rule is suggested. A complete system of determining the relationship of the flow including analytical approximations of yield surfaces is obtained. © 2016 Elsevier B.V

Region of Excessive Flux of PeV Cosmic Rays in the Direction Toward Pulsars PSR J1840+5640 and LAT PSR J1836+5925

An analysis of arrival directions of extensive air showers (EAS) registered with the EAS MSU and EAS-1000 prototype arrays has revealed a region of excessive flux of PeV cosmic rays in the direction toward pulsars PSR J1840+5640 and LAT PSR J1836+5925 at significance level up to 4.5sigma. The first of the pulsars was discovered almost 30 years ago and is a well-studied old radio pulsar located at the distance of 1.7pc from the Solar system. The second pulsar belongs to a new type of pulsars, discovered by the space gamma-ray observatory Fermi, pulsations of which are not observed in optical and radio wavelengths but only in the gamma-ray range of energies (gamma-ray-only pulsars). In our opinion, the existence of the region of excessive flux of cosmic rays registered with two different arrays provides a strong evidence that isolated pulsars can give a noticeable contribution to the flux of Galactic cosmic rays in the PeV energy range.Comment: 14 pages; v.2: a few remarks to match a version accepted for Astronomy Letters added. They can be found by redefining the \NEW command in the preamble of the LaTeX fil

Enzyme-Linked Immunosorbent Assay Method Application in the Study of Comparative Pharmacokinetics of Insulin Glargin Preparations

Aims: adaptation and validation of the ELISA method insulin glargine determination for the pharmacokinetic study, practical approval in the biosimilars clinical trial.Materials and methods. Serum insulin glargine determination was measured using a commercial ELISA kit. All tests were run on a Personal LAB machine (Adaltis S.r.l., Rome, Italy) with test systems for measuring the concentration of insulin glargine (Invitron Ltd., United Kingdom); human insulin concentrations were measured in the samples from the study for correction of cross-reactivity. Clinical part of this study included 42 male patients aged 18–65 with diabetes mellitus type 1. This was a double-blind, randomized, crossover clamp study with wash-out period of 7–14 days. Comparisons drugs: Insulin Glargine (glargine) solution for subcutaneous administration, 100 U/ml (GEROPHARM, Russia) and Lantus® (glargine) solution for subcutaneous administration, 100 U/ml (Sanofi-Aventis Deutschland GmbH, Germany).Results. At the stage of the method adaptation the modification of original manufacturer’s method was performed; the full validation of modified analytical method for all parameters (selectivity, specificity, precision of calibration curves, intra- and inter-batch precision and accuracy, carry-over, dilution integrity, stability of solutions, stability in biologic matrix, parallelism) in accordance with regulatory authorities requirements has been done. The primary endpoint for long-acting insulins – AUCins.0-τ was calculated. Insulin Glargine and Lantus® are equivalent based on AUCins.0-τ data (point estimation for ratio of geometric means was 99 %, the confidence intervals for the ratio of the geometric mean for AUCins.0-τ was 81.02–120.62 %, that correspond to acceptance range 80.00–125.00 %)

Absorption of Gamma-Ray Photons in a Vacuum Neutron Star Magnetosphere: I. Electron-Positron Pair Production

The production of electron-positron pairs in a vacuum neutron star magnetosphere is investigated for both low (compared to the Schwinger one) and high magnetic fields. The case of a strong longitudinal electric field where the produced electrons and positrons acquire a stationary Lorentz factor in a short time is considered. The source of electron-positron pairs has been calculated with allowance made for the pair production by curvature and synchrotron photons. Synchrotron photons are shown to make a major contribution to the total pair production rate in a weak magnetic field. At the same time, the contribution from bremsstrahlung photons may be neglected. The existence of a time delay due to the finiteness of the electron and positron acceleration time leads to a great reduction in the electron-positron plasma generation rate compared to the case of a zero time delay. The effective local source of electron-positron pairs has been constructed. It can be used in the hydrodynamic equations that describe the development of a cascade after the absorption of a photon from the cosmic gamma-ray background in a neutron star magnetosphere.Comment: 29 pages, 1 figur

Measurement of double beta decay of ¹⁰⁰Mo to excited states in the NEMO 3 experiment

The double beta decay of ¹⁰⁰Mo to the 0_{1}^{+} and 2_{1}^{+} excited states of ¹⁰⁰Ru is studied using the NEMO 3 data. After the analysis of 8024 h of data the half-life for the two-neutrino double beta decay of ¹⁰⁰Mo to the excited 0_{1}^{+} state is measured to be T_{1/2}^{2v} = [5.7_{-0.9}^{+1.3} (stat.) ± 0.8 (syst.)] x 10²⁰ y. The signal-to-background ratio is equal to 3. Information about energy and angular distributions of emitted electrons is also obtained. No evidence for neutrinoless double beta decay to the excited 0_{1}^{+} state has been found. The corresponding half-life limit is T_{1/2}^{0v} (0⁺→0_{1}^{+}) > 8.9 x 10²² y (at 90% C.L.). The search for the double beta decay to the 2_{1}^{+} excited state has allowed the determination of limits on the half-life for the two neutrino mode T_{1/2}^{0v} (0⁺→2_{1}^{+}) > 1.1 x 10²¹ y (at 90% C.L.) and for the neutrinoless mode T_{1/2}^{0v} (0⁺→2_{1}^{+}) > 1.6 x 10²³ y (at 90% C.L.)