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Surfactants are commonly used in biopharmaceutical formulations to stabilize proteins against aggregation. However, the choice of a suitable surfactant for a particular protein is decided mostly empirically, and their mechanism of action on molecular level is largely unknown. Here we show that a straightforward label-free method, saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy, can be used to detect protein-surfactant interactions in formulations of a model protein, interferon alpha. We find that polysorbate 20 binds with its fatty acid to interferon, and that the binding is stronger at pH closer to the isoelectric point of the protein. In contrast, we did not detect interactions between poloxamer 407 and interferon alpha. Neither of the two surfactants affected the tertiary structure and the thermal stability of the protein as evident from circular dichroism and nanoDSF measurements. Interestingly, both surfactants inhibited the formation of subvisible particles during long-term storage, but only polysorbate 20 reduced the amount of small soluble aggregates detected by size-exclusion chromatography. This proof-of-principle study demonstrates how STD-NMR can be employed to quickly assess surfactant-protein interactions and support the choice of surfactant in protein formulation.

The article presents predictive estimates of changes in river water resources in eleven economic regions of the Russian Federation for the period of 2030 and 2050 based on the use of river runoff data of the atmospheric and ocean general circulation models (AOGCM) of the CMIP5 project. An overview of the design schemes of the AOGCM river runoff used in the research is made. The methodology uses an ensemble approach. The predictive estimates were carried out for two forecast periods 2021-2040 and 2041-2060 in relation to the period 1981-2000, which was chosen as the base one. The calculations were made on the basis of an ensemble of 24 selected models for both the moderately aggressive RCP4.5 scenario and the “hard” RCP8.5 scenario. The results obtained were averaged over 20-year periods and compared with the corresponding values for the period 1981-2000. According to the results obtained, in the coming decades there is no reason to expect any significant changes in river flow as a result of climate change. For most of the country's territory, a slight increase in annual runoff is most likely, which is within the limits of its natural variability. The most abundant river water resources will be the Asian part of the Russian Federation and the adjacent eastern part of the European territory of Russia. The most problematic from the point of view of water resources provision will be the Central Black Earth, North Caucasus and Volga economic regions. There will be more water in those regions where it is sufficient, and less where it is most needed. It should be noted that the technique presented in this article is considered by the authors primarily as one of the alternative forecasting methods that must be used in conjunction with other accepted methods. However, given the continuous process of improving the AOGCMs, as well as the quality of the information they provide, this approach should be considered as one of the most promising.

Reaction of conjugated enynones,1,5-diarylpent-2-en-4-yn-1-ones, with malononitrile and sodium alkoxides in the corresponding alcohols at room temperature for 3–23 h results in the formation of two types of compounds (E)-/(Z)-6-aryl-4-(2-arylethenyl)-2-alkoxypyridine-3-carbonitriles (substituted nicotinonitriles), as the major reaction products in yields up to ca. 40–80%, and 6-aryl-4-arylethynyl-2-alkoxypyridines, as the minor reaction products in yields of 5–17%. Plausible mechanism of this complex and multistep reaction is discussed. The obtained pyridines possess fluorescent properties.

We report an efficient domino reaction for synthesizing new pyrrolo[2,1-a]isoquinolines from 1-aryl-3,4-dihydroisoquinolines and vinyl ethynyl ketones. We also address the chemical selectivity of vinyl ethynyl ketones; i.e., adduct formation by the double or triple bond. The reaction outcome depends on the solvent, temperature, microwave irradiation, and catalyst. Donor substituents in the initial isoquinolines provide a regioselective addition to double or triple bonds.

We report here for the first time a fabrication of betavoltaic battery prototype consisting of 200 single conversion cells based on Schottky barrier diamond diodes which have been vertically stacked with ~24% 63Ni radioactive isotope. The maximum electrical output power of about 0.93 μW was obtained in total volume of 5 × 5 × 3.5 mm3. We used the ion-beam assisted lift-off technique to obtain conversion cells of minimal thickness comparable with the characteristic penetration length of beta-particles emitted by 63Ni isotope. The obtained value of 15 μm was limited by the mechanical strength of produced structures and process reliability. To check the performance of thin diamond based conversion cells we carried out IV-curves measurements at electron beam irradiation in SEM. We found that the sacrificial layer for the splitting of such thin conversion cell from HPHT diamond substrate did not cause a considerable degradation of device charge collection efficiency. As a result, the fabricated prototype provided the output power density of about 10 μW/cm3, that is the best known value for nuclear batteries based on 63Ni radioisotope. Moreover, the long half-life of 63Ni isotope gives the battery specific energy of about 3300 mWh/g that is an order of magnitude higher than the typical value of commercial chemical cells.

An experimental full phase diagram for the binary system low-density polyethylene – thymol was for the first time constructed in a broad temperature-concentration range using an original optical method, turbidimetry, and differential scanning calorimetry. Limitations of the two latter techniques were critically analyzed. The diagram belongs to the type semicrystalline polymer – thermodynamically poor solvent so that in the whole concentration range polyethylene and thymol play the role of a solvent and solute, respectively. Thermally induced phase separation leads to the formation of a capillary-porous body. Thymol crystals formed in its pores melt at lower temperatures than crystals from pure thymol solution. The data obtained by different methods can be used for developing the technology of fabricating films with antimicrobial properties.

In this study, two novel Pr 3 + complexes with different 1,3-diketonate ligands were synthesized and investigated. To study the effect of the ancillary ligand on the energy transfer mechanisms in the complexes, a phenanthroline ligand was introduced. To take into account the influence of the ligand environment composed of different ligands on the energy transfer and relaxation processes, we compared the synthesized compounds with a similar complex containing the phenanthroline ligand. The spectroscopic studies in the visible and near-infrared spectral regions were supplemented with DFT and TD-DFT calculations. We found two ligand-to-ligand charge transfer (LLCT) states, with one state corresponding to energy transfer between 1,3-diketones and the other – to energy transfer from the 1,3-diketone to the phenanthroline motif. It was demonstrated that optical excitation via the latter channel leads to a fourfold increase in the luminescence quantum yield as compared with excitation via the π - π ∗ transitions in 1,3-diketones. Moreover, both LLCT states provide sensitization of the Pr 3 + luminescence involving the 3 P 0 and 3 P 1 levels.

Thermally-induced phase separation in semicrystalline polymer – solvent systems is revisited to analyze the formation of membrane precursors beyond the existing concepts. It is argued that the phase diagrams of such systems should include a commonly overlooked curve describing the solubility of a low-molar-mass liquid in the amorphous regions of a semicrystalline polymer. To illustrate our approach, the binary mixtures of isotactic polypropylene with dioctyl phthalate (good solvent), dibutyl phthalate (poor solvent), and their ternary mixtures are considered. Quasi-equilibrium phase diagrams are constructed using an original optical method and analyzed in terms of phenomenological thermodynamics, including the previously poorly studied region below the polymer crystallization temperature. The proposed scenario of morphology development during the cooling of pre-homogenized mixtures is illustrated with the data of optical and scanning electron microscopy, small-angle X-ray scattering, differential scanning calorimetry, and cloud point methods. It is found that cooling down and subsequent solvent extraction generally lead to the formation of capillary-porous bodies with large (micron-sized) pores formed via the liquid-liquid phase separation and small (submicron-sized) pores appeared due to the microphase separation of amorphous polymer regions under strain imposed by the presence of crystallites. The composition range most suitable for the formation of filtration membrane precursors extends between the polymer mass fraction values corresponding to the upper critical solution point and “monotectic” point, in which the solubility curve meets the curve of complete polymer amorphization.

The micromorphological and microtomographic studies of differently aged extremely aridic soils in the Trans-Altai Gobi Desert of Mongolia allowed us to determine the rates and sequences of processes associated with sedimentogenesis and pedogenetic transformation of the parent material. In the most developed extremely aridic soils, the topsoil or the surface Aye horizon consisting of the layers of different compositions and geneses (eolian and colluvial sediments) displays vesicular voids, which are virtually absent in the young soils. Two different mechanisms of the origin of vesicular voids are suggested: (a) in the case of the fresh eolian material, the bicarbonate–calcium equilibrium is displaced towards the formation of calcite with the release of CO 2 under the impact of changes in the moisture and temperature; (b) in the case of the dense silty clay material, the release of sorbed air (nitrogen and oxygen) from the dry soil particles takes place under the impact of atmospheric precipitation. The locally acting pedogenesis in these soils specify the development of hypocoatings and typical coatings consisting of the amorphized phyllosilicates with the disordered structure inside the vesicular voids and the formation of iron microconcentrations and iron films on mineral grains.

Fluorescent D-A1-π-A2 dyes containing the 9-hexyl-9H-carbazole electron-donor unit and 2,1,3-benzochalcogenadiazoles as electron-withdrawing, were synthesized. These dyes displayed high luminescence quantum yields up to 20% in the solid phase and 80% in solutions. A series of ClsOLEDs with high luminance up to 6256 cd/m2 and low color temperature (1800–1900 K) based on these dyes were constructed. The electroluminescence color temperature of the fabricated OLEDs is independent of the operating voltage making these compounds potentially very useful for night time illumination. It was shown that the aggregation process of the investigated dyes led to the formation of planar crystalline structures. Scanning electron microscopy (SEM) and fluorescence lifetime imaging (FLIM) experiments, showed that luminescence quenching caused by interactions between aggregates of different sizes takes place. Spectroscopic studies were supported by Density Functional Theory (DFT) and Time Dependent Density Functional Theory (TD-DFT) calculations. As a result, we elucidated that replacement of [1,2,5]chalcogenadiazolo[3,4-c]pyridines by 2,1,3-benzochalcogenadiazoles led to a substantial improvement in intramolecular charge transfer (ICT) from the donor to acceptor units due to favourable distortion of the excited state geometry.

An analytical piecewise-homogeneous model for electron side injection into linear plasma waves is developed. The dynamics of transverse betatron oscillations are studied. Based on the characteristics of the transversal motion the longitudinal motion of electrons is described. The electron parameters for which the electron trapping and subsequent acceleration are possible are estimated. The analytical results are verified by numerical simulations in the scope of the piecewise-homogeneous model. The results predicted by this model are also compared to the results given by a more realistic inhomogeneous model.

Department of Energy (United States of America); National Science Foundation (United States of America); Alternative Energies and Atomic Energy Commission (France); National Center for Scientific Research/ National Institute of Nuclear and Particle Physics (France); Ministry of Education and Science of the Russian Federation (Russia); National Research Center "Kurchatov Institute" of the Russian Federation (Russia); Russian Foundation for Basic Research (Russia); National Council for the Development of Science and Technology (Brazil); Carlos Chagas Filho Foundation for the Support of Research in the State of Rio de Janeiro (Brazil); Department of Atomic Energy (India); Department of Science and Technology (India); Administrative Department of Science, Technology and Innovation(Colombia); National Council of Science and Technology (Mexico); National Research Foundation of Korea (Korea); Foundation for Fundamental Research on Matter (The Netherlands); Science and Technology Facilities Council (United Kingdom); The Royal Society (United Kingdom); Ministry of Education, Youth and Sports (Czech Republic); Bundesministerium fur Bildung and Forschung (Federal Ministry of Education and Research) (Germany); Deutsche Forschungsgemeinschaft (German Research Foundation) (Germany); Science Foundation Ireland (Ireland); Swedish Research Council (Sweden); China Academy of Sciences (China); National Natural Science Foundation of China (China); Ministry of Education and Science of Ukraine (Ukraine)

The effects of an equimolar mixture of l-arginine and l-glutamate (Arg·Glu) on cell viability and cellular stress using in vitro cell culture systems are examined with reference to NaCl, in the context of monoclonal antibody formulation. Cells relevant to subcutaneous administration were selected: the human monocyte cell line THP-1, grown as a single cell suspension, and adherent human primary fibroblasts. For THP-1 cells, the mechanism of cell death caused by relatively high salt concentrations was investigated and effects on cell activation/stress assessed as a function of changes in membrane marker and cytokine (interleukin-8) expression. These studies demonstrated that Arg·Glu does not have any further detrimental effects on THP-1 viability in comparison to NaCl at equivalent osmolalities, and that both salts at higher concentrations cause cell death by apoptosis; there was no significant effect on measures of THP-1 cellular stress/activation. For adherent fibroblasts, both salts caused significant toxicity at ~400mOsm/kg, although Arg·Glu caused a more precipitous subsequent decline in viability than did NaCl. These data indicate that Arg·Glu is of equivalent toxicity to NaCl and that the mechanism of toxicity is such that cell death is unlikely to trigger inflammation upon subcutaneous injection in vivo.

First-principles density functional theory calculations in the generalized gradient approximation, with plane wave basis set and pseudopotentials, have been used to investigate the desorption pathways of molecular oxygen species adsorbed on the SnO2 (110) surface. Energetics of the thermodynamically favored precursors is studied in dependence on the surface charge provided either by surface defects or by donor type impurities from the near-surface region. The resonant desorption modes of O2 molecules are examined in the framework of ab initio atomic thermodynamics and relationship of these results to experimental observations is discussed. acceptedVersion

The main goal of the Vernov mission is the study of magnetospheric relativistic electron precipitation and its possible influence on the upper atmosphere as well as the observation of Transient Luminous Events (TLE) and Terrestrial Gamma Flashes (TGF) across a broad range of the electromagnetic spectrum. The RELEC (Relativistic Electrons) instrument complex onboard the Vernov spacecraft includes two identical X- and gamma-ray detectors of high temporal resolution and sensitivity (DRGE-1 and DRGE-2), three axis position detectors for high-energy electrons and protons (DRGE-3), a UV TLE imager (MTEL), a UV detector (DUV), a low frequency analyser (LFA), a radio frequency analyser (RFA), and AN electronics module responsible for control and data collection (BE). The RELEC mission conducts the following experiments: – simultaneous observations of high-energy electron and proton fluxes (within the energy range of ∼0.1–10.0 MeV) and low-frequency (∼0.1–10 kHz) electromagnetic wave field intensity variations with high temporal resolution (∼1 ms); – fine time structure (∼1 μs) measurements of transient atmospheric events in UV, X- and gamma rays with an optical imaging capability with a resolution of ∼1 km in wide field of view (FOV); – measurements of electron flux pitch-angle distributions in dynamical ranges from ∼0.1 up to 105 part/cm2/s; – monitoring of charged and neutral background particles in different areas of near-Earth space.

The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions.

The successful circumpolar flight of the X-ray polarimeter PoGOLite in the northern hemisphere during the summer campaign of 2013 inspired us, the team consisting mostly of students and senior researchers, to develop a Modular Monitor of the Cosmic Neutral Emission (MMCNE) prototype that can be flown on the high-altitude balloons to study two components of neutral emission, namely spectra of neutrons and of gamma-rays in the upper layers of Earth atmosphere. Instrument modular concept, and some of the simulated detection characteristics for the selected layout will be presented in this paper.