We studied the cytotoxicity of acadesine (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) for tumor and normal cells of various species and tissue origin. In tumor cells, acadesine triggered non-apoptotic death; the potency of the compound to normal cells was substantially lower. Acadesine was toxic for tumor cells with multidrug resistant phenotypes caused by the transmembrane transporter P-glycoprotein or lack of proapoptotic p53. Activity of adenosine receptors was required for acadesine-induced cell death, whereas functioning of AMP-dependent protein kinase was not required. A more pronounced cytotoxicity for tumor cells, as well as the non-canonical death mechanism(s), makes acadesine a promising candidate for antitumor therapy.
The methods and algorithms of XFEL data analysis for protein molecules are discussed. Experimental data on the structure and spatial distribution of the electron density in biomacromolecules and their complexes, algorithms, data analysis and integration of X-ray scattering, electron microscopy and molecular modeling techniques to study the structure and dynamics of biological macromolecules and their complexes are discussed as well.
Alcoholism as a cause of regression in learning and in pro-social behavior
Alexandrov Yu.I., Svarnik O.Ye., Znamenskaya I.I., Arutiunova K.R., Kolbeneva M.G., Krylov A.K., Bulava A.N.
Despite a long history of the notion of regression, its manifestations and mechanisms are still poorly researched, specific experimental studies are rare, points of view conflict. A study was conducted to discover dynamics of subjective experience and brain activity lying at the foundation of phenomena described as regression and observed in seemingly heterogeneous phenomena, such as stress, illness, violent emotions, alcoholic intoxication. The paper discusses the notion of regression from different angles, including the systemic evolutionary approach, and analyzes its potential brain and neuroenetic mechanisms. It has been experimentally proved that a high degree of alcoholic intoxication causes regression brought about by reverse de-differentiation: a relative increase of representation of lowly differentiated systems in actual experience.In experimental situations of learning in animals lowered activation of neurons of the first (drinking) skill was observed in the process of development of the second (eating) skill. In order to discover effects of alcohol on the general pattern of moral judgements the authors analyzed dynamics of the index of moral acceptance of the death of one for the sake of many. Complexity of behavior is simplified under alcohol and individual differences in pro-social behavior become less expressed. Findings demonstrate similarities in assessments of socially meaningful actions under alcohol, which, the authors believe, points to the effect of alcohol as “de-differentiator” causing regression. The effects may be linked to the general mechanism of reversible de-differentiation which determines repression of a number of systems (and, consequently, of activity of a number of neurons) in the most differentiated “complex” systems. This simplification may be linked to accelerated learning and also to the fact that organization of behavior becomes more uniform.
The paper considers the methods of acquisition and processing of optical data from small Unmanned Air Vehicles (UAVs) ― photogrammetric point clouds and derivative 3d-models — for the automatic extraction of explicit structure variables in sparse boreal forests of the central part of Kola Peninsula. We review main technological issues of UAV optical surveys, present flowcharts of point clouds classi-fication for the extraction of canopy height model (CHM), further CHM analysis, tree-level and area-based estimation of structural forest variables. Main tree-level variables are crown heights and extent; for forest stands CHM analysis leads to gridded data on tree canopy heights, amount of canopy peaks and tree density, share of tree cover. The definite limitations of optical photogrammetry connected with CHM extraction in dense forests can be partly overcome due to the complex use of point clouds from summer and winter (leaf-off) surveys and independent processing flow of CHM in forest stands with sparser and denser tree canopies.
Broadway is the most famous street of New York City. It follows the island of Manhattan along its whole length and through many of its vernacular regions. Field research of functional, social-economic, architectural and mental differentiation of the street from Bowling Green to 142 Street in Spanish Harlem shaped the methods of linear zoning and revealed 16 unique regions in the researched segment. These regions turned out to be functional, but their borders and composition are based on the vernacular regions of Manhattan. It appears that Broadway, as a major trade and social thruway, forms the surrounding urban landscape. But the role of vernacular regions, through which street passes, remains important and sometimes even crucial.
Verification of the PREFAB database containing golden standard protein alignments was performed. It has revealed a significant number of differences between the sequences from PREFAB and PDB databases. It was shown that, compared with the sequences given in the PDB, 575 alignments referred to a sequence with a gap; such alignments were excluded. Furthermore, compared with the PDB sequences, single substitutions or insertions were found for 440 amino acid sequences from PREFAB; these sequences were edited. SCOP domain analysis has shown that only 502 alignments in the resulting set contain sequences from the same family. Finally, eliminating duplicates, we have created a new golden standard alignment database PREFAB P based on PREFAB; the PREFAB P database contains 581 alignments.
Housing construction in Moscow agglomeration is a key mechanism stimulating migration inflow because it forms a downward pressure on housing prices, which are the most important barrier for migration. Positive feedback between extensive way of development of the Moscow agglomeration and migration inflow into the capital region stimulates hyperconcentration of the population and economic activity. Theoretical analysis shows that there is equilibrium between housing construction and migration inflow to the Moscow region. According to our estimates, in the 2000-s the relation of migration inflow to housing construction volume (capability of the Moscow agglomeration to accumulate migration) has halved in comparison to the 1990s. Mathematical modeling and empirical data show that this shift was determined by the increase in natural rent distributed in Russia and in agglomeration economies in other major cities of the country. Especially favorable for migration inflow is oil-spot-style extensive way of development of the agglomeration due to the dominance of large greenfield projects of affordable housing in the 30-km zone outside the Moscow Ring Road in housing construction. It is shown that the development of this zone is a key regulator of the migration balance at the national level. Extensive way of development is subsidized by the government through multiple channels, primarily investments in transport infrastructure, what contradicts official goals of the regional policy and the government efforts to mitigate interregional inequality through the fiscal redistribution.
The generalized Wiedemann-Franz law for a nonisothermal quasi-neutral plasma with developedion-acoustic turbulence and Coulomb collisions has been proven. The results obtained are used to explain the anomalously low thermal conductivity in the chromosphere-corona transition region of the solar atmosphere. Model temperature distributions in the lower corona and the transition region that correspond to well-known experimental data have been determined. The results obtained are useful for explaining the abrupt change in turbulent-plasma temperature at distances smaller than the particle mean free path.
The influence of nonlinear interaction of oppositely directed nonlinear waves in a shallow basin is studied theoretically and numerically within the nonlinear theory of shallow water. It is shown that this interaction leads to a change in the phase of propagation of the main wave, which is forced to propagate along the flow induced by the oncoming wave. The estimates of the undisturbed wave height at the time of interaction agree with the theoretical predictions. The phase shift during the interaction of undisturbed waves is sufficiently small, but becomes noticeable in the case of the propagation of breaking waves.