We analyzed advantages of the liposomal form of Xymedon (50 and 100 mg/kg) over free Xymedon (in the corresponding doses) in leukopoiesis restoration in rats with Walker-256 carcinoma treated with ...liposomal combination of doxorubicin (4 mg/kg) and cyclophosphamide (45 mg/kg) (single intravenous injection on day 11 after transplantation of tumor cells). Liposomal and free Xymedon were injected intravenously over 5 days starting from day 11 of the experiment. Changes in leukopoiesis in peripheral blood and myelograms were assessed on days 3 and 7 after chemotherapy. Liposomal Xymedon in both doses (unlike its free form) 2-fold increased the number of lymphocytes on day 3 after chemotherapy in comparison with the level observed after administration of liposomal cytostatics alone. Liposomal Xymedon in a dose of 50 mg/kg (but not 100 mg/kg) promoted the maintenance of monocyte count at the level of intact control on days 3 and 7 after chemotherapy. Liposomal Xymedon in a dose of 50 mg/kg and free Xymedon in a dose of 100 mg/kg equally stimulated the increase in myelocytes content in the bone marrow to the level of intact control on day 3 after chemotherapy, thus promoting restoration of granulocytopoiesis.
The paper suggests considering neo-industrial development that is represented as alternative to post-industrialism from the perspective of provision of innovation and investment safety of the ...country. Authors make an effort to determine economic and institutional backgrounds and criteria of safety of innovation and investment activities. Specification of categorical framework used in researched sphere was conducted; in particular, it was suggested to consider innovation and investment safety the key part of national economic safety. On the basis of regression analysis the appraisal of relation between the size of internal expenditures for research and development and living standards in the country was held--it has demonstrated rather weak relation between researched variables during a short period of time. In addition, the work formulates the key problems in the sphere of innovation and investment safety in Russia and suggests proposals on their solution.
Abstract
Uptake of atmospheric carbon by the ocean, especially at high latitudes, plays an important role in offsetting anthropogenic emissions. At the surface of the Southern Ocean south of 30
∘
S, ...the ocean carbon uptake, which had been weakening in 1990s, strengthened in the 2000s. However, sparseness of in-situ measurements in the ocean interior make it difficult to compute changes in carbon storage below the surface. Here we develop a machine-learning model, which can estimate concentrations of dissolved inorganic carbon (DIC) in the Southern Ocean up to 4 km depth only using data available at the ocean surface. Our model is fast and computationally inexpensive. We apply it to calculate trends in DIC concentrations over the past three decades and find that DIC decreased in the 1990s and 2000s, but has increased, in particular in the upper ocean since the 2010s. However, the particular circulation dynamics that drove these changes may have differed across zonal sectors of the Southern Ocean. While the near-surface decrease in DIC concentrations would enhance atmospheric CO
2
uptake continuing the previously-found trends, weakened connectivity between surface and deep layers and build-up of DIC in deep waters could reduce the ocean’s carbon storage potential.
Abstract
Linear theory for steady stratified flow over topography sets the range for topographic wavenumbers over which freely propagating internal waves are generated, and the radiation and breaking ...of these waves contribute to energy dissipation away from the ocean bottom. However, previous numerical work demonstrated that dissipation rates can be enhanced by flow over large scale topographies with wavenumbers outside of the lee wave radiative range. We conduct idealized 3D numerical simulations of steady stratified flow over 1D topography in a rotating domain and quantify vertical distribution of kinetic energy dissipation. We vary two parameters: the first determines whether the topographic obstacle is within the lee wave radiative range and the second, proportional to the topographic height, measures the degree of flow non-linearity. For certain combinations of topographic width and height, breaking occurs in pulses every inertial period, such that kinetic energy dissipation develops inertial periodicity. In these simulations, kinetic energy dissipation rates are also enhanced in the interior of the domain. In the radiative regime the inertial motions arise due to resonant wave-wave interactions. In the small wavenumber non-radiative regime, instabilities downstream of the obstacle can facilitate the generation and propagation of non-linearly forced inertial motions, especially as topographic height increase. In our simulations, dissipation rates for tall and wide non-radiative topography are comparable to those of radiative topography, even away from the bottom, which is relevant to the ocean where the topographic spectrum is such that wider abyssal hills also tend to be taller.
Abstract
One of the proposed mechanisms for energy loss in the ocean is through dissipation of internal waves, in particular above rough topography where internal lee waves are generated. Rates of ...dissipation and diapycnal mixing are often estimated using linear internal wave generation theory and a constant value for mixing efficiency. However, previous oceanographic measurements found that nonlinear dynamics may be important close to topography. To investigate the role of nonlinear interactions, we conduct idealized 3D direct numerical simulations (DNS) of steady flow over 1D topography and vary the topographic height, which correlates to the degree of flow nonlinearity. We analyze the spatial distribution of energy transfer rates between internal waves and the nongeostrophic portion of the time-mean flow, and of dissipation and diapycnal mixing rates. In our simulations with taller, more nonlinear topographies, energy transfer rates are similar to previously unexplained oceanographic observations near topography: internal waves gain energy from time-mean flow through horizontal straining and lose energy through vertical shearing. In the tall topography simulations, buoyancy fluxes also play a significant role, consistent with observations but contrary to linear wave theory, suggesting that quasigeostrophy-based approximations and linear theory may not hold in some regions above rough topography. Both dissipation and mixing rates increase with topographic height, but their vertical distributions differ between topographic regimes. As such, the vertical profile of mixing efficiency is different for linear and nonlinear topographic regimes, which may need to be incorporated into parameterizations of small-scale processes in models and estimates of ocean energy loss.
Inorganic Polyphosphate and Cancer Kulakovskaya, E. V.; Zemskova, M. Yu; Kulakovskaya, T. V.
Biochemistry (Moscow),
08/2018, Letnik:
83, Številka:
8
Journal Article
Recenzirano
This review presents data on the relationship between inorganic polyphosphate metabolism and carcinogenesis including participation of polyphosphates in the regulation of activity of mTOR and other ...proteins involved in carcinogenesis, the role of h-prune protein (human polyphosphatase) in cell migration and metastasis formation, the prospects for using polyphosphates and inhibitors of polyphosphate metabolism enzymes as agents for controlling cell proliferation and migration.
The genotoxic action of ozone and hydrogen peroxide on healthy peripheral blood leukocytes from Kv:SHK mice and the human breast adenocarcinoma cell line MDA-MB-231 in vitro has been tested by comet ...assay. The results show that the concentration range in which the lowest ozone concentration in the ozone–oxygen mixture that damages tumor cell DNA to the lowest ozone concentration that induces genotoxic effects on healthy blood cells is 0.2–0.4 mg/L, whereas the corresponding range of hydrogen peroxide concentrations is 0.1–3.0 μM. In these ranges, the genotoxic effect of ozone on breast adenocarcinoma cells is less than that of hydrogen peroxide. The genotoxic effect of gemcitabine, a cytostatic drug, is potentiated in combination with ozone–oxygen (0.4 mg/L ozone in the mixture): the DNA damage increases more than twofold. It is assumed that the enhanced genotoxic effect of gemcitabine in combination with ozone is associated with the intensification of the incorporation of major gemcitabine metabolites into DNA strands owing to DNA repair process stimulation.
Abstract
We present numerical results for an idealized rotating, buoyancy- and windforced channel as a simple model for the Southern Ocean branch of the Meridional Overturning Circulation (MOC). ...Differential buoyancy forcing is applied along the top horizontal surface, with surface cooling at one end (to represent the pole) and surface warming at the other (to represent the equatorial region) and a zonally re-entrant channel to represent the Antarctic Circumpolar Current (ACC). Zonally-uniform surface wind forcing is applied with a similar pattern to the westerlies and easterlies with varying magnitude relative to the buoyancy forcing. The problem is solved numerically using a 3D DNS model based on a finite-volume solver for the Boussinesq Navier-Stokes equations with rotation. The overall dynamics, including large-scale overturning, baroclinic eddying, turbulent mixing, and resulting energy cascades are studied by calculating terms in the energy budget using the local Available Potential Energy framework. The basic physics of the overturning in the Southern Ocean are investigated at multiple scales and the output from the fully-resolved DNS simulations is compared with the results from previous studies of the global (ECCO2) and Southern Ocean eddy-permitting state estimates. We find that both the magnitude and shape of the zonal wind stress profile are important to the spatial pattern of the overturning circulation. However, the available potential energy budget and the diapycnal mixing are not significantly affected by the surface wind stress and are primarily set by the buoyancy forcing at the surface.
Abstract The generation of internal tides at coastal margins is an important mechanism for the loss of energy from the barotropic tide. Although some previous studies attempted to quantify energy ...loss from the barotropic tides into the deep ocean, global estimates are complicated by the coastal geometry and spatially and temporally variable stratification. Here, we explore the effects of supercritical, finite amplitude bottom topography, which is difficult to solve analytically. We conduct a suite of 2D linear numerical simulations of the barotropic tide interacting with a uniform alongshore coastal shelf, representing the tidal forcing by a body force derived from the vertical displacement of the isopycnals by the gravest coastal trapped wave (of which a Kelvin wave is a close approximation). We explore the effects of latitude, topographic parameters, and nonuniform stratification on the baroclinic tidal energy flux propagating into the deep ocean away from the shelf. By varying the pycnocline depth and thickness, we extend previous studies of shallow and infinitesimally thin pycnoclines to include deep permanent pycnoclines. We find that scaling laws previously derived in terms of continental shelf width and depth for shallow and thin pycnoclines generally hold for the deeper and thicker pycnoclines considered in this study. We also find that baroclinic tidal energy flux is more sensitive to topographic than stratification parameters. Interestingly, we find that the slope of the shelf itself is an important parameter but not the width of the continental slope in the case of these steep topographies. Significance Statement The objective of this study is to better understand how vertical density stratification, which can vary seasonally in the ocean, affects the interaction of tides with steep coastal topography and the generation of waves that travel away from the coast in the ocean interior. These waves in the interior can travel over long distances, carrying energy offshore into the deep ocean. Our results suggest that the amount of energy in these internal waves is more sensitive to changes in topography and latitude than to the vertical density profile. The scaling laws found in this study suggest which parameters are important for calculating global estimates of the energy lost from the tide to the ocean interior at the coastal margins.
Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic ...agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (
) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent
values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1-0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatics analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect the efficacy of anti-TNF treatment in various diseases.
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