42 research outputs found

    Криптовалюта: особенности и риски монетарного использования в экономике России

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    В данной статье рассматриваются ключевые особенности криптовалют, а также реакция с

    Effect of mechanical activation on the composition if mineral components in humic acids isolated from carbons

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    It is shown that the mechanical activation of oxidized and brown coals is accompanied by an increase in the yield of humic acids and in their content of functional groups. It was demonstrated by atomic-emission spectroscopy that, under a high-intensity mechanical treatment, mineral elements are redistributed in the coal substance and incorporated into the structure of humic acids

    Study of application of hydrophobic fibrous sorbents for water purification from metal ions

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    Sorption properties of hydrophobic fibrous sorbents on the basis of polypropylene and polyethylene terephthalate produced from thermoplastic polymer wastes to metal ion series in aqueous media has been studied. Based on the experimental data of extraction degree dependencies on fibre laying density, dispersity, presence of air in sorbent, volume of pass solution the mechanism of metal ion sorption from aqueous media with hydrophobic fibrous materials is suggested

    New method of spectral analysis of human hair

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    A new optimal method of preparing one of the human biosubstrates (hair) to an arc atomic emission spectral analysis is proposed on the basis of complex physical and chemical studies. A new method of determining the content of macro- and micro-elements is developed. Following the developed technique we performed analysis of hairs in group of patients in order to diagnose diseases additionally, assess the habitat, and restore the element balance in the body. Comparing the content of elements in the human hair with reference values, it is possible to assess the degree of element imbalance in the body. This technique has passed metrological certification. Obtained by this method results of analysis of hair were used to identify clinical and laboratory correlations, to determine the elemental human status, and to diagnose various diseases

    Voltammetric Determination of Organic Ecotoxicants on Modified Electrodes

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    In this paper the contemporary state and the use of voltammetric methods for the determination of organic toxicants on the modified electrodes are shown. A review of works on the application of voltammetric methods for the analysis of environmental objects - water (natural, drinking, waste, etc.), published in the last 5 years, has been made. The main trends in electroanalytical control over the content of toxicants in the waters are noted. The experimental results on the expansion of determined organic toxicants are represented

    Complex 99mTc-PDA-DTPA for myocardial imaging

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    The 123I-labeled fatty acids such as 123I-Iodophenylpentadecanoic acid and 123I-Beta-methyliodophenylpentadecanoic acid are the agents used clinically for myocardial imaging. Fatty acids are the major source of energy for the normal myocardium. However, under ischemic conditions the myocardial cells switch to glucose metabolism for their energy needs. Fatty acids undergo prolonged metabolic stunning in patients with reversible ischemia, thereby helping in early diagnosis of coronary artery disease in highrisk patients. High cost andlimited availability of cyclotron-produced 123I, makes 99mTc-labeled fatty acids more desirable for the purpose. In diagnosis the dominant radionuclide is 99mTc. It is estimated that it is involved in about 85% of all imaging procedures in nuclear medicine. The method for preparation of new 99mTc-fatty chemical systems based on modified diethylene triamine pentaacetic acid (DTPA) molecule has been elaborated in this work . The main advantage using DTPA as chelate agent for radioactive label, is the molecule or it's derivative ability to form sufficiently stable complexes with different radioactive metals including technetium-99. Moiety of pentadecanoic acid addition gave the ability to prepare modified complex of DTPA. In a labeling procedure, freshly eluted Na99mTcO4 (20mCi) was added to a mixture of cysteine, stannous chloride, PDK-DTPA and ethanol in a vial. On keeping the reaction mixture at 90 0C for 30 min, [99mTc-PDK-DTPA] radiopharmaceutical was formed. Thereafter, the reaction mixture was cooled over ice and characterized by HPLC. The result of dynamic scintigraphic research showed, that after being injected, the substance is actively acumulated into myocardium. Eventually one can say that modified DTPA-moleculs are functionally suitable for myocardial imaging

    Lobe Specific Ca2+-Calmodulin Nano-Domain in Neuronal Spines: A Single Molecule Level Analysis

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    Calmodulin (CaM) is a ubiquitous Ca2+ buffer and second messenger that affects cellular function as diverse as cardiac excitability, synaptic plasticity, and gene transcription. In CA1 pyramidal neurons, CaM regulates two opposing Ca2+-dependent processes that underlie memory formation: long-term potentiation (LTP) and long-term depression (LTD). Induction of LTP and LTD require activation of Ca2+-CaM-dependent enzymes: Ca2+/CaM-dependent kinase II (CaMKII) and calcineurin, respectively. Yet, it remains unclear as to how Ca2+ and CaM produce these two opposing effects, LTP and LTD. CaM binds 4 Ca2+ ions: two in its N-terminal lobe and two in its C-terminal lobe. Experimental studies have shown that the N- and C-terminal lobes of CaM have different binding kinetics toward Ca2+ and its downstream targets. This may suggest that each lobe of CaM differentially responds to Ca2+ signal patterns. Here, we use a novel event-driven particle-based Monte Carlo simulation and statistical point pattern analysis to explore the spatial and temporal dynamics of lobe-specific Ca2+-CaM interaction at the single molecule level. We show that the N-lobe of CaM, but not the C-lobe, exhibits a nano-scale domain of activation that is highly sensitive to the location of Ca2+ channels, and to the microscopic injection rate of Ca2+ ions. We also demonstrate that Ca2+ saturation takes place via two different pathways depending on the Ca2+ injection rate, one dominated by the N-terminal lobe, and the other one by the C-terminal lobe. Taken together, these results suggest that the two lobes of CaM function as distinct Ca2+ sensors that can differentially transduce Ca2+ influx to downstream targets. We discuss a possible role of the N-terminal lobe-specific Ca2+-CaM nano-domain in CaMKII activation required for the induction of synaptic plasticity

    Improving a Natural CaMKII Inhibitor by Random and Rational Design

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    CaM-KIIN has evolved to inhibit stimulated and autonomous activity of the Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) efficiently, selectively, and potently (IC50 ∼100 nM). The CN class of peptides, derived from the inhibitory region of CaM-KIIN, provides powerful new tools to study CaMKII functions. The goal of this study was to identify the residues required for CaMKII inhibition, and to assess if artificial mutations could further improve the potency achieved during evolution.First, the minimal region with full inhibitory potency was identified (CN19) by determining the effect of truncated peptides on CaMKII activity in biochemical assays. Then, individual residues of CN19 were mutated. Most individual Ala substitutions decreased potency of CaMKII inhibition, however, P3A, K13A, and R14A increased potency. Importantly, this initial Ala scan suggested a specific interaction of the region around R11 with the CaMKII substrate binding site, which was exploited for further rational mutagenesis to generate an optimized pseudo-substrate sequence. Indeed, the potency of the optimized peptide CN19o was >250fold improved (IC50 <0.4 nM), and CN19o has characteristics of a tight-binding inhibitor. The selectivity for CaMKII versus CaMKI was similarly improved (to almost 100,000fold for CN19o). A phospho-mimetic S12D mutation decreased potency, indicating potential for regulation by cellular signaling. Consistent with importance of this residue in inhibition, most other S12 mutations also significantly decreased potency, however, mutation to V or Q did not.These results provide improved research tools for studying CaMKII function, and indicate that evolution fine-tuned CaM-KIIN not for maximal potency of CaMKII inhibition, but for lower potency that may be optimal for dynamic regulation of signal transduction

    A Significant but Rather Mild Contribution of T286 Autophosphorylation to Ca2+/CaM-Stimulated CaMKII Activity

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    Autophosphorylation of the Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) at T286 generates partially Ca(2+)/CaM-independent "autonomous" activity, which is thought to be required for long-term potentiation (LTP), a form of synaptic plasticity thought to underlie learning and memory. A requirement for T286 autophosphorylation also for efficient Ca(2+)/CaM-stimulated CaMKII activity has been described, but remains controversial.In order to determine the contribution of T286 autophosphorylation to Ca(2+)/CaM-stimulated CaMKII activity, the activity of CaMKII wild type and its phosphorylation-incompetent T286A mutant was compared. As the absolute activity can vary between individual kinase preparations, the activity was measured in six different extracts for each kinase (expressed in HEK-293 cells). Consistent with measurements on purified kinase (from a baculovirus/Sf9 cell expression system), CaMKII T286A showed a mildly but significantly reduced rate of Ca(2+)/CaM-stimulated phosphorylation for two different peptide substrates (to ~75-84% of wild type). Additional slower CaMKII autophosphorylation at T305/306 inhibits stimulation by Ca(2+)/CaM, but occurs only minimally for CaMKII wild type during CaM-stimulated activity assays. Thus, we tested if the T286A mutant may show more extensive inhibitory autophosphorylation, which could explain its reduced stimulated activity. By contrast, inhibitory autophosphorylation was instead found to be even further reduced for the T286A mutant under our assay conditions. On a side note, the phospho-T305 antibody showed some basal background immuno-reactivity also with non-phosphorylated CaMKII, as indicated by T305/306A mutants.These results indicate that Ca(2+)/CaM-stimulated CaMKII activity is mildly (~1.2-1.3fold) further increased by additional T286 autophosphorylation, but that this autophosphorylation is not required for the major part of the stimulated activity. This indicates that the phenotype of CaMKII T286A mutant mice is indeed due to the lack of autonomous activity, as the T286A mutant showed no dramatic reduction in stimulated activity

    Криптовалюта: особенности и риски монетарного использования в экономике России

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    В данной статье рассматриваются ключевые особенности криптовалют, а также реакция с
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