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306 result(s) for "Gorbunov, N."
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Rough Statistics in Radio Measurements: Randomization of Uninformative Signal Parameters
This paper analyses the problems of measuring the parameters of a repetitive periodic signal with the monobit (binary 1/0 or signed binary ±1) quantization, which is called “rough statistics” here. The consideration is carried out in relation to radio equipment with phased antenna arrays using spatiotemporal sampling. The system constructed is based on the Monte Carlo method. Randomization of noninformative parameters of the processed signals is used for linearization of the quantization nonlinearity. This paper brings into balance the conventional approach based on an extensive increase in resources (that is, an increase in the resolution and rate of the analogto-digital converter) and the alternative approach involving an increase in the sample size.
Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin
The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1 ligands, especially lactoferrin (Lf) and transferrin (Tf). We hypothesized molecular mimicry of Spike protein as cross-reactivity of Spike-specific antibodies with Tf and Lf. Thus, strong positive correlations (R2 > 0.95) were found between the level of Spike-specific IgG antibodies present in serum samples of COVID-19-recovered and Sputnik V-vaccinated individuals and their Tf-binding activity assayed with peroxidase-labeled anti-Tf. In addition, we observed cross-reactivity of Lf-specific murine monoclonal antibody (mAb) towards the SARS-CoV-2 Spike protein. On the other hand, the interaction of mAbs produced to the receptor-binding domain (RBD) of the Spike protein with recombinant RBD protein was disrupted by Tf, Lf, soluble TfR1, anti-TfR1 aptamer, as well as by peptides RGD and GHAIYPRH. Furthermore, direct interaction of RBD protein with Lf, but not Tf, was observed, with affinity of binding estimated by KD to be 23 nM and 16 nM for apo-Lf and holo-Lf, respectively. Treatment of Vero E6 cells with apo-Lf and holo-Lf (1–4 mg/mL) significantly inhibited SARS-CoV-2 replication of both Wuhan and Delta lineages. Protective effects of Lf on different arms of SARS-CoV-2-induced pathogenesis and possible consequences of cross-reactivity of Spike-specific antibodies are discussed.
Biocatalytic Synthesis of New Cephalosporins Using Immobilized Cephalosporin-Acid Synthetase
Acylation of 1-methyl-5-mercapto-1,2,3,4-tetrazolyl-7-aminocephalosporanic acid, which is the β-lactam nucleus of antibiotics such as Cefamandole, Cefazaflur, Cefotetan, and Cefoperazone, has been carried out using immobilized cephalosporin-acid synthetase as a biocatalyst. Methyl esters of D -mandelic acid, 1(H)-tetrazolylacetic acid, cyanomethylthioacetic acid, thienylacetic acid, D -phenylglycine, and D - p -hydroxyphenylglycine were used as acylating agents. Cefamandole and six chimeric compounds composed of the C3-modified β-lactam nucleus and the acyl parts of various known antibiotics were obtained by the method of kinetically controlled synthesis. Potentially, it is possible to test the antimicrobial activity of the synthesized new chimeric cephalosporins under mild conditions without isolation, directly in the aqueous medium of reaction mixtures after biocatalytic synthesis. The high efficiency of cephalosporin-acid synthetase in the acylation of 1-methyl-5-mercapto-1,2,3,4-tetrazolyl-7-aminocephalosporanic acid with methyl esters of 1(H)-tetrazolylacetic acid and cyanomethylthioacetic acid was demonstrated.
A Comparative Study of Biocatalytic Acylation of 7-Aminocephalosporanic Acid and its C3 Derivatives
The efficiency has been compared of the optimized acylation processes of 7-aminocephalosporanic acid (7-ACA) and its С3 derivatives (7-amino-3-[2-methyl-1,3,4-thiadiazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid (TDA), and 1-methyl-5-mercapto-1,2,3,4-tetrazolyl-7-aminocephalosporanic acid (7-TMCA)) by methyl esters of 1(H)-terazolylacetic and D -mandelic acids (METzAA and MEMA). These processes are catalyzed by immobilized cephalosporin-acid synthetase (IECASA) and are the biocatalytic stages of two different chemical-biocatalytic pathways for the synthesis of cefazolin (CEZ) and cefamandole (CFM). Biocatalytic acylation of 7-ACA resulting in the formation of semi-products of the synthesis of antibiotics proceeded more efficiently than acylation of the corresponding C3 derivatives of 7-ACA, leading to the formation of CEZ and CFM, in terms of both the achieved product yield and the possibility of obtaining compounds in high concentration in the reaction mixture. At the same time, the synthetase ability of IECASA is highest in the acylation of 7-ACA using METzAA. It was shown that the chemical-biocatalytic synthesis of CEZ and CFM by direct biocatalytic acylation of 7-ACA followed by chemical modification of the semi-product at the C3 position of the β-lactam nucleus is a promising alternative to the traditional pathway using the biocatalytic acylation of 7-ACA derivatives with a substituted 3-acetoxy group.
Hypochlorous Acid-Modified Serum Albumin Causes NETosis in the Whole Blood Ex Vivo and in Isolated Neutrophils
Type 2 diabetes mellitus (T2DM) is accompanied by halogenative stress resulting from the excessive activation of neutrophils and neutrophilic myeloperoxidase (MPO) generating highly reactive hypochlorous acid (HOCl). HOCl in blood plasma modifies serum albumin (Cl-HSA). We studied the formation of neutrophil extracellular traps (NETs) in the whole blood and by isolated neutrophils under the action of Cl-HSA. It was found that Cl-HSA induces neutrophil priming and NETosis. MPO-containing as well as MPO-free NETs were found. These NETs with different composition can be a product of NETosis of one and the same neutrophil. NET formation in neutrophils with vacuolated cytoplasm was detected. In the presence of Cl-HSA, acceleration of NET degradation was observed. Accelerated NET degradation and neutrophil priming can be the factors contributing to the development of complications in T2DM.
Model of the cathode region of a plasma photoelectric converter of concentrated solar radiation
A model of the cathode region of a plasma photoelectric converter of concentrated solar radiation in the regime of an open external circuit is considered. Plasma is analyzed in sodium vapor at a pressure of 104 -105 Pa. The necessary optical power is calculated for creating plasma in the state of Local Thermodynamic Equilibrium (LTE), whose temperature is in the range 4000-4500 K. This temperature provides a small internal resistance of the plasma voltage source. A large value of radiative heat conduction coefficient ensures a small temperature drop between the central part and the plasma LTE boundary near the walls of the converter. The model of a Non-LTE zone near the wall of the cathode is analyzed to specify the boundary conditions in the energy balance equation for LTE plasma. The thermal non-equilibrium plasma model resulted in the electron temperature gradient in the Non-LTE zone. The energy losses of electrons in the ionization layer near the cathode are counterbalanced by the thermal conductivity of the electron gas. The specificity of the conditions under consideration consists in the non-local nature of the balance of the electron temperature in the Non-LTE zone.
Stochastic signal processing in adaptive measurement systems with rough space-time statistics: Method of invertible spectral analysis
We propose a modified method for the efficient spectral and correlation space-and- time signal processing intended for operation under the conditions of high dynamics of variations of the intensity of input flow and changes in the frequency-time resource of digital processing. The method is based on the adaptation of algorithms and refinement of the aims and tasks of processing. We develop a methodology of getting high instrumental resolution of signals according to the spectral and/or correlation features. We also consider some aspects of increasing the efficiency of space-time signal processing actual for the radio-engineering measuring systems with digital phased-array antennas and systems aimed at the selection of moving targets. In the updated method, we take into account the variations (type changes) of processed signals. We propose special measures aimed at reducing the requirements to the dynamic range of the input flow by using rough (low-bit and binary) statistics. The frequency range is extended to include the time and space spectra of the distribution laws (of characteristic functions). The engineering (hardware and software) constraints connected with the use of coarse quantization of signals are also taken into account. The efficiency of processing is attained by whitening (rejection of the predominant components) of passive interference prior to the main stage, i.e., the application of the method of invertible spectral analysis and traditional stochastic algorithms, including the increase in sample sizes (apertures and windows) and elevation of the rate of convergence of the measurement data in the basic Monte-Carlo method. The obtained results can be used in radio-engineering measuring complexes, including radar systems, for solving the problems of radio and radio-engineering monitoring and measuring the range and bearing coordinates.
Comparative Evaluation of the Effectiveness of Biocatalytic Synthesis and Antibacterial Activity of Known Antibiotics and “Chimeric” Cephalosporin Compounds
The processes of biocatalytic synthesis of cefamandole and cefazoline, as well as four “chimeric” cephalosporins carrying functional groups of these antibiotics in the C3 or C7 position of β-lactam, were carried out using immobilized cephalosporin-acid synthetase under mild standard conditions. A higher efficiency of biocatalytic acylation of β-lactams with a 1(H)-tetrazolylacetic acid residue was demonstrated compared to acylation with mandelic acid residue. The chemical structure of the obtained compounds was confirmed using the HPLC-MS method. The possibility of using directly reaction mixtures for evaluating the antibacterial activity of the compounds synthesized without isolating the target products is demonstrated. The activity of the obtained cephalosporins against twelve microorganisms belonging to the genera Enterococcus , Acinetobacter , Serratia , Pseudomonas , Staphylococcus, and Escherichia was evaluated by the method of diffusion into agar. The activity of synthesized “chimeric” cephalosporins against four microorganisms was found: Escherichia coli VKPM B-6695, Staphylococcus aureus VKPM B-6646, Staphylococcus aureus VKPM B‑8171, and Staphylococcus epidermidis VKPM B-12635.
Detection of the Brominating Activity of Myeloperoxidase Using Fluorescein
A study was carried out on the spectralluminescent properties of fl uorescein after its reaction with various reactive oxygen and halogen species ( O 2 ∙ - , H 2 O 2 , HOCl, HOBr, HOSCN, N-chloramine, taurine N-chloramine, and taurine N-bromamine) as well as in the myeloperoxidase (MPO)–H 2 O 2 –Cl – /Br – /SCN – system. Reaction with only HOBr or with the MPO–H 2 O 2 –Br system turns fluorescein into a compound with an absorption maximum at 518 nm. The fluorescence maximum is recorded at 540 nm when excited at 520 nm, corresponding to eosin Y (brominated fluorescein). Conditions with phosphatebuffered saline (PBS) at pH 7.4 containing 137 mM NaCl, 5 mM fluorescein, 15–30 mM NaBr, and 25–50 mM H 2 O 2 were found to be optimal for detecting HOBr in solution. A qualitative method for determining the brominating activity of MPO in vitro has been proposed. This method was used to study the effect of physiological and synthetic inhibitors as well as reactive oxygen and halogen species scavengers on the brominating activity of MPO. Our results indicate that fluorescein holds promise for use in a fluorescent method for detecting the brominating activity of mammalian hemecontaining peroxidases.
Characterization of Combined Effects of Reactive Oxygen Metabolites, Complement System, and Antimicrobial Peptides In Vitro
Objective: Phagocytes activation results in the production of reactive oxygen metabolites exerting antimicrobial and host-damaging activity. Although the main pool of papers shows their potentiating action on a key humoral nexus of innate immunity, complement system, the data are controversial. Combined action of reac­tive oxygen metabolites with antimicrobial peptides of phagocytes also remains poorly characterized. Methods: We have investigated the influence of oxidative burst products on complement activation in various in vitro models and assessed the combined bactericidal action of hypochlorous acid with antimicrobial peptides. Results and Discussion: Hydrogen peroxide, including that in medium with Fe-EDTA did not affect parameters of complement activity in human blood serum. HOCl in millimolar concentrations stimulated production of C3a and C5a anaphylatoxins in 80% serum, the effect was inhibited by EDTA. We have identified bivalent ions-independent C5 cleavage in the presence of 16 mM HOCl. At the same time, HOCl served as an inhibitor of the alternative complement pathway in the model of membrane-associated activation in 5% serum in the presence of Mg-EGTA and rabbit erythrocytes. It inhibited production of C3a (IC 50 ~4 mM) and C5a as well as serum hemolytic activity (IC 50 ~0.2 mM). The inhibition of C5a generation was less pro­nounced in the presence of relatively high HOCl concentration (4–16 mM). Decrease in anaphylatoxins generation was also observed in the system with zymosan in 5% serum with Mg-EGTA. Under similar conditions but without activating surfaces, moderate HOCl concentrations enhanced C3a accumulation and C5a accumulation; EDTA inhibited this effect completely (C3a) or partially (C5a). Finally, in 70% serum, 16 mM HOCl enhanced the anaphylatoxins accumulation in the absence of zymosan but it inhibited this process almost completely under the conditions of the zymosan-triggered amplification loop. According to our hypothesis, HOCl can attack the thioester bond in C3 protein to form C3(HOCl) adduct which is capable of fluid-phase C3 and C5 convertases formation; however, the attack of the same group in C3b can prevent its covalent fixation on membranes and blocks the complement amplification loop. In addition, the transformation of C3 to C3(HOCl) which is not able to serve as a substrate of C3 convertases may also be responsible for complement inhibition. Besides, we have demonstrated the additive character of the combined action of HOCl with antimicrobial peptides (LL-37 cathelici­din and α-defensins HNPs) against Listeria monocytogenes and Escherichia coli . Conclusions: According to our results, hydrogen peroxide and hydroxyl radical do not participate in complement modulation. HOCl is an activator of fluid-phase and an inhibitor of surface complement activation. HOCl may also induce complement-independent C5 cleavage in serum. HOCl and antimicrobial peptides of phagocytes kill bacteria in an additive manner. The data obtained clarify the picture of the interaction between bactericidal factors of phagocytes and complement as key participants of the immune defense and host damage.