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Using Recombinant DNA Technology, the novel bacterial recombinant strain Escherichia coli DAC-22, a source of diadenylate cyclase that catalyzes the transformation of adenosine-5′-triphosphate into cyclic 3′,5′-diadenylate (cyclo-di-AMP), was developed. The strain was derived by the transformation of E. coli Rosetta (DE3) pLysS cells with the recombinant plasmid pET42a+ wherein the disA gene responsible for the synthesis of the diadenylate cyclase of Bacillus thuringiensis was inserted. The producing capacity of the new strain with respect to diadenylate cyclase localized in catalytically active inclusion bodies equaled 720 units per liter of liquid culture. The newly engineered strain is destined for use in the technology related to the production of pharmaceutically promising cyclo-di-AMP.

Using the DNA recombination technique, a new bacterial strain Escherichia coli DAC-22 was derived, whose cells are able to carry out the heterologous expression of Bacillus thuringiensis diadenylate cyclase – the enzyme catalyzing the reaction of adenosine-5′-triphosphate (ATP) transformation into cyclic 3′,5′-diadenylate (cyclo-di-AMP). To derive the strain, E. coli “Rosetta (DE3) pLysS” cells were originally used as recipients of plasmid pET42a+ with the inserted gene disA encoding diadenylate cyclase of B. thuringiensis. The cells of the recombinant strain are able to produce heterologous diadenylate cyclase localized predominantly (by 90 %) in the fraction of the catalytically active inclusion bodies. The productivity of the new strain with respect to diadenylate cyclase structurally arranged as the inclusion bodies was 720 units/l of cultural fluid. The inclusion bodies formed by the newly engineered strain are intended for use in the technology of producing pharmacologically promising cyclo-di-AMP.

The ongoing COVID-19 pandemic accompanied by the emergence of new successive pathogenic variants makes problematic the prospects of the approach based on application of exclusively prophylactic vaccines to combat SARSCoV-2. This reason motivated the urgent need in search and development of chemical formulas showing direct antiviral action.The present mini-review provides data on chemical and enzymatic methods of producing molnupiravir regarded so far as one of the most effective pharmaceuticals for treatment of COVID-19. In conclusion of the literature survey it is suggested to administer lipid-containing analog instead of molnupiravir in COVID-19 therapeutic protocols. In this respect the authors reported the successful synthesis catalyzed by bacterial phospholipase D of 5′-dimyristoyl derivative of N4-hydroxycytidine – the compound allegedly more efficient than molnupiravir in inhibiting SARS-CoV-2 replication.

В статье рассмотрена роль нефтегазовой отрасли в экономике Казахстана, а также современные тенденции цифровой трансформации отрасли в стране, включающие такие технологии, как искусственный интеллект, большие данные, интернет вещей, машинное обучение и цифровой двойник.

With the transition from natural to virtual communication, there are new technologies for presenting information, the perception of which depends on its presentation by modern multimedia. Visual perception plays an important role in everyday life, helping in learning and communicating with other people. Behind the most effective perception is a complex process of understanding the information obtained. Visual perception of information includes the processes of seeing and reading. Building assumptions on what we see, we rely on expectations, beliefs, past knowledge and previous experience. Reading is a complex activity that involves both the process of perception and thought. At the very beginning of the formation of reading, understanding is not common, but only after perception, as the development and automation of reading skills, understanding begins to outpace the process of perception, manifested in the emergence of semantic assumptions, guessing meaning within words. Perception of visual image is accompanied by the actualization of its auditory-motor image, without which it is impossible to recognize. Reading is accompanied by inner speech. The same information can be understood by different people with different degrees of depth, which entails the existence of factors that affect the process of perception and understanding of texts. Such factors can be divided into the following groups: characteristics of the individual who acts as a subject of perception and understanding; parameters of the text and the reality that is reflected in this text; features of the situation in which the process of perception and understanding takes place. Text in a virtual environment, ie media information - is more accurately and quickly perceived by a person and it depends on various factors influencing perception, as well as the type and method of presenting information. The purpose of the study is to analyze the perception of digitalized information, the formation of recommendations for professionals with UI / UX, which will be further formed into a prototype of a possible web directory. The aim is also to develop a possible tool model that can be used not only by the above specialists, but also by SMM-managers, business analysts and others. The methods of research were chosen analysis - the study of individual parts of the objects of study, comparing different approaches or their individual components to obtain a holistic picture of the subject area.

We present results of the investigations of the properties of the methanol $J_1 - J_0$ A$^{-+}$ line series motivated by the recent serendipitous detection of the maser emission in the $14_1 - 14_0$ A$^{-+}$ line at 349~GHz in S255IR-SMA1 soon after the accretion burst. The study includes further observations of several lines of this series in S255IR with the SMA, a mini-survey of methanol lines in the 0.8 mm range toward a sample of bright 6.7~GHz methanol maser sources with the IRAM-30m telescope, and theoretical modeling. We found that the maser component of the $14_1 - 14_0$ A$^{-+}$ line in S255IR decayed by more than order of magnitude in comparison with that in 2016. No clear sign of maser emission is observed in other lines of this series in the SMA observations except the $7_1 - 7_0$ A$^{-+}$ line where an additional bright component is detected at the velocity of the maser emission observed earlier in the $14_1 - 14_0$ A$^{-+}$ line. Our LVG model constrains the ranges of the physical parameters that matches the observed emission intensities. No obvious maser emission in the $J_1 - J_0$ A$^{-+}$ lines was detected in the mini-survey of the 6.7~GHz methanol maser sources, though one component in NGC7538 may represent a weak maser. In general, the maser effect in the $J_1 - J_0$ A$^{-+}$ lines may serve as a tracer of rather hot environments and in particular luminosity flaring events during high mass star formation., Comment: 16 pages, 12 figures

An Esсherichia coli 42cpa-c strain synthesizing C-terminal fragment of Clostridium perfringens alpha-toxin was engineered. The strain is distinguished by productive capacity 1.2 mg of target protein per 1 L of cultural liquid. The protein contains octahistidine peptide at C-end of the molecule, enabling to carry out its one-stage purification by metal-affine chromatography on Ni2+-NTA resin. The resulting CPA-C protein preparation is potentially suitable for formulation of the derived vaccine.

The method of continuous overlapping polymerase chain reaction was applied to clone gene encoding keratinase of Bacillus licheniformis within vector pET42a(+). The resulting genetic construction was used to transform Escherichia coli BL21 (DE3) cells. The strain with maximum level of protein synthesis was selected. Specific activity of purified enzyme solution (purity grade ~95 %) in the reaction with azocasein substrate equaled 73.18 units/mg protein. The recombinant E. coli strain could serve as a source of enzyme capable to process keratinous wastes.

The parameters and description of promising objects for observing with the RT-70 millimeter-wave radio telescope under construction on the Suffa plateau (Uzbekistan) are presented. The possible problems of their study using the RT-70 telescope are considered. The necessary time consumptions are estimated. The planned characteristics of the RT-70 are briefly compared with parameters of other large radio telescopes of the millimeter wavelength range.

COVID-19 pandemic caused by coronavirus SARS-CoV-2 affected virtually all life aspects in most countries and nations. During 2020 around 100 mln of Earth inhabitants contracted this morbid infection and 2 mln people died thereafter. It is natural therefore that many pharmaceutical companies around the globe have joined into the race aimed at elaboration of prophylactic antiviral vaccines. However, the option can not be ruled out that parenteral vaccines to counter rapidly mutating pandemic coronavirus may be designed hastily, neglecting due tests of remote side effects, so that in the long run they risk to be expelled from the marked due to doubtful safety and efficiency.As a real alternative to traditional vaccination techniques the present mini-review has proposed application of intranasal adjuvant nano-vaccine. If necessary, this approach may be complemented with pharmacological inactivation of coronavirus under the impact of ribo-favipiravir, recombinant arginine deiminase, RNAse L or lactoferrin, as well as biogenic silver or copper nanoparticles - the preparations derived from up-to-date molecular biotechnological processes.

The study was aimed at determining cardiorespiratory coordination under the influence of acute hypoxia in athletes with different levels of sports qualifications. Eighteen runners aged 17 to 25 were exposed to acute (10% O2) hypoxia for 10 min. Respiration, gas exchange, and heart rate were measured during normoxia and hypoxia. The principal component (PC) analysis was used to assess cardiorespiratory coordination; the stability of PCs under the influence of hypoxia was evaluated by the Tucker’s Congruence Coefficient. The analysis was performed on a time series of 10 min of normoxia and hypoxia with the inclusion of heart rate, minute ventilation, the expired fraction of O2 and CO2. According to the level of qualification, athletes were divided into two groups: highly trained (HT, no less than category I, n = 9) and medium-trained (MT, category II, n = 9). Under normoxia, cardiorespiratory coordination in athletes of both groups was higher than in normobaric hypoxia (p = 0.001): during normoxia, the model included one PC from coordinated variables according to the Kaiser criterion in 44% of the athletes; during hypoxia, the model consisted of two PCs in 100% of the athletes. During hypoxia, the percentage of total variance explained by PC2 increased significantly (p < 0.001), regardless of the level of qualification. In hypoxia, there was a change in the variable contributions to PC1 and PC2, more pronounced in the MT group: the contribution of heart rate to PC1 increased, and the expired fraction of CO2 decreased (p < 0.001). The congruence coefficient of the first PC between normoxia and hypoxia in the HT group showed a high level of similarity (median = 0.88; 25/75% = 0.84/0.93) and was significantly (p < 0.05) higher than in MT (0.82; 0.46/0.94). Thus, highly qualified athletes have the higher cardio-respiratory stability under hypoxic exposure. This can be an additional predictive sign of good athletic performance.

The environment of S187, a nearby H ii region (1.4 ± 0.3 kpc), is analyzed. A surrounding shell has been studied in the H i line, molecular lines, and also in infrared and radio continua. We report the first evidence of a clumpy H i environment in its photodissociation region. A background radio galaxy enables the estimation of the properties of cold atomic gas. The estimated atomic mass fraction of the shell is ∼260 M⊙, the median spin temperature is ∼50 K, the shell size is ∼4 pc with typical wall width around 0.2 pc. The atomic shell consists of ∼100 fragments. The fragment sizes correlate with mass with a power-law index of 2.39–2.50. The S187 shell has a complex kinematical structure, including the expanding quasi-spherical layer, molecular envelope, an atomic sub-bubble inside the shell and two dense cores (S187 SE and S187 NE) at different stages of evolution. The atomic sub-bubble inside the shell is young, contains a Class II young stellar object and OH maser in the centre and the associated YSOs in the walls of the bubble. S187 SE and S187 NE have similar masses (∼1200 and ∼900 M⊙, respectively). S187 SE is embedded into the atomic shell and has a number of associated objects, including high-mass protostars, outflows, maser sources, and other indicators of ongoing star formation. No YSOs inside S187 NE were detected, but indications of compression and heating by the H ii region exist.

Colibacteriosis is an acute zoonotic disease manifested by septicaemia, toxemia, enteritis, body dehydration, and central nervous system damage. Depending on the presence of virulence factors and the nature of interaction with the intestinal mucosa, enterotoxigenic, enteroinvasive, enteropathogenic, and enterohemorrhagic E. coli are isolated. Enterotoxigenic strains of E. coli occupy one of the leading places in the etiological structure of calf colibacteriosis in many livestock farms of the Republic of Belarus. The main reason why this disease develops is the presence of thermolabile and thermostable toxins in the causative strain. The thermolabile toxin subunit B is a potent antigen that allows pet immunity to be acquired against E. coli-induced cattle diarrhea. Many foreign vaccines used against intestinal infections of cattle contain either a native or recombinant variant of the subunit B. As a result of the work, we have created a new strain of E. coli 42eLTB – the producer of the recombinant subunit B of the thermolabile toxin E. coli. The producing capacity of the obtained strain is 480 mg with 1 culture liquid liter, which exceeds the already known strains 1.37 times.

The novel promising trend of biotechnology is cell-free synthesis of proteins. Possibility of producing two chimeric proteins: adenosine deaminase of Escherichia coli fused with human annexin-A5, DNA-affine domain of bacteria Sulfolobus solfataricus fused with modified Taq-DNA-polymerase and bacterial enzyme diguanylatecyclase of Thermotoga maritima, by cell-free synthesis procedure as an alternative to conventional cultivation of microbial strains-producers in a bioreactor was studied in this research. Chimeric RNA polymerase of T7 bacteriophage, S30-cell extract of E. coli and multicopy plasmid pET42mut were engaged for protein synthesis by cell-free protein synthesis system. The first successful production of these proteins was demonstrated in CFPS system.

We give a review of both our own original scientific results of the development of superconducting receivers for sub-terahertz astronomy and the main leading concepts of the global instrumentation. The analysis of current astronomical problems, the results of microwave astroclimate research, and the development of equipment for sub-terahertz radio astronomy studies justify the need and feasibility of a major infrastructure project in Russia to create a sub-terahertz telescope, as well as to enhance the implementation of the ongoing Millimetron and Suffa projects. The following results are discussed: i) superconducting coherent receivers and broadband subterahertz detectors for space, balloon, and ground-based radio telescopes have been developed and tested; ii) ultrasensitive receiving systems based on tunnel structures such as superconductor-insulator-superconductor (SIS) and superconductor-insulator-normal metal-insulator-superconductor (SINIS) have been created, fabricated, and examined; iii) a receiving array based on SINIS detectors and microwave readout system for such structures has been implemented; iv) methods for manufacturing high-quality tunnel structures Nb/AlOx/Nb and Nb/AlN/NbN based on niobium films with a current density of up to 30 kA/cm(2) have been developed. Receivers operated at 200 to 950 GHz and having a noise temperature only a factor of 2 to 5 higher than the quantum limit have been created and tested.

Today the environmental problem of modern society is the rapid contamination of water resources around the world for pharmaceutical products, including antibiotics. According to the University of York (UK), contamination with antibiotics had covered two-thirds of the waterways of the planet. It was established experimentally that 90 % of antibiotics are applied into the surrounding environment: soil and water. Residues of medical drugs fall into rivers via human waste and animals and through the treatment plant, including pharmaceutical companies. On the other hand, under the influence of antibiotics can significantly change the biocenosis of water bodies. And bacteria gradually become immune to the effects of antibiotics. Therefore, the Ukrainian research Institute of ecological problems in cooperation with the National scientific center Kharkiv Institute of physics and technology experimental studies aimed at inactivation of bactericidal properties of antibiotic solution during processing ozone-air mixture. The study assessed the effectiveness of inactivation of antibiotic ciprofloxacin hydrochloride by methods related to deep oxidation AOPs technologies (Advanced Oxidation Processes) on the basis of combinations of ozonation, UV irradiation, treatment with hydrogen peroxide. Shown the prospects of using ozonation and O3/UV and O3/UV/H2O2 to reduce the toxic effect of the antibiotic residues of ciprofloxacin relative to the test object E. coli in the aquatic environment. Found that ozonation of activated sludge treated with ciprofloxacin, reduces the toxic effect of the antibiotic and promotes the enzymatic activity of the biocenosis of activated sludge

It is known that bacterial purine nucleoside phosphorylase (PNPase), unlike mammalian PNPase, is capable of phosphorolytic cleavage of adenosine and its derivatives to form free nitrogen bases. This makes it possible to use bacterial PNPase (provided the problem of delivering this enzyme or its gene to target cells is solved) as a prodrug therapy for cancer. In addition, PNPase in a tumor bed can destroy extracellular adenosine, which is known to protect cancer cells from antitumor immunity.As a result of the study, a new strain of Escherichia coli was constructed, producing a chimeric protein whose molecule consists of a homologous PNPase fused to human annexin A5, a protein showing affinity for cancer cells.The production capacity of the producer strain of the chimeric protein “Annexin-PNPase” with respect to PNPase calculated from the results of the inosine phosphorolysis reaction, was 10,200 units/ml of culture liquid. The obtained strain is intended for creation of a technology for obtaining new antitumor preparations.

The flow of a gas over a conic body, having a nose blunted over a sphere, with a supersonic velocity at different angles of attack was considered. The possibility of control of the temperature regime of such a body in the case of three-dimensional gas flow over it was investigated. The dependence of the temperature of the surface of the indicated body on the material of which it is made, the angle of attack of the body, and other constitutive parameters of the problem on conjugate nonstationary heat exchange between the body and the gas fl ow over it was determined for standard conditions of an aerodynamic experiment. Results of numerical solution of this problem for different angles of attack of the body were processed in the criteria form. The dependences obtained allow one to estimate the degree of decrease in the maximum temperature at the surface of a blunt-nosed conic body depending on the thermophysical parameters of the material of which this surface is made, including in the case of nonstationary gas fl ow over it. It is shown that a uniform heating of the peripheral part of such a body and a marked decrease in the temperature of its windward part at large angles of attack can be provided with the use of highly heat-conducting materials for these parts of the body.

A series of conjugates of pharmacologically promising modified nucleosides with phospholipid was synthesized. Some liponucleotides were originally produced. Soybean lecithin served as the donor of phosphatidyl residue. Phospholipase D from strain Streptomyces netropsis BIM B-428D was engaged as biocatalyst in transphosphatidylation reaction. The yield of liponucleotide synthesis reaction varied in the range 44–95 mol% depending on the acceptor of phosphatidyl residue. 65 mg (about 68 µmoles) of pure phosphatidylclofarabine was recovered by chromatography on silica gel column, resulting in 68 mol% yield calculated from the amount of modified nucleoside supplied into the reaction mixture.

Objective The aim: Was hygienic substantiation of necessity for monitoring in the environmental objects of SDHI fungicides considering their possible impact on the thyroid gland. Patients and methods Materials and methods: To test the proposed selection criteria for hygienic monitoring of pesticides that affect the thyroid gland, we evaluated 4 new SDHI fungicides from the chemical class of pyrazolecarboxamides (isopyrazam, pentiopyrad, sedaxan, fluxapyroxad). Results Results: Based on the results obtained, all studied compounds are assigned to the second pesticide group, hygienic monitoring of which is desirable but not required. This is due, on the one hand, to their low toxicity, to the other, to low environmental sustainability. Conclusion Conclusions: It was shown, that compared to other classes of pesticides, the studied are much less dangerous in terms of groundwater contamination.

A supernova remnant (SNR) candidate SRGe~J0023+3625 = G116.6-26.1 was recently discovered in the \textit{SRG}/eROSITA all-sky X-ray survey. This large ($\sim 4$ deg in diameter) SNR candidate lacks prominent counterparts in other bands. Here we report detection of radio emission from G116.6-26.1 in the LOFAR Two-metre Sky Survey (LoTTS-DR2). Radio images show a shell-like structure coincident with the X-ray boundary of the SNR. The measured surface brightness of radio emission from this SNR is very low. Extrapolation of the observed surface brightness to 1~GHz places G116.6-26.1 well below other objects in the $\Sigma-D$ diagram. We argue that the detected radio flux might be consistent with the minimal level expected in the van der Laan adiabatic compression model, provided that the volume emissivity of the halo gas in the LOFAR band is $\sim 10^{-42}\,{\rm Wm^{-3}Hz^{-1} sr^{-1}}$. If true, this SNR can be considered as a prototypical example of an evolved SNR in the Milky Way halo. In the X-ray and radio bands, such SNRs can be used as probes of thermal and non-thermal components constituting the Milky Way halo., Comment: 6 pages, submitted to MNRAS Letters

We present line and continuum observations (resolution ~0.3"-3.5") made with the Atacama Large Millimeter/submillimeter Array (ALMA), Submillimeter Array, and Very Large Array of a young O-type protostar W42-MME (mass: 19-4 Msun). The ALMA 1.35 mm continuum map (resolution ~1") shows that W42-MME is embedded in one of the cores (i.e., MM1) located within a thermally supercritical filament-like feature (extent ~0.15 pc) containing three cores (mass ~1-4.4 Msun). Several dense/hot gas tracers are detected toward MM1, suggesting the presence of a hot molecular core with the gas temperature of ~38-220~K. The ALMA 865 micron continuum map (resolution ~0.3") reveals at least five continuum sources/peaks ("A-E") within a dusty envelope (extent ~9000 AU) toward MM1, where shocks are traced in the SiO(8-7) emission. The source "A" associated with W42-MME is seen almost at the center of the dusty envelope, and is surrounded by other continuum peaks. The ALMA CO(3-2) and SiO(8-7) line observations show the bipolar outflow extended below 10000 AU, which is driven by the source "A". The ALMA data hint the episodic ejections from W42-MME. A disk-like feature (extent ~2000 AU; mass ~1 Msun) with velocity gradients is investigated in the source "A" (dynamical mass ~9 Msun) using the ALMA H13CO+ emission, and is perpendicular to the CO outflow. A small-scale feature (below 3000 AU) probably heated by UV radiation from the O-type star is also investigated toward the source "A". Overall, W42-MME appears to gain mass from its disk and the dusty envelope., 28 pages, 14 figures, Accepted for publication in The Astrophysical Journal

Searches for the lepton number violating $K^{+} \rightarrow \pi^{-} \mu^{+} e^{+}$ decay and the lepton flavour violating $K^{+} \rightarrow \pi^{+} \mu^{-} e^{+}$ and $\pi^{0} \rightarrow \mu^{-} e^{+}$ decays are reported using data collected by the NA62 experiment at CERN in $2017$-$2018$. No evidence for these decays is found and upper limits of the branching ratios are obtained at 90% confidence level: $\mathcal{B}(K^{+}\rightarrow\pi^{-}\mu^{+}e^{+})

The effects of biofeedback trainings (BFT) are sufficiently detailed in scientific literature. However, the mechanism of their formation and individual characteristics of the reactions are not fully disclosed. The purpose of the paper is to study the indirect effect of biofeedback trainings aimed at managing arterial pulse on hypoxic stability and ANS state in healthy people, taking into account the individual characteristics of the response. Materials and Methods. The study involved 28 young women and 26 young men (19–23 years old), who underwent a 15-day biofeedback training. The authors measured the trial subjects’ heart rate (HR), duration of RR-intervals, blood pressure before and after the training. A hypoxic stress test was also carried out. Results. According to the results of the biofeedback trainings, all the volunteers were retrospectively divided into two groups: “reducing heart rate” (R) and “non-reducing heart-rate” (N). All females and N males demonstrated an almost twofold decrease in the number of low-resistant-to-hypoxia persons with their transition into a group of medium- and high- resistant ones. N-girls, if compared with R-girls, showed a greater increase in the number of highly resistant persons (p=0.06). Resistance comparison between male groups also showed a significant increase in highly resistant persons in N-males, if compared to R-males (p=0.01). Biofeedback-training in all groups led to a steady blood pressure decrease (both systolic (p

In one of our earlier papers, we considered supersonic, laminar boundary-layer flows past bodies made of different materials and examined the possibility of controlling the temperature regime of a body immersed in flow. In the present work, for the conditions corresponding to aerodynamic experiments and to long flight times, we analyzed such values of deceleration parameters when regions of laminar, transitional, and turbulent regimes of flow are realized simultaneously in a boundary layer. The possibility of decreasing the level of maximal temperatures depending on the determining criteria of the problem has been evaluated for bodies made of different materials. The expediency of using simplified approaches is shown, including those for nonstationary conditions based on stationary solutions and on well-studied limiting cases of isothermal and adiabatic surface temperatures and allowing the determination of the temperature regimes in the entire range of thermophysical characteristics.