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The aim of the article is to present a method of project portfolio management for the regional development of dual education under conditions of uncertainty using expert methods. In the project portfolio management standard, portfolio formation is represented by a group of alignment processes, but their practical application in a specific subject area remains at the discretion of the developer. For the design and development of software systems, visual process models are developed for a specific subject area. The article presents the development of a complex system of dual education through the formation of a portfolio of projects. The data obtained allowed to determine that the portfolio management methodology can be successfully implemented in Ukrainian dual education. To improve the processes of portfolio management, a practical implementation of the processes of portfolio formation in the IDEF0 notation was carried out. A simplified algorithm for forming a project portfolio has been developed, which allows increasing the speed of response to changes in portfolio management in educational sphere. The proposed solution of the educational system development through portfolio using expert methods that are distinguished by the application of the Pareto rule for building a scenario for the system development. On the basis of the developed methodology for forming a portfolio of innovative projects, the process of optimizing the efficiency of the portfolio of innovative projects with determining their individual priorities is studied on the example. The application of the developed procedures for planning the portfolio management of the dual education system in the central region of Ukraine is demonstrated. The results obtained have made it possible to make sure that the system development management in conditions of incomplete information covers the areas of process management, and helps to minimize the impact of uncertainty on the efficiency of the portfolio of projects implementation

The article aims to present a method of specialties cases management based on models of system evolution within the frame-work of a pilot projectin institutions of professional pre-higher and higher education of Ukraine for the training of specialists in the dual form of education. The obtained data allowed determining that the methodology of project management can be successfully implemented in Ukrainian dual education. However, the Ukrainian system of dual education still lacks many elements, and some of them cannot be reproduced in the national environment, because the student himself can choose a form of education. The article pre-sents a simulation of the dual education system evolution in a specific specialty in the form of a multicriterial optimization problem. Well-known McKinsey model is adapted to determine the variant of the strategy for managing the dual education system. With the help ofsuch model, the specialties of the educational institution were ranked as candidates for investment according to the criterion of future profit. The trajectory of the specialty evolution has been developed by means of the method for assessing of qualitative factors, such as the attractiveness of the labor market and the competitive status of the educational institution. The inclusion of the specialty evolution trajectory in the integral criteria of the McKinsey model, made it possible to not onlyestablisha competitive sta-tus for the current period, but also extrapolate it without significant changes to the entire strategic period to predict the competitive status of a particular specialty. It is proposed to apply a decision support system based on the useof an apparatus of fuzzy sets and fuzzy logic to formalize decision-making in an intelligent system. The using of the fuzzy logic apparatus made it possible to adjust and clarify the strategic positions of each business unit of the dual education project portfolio. Thus, a significant practical effect was obtained, since the using of this fuzzy system allows to quickly assessingthe forecast positions of dual education projects, to evaluate the future competitive status of the educational product and the management strategy of this project

In this work, we developed the method of preparative production of recombinant human cyclophilin A (rhCypA) in Escherichia coli. The full-length cDNA encoding the gene of human CypA (CYPA) was amplified by RT-PCR from the total RNA of human T cell lymphoma Jurkat. The nucleotide sequence of CYPA was optimized to provide highly effective translation in E. coli. Recombinant CYPA DNA was cloned into the pET22b(+) vector, and the resulted expression plasmid was used to transform E. coli strain BL21(DE3)Gold. The recombinant producer strain of E. coli produced soluble rhCypA in the bacterial cytoplasm. The synthesis efficiency of rhCypA was up to 50% of the total cell protein allowing to produce rhCypA in the amount of 1 g per liter of the culture. We also developed the method for rhCypA purification, consisting of a single-step tandem anion exchange chromatography on DEAE- and Q-Sepharose columns. The protein purity was 95% according to electrophoresis (SDS-PAGE), and its contamination with endotoxin did not exceed 0.05 ng per 1 mg of the protein that met the requirements of European pharmacopoeia for injectable preparations. The produced recombinant protein exhibited functional features of native CypA, i.e., isomerase activity and chemokine activity as assessed by stimulation of migration of mouse bone marrow hematopoietic stem cells in vivo. The generated producer strain of E. coli is a super-producer and could be used for large-scale experimental studies of rhCypA and in its preclinical and clinical trials as a drug.

Background. Nowadays, dermatoses with mixed clinical picture and resistant to classical management become more common. The presence of various genetic disorders typical for most chronic dermatoses may indicate possible combination of several nosologies.Clinical Case Description. The article presents the clinical case of multimorbid condition in 10 years old patient who has nucleotide variants in CARD14 and EXPH5 genes. Mutations in CARD14 gene are typical for patients with type 2 psoriasis and pityriasis rubra pilaris (autosomal dominant type), while mutations in EXPH5 gene are typical for patients with non-specific epidermolysis bullosa (autosomal recessive type). Mutation in the TGM1 gene that is described in patients with congenital ichthyosis (autosomal recessive type), pathogenic mutations in KRT74 gene typical for ectodermal dysplasia, hypotrichosis and uncombable hair syndrome, and mutations in the KRT86 gene typical for monilethrix were also revealed. Medical history taking and histological examination as well as clinical data evaluating are crucial for correct diagnosis. They allow to understand the absence of the such manifestations in relatives and reveal various pathological processes in the epidermis. Molecular genetic testing with new generation sequencing (NGS) helps to finally establish the diagnosis and determine the further tactics for patient management.Conclusion. Multidisciplinary approach and use of high-technology methods of examination and treatment (such as molecular genetic testing and biological therapy) are required for final diagnosis in severe forms of chronic dermatosis resistant to treatment and for decision on correct tactics for the further management of such patients.

Psoriasis is multifactorial systemic disease characterized by excessive hyperkeratosis due to impaired keratinocytes proliferation and differentiation. This disease often manifests in childhood and it is usually associated with the development of comorbid conditions some of which are combined by the term «psoriatic march» (obesity, metabolic syndrome, etc.). The course of psoriasis and related comorbidities in children has several specific features that determine topicality of studying all the aspects of clinical diagnosis and prevention in childhood. The article summarizes recent ideas on the prevalence, pathogenesis features and early diagnosis of comorbid diseases in children with psoriasis.

Background. The study of psoriasis biological therapy aspects in children has certain topicality due to the small number and disunity of individual observations and the lack of special registers for pediatric patients.Objective. Our aim was to study ustekinumab efficacy and safety in children with plaque (PP), erythrodermic (EP) and palmoplanar (PPP) forms of psoriasis.Methods. The analysis of ustekinumab efficacy and safety has been carrying out for 1 year. The evaluation of therapy efficacy was based on definition of improvement of PASI scores (PASI 75, PASI 90 and PASI 100) on the 16th, 28th, 40th and 52nd weeks of follow-up and children's dermatology life quality index (CDLQI). Ustekinumab therapy safety analysis was based on registration and evaluation of adverse effects. Results. The study included 67 children with PP, EP and PPP aged 12 to 18 years. PP group results: the PASI 75 response at the 52nd week of therapy was observed in 35 children (100%), PASI 90 — in 33 (94%), PASI 100 — in 30 (86%). EP group results: 10 patients (56%) have reached PASI 75 on the 16th week, while none of patients have improved to PASI 90 and PASI 100 scores. The PASI 75 response at the 52nd week of therapy was observed in 18 children (100%), PASI 90 — in 17 (94%), PASI 100 — in 7 (39%). Only 1 patient (7%) with PPP has showed the score decrease to PASI 75 on the 16th week. Adverse effects were reported in 2 patients.Conclusion. Ustekinumab is the effective and safe treatment for moderate and severe forms of PP and EP in children, and it can also be considered as one of the alternative methods for PPP treatment in pediatrics.

Goal. Multifaceted comprehensive identification of potential opportunities for meat productivity of calves of the Simmental Ukrainian breed in ecological, economic, and fodder conditions of non-pastoral growing in the central Steppe of Ukraine. Methods. 20 clinically healthy Simmental bulls analogs by the age, type, and other economically useful characteristics were placed on long-term cultivation (from birth to the age of 30 months) in the experimental farm «Polyvanivka» of Dnipropetrovsk region by the method of group-periods. Types of feed and level of feeding (typical for the steppe zone) provided medium growth and high enough live weight at the end of the experiment. The animals were kept loosely on feeding grounds for up to the age of 18 months, and then — on a leash indoors. Analysis of growth and development and control slaughter of bulls was performed at the age of 12, 18, 24, and 30 months (5 animals each). Biometric processing of research results was carried out by the method of variation statistics. Results. It is proved that growing Simmentals to a later age is expedient and economically justified. Not only the weight of the carcass (growth rate 1.59; 2.05 and 2.39) but also the weight of the flesh (growth rate 1.66; 2.10 and 2.45) grew with age (18, 24, and 30 months) compared to 12 months. Bone mass growth rate (1.34; 1.86 and 2.18) lagged. Thus, the muscle-bone ratio (meat ratio) improved. It varied with the age of the animals from 3.7 (12 months) to 4.24 (2.5 years). The share of flesh increased from 79 to 81%, and the proportion of bones decreased from 21.9 to 19%. Despite the age of slaughter of animals, their meat had optimal physical and technological properties and was suitable for culinary use and long-term storage. Conclusions. The calves of the combined Simmental breed can show high meat productivity up to 30 months of age in the ecological, economic, and fodder conditions of the Steppe zone of Ukraine with economic expediency. In terms of morphological composition and quality of carcasses, Simmental bulls are superior to dairy breeds and are close to beef cattle. The meat of Simmental bulls has a high taste and is suitable for both dietary nutrition (from young animals) and people of physical labor (from animals aged 24 – 30 months).

The main purpose of this article is to create a mathematical apparatus for calculating premiums for control and discounts for the lack of control when calculating share interests in business. The article covers the issue of estimating premium and discount rates for the presence or lack of control when switching from one to another level of value taking into account changes in a controlling number of shares exercised by the owners of corresponding stock shares, equity holding structure, market conditions and applicable laws covering stock corporations. The article also provides corresponding mathematical tools and calculation examples.

This paper provides a solution to the problem of investment choice between cash and income-generating assets and also describes a possible approach to valuation the relative and absolute value of liquidity in such a situation.

Background.The availability of drug-eluting stents with evidence-based clinical safety and efficacy produced in the Russian Federation is one of the relevant goals for successful treating of patients with coronary artery disease, including acute coronary syndrome. Aim To confirm clinical rationale and experimental feasibility of the first Russian drugeluting stent, Calypso (Angioline, LLC, Russian Federation), for the clinical practice.Methods.The study included four phases. The first phase was aimed at selecting the optimal stent platform with superior healing properties. Then, the selected Russian coronary stents based on the optimal platforms underwent preclinical studies. The third phase included the clinical assessment using optical coherence tomography (OCT) in order to confirm the preclinical results. The last phase was focused on assessing clinical safety and efficacy of the Russian coronary stent based on the comparative analysis of angiographic findings within the 12-months follow-up.Results.At the first phase, biodegradable polymer sirolimus-eluting stent showed superior healing properties in comparison with the healing score of 18±14.97 for Orsiro stents (Biotronik, Germany) versus 25.6±1.0 for Xience stents (Abbott Vascular, USA) versus 32.5±20.3 for Synergy (Boston Scientific, USA), pConclusion.The biodegradable polymer sirolimus-eluting stent Calypso manufactured in the Russian Federation demonstrated superior neointimal healing pattern with no signs of chronic inflammation in the experiment. This stent reported high neointimal healing properties according to the clinical OCT study. According to the angiographic findings, the incidence of binary restenosis between the Russian biodegradable polymer sirolimus-eluting stent and durable polymer everolimuseluting stents was similar at the 12-months follow-up (p>0.05).

Psoriasis is one of the most common chronic recurrent dermatoses, which is not limited to skin lesions, leading to a violation of the functions of various body organ systems. The article presents the results of the analysis of the medical histories of patients of Clinical dermatovenerologic dispensary (Krasnodar Region of Russia) with moderate-severe and severe forms of psoriasis and concomitant cardiological pathology. The article presents data from 70 case histories of patients with moderate to severe psoriasis, the analysis of which shows the clinical and practical significance of comorbidity of psoriasis. From the analysis, we conclude that there is a direct relationship between the severity of the course of the cutaneous pathological process and the aggravation of the cardiological diagnosis. The higher the severity of psoriasis, the higher the risk of developing acute coronary syndrome, myocardial infarction and other cardiac pathology.

Background. In recent years, transcatheter implantation of the aortic valve has become increasingly performed as an alternative to "open" prosthetics. The undoubted advantage of this technology is its minimally invasive nature, which in most cases provides a favorable clinical outcome of the intervention. The transcatheter method of aortic valve prosthetics does not require sternotomy and connection of an artificial circulation device, which significantly reduces the risk of postoperative mortality and complications. However, despite all the advantages of the existing models, they are not without drawbacks that force researchers to develop and test new transcatheter valves. The problem of experimental studies of new models of self-opening transcatheter aortic valves is mainly determined by the anatomical features of the aortic root of animals. In this regard, the development of a reliable method of implantation of valve prostheses in the experiment is an urgent problem of preclinical testing.Aim. Development of a protocol for open implantation of a transcatheter aortic valve in experiment and evaluation of long-term results.Methods. To develop an experimental model, pigs of the "Landras" breed, females weighing 129.83 ± 9 kg were used. Transcatheter aortic valve implantation was performed under conditions of artificial circulation and moderate hypothermia (33-34°C) through a transverse aortotomy under the control of vision. During the experiment, invasive monitoring of blood pressure, central venous pressure, heart rhythm, body temperature, blood gas composition, activated clotting time was performed. The correct positioning and hemodynamic parameters after implantation were evaluated using transesophageal echocardiography.Results. In a series of chronic experiments, 18 open implantations of self-opening transcatheter aortic valves were performed. Successful positioning was achieved in 100% of cases. The developed protocol of open implantation made it possible to achieve reliable fixation of the prosthesis in the orthotopic position, as well as to prevent the migration of the prosthesis, the development of mitral regurgitation, paraaortic fistulas and coronary circulation disorders.Conclusion. In the course of the study, a simple and effective method of open implantation of a transcatheter aortic heart valve prosthesis was developed in an experiment.Received 1 October 2021. Revised 1 November 2021. Accepted 12 November 2021.Funding: This work was carried out within the framework of the state task of Ministry of Health of Russian Federation No. 121032300337-5.Conflict of interest: Authors declare no conflict of interest.Contribution of the authorsConception and study design: M.O. Zhulkov, D.A. Sirota, K.V. Kozyr, D.S. SergeevichevData collection and analysis: M.O. Zhulkov. Drafting the article: M.O. ZhulkovCritical revision of the article: D.A. Sirota, A.M. ChernyavskiyExperimental part: M.O. Zhulkov, H.A. Agaeva, A.K. Sabetov, I.S. Zykov, A.R. TarkovaFinal approval of the version to be published: M.O. Zhulkov, K.V. Kozyr, I.S. Zykov, A.R. Tarkova, H.A. Agaeva, A.K. Sabetov, D.A. Sirota, D.S. Sergeevichev, A.M. Chernyavski

The rapid development of space-based technologies and services continuously increases the requirements for specialists developing, testing, and operating space technology. Conventional teaching methods are not enough to train highly qualified and competitive specialists in the space industry. This paper presents an example of a project for improving the quality of educational programs for engineering students. The project is run based on the Amur State University. The purpose of the project is to train personnel to ensure the effective operation of the new Vostochny cosmodrome in Russia. The problem of improving the quality of students’ training is solved in a threefold manner. First, the first university center for spacecraft flight control was created in the Far East. Second, an educational program based on laboratory practices using telemetry information from small spacecraft “AIST” was introduced. Third, engineering training based on completing a project to develop a real CubeSat class spacecraft was tested and integrated into the curriculum. Solving these tasks allowed expanding and intensifying educational programs for engineering majors, increasing their competence in the development and operation of spacecraft. Thus, the educational program is capable of providing the fledging Vostochny cosmodrome with highly qualified young specialists.

The purpose. To determine ethological methods for growing bulls and stimulating their sexual function. Methods. Method of groups-analogues under equal conditions of growing, feeding and use of producers; ethological methods of study of behaviour of animals in herd and mini-herd; zoo-technical and statistical. Results. It is proved that sexual function and quality of bulls’ sperm can be raised due to mechanopressure and electrostimulation of their erogenous zones. Conclusions. Limitation of intersexual selection at bulls is possible at lowering stressful situation. Sexual dynamical stereotype develops at gobies on the basis of imprinting after the first delivery of sperm in artificial vagina. The designed methods and devices for electrostimulation by sinusoidal modulated currents and mechanopressure of erogenous acupuncture zones can restore libido and erection at bulls.

The article analyzes the components of the energy structure based on carbon-free energy, shows the catalysts and risks. An assessment of the reserves for increasing the energy efficiency of large cities in Russia is presented on the example of the Moscow metropolis. The ranking of the technical and economic feasibility of introducing modern energy-saving technologies based on a large-scale analysis of projects implemented in Moscow is given. Revealed and assessed the magnitude of the effects of the main stakeholders of “green building”: city; investor and owner of premises; resident and tenant; specialist-designer, engineer, architect. Sectors are shown that are most expedient both from the point of view of the achieved effects, and from the point of view of achieving the maximum economic effect.

Traditional technologies for the production of beef in the conditions of industrial production of livestock products in the middle of the 20th century were schematically transferred from dairy cattle breeding and do not take into account the behavioral characteristics of animals. The traditional approach to the cultivation of young animals involves a stall-and-loose keeping system, mechanized distribution of feed and manure cleaning. Under such conditions the labor costs for the production of 1 kg of beef are within 15-30 man-hours, the total specific weight of feed, electricity, fuel and lubricants, depreciation costs of livestock buildings and technological equipment in the cost structure of this product reaches 50-55%. Beef production remains unprofitable regardless of animal breed – the cost of 1 kg of meat is 1.5-2 times higher than the sales price, which hinders further development of the industry. The paper shows the results of the assessment of meat productivity of bulls of various breeds when raised using traditional and low-cost technologies. Research results are relevant for beef production in steppe regions.

This review article presents results of studies on adherence to drug therapy of patients after discharge from hospital. It contains analysis of the reasons for poor adherence, assessment of the impact of quality of adherence on the immediate and long-term results of surgical and medical treatment, structured methods of improvement of adherence to therapy; as well as economic aspects of the problem.

Aim. To investigate the infl uence of natural selection of bulls during tethered and non-tethered keeping on their reproductive function. Methods. Observation of analogue groups in different conditions of keeping, yet with the identical level of feeding and using, ethological methods of the behavior of animals in a herd and in a “mini- herd”, zootechnical, genetic-mathematical, biometric and modelling methods. Results. It was established that dominant animals in the herd oppress the sexual ability of their subordinates, causing the decrease in their libido, erection, quality of sperm (as far as to the impotence). Conclusions. The infl uence of natural selection on the sexual potency of breeding bulls during their non-tethered keeping and some ethological specifi cities during the tethered keeping were established along with the reactions of an organism depending on the type of body composition and build. The application of the revealed regularities facilitates the work regarding the selection of bulls while evaluating the quality of the sperm production and ensuring the increase in the number of their offspring in further generations.

Aim. The article looks at the effect of the program "Confidence" to increase the proportion of patients’ therapy in patients with coronary heart disease for two years after successful revascularization using thrombolytic or stenting of the coronary arteries on the myocardial infarction.Methods. This is a prospective, randomized, controlled, parallel-group trial including 4.000 patients. They will be divided into two groups: patients receiving standard outpatient observation (n=2000) and those enrolled for the program "Confidence" (n=2000). The total duration is 24 months. The trial will take place in two stages. In the first stage (0-12 months) the impact of the program "Confidence" on therapy adherence and outcomes of cardiovascular diseases will be assessed. In the second stage (after the change of groups in 12 months, 12-24 months) the effect of changing the way to remind patients of therapy adherence will be evaluated.Conclusion. The trial was designed in such a way as to show that the proposed program "Confidence" increases the proportion of patients who adhere to therapy in the cohort of those with coronary heart disease for two years after successful revascularization by using thrombolytic or stenting of the coronary arteries against the background of myocardial infarction.Received 13 February 2017. Accepted 9 March 2017.Financing: KRKA company’s grant. Sponsorship had no effect on data acquisition, analysis and interpretation.Conflict of interest: Kretov E.I. served as executive editor of “Endovascular surgery” section. All other authors declare no conflict of interest.Author contributionsStudy conception and design: Kretov E.I., Grazhdankin I.O., Baystrukov V.I., Zubarev D.D. Statistical data processing: Krestyaninov O.V., Kozyr K.V., Obedinskiy A.A., Prokhorikhin A.A.Drafting the article: Tarkova A.R., Anisimova V.D.Critical revision: Tarkova A.R., Anisimova V.D., Kretov E.I.

It is shown that electrospark processing is the outstanding achievement in industrial technolo-gies. Nowadays, electrospark processing in many cases does not have any alternative: hard-processing, tough and supertough electricity conductor forming, surface reinforcement, dispersion. It is shown that this method, established by our compatriots B. R. Lazarenko and N. I. Lazarenko more than 70 years ago, met difficulties in its development, having tested creation and destruction stages twice. Unfortunately, over the last years this method does not develop in our country.

This review article presents results of studies on adherence to drug therapy of patients after discharge from hospital. It contains analysis of the reasons for poor adherence, assessment of the impact of quality of adherence on the immediate and long-term results of surgical and medical treatment, structured methods of improvement of adherence to therapy; as well as economic aspects of the problem.

An efficient method of highly sensitive, specific determination of botulinic type A neurotoxin (which allows the detection of a toxin in a concentration from 1 pg/mL (10 fg per one PCR reaction) was created based on the technology of immuno-PCR. Solid phase consisting of paramagnetic organo–silicious particles carrying a detection complex of the toxin heavy chain with a pair of polyclonal antibodies to it was the most appropriate in the optimal scheme of the analysis. One of the antibodies bound to DNA (which is a matrix for PCR amplification) by means of biotin–neutravidin interaction. Matrix DNA was a molecular “net” generated by biotinylated DNA molecules with tetravalent neutravidin. The binding signal was detected by real time PCR (by the TaqMan method). An immuno-PCR method for determination of type A botulotoxin was developed.

Category A select agents continue to be major threat to human population both as naturally occurring diseases and as potential weapon of bioterrorists. Anthrax and botulism are probably the most threatening agents as both have virtually uncontrolled natural reservoirs from which they can be isolated and propagated. Available specific antitoxin therapy of both diseases is outdated; its efficiency is questionable as well as safety of reactogenic or human-derived components used in treatment. Highly sensitive toxin detection techniques are still not as widespread as it needed for timely alerting medical services. There is urgent need of pre-exposure prophylaxis and postexposure specific antitoxin therapy for anthrax and botulism. Analysis of modern studies in the field suggests oligoclonal antibodies acting against receptor-binding toxin subunits and nucleic acid aptamers as allosteric inhibitors of metlloproteolytic toxin components as the most promising candidates for development of efficient antitoxin therapy

Currently all nuclear power plants with VVER -reactors used data measuring systems called a Boron Concentration Meter (NAR). They are necessary for the boron control implementation. NAR consists of sensors and auxiliary devices, and it includes the device of storage and data processing (UNO). Both the rapid evolution of computer architectures, and associated microprocessor hardware updates in the electronics market create a necessity of a new device development. The main design goals both are to optimize the hardware solutions and to use a new software and algorithmic capabilities. However, another development goal is not only the upgrading of circuitry and software, but the optimization of calibration process in the NAR and testing it.

Aptamers are short single-stranded oligonucleotides which are selected via targeted chemical evolution in vitro to bind a molecular target of interest. The aptamer selection technology is designated as SELEX (Systematic evolution of ligands by exponential enrichment). SELEX enables isolation of oligonucleotide aptamers binding a wide range of targets of interest with little respect for their nature and molecular weight. A number of applications of aptamer selection were developed ranging from biosensor technologies to antitumor drug discovery. First aptamer-based pharmaceutical (Macugen) was approved by FDA for clinical use in 2004, and since then more than ten aptamer-based drugs undergo various phases of clinical trials. From the medicinal chemist’s point of view, aptamers represent a new class of molecules suitable for the development of new therapeutics. Due to the stability, relative synthesis simplicity, and development of advanced strategies of target specific molecular selection, aptamers attract increased attention of drug discovery community. Difficulties of the development of next-generation antibiotics basing on the conventional basis of combinatorial chemistry and high-throughput screening have also amplified the interest to aptamer-based therapeutic candidates. The present article reviews the investigations focused on the development of antibacterial aptamers and discusses the potential and current limitations of the use of this type of therapeutic molecules.

The method of the electrical discharge machining (EDM) with the application of the solid metal wire electrode-tools (WET) is known. The wear of the WET and limits of the values of the current and the tension force are the disadvantages of the EDM method. The EDM with the application of the conductive laser channel (CLC) as an electrode-tool is offered. The equivalent electric scheme of the electroerosive cell with two plasma channels: CLC and electrical discharge, is considered. The distribution of the heat in the workpiece after the current pulse passing through electroerosive cell is studied. The experimental research of the EDM process with the use of the CLC as an electrode-tool are carried out.

Pre-steady state kinetic analysis of mechanistic features of substrate binding and processing is crucial for insight into the evolution of inhibitor-resistant forms of HIV-1 protease. These data may provide a correct vector for rational drug design assuming possible intrinsic dynamic effects. These data should also give some clues to the molecular mechanism of protease action and resistance to inhibitors. Here we report pre-steady state kinetics of the interaction of wild type or mutant forms of HIV-1 protease with a FRET-labeled peptide. The three-stage "minimal" kinetic scheme with first and second reversible steps of substrate binding and with following irreversible peptide cleavage step adequately described experimental data. For the first time, a set of "elementary" kinetic parameters of wild type HIV-1 protease and its natural mutant inhibitor-resistant forms MDR-HM, ANAM-11 and prDRV4 were compared. Inhibitors of the first and second generation were used to estimate the inhibitory effects on HIV-1 protease activity. The resulting set of kinetic data supported that the mutant forms are kinetically unaffected by inhibitors of the first generation, proving their functional resistance to these compounds. The second generation inhibitor darunavir inhibited mutant forms MDR-HM and ANAM-11, but was ineffective against prDRV4. Our kinetic data revealed that these inhibitors induced different conformational changes in the enzyme and, thereby they have different mode of binding in the enzyme active site. These data confirmed hypothesis that the driving force of the inhibitor-resistance evolution is disruption of enzyme-inhibitor complex by changing of the contact network in the inhibitor binding site.

The relationship between RSFSR and USSR social organizations in the sphere of liquidation of illiteracy is studied on the basis of archive and published sources. The author of the article characterizes the main stages of collaboration, gives examples of joint events, describes the specific features of all-union campaigns against illiteracy and determines the main forms and methods of collaboration. The author also emphasizes on the key reasons that lead to problems in the process of liquidation of illiteracy within the determined term: the methodological helplessness in the campaign against illiteracy among adults, critical lack of books and periodical editions necessary for effective conduction of the campaign. The relationship between Ukrainian and Russian Federation social organizations that specialized in anti-illiteracy campaigns are investigated by the example of social competitions. The conduction of patron work of ‘Out Illiteracy Organization’ in the Chechen Autonomous Republic is also described in the article. The author analyzed the role of social organizations in the work connected with enhancing cultural and educational level of population. This question remains relevant also in the modern conditions.Purchase on Elibrary.ru > Buy nowDOI: http://dx.doi.org/10.12731/2070-7568-2014-3-10

The spread of the New Delhi metallo-beta-lactamase (NDM-1), a plasmid-borne enzyme conferring bacterial resistance to any known beta-lactam antibiotics, represents the global health threat. There is an urgent need to develop the efficient NDM-1 inhibitors of various mode of action thereby necessitating structural studies of the enzyme as well as analysis of the secretion pathway and localization of the protein. The recombinant full-length NDM-1 is produced in E. coli in the inactive form and is mostly accumulated in the inclusion bodies. The secreted recombinant NDM-1 forms are several N-terminally truncated species. The robust expression system capable of high-level production of the full-length NDM-1 and derivatives thereof is required to obtain NDM-1 in the quantities necessary for drug discovery, diagnostics, and research purposes. Therefore, we developed a new system that utilizes antibiotic pressure to select E. coli producing increased quantity of soluble NDM-1 and showed that an increase in the NDM-1 solubility occurs in the bacterial clones producing increased amounts in the chaperones.

A model of a controlled conversion of polysaccharide Vi-antigen of S. typhi into zwitterionic antigen is proposed. The immunological properties of modifications of this antigen conjugated to a protein support were studied.

У статті зроблено спробу дослідити оптимальні шляхи вирішення проблеми формування інформаційної компетентності сучасного менеджера в галузі освіти; теоретично висвітлено особливості процесу формування інформаційної компетентності як пріоритету успішного менеджменту у сучасному інформаційному середовищі.

Electro-spark alloying (ESA) method was used to create a coating on the surface of TC11 alloy (Ti–6.5Al–3.5Mo–1.5Zr-0.3Si wt%). The oxidation behavior of the TC11 alloy and its deposited coating was investigated in air at 700°C. The resulting structures were analyzed in great detail by metallographic analysis and by scanning electron microscopy (SEM)

Nucleic acid-based aptamers are widely accepted as promising tools for development of a plethora of diagnostic and therapeutic preparations, as well as means of environmental monitoring. The properties of aptamers permit them to be regarded as fully synthetic analogs of antibodies. Moreover, certain properties of aptamers render them superior to antibodies in terms of the development of new diagnostic and monitoring systems that combine high sensitivity and specificity with high reproducibility and inexpensive manufacture. In particular, aptamer-based technologies for detection of biomolecules and whole microorganisms can be employed in solving the problems of highly sensitive express diagnostics of bacterial pathogens. The present review summarizes the current state of the techniques developed for aptamer-based detection of bacteria and their components and discusses the potential of their practical application.

The immunoglobulin molecule is a perfect template for the de novo generation of biocatalytic functions. Catalytic antibodies, or abzymes, obtained by the structural mimicking of enzyme active sites have been shown to catalyze numerous chemical reactions. Natural enzyme analogs for some of these reactions have not yet been found or possibly do not exist at all. Nowadays, the dramatic breakthrough in antibody engineering and expression technologies has promoted a considerable expansion of immunoglobulin's medical applications and is offering abzymes a unique chance to become a promising source of high-precision "catalytic vaccines." At the same time, the discovery of natural abzymes on the background of autoimmune disease revealed their beneficial and pathogenic roles in the disease progression. Thus, the conflicting Dr. Jekyll and Mr. Hyde protective and destructive essences of catalytic antibodies should be carefully considered in the development of therapeutic abzyme applications.

This article considers the structure of interest rate, applied for discounting of risky cash flows. The purpose of the article is a presentation of ways of reflecting inflation and risks in the calculation of risk discount rate. In introduction on base of well-known dependences is shown that risk premium depends on inflation rate and (for multiplicative-type models) risk free rate. In the first part of the article three Interest rate algebras are presented. They describe the attitude between nominal discount rate, risk free rate, inflation rate and risk-premium. This algebras can presents in additive-type or multiplicative-type versions and have given risk premium value without detailed description the structure of risk premium. The second part of the paper has more detailed attitude between risk premium, risk free rate and mathematical expectation of losses because of bankruptcy/default. It is shown that the obtained dependences are slightly different and depends on the initial preconditions calculation: the principle of arbitration or the principle of certainly equivalent.

Functional imaging of subtilisin Carlsberg active center by the idiotypic network yielded a catalytic anti-idiotypic antibody with endopeptidase, amidase, and esterase activities. A monoclonal antibody inhibitory to subtilisin (Ab1 5-H4) was employed as the template for guiding the idiotypic network to produce the catalytic anti-idiotypic Ab2 6B8-E12. Proteolytic activity of 6B8-E12 was demonstrated by zymography using self-quenched fluorescein-BSA conjugate and in a coupled assay detecting Ab2- dependent RNase A inactivation. Cleavage of peptide substrates by 6B8-E12 revealed distinct patterns of hydrolysis with high preference for aromatic residues before or after the scissile bond. Catalytic activity of Ab2 was inhibited by phenylmethylsulfonyl fluoride, a mechanism-based inhibitor of serine hydrolases. 5-H4 and 6B8-E12 were cloned, produced in Escherichia coli as single-chain variable fragments (scFvs), and purified. Kinetic parameters for amidolytic and esterolytic activities were similar in Ab2 and its scFv derivative. Although the antigen-specific portion of 6B8-E12 possesses no primary structure similarity to subtilisin, it mimics proteolytic and amidolytic functions of the parental antigen, albeit with 4 orders of magnitude slower acceleration rates. The lack of detectable endopeptidase activity of 6B8-E12 scFv raises interesting issues concerning general evolution of catalytic activity. The in silico 3D models of Ab1 and Ab2 revealed strong structural similarity to known anti-protease antibodies and to abzymes, respectively. These results indicate that the idiotypic network is capable, to a significant extent, of reproducing catalytic apparatus of serine proteases and further validate the use of imaging of enzyme active centers by the immune system for induction of abzymes accelerating energy-demanding amide bond hydrolysis.

Category A select agents continue to be major threat to human population both as naturally occurring diseases and as potential weapon of bioterrorists. Anthrax and botulism are probably the most threatening agents as both have virtually uncontrolled natural reservoirs from which they can be isolated and propagated. Available specific antitoxin therapy of both diseases is outdated; its efficiency is questionable as well as safety of reactogenic or human-derived components used in treatment. Highly sensitive toxin detection techniques are still not as widespread as it needed for timely alerting medical services. There is urgent need of pre-exposure prophylaxis and postexposure specific antitoxin therapy for anthrax and botulism. Analysis of modern studies in the field suggests oligoclonal antibodies acting against receptor-binding toxin subunits and nucleic acid aptamers as allosteric inhibitors of metlloproteolytic toxin components as the most promising candidates for development of efficient antitoxin therapy.

Anthrax and botulism are dangerous infectious diseases that can be fatal unless detected and treated quickly. Fatalities from these diseases are primarily due to endopeptidase toxins secreted by the pathogens. Rapid and sensitive detection of the presence of active toxins is the key element for protection from natural outbreaks of anthrax and botulism, as well as from the threat of bioterrorism. We describe an ultrasensitive polymerase chain reaction (PCR)-based assay for detecting proteolytic activity of anthrax and botulinum toxins using composite probes consisting of covalent peptide-DNA conjugate for the detection of anthrax, and noncovalent protein-aptamer assembly to assay botulinum toxin activity. Probes immobilized on the solid-phase support are cleaved by toxins to release DNA, which is detected by real-time PCR. Both assays can detect subpicogram quantities of active toxins isolated from composite matrices. Special procedures were developed to isolate intact toxins from the matrices under mild conditions. The assay is rapid, uses proven technologies, and can be modified to detect other proteolytic and biopolymer-degrading enzymes.

Vaccination remains the most effective method of control of spread of a whole range of infections of both viral and bacterial nature. Many bacterial pathogens (Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae) carry polysaccharide capsule on the surface, that is one of the elements of protection from host organism immune system. At the same time, vaccination with bacteria exopolysaccharides (EPS) ensures infection neutralization. Effectiveness of such vaccine prophylaxis is limited by age of the vaccinated, intensity and duration of the immunity, development of secondary immune response. EPS conjugation with protein antigens was known for a long time to ensure activation of T-cell immunity against EPS and formation of secondary immune response. However, detailed studies of mechanism of immunity modulation by a protein partner as part of a glycoconjugate has not been carried out. T-lymphocyte activation was traditionally thought to occur exclusively due to peptide presentation, that are products of processing of protein component of the conjugate. Recently, information, accumulated in the field of natural carbohydrate, glycolipid and glycoprotein antigen presentation to T-cells, has generated interest in studying mechanisms of cell immunity activation by conjugated vaccines. Progress in this field, as well as development of novel chemical and biochemical, including combinative technologies of synthesis and study of these molecules, opens new opportunities for detailed understanding of mechanism of action for conjugated vaccines and creation of glycoconjugates with increased effectiveness of protective action.

Phage display has proved itself as a powerful and convenient approach for rapid sampling of billions of protein-aceous structures against a ligand of interest. The most widespread system uses display of proteins and peptides as fusions to coat proteins III or VIII of the M13/fd phage. Efficient screening of phage display library requires high purity of the input phage particles. Double precipitation by polyeth-ylene glycol (PEG) with an average molecular weight of 8000 Da (PEG-8000) is a standard technique for purification of filamentous bacterio-phages (1,2). Certain contaminants could still remain in the PEG-purified phage preparation. Although efficient removal of contaminating RNases from bacteriophage preparation using treatment by ionic detergent followed by ultracentrifugation in CsCl gradient was reported (3), this method is costly, time-consuming, and is not applicable if the native state of the phage-displayed protein or peptide is affected by ionic detergents and high salt. Size-exclusion chromatography (SEC) has been used in preparation of pure eukaryotic viruses (4,5) and bacteriophage λ (6). We assumed that SEC can be the method of choice for efficient purification of filamentous phages under mild conditions. In this work we describe a rapid and simple technique for chromatographic purifi-cation of filamentous phage particles in Sephacryl™ S-500 resin (Amersham Biosciences, Piscataway, NJ, USA).The purity of phage preparations obtained after double PEG precipi-tation was assayed by electrophoresis in Tris-tricine (7). Phage particles displayed the single-chain variable fragment (scFv) of the MRL-4 anti-DNA monoclonal antibody (MAb) (8) fused to the C-terminal portion of the pIII minor phage coat protein (δpIII). Production of the scFv-δpIII fusion cloned into the pTScDisp phagemid (GenBank

Lipid-1a-phosphatase LpxE cleaves the phosphate group in the first position of lipid A of lipopolysaccharide in Gram-negative bacteria, which reduces toxicity and reactogenicity of bacterial endotoxin while maintaining its immunogenicity. Treatment with these enzymes in preparations of recombinant proteins obtained in bacterial producers, for example, in E. coli, may find application in the purification techniques of various pharmaceutical substances, primarily various protein components of vaccines. This work is devoted to the creation of an efficient method for obtaining an F. tularensis LpxE soluble protein in a heterologous expression system based on E. coli. Optimization of the bacterial production of LpxE enzyme is achieved by creating a SUMO-LpxE chimeric protein in which the SUMO polypeptide acts as a folding catalyst and an affinity target carrier for purifying the expression product. An additional increase in the level of synthesis of LpxE and reduction of its toxicity for a bacterial strain is achieved against the background of superproduction of bacterial periplasmic chaperones encoded by an auxiliary low copy plasmid. Subsequent chromatographic purification of the target recombinant protein involves the use of affinity metal chelate chromatography and a SUMO protease cleavage step of the SUMO peptide carrying the His6 N-terminal peptide with the reduction of natural primary structure of the enzyme. The developed method makes it possible to obtain a highly purified active enzyme LpxE F. tularensis with a yield of 0.26 g/L of bacterial culture without fermentation.

This article presents a generalized dividend discount model, in relation to which a number of well-known models of the discount and capitalization of the revenue stream (dividends) are only special modifications possible under certain circumstances.