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At the present stage of economic development, the ultimate goal of the strategies of any multinational company in the global market is to increase business efficiency, which is largely ensured by the development and implementation of modern technologies. Artificial intelligence for the subjects of international economic relations is a set of tools that provide digital transformation of business. The development of artificial intelligence can not only change the business, but also modify the format of the country’s competition in the world market. Under the influence of the development of artificial intelligence systems, there is an intensive diversification of objects of international trade in goods and services, which leads to a fundamental, radical renewal of production strategies of leading companies in each country. All this in the context of globalization makes it necessary to pay much attention to the intellectualization of the Ukrainian economy. In particular, this process involves the intensification of the use of the Internet, information and communication technologies, Internet of Things. Digital technologies have a significant impact on the development of traditional sectors of the economy and become an integral part of modern management systems in the public sector, industrial production, medicine, entrepreneurship, creating new business models. It actualizes research of theoretical and applied aspects of economy digitalization on the basis of the analysis possibilities of artificial intelligence application in various spheres of digital economy development. To research the development of economy digital transformation, a systematic approach was used, on the basis of which the possibilities of digitalization of individual sectors of the economy were analyzed. Economic and managerial relations, which mediate the processes of digital transformation, have identified and systematized the prerequisites for digitalization, taking into account the trend of increasing the country’s competitiveness. The leading role of artificial intelligence in the digital transformation of the economy is substantiated. Various aspects related to the issues of digital transformation of the economy are highlighted. Trends in the development of intellectualization process of economic sectors – industrial, business, public administration – are studied. The main drivers of digital transformation are considered, which will contribute to the sustainable development of each sector of the economy, and their synergy will increase the competitiveness of the national economy in world markets. The main directions of development of digitalization of the economy of Ukraine are outlined. Projects of digital transformation of Ukraine are considered. The importance of digital infrastructure platforms based on artificial intelligence has been identified. Two scenarios for the development of Ukraine’s digital economy are proposed for consideration.

The digital transformation problems of modern urban economy are considered. Their relevance for Ukrainian cities is caused by the fact that there are already a significant number of "smart cities" in the world, which are comfortable for their residents and for the management of urban services. The outlined problem for Ukraine is that a complex scenario of intellectualization and digital transformation of Ukrainian cities has not been formed yet. Unresolved problems and challenges that hinder the digital transformation of Ukrainian cities, namely the lack of municipal information networks, are described. Areas of further research are outlined, in particular, the statistical study of "smart cities", which is based on the collection and application of large data for this purpose, as well as the implementation of foreign experience in the Ukrainian realities of the economy. The digital transformation of cities is reviewed as a change of existing business models of urban services, the creation of smart mobility, smart resource consumption. An infographic unity of resources, services and management systems should be created in order to coordinate the actions of related structures and services in case of emergencies and unforeseen situations. This involves increasing technological literacy for different segments of the urban population. Three models of "smart cities" are proposed, the successful operation of each depends on investment, their rational management, as well as improving the level of digital skills of the population. The manufacturability of urban infrastructure should be based on megatrends in the field of information technology, namely: mobility, social communications, cloud technologies, big data and predictive analytics, machine learning and artificial intelligence, cybersecurity technology, the Internet of Things. These technologies are end-to-end for the whole set of technological solutions developed for "smart" cities. The scenario of development of "smart city" from the technological point of view is described; its basic components are: smart physical infrastructure; smart digital infrastructure; digital platforms; integrated digital platforms. The idea of building a digital duplicate, which is an accurate reflection of the real city in digital reality - the information comes to it from various sensors, monitoring systems and resource counters. The received experience of functioning can be translated into reality if it is successful, or to refuse it. All this is done at minimal cost, time savings and without harm to the real city. It is concluded that: information and communication technologies in the field of housing and communal services ensure the reliability and security of urban systems and resource efficiency; the formation of "smart cities" in Ukraine is limited by the lack of technical base for the creation of information technology platforms; a roadmap for the digital transformation of the national economy has not been developed.

A new 1:1 molecular complex of triterpene glycoside ammonium glycyrrhizate (GC) with flavonoid glycoside rutin (Rut) was obtained in aqueous ethanol. The stability constant (9.7±0.2)×104 (mol/L)–1 was calculated for the complex via isomolar curves. The complexation was studied by UV- and ATR IR-Fourier spectroscopy and a method of isomolar series. The hydrogen bonds and hydrophobic interactions are formed in the molecular complex. A preliminary antioxidant activity assessment of the complex was made.

Scientific studies focused on search for ways of building and operating cyber-physical systems are important because integration of physical processes, devices and data by use of cyber-physical systems creates new capacities for control of the physical world, including devices, manufacturing facilities and infrastructures, and opens up new real perspectives for national economies. The object of the study is cyber-physical systems for solving the problems of intellectual control of physical objects. The study is conducted as a contribution in building up a conceptual model of the cyber-physical system’s interactions with the external environment. A generalized scheme of such interaction model is proposed with accounting for feedback, which positive role is that it enables for identification of disturbing impacts on the state of the physical environment, resulting in uncertainties of the latter’s operation. The main functions of feedback in a cyber-physical system is to help produce controlling impacts on a controlled object by use of intellectual control, due to compensating disturbances and maintaining the state of stable equilibrium of the system. Several existing approaches to building conceptual models of cyber-physical systems which interaction with the environment are two-dimensional: cybernetic and physical. The article’s objective is to build a model for taking a controlling decision in cybernetic systems. Its result is an elaborated generalized scheme for taking a controlling decision in such systems. This generalized scheme is based on the information model, which components are interaction of a cyber-physical system with objects of the physical environment, with other systems and a system of artificial intellect, and with the following processes: measuring and computing processes, controlling processes, and communication processes. The described information model helps eliminate the consequences of unpredictable behavior of a cyber-physical system. The presented results are a contribution in the studies on effective control of physical objects, actively elaborated today. Use of the proposed components of the conceptual model will enable to increase the effectiveness of system monitoring of the operation of a physical object given better justification of taken decisions.

Aim. The aim of the study was to evaluate the ability of pMEL-TCI and pMEL-A0201 DNA-constructs encoding artificial polyepitope melanoma antigens to induce antitumor T cell immune response ex vivo. material and methods. Dendritic cells were obtained from peripheral blood mononuclear cells of HLA-A02:01-positive donors; DCs transfected with target DNA vaccine constructions were co-cultured with autologous T lymphocytes to stimulate anti-tumor effector T cells. Specific activity of ex vivo stimulated PBMC was assessed (1) by their ability to cause lysis of human melanoma Mel Is cells, and (2) by the level of their granzyme-producing activity. A recombinant plasmid encoding the full-length MART-1 melanoma antigen was used as a positive control. results. All DNA vaccine constructions as well as positive control construction were found to be able to stimulate specific anti-tumor immune responses of autologous PBMC ex vivo, and these PBMC were found to induce melanoma Mel Is cells lysis. Both the efficiency of induced cytotoxic responses and the level of granzymes production stimulated with DCs transfected with pMel-A0201 significantly exceeded those stimulated with DCs transfected with either pMel-TCI or with DNA construction encoding the full-length MART-1 protein. The cytotoxicity level correlates with the level of granzyme B production in CD8+ T lymphocytes. conclusion. DNA vaccine constructions encoding artificial polypeptides composed of tumor antigen epitopes can stimulate the antitumor cytotoxic response. This approach can be used as the basis for the development of new methods of immunotherapy for cancer.

Nucleic acid-based influenza vaccines are a promising platform that have recently and rapidly developed. We previously demonstrated the immunogenicity of DNA vaccines encoding artificial immunogens AgH1, AgH3, and AgM2, which contained conserved fragments of the hemagglutinin stem of two subtypes of influenza A—H1N1 and H3N2—and conserved protein M2. Thus, the aim of this study was to design and characterize modified mRNA obtained using the above plasmid DNA vaccines as a template. To select the most promising protocol for creating highly immunogenic mRNA vaccines, we performed a comparative analysis of mRNA modifications aimed at increasing its translational activity and decreasing toxicity. We used mRNA encoding a green fluorescent protein (GFP) as a model. Eight mRNA-GFP variants with different modifications (M0–M7) were obtained using the classic cap(1), its chemical analog ARCA (anti-reverse cap analog), pseudouridine (Ψ), N6-methyladenosine (m6A), and 5-methylcytosine (m5C) in different ratios. Modifications M2, M6, and M7, which provided the most intensive fluorescence of transfected HEK293FT cells were used for template synthesis when mRNA encoded influenza immunogens AgH1, AgH3, and AgM2. Virus specific antibodies were registered in groups of animals immunized with a mix of mRNAs encoding AgH1, AgH3, and AgM2, which contained either ARCA (with inclusions of 100% Ψ and 20% m6A (M6)) or a classic cap(1) (with 100% substitution of U with Ψ (M7)). M6 modification was the least toxic when compared with other mRNA variants. M6 and M7 RNA modifications can therefore be considered as promising protocols for designing mRNA vaccines.

One of the key stages in the development of mRNA vaccines is their delivery. Along with liposome, other materials are being developed for mRNA delivery that can ensure both the safety and effectiveness of the vaccine, and also facilitate its storage and transportation. In this study, we investigated the polyglucin:spermidine conjugate as a carrier of an mRNA-RBD vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The conditions for the self-assembling of mRNA-PGS complexes were optimized, including the selection of the mRNA:PGS charge ratios. Using dynamic and electrophoretic light scattering it was shown that the most monodisperse suspension of nanoparticles was formed at the mRNA:PGS charge ratio equal to 1:5. The average hydrodynamic particles diameter was determined, and it was confirmed by electron microscopy. The evaluation of the zeta potential of the investigated complexes showed that the particles surface charge was close to the zero point. This may indicate that the positively charged PGS conjugate has completely packed the negatively charged mRNA molecules. It has been shown that the packaging of mRNA-RBD into the PGS envelope leads to increased production of specific antibodies with virus-neutralizing activity in immunized BALB/c mice. Our results showed that the proposed polycationic polyglucin:spermidine conjugate can be considered a promising and safe means to the delivery of mRNA vaccines, in particular mRNA vaccines against SARS-CoV-2.

Background: According to current data, an effective Ebola virus vaccine should induce both humoral and T-cell immunity. In this work, we focused our efforts on methods for delivering artificial T-cell immunogen in the form of a DNA vaccine, using generation 4 polyamidoamine dendrimers (PAMAM G4) and a polyglucin:spermidine conjugate (PG). Methods: Optimal conditions were selected for obtaining complexes of previously developed DNA vaccines with cationic polymers. The sizes, mobility and surface charge of the complexes with PG and PAMAM 4G have been determined. The immunogenicity of the obtained vaccine constructs was investigated in BALB/c mice. Results: It was shown that packaging of DNA vaccine constructs both in the PG envelope and the PAMAM 4G envelope results in an increase in their immunogenicity as compared with the group of mice immunized with the of vector plasmid pcDNA3.1 (a negative control). The highest T-cell responses were shown in mice immunized with complexes of DNA vaccines with PG and these responses significantly exceeded those in the groups of animals immunized with both the combination of naked DNAs and the combination DNAs coated with PAMAM 4G. In the group of animals immunized with complexes of the DNA vaccines with PAMAM 4G, no statistical differences were found in the ability to induce T-cell responses, as compared with the group of mice immunized with the combination of naked DNAs. Conclusions: The PG conjugate can be considered as a promising and safe means to deliver DNA-based vaccines. The use of PAMAM requires further optimization.

Background: The lack of effective vaccines against Ebola virus initiates a search for new approaches to overcoming this problem. The aim of the study was to design artificial polyepitope T-cell immunogens—candidate DNA vaccines against Ebola virus and to evaluate their capacity to induce a specific immune response in a laboratory animal model. Method: Design of two artificial polyepitope T-cell immunogens, one of which (EV.CTL) includes cytotoxic and the other (EV.Th)—T-helper epitopes of Ebola virus proteins was carried out using original TEpredict/PolyCTLDesigner software. Synthesized genes were cloned in pcDNA3.1 plasmid vector. Target gene expression was estimated by synthesis of specific mRNAs and proteins in cells transfected with recombinant plasmids. Immunogenicity of obtained DNA vaccine constructs was evaluated according to their capacity to induce T-cell response in BALB/c mice using IFN ELISpot and ICS. Results: We show that recombinant plasmids pEV.CTL and pEV.Th encoding artificial antigens provide synthesis of corresponding mRNAs and proteins in transfected cells, as well as induce specific responses both to CD4+ and CD8+ T-lymphocytes in immunized animals. Conclusions: The obtained recombinant plasmids can be regarded as promising DNA vaccine candidates in future studies of their capacity to induce cytotoxic and protective responses against Ebola virus.