Differentiated approach to the diagnostics of economic security and resilience of Russian regions (case of the Volga federal district)

Relevance. Given the volatile global economy, unfriendly policy towards Russia and other external challenges, it is necessary to improve tools for predicting threats and risks to regional economic security and resilience. To this end, individual projections and indicators, as well as complex models should be examined.Research objective. The study aims to develop a new differentiated approach to diagnostics of indicators (projections) of economic security and resilience at the regional level, which can help visualize and evaluate threats to economic meso-systems.Data and Methods. Comparative and indicative approaches, ranking, piecewise linear approximation (scaling) and correlation analysis were used in the study.Results. As a result, the study presents the author's system of indicators of economic security and risks to the regional economy based on a differentiated approach. 36 indicators were grouped into 4 projections – general economic, social, technological and financial – and divided into sub-projections. In order to provide adequate and comparable estimates in the regional and temporal context, various methodological principles were used: application of relative indicators; assessment of cost indicators of regional development using the number of fixed market baskets (FMB) of the region (ratio of the regional cost indicator and the cost of a fixed market basket). Such approach allowed us to evaluate regional economic security in dynamics. The diagnostics of resilience of regional economic systems was performed in the context of individual projections by comparing crisis and relatively stable periods.Conclusions. The methodology was tested using data from regions of the Volga Federal District. The study revealed specific projections, sub-projections and indicators affected by threats, as well as demonstrated the ability of regions of the Volga Federal District to face the crisis and, in particular, resist sanctions

Modern T cell technologies for immunotherapy of solid tumors

According to the common concept of immune editing, the interaction of malignant tumor cells and immune system is a complex multifactorial process, which may result in both antitumor effector activity and development of suppressor mechanisms that promote tumor growth. Accumulation of scientific knowledge in the field of studying the antitumor immune response and tolerance has led to emergence of many research and therapeutic approaches that use different components of the immune system to combat neoplastic processes. Along with currently available approaches, there are strategies that use the potential of antigen-specific T lymphocytes, the main effectors of adaptive immunity, in order to fight malignant neoplasms which appeared more than a century ago and have built the scientific basis of cancer immunotherapy. One line of evidence of the significant antitumor potential of T cells in immunotherapeutic schemes for the cancer treatment was presented by successful therapy of hemato-oncological diseases, achieved at the end of the past decade. At the same time, however, the therapy of solid malignant neoplasms still faces significant difficulties that limit the efficiency of treatment. In this regard, the main objective of the review is to accumulate up-to-date information on the successes and limitations of T cell immunotherapy in the patients with solid tumors. To date, the phenotype and functionality of T cells is being investigated and modulated both towards enhancing antitumor cytotoxicity, increasing viability and proliferative activity of T cells, and in overcoming the immunosuppressive effect of the tumor and its tolerogenic microenvironment upon T cells, as well as ensuring targeted migration of the effector T cells to the malignant tissues. This review discusses immunotherapeutic approaches exploiting the potential of effector T lymphocytes, e.g., current clinical trials or applied therapeutic regimens for the treatment of solid malignant neoplasms. Antigen-independent approaches aimed at nonspecific enhancement of the T cell responses, i.e., therapy with recombinant cytokines and inhibition of immune checkpoint molecules. Antigendependent, or antigen-specific approaches such as adoptive T cell therapy with endogenous T lymphocytes are also discussed as well as trials on T cells with modified antigen-recognition receptor (CAR-Tcells, TCR-Tcells), like as usage of bispecific antibodies as T cell engagers. The review describes the benefits and disadvantages of these approaches in monotherapy, as well as current results and prospects for their mutual combinations

Organization of live animal transportation process in the Russian Federation

The paper covers the issues of organization of live animal transportation process in the Russian Federation as one of the factors of epidemiological risk associated with the spread of infectious animal disease pathogens. The legal framework, regulating the organization of live animal transportation using different vehicles, as well as quantitative data on live animal movements, taken from state veterinary information system “VetIS” (“Mercury” and “Cerberus” components) were analyzed. The analysis showed that live farmed animals are moved using all transportation means available, motor vehicles, planes, trains, ships as well as by driving. It was established that the major means of transport used to move live animals in the territory of the Russian Federation are motor vehicles. According to the analysis results 4.49 billion animals, including 4.41 billion poultry, 79.8 million large and small ruminants, pigs, horses, fur animals and bees were moved within the country in 2021. At the same time the number of issued veterinary accompanying documents for movements of cattle, poultry and pigs (i.e. in fact the transportations themselves) is much higher than the number of movements of other species. It was revealed that today only the movement of animals by railway is regulated in one way or another. The paper presents the suggestions to introduce the procedures aimed at improvement of biological safety and animal welfare during transportation. The results of the analysis performed can be used to optimize the control of animal transportation in the territory of the Russian Federation by competent authorities

Contemporary issues in ensuring biological safety during disposal of biological wastes of animal origin by incineration in the Russian Federation

Animal management and breeding as well production, transportation, preparation, and processing of animal products and raw material result in generation of a considerable amount of biological wastes being a source of biological contamination of the environment and a clear threat to human and animal health. The animal biowaste incineration units are high threat facilities and require constant surveillance and control. Collection and analysis of data provided by the RF veterinary executive authorities were performed to objectively reflect the actual situation of the biological waste incineration facilities in the RF Subjects and to create a holistic view on the problem of interest in the country. The following parameters were analyzed: their number, type (stationary and mobile), type of ownership, location, availability of the certificate and highly-qualified specialists serving the biological waste incineration equipment as well as the availability of such facilities in the RF Subjects as for January 1, 2021. The analysis demonstrated that 4,459 biowaste incinerators were registered in the country. Most of these units are stationary and they belong to establishments involved in farm animal keeping, animal product processing, production and storing. Such equipment is mostly serviced by non-qualified staff ignorant of the technical characteristics and operating principles of this equipment. Almost one third of these units in the country are home made that is why their use does not guarantee complete destruction of biological wastes and pathogen inactivation. It was also revealed that the procedure for the incineration of biological waste of animal origin using home made incinerators is not legally fixed in the country. The results obtained show that the situation of the animal biowaste incineration in the Russian Federation is quite complicated

INFLUENCE OF ANTIBODIES AGAINST CTLA-4 AND PD-1 UPON QUANTITIES OF THEIR TARGET RECEPTORS

Inhibitory receptors CTLA-4 and PD-1 (immune checkpoints) play a key role in regulation of immune reactions. They suppress excessive immune response against pathogenic microbes and prevent autoimmune reactions. The immune checkpoints are targets of the modern effective therapy based on human and humanized monoclonal antibodies (ipilimumab and nivolumab, tremelimumab, pembrolizumab, etc). However, despite its high efficiency compared to standard chemotherapy, the therapy based on blocking immune check points is facing several problems, i.e., high therapy cost and severe negative autoimmune-related side effects. Unfortunately, this therapy helps to minority of the patients. Hence, further studies are required to improve its efficiency and safety, as well as to search for selection criteria of the patients who would benefit from the therapy. An appealing approach to reduce negative side effects from immune checkpoint inhibition is application of the blocking antibodies, aiming for ex vivo generation of patients’ activated immune cells for cancer therapy, thus avoiding systemic drug administration. Our aim was to elucidate influence of immune checkpoint blocking antibodies on the expression of CTLA-4 and PD-1 in such an in vitro model. First of all, we have determined quantities of lymphocyte receptors in peripheral blood of healthy volunteers, or cancer patients with disseminated melanoma. Moreover, we defined effect from the addition of antibodies against immune checkpoints on proportions of cells expressing CTLA-4 and PD-1 in the population of phytohemagglutininactivated lymphocytes. Our study demonstrated that, in presence of antibodies to either of the two checkpoints during in vitro cell activation, the blockade of specific target receptor is accompanied by reduced number of cells positive for another checkpoint. Hence, the antibodies directed against PD-1 or CTLA-4 seem to suppress both negative signal cascades at once, if tested under such experimental conditions. Noteworthy, the response to blocking antibodies for different immune checkpoints varied for different donors. Our data may be used for development of effective combinations of lymphocyte activators and immune check-point inhibitors, for in vitro generation of activated lymphocytes applied for adoptive cancer therapy, as well as for prediction of possible responses to antibodies against CTLA-4 or PD-1, aiming to select the best personalized cancer immunotherapy

Mobile synbiotope microbiocenosis against pathogens

Based on own results, conception of mobile synbiotope microcenosis against pathogens as well as new antimicrobial strategies connected to conception are proposed. Synbiotope mobility is determined by the presence (in varying combinations] of cofunctioning antimicrobial ways which can be realized with participation of highly molecular mass metabolites of probiotic bacterial cultures. Thus, probiotic enzymatic systems (proteinases, EPS-depolymerases and/ or oxidoreductases] reveal cofunctioning with probiotic lectins. New antipathogen strategies use technological advantages of choice and selection of symbiotic strains and consortia producing synergistical enzyme-lectin-glycoconjugate systems against microfungal and Gram-positive pathogens. Additional strategies involve construction of synbiotic systems supporting probiotic compartment of biotope

ROLE OF MESENCHYMAL MULTIPOTENT STROMAL CELLS IN REMODELING OF BONE DEFECTS

Ability of mesenchymal multipotent stromal cells (MSCs) to differentiate into several types of mesenchymal tissues allows to consider these cells the main candidates for creating tissue engineering constructions for regenerative medicine. MSCs promote integration of bio-implants into the native bone and stimulate osteogenesis. MSCs are characterized by immunomodulatory properties, due to inflammation control and modification of immune cells. MSCs affect not only the in vivo immune response by preventing immunological rejection of implanted tissue engineering designs, but it can also influence the bone tissue immunity. MSCs play an important role in bone regeneration, by regulating the osteoblastic generation, and suppressing activity of inflammation effectors and osteoclastogenesis. Some pre-clinical and first clinical trials of bone bio-implants colonized with MSC, demonstrate promising outlooks for this strategy in order to obtain tissue engineering constructions for bone regeneration

Preliminary results from the Russian-American Gallium Experiment Cr-neutrino source measurement

The Russian-American Gallium Experiment has been collecting solar neutrino data since early 1990. The flux measurement of solar neutrinos is well below that expected from solar models. We discuss the initial results of a measurement of experimental efficiencies by exposing the gallium target to neutrinos from an artificial source. The capture rate of neutrinos from this source is very close to that which is expected. The result can be expressed as a ratio of the measured capture rate to the anticipated rate from the source activity. This ratio is 0.93 + 0.15, - 0.17 where the systematic and statistical errors have been combined. To first order the experimental efficiencies are in agreement with those determined during solar neutrino measurements and in previous auxiliary measurements. One must conclude that the discrepancy between the measured solar neutrino flux and that predicted by the solar models can not arise from an experimental artifact

Measurement of the response of a gallium metal solar neutrino experiment to neutrinos from a [Formula Presented] source

The neutrino capture rate measured by the Russian-American Gallium Experiment is well below that predicted by solar models. To check the response of this experiment to low-energy neutrinos, a 517 kCi source of [Formula Presented]Cr was produced by irradiating 512.7 g of 92.4%-enriched [Formula Presented]Cr in a high-flux fast neutron reactor. This source, which mainly emits monoenergetic 747-keV neutrinos, was placed at the center of a 13.1 ton target of liquid gallium and the cross section for the production of [Formula Presented]Ge by the inverse beta decay [Formula Presented] was measured to be [Formula Presented] The ratio of this cross section to the theoretical cross section of Bahcall for this reaction is 0.95 ±0.12 [Formula Presented] (theor) and to the cross section of Haxton is 0.87±0.11 (expt)±0.09 (theor). This good agreement between prediction and observation implies that the overall experimental efficiency is correctly determined and provides considerable evidence for the reliability of the solar neutrino measurement. © 1999 The American Physical Society

The russian-american gallium experiment (sage) cr neutrino source measurement

The solar neutrino capture rate measured by SAGE is well below that predicted by solar models. To check the overall experimental efficiency, we exposed 13 tonnes of Ga metal to a reactor-produced 517 kCi source of 51Cr. The ratio of the measured production rate to that predicted from the source activity is 0.95+/-0.11$stat$+0.05/-0.08$syst$. This agreement verifies that the experimental efficiency is measured correctly, establishes that there are no unknown systematic errors at the 10% level, and provides considerable evidence for the reliability of the solar neutrino measurement. © 1996 The American Physical Society