Prolonged residence of an albumin–IL-4 fusion protein in secondary lymphoid organs ameliorates experimental autoimmune encephalomyelitis

Interleukin-4 (IL-4) suppresses the development of multiple sclerosis in a murine model of experimental autoimmune encephalomyelitis (EAE). Here, we show that, in mice with EAE, the accumulation and persistence in the lymph nodes and spleen of a systemically administered serum albumin (SA)–IL-4 fusion protein leads to higher efficacy in preventing disease development than the administration of wild-type IL-4 or of the clinically approved drug fingolimod. We also show that the SA–IL-4 fusion protein prevents immune-cell infiltration in the spinal cord, decreases integrin expression in antigen-specific CD4+ T cells, increases the number of granulocyte-like myeloid-derived suppressor cells (and their expression of programmed-death-ligand-1) in spinal cord-draining lymph nodes and decreases the number of T helper 17 cells, a pathogenic cell population in EAE. In mice with chronic EAE, SA–IL-4 inhibits immune-cell infiltration into the spinal cord and completely abrogates immune responses to myelin antigen in the spleen. The SA–IL-4 fusion protein may be prophylactically and therapeutically advantageous in the treatment of multiple sclerosis

Study of Operating Characteristics of Pyrotechnic Reserve Power Source Based on Magnesium and Zinс

This paper presents the results of studies of operating parameters of pyrotechnic reserve power source (PRPS). This battery was activated by the pyrotechnic compositions contained in the electrodes. Once the ignition impulse worked, the pyrotechnic compositions took fire immediately and melted the electrolyte. Then the rest pyrotechnic compositions served as anode and cathode. The battery began to discharge. The following characteristics of PRPS were evaluated during the study: release time to operating regime of the electric current, the duration of the PRPS work and initiation temperature of PRPS. A detailed evaluation of the Mg/LiF/PbF2 electrochemical system and Zn/LiF/PbF2 one is undertaken. Test results show that the electric current value using powder of zinc and granular zinc in these experiments was 0.179 A and 0.1 A, respectively, and the operating time at these values of elecrtic current was 40 and 151 sec, respectively

Enhanced lymph node trafficking of engineered IL‐10 suppresses rheumatoid arthritis in murine models

Objective Rheumatoid arthritis (RA) is a major autoimmune disease that causes synovitis and joint damage. Although clinical trials using interleukin‐10 (IL‐10), an anti‐inflammatory cytokine, have been performed as a potential treatment of RA, its therapeutic effects have been limited, potentially due to insufficient residence in lymphoid organs, where antigen recognition primarily occurs. Here, we engineered IL‐10 as a fusion with serum albumin (SA). Methods SA‐fused IL‐10 was recombinantly expressed. After intravenous injection to mice, retention of SA‐IL‐10 at lymph node (LN), immune cell compositions at paws, and therapeutic effect on arthritis model mice were assessed. Results SA fusion to IL‐10 led to enhanced LN accumulation compared with unmodified IL‐10. Intravenous SA‐IL‐10 treatment restored immune cell composition in the paws to a normal status, elevated the frequency of suppressive M2 macrophages, reduced IL‐17A amount in the paw‐draining LN, and protected joint morphology. Intravenous SA‐IL‐10 treatment showed similar efficacy as treatment with an anti‐TNF‐α antibody. SA‐IL‐10 was equally effective when administered intravenously, locally or subcutaneously, which benefits clinical translation of this molecule. Conclusion SA fusion to IL‐10 is a simple but effective engineering strategy for RA therapy and holds clinical translational potential

Formation systems approach to the process of development strategy development and selection of effective solution

The article deals with strategic planning as a basis for all decisions taken at the level of management. Various approaches to disclosure, the main aspects of strategic planning, and explores the most important strategic factors for the enterprise and identify the necessary components ofan effective strategy

Professional Dynasties as a Social Mechanism of Reproduction of Professional Groups: on the Example of Engineering Dynasties of Russia

The article deals with the economic and social conditions for the emergence and reproduction of professional engineering dynasties in the context of Russia’s historical development, of the analysis of the profile education system, and the state policy that supports the maintenance of the processes of professional continuity. The formation of dynasties is conditioned by a number of circumstances lying in the plane of a thoughtful choice or inertial action. Among the problems that require immediate resolution, experts call: the lack of developed socio-economic support for conditions for the development of engineering activities; shortage of qualified engineering personnel; lack of career prospects in the engineering profession. The prestige and social status of the profession of an engineer is low; the system of training an engineer in universities does not ensure the release of a specialist who meets modern requirements of the industrial and postindustrial society; the partnership relations of industrial, scientific, design enterprises with higher education are poorly developed, which entails the training of specialists not in demand on the labor market, with insufficient level of practical-oriented training, knowledge of the specifics of production at enterprises of the real economy. There is no well-functioning and effective system of early and advanced career guidance, starting with pre-school institutions; the engineering community is not consolidated; there is no non-state system of certification of specialists based on professional associations that would control the entrance to a professional group, would monitor the adherence of professional rules, ethical standards of the engineer’s profession.В статье рассматриваются экономические, социальные условия возникновения и воспроизводства профессиональных инженерных династий в контексте исторического развития России, анализа системы профильного образования, а также государственной политики, способствующей поддержанию процессов профессиональной преемственности. Формирование династий обуславливается рядом обстоятельств, лежащих в плоскости продуманного выбора или инерционного действия. Среди проблем, требующих немедленного решения эксперты называют: отсутствие развитой социально-экономической поддержки условий для развития инженерной деятельности; дефицит квалифицированных инженерных кадров; отсутствие перспективы карьерной реализации в инженерной профессии; престижность и социальный статус профессии инженера низок; система подготовки инженера в вузах не обеспечивает выпуск специалиста, отвечающего современным требованиям индустриального и постиндустриального общества; слабо развиты партнерские отношения промышленных, научных, проектных предприятий с высшей школой, что влечет за собой подготовку специалистов, не востребованных на рынке труда, с недостаточным уровнем практико-ориентированной подготовки, знанием специфики производства на предприятиях реальной экономики; отсутствует отлаженная и эффективная система ранней и опережающей профориентации, начиная с дошкольных учреждений; инженерное сообщество не консолидировано; не существует негосударственной системы сертификации специалистов на базе профессиональных ассоциаций, которые контролировали бы вход в профессиональную группу, контролировали бы следование профессионалом правил, этических норм профессии инженера.Грант РФФИ 18-011-01129