In Vitro Modeling of the Interaction between Human Epithelial Cells and Lymphocytes upon Influenza Infection

Influenza viruses are a continuous threat to humans because of their ability to cross species barriers and adapt to new hosts. Data from murine studies, along with limited human data, suggest that CD8(+) cytotoxic T lymphocytes (CTL) that recognize conserved epitopes of structural influenza proteins are the main mediators of influenza virus clearance. Additionally, the fact that many CTLs recognize epitopes shared between different influenza strains offers the potential for broad cross-strain immunity. However, the mechanisms of cellular immunity against influenza viruses are poorly defined in humans, where the CTL response has been hard to measure and interpret. We developed a novel CTL assay that utilizes fully differentiated nasal human epithelial cells taken from volunteers as permissive targets for autologous peripheral blood-derived influenza virus-specific cytotoxic T lymphocytes. This in vitro system of human lymphocyte-epithelial cell co-cultures can be considered as the closest approximation to events in vivo and can be employed for studying the interactions between the pathogen and human host. Modeling of the natural interaction process between the primary cell type that supports the productive replication of influenza and immune cells may allow us to put in perspective CTLs as a correlate of immunity to influenza in humans

THE SYSTEM OF ADDITIONAL PROFESSIONAL EDUCATION AS A TOOL PEDAGOGICAL ACMEOLOGY

Professional competitive ability and personal mobility of people on the labor market directly depend on the constant, working-life-long development of social and professional competences and additional qualifications that appear followed by the development of society and production. The further vocational education system becomes an educational space that can provide both the forward-looking education and «the fine finishing» of a specialist for a particular work place.Профессиональная конкурентоспособность и личностная мобильность человека на рынке труда напрямую зависит от постоянного, в течение всей трудовой жизни, развития социально-профессиональных компетенций и дополнительных квалификаций, которые появляются вслед за развитием социума и производства. Система дополнительного профессионального образования, будучи более гибкой, становится тем образовательным пространством, которое может обеспечить как опережающее обучение, так и «тонкую доводку» специалиста под конкретное рабочее место

SUBJECTIVE RESOURCESTHE PSYCHOLOGICAL AND ACMEOLOGICAL PHENOMENON

Статья посвящена актуальной на сегодняшний момент теме – ресурсам личности. В результате неиспользования, «потери» ресурсов возможны: недостаточная личностная самореализация, дезадаптация личности в социальной среде, затрудненная самоидентификация, которая в ряде случаев сопровождается неполными личностной самоактуализацией и самодостаточностью. В статье подчёркивается важность субъективного компонента в осознании, определении, понимании, мобилизации, сохранении и накоплении ресурсов личности.Человек выступает активным преобразователем своей действительности, где и он, и действительность являются как результатом преобразования, так и источником этого преобразования. Автором предложено понятие «субъективной ресурсности», как необходимого фактора для качественной жизнедеятельности личности, достижения вершин ее самосовершенствования и саморазвития как в профессиональном, так и в личностном плане. Субъективный компонент подчеркивает роль самой личности в сохранении, преобразовании, накоплении, перераспределении ресурсов.Цель. Предметом анализа выступает осознание, понимание личностью наличия собственных ресурсов – субъективная ресурсность. Автор ставит целью описать субъективную ресурсность как психолого-акмеологический феномена, раскрыть его сущность и предложить методику исследования данного феномен, показав значимость вербализации ресурсов посредством ассоциативного образа без опоры на наглядность и с опорой на нее.Метод или методология проведения работы. Основу исследования составляют общенаучные теоретические методы (теоретический анализ, в том числе психологический анализ, обобщение, систематизация, системные описания).Результаты. Результаты работы заключаются в том, что автор определил понятие «субъективная ресурсность», а также предложил методику ее изучения. Полученные результаты могут представлять интерес для повышения результативности работы по определению ресурсов личности. Также результаты и методика определения субъективной ресурсности способствуют обогащению профессионального инструментария психологов.Область применения результатов. Результаты исследования могут быть применены в сфере психологического консультирования, образования, повышения квалификации психологов.The article is devoted to the moment the subject – resources of a person. Be caused, “loss” possible resources: lack of personal self-realization, the maladjustment of the individual in a social environment, obstructed line of identity, which in some cases is accompanied by incomplete personal self-actualization and self-sufficiency. The article emphasizes the importance of the subjective component in understanding, identifying, understanding, mobilization, conservation and accumulation of resources of the individual. Man is an active Converter to your reality, where he and reality are the result of the conversion and source conversion. The author proposed the concept of “subjective resource” as a necessary factor for quality of life of the individual, achievement of tops of her self-improvement and self-development, both professionally and personally. Subjective component emphasizes the role of the individual in the conservation, transformation, accumulation, the reallocation of resources.Purpose. The subject of analysis is the awareness, understanding person own resources – the subjective resourcest. The author aims to describe the subjective resourcest as psychological and acmeological phenomenon to reveal its essence and to suggest the methodology of the study of this phenomenon, showing the importance of verbalization resources through associative image without relying on the visibility and relying on her.Methodology. The basis of the study form a General theoretical methods (theoretical analysis, including psychological analysis, generalization, systematization, system description).Results. The results of the work lies in the fact that the author has defined the concept of “subjective resourcesthe” and proposed methodology of the study. The obtained results may be of interest to improve the efficiency of the work to define the resources of the individual. The results and method of determining a subjective resource contribute to the enrichment of the professional Toolkit of psychologists.Practical implications. The results of the study can be applied in the field of counseling, education, training of psychologists

Monoclonal antibodies differentially affect the interaction between the hemagglutinin of H9 influenza virus escape mutants and sialic receptors

AbstractTo determine the receptor binding properties of various H9 influenza virus escape mutants in the presence and absence of antibody, sialyloligosaccharides conjugated with biotinylated polyacrylamide were used. A mutant virus with a L226Q substitution showed an increased affinity for the Neu5Acα2-3Galβ1-4Glc. Several escape mutants viruses carrying the mutation N193D bound to Neu5Acα2-6Galβ1-4GlcNAc considerably stronger than to Neu5Acα2-6Galβ1-4Glc. Several monoclonal antibodies unable to neutralize the escape mutants preserved the ability to bind to the hemagglutinin as revealed by enzyme-linked immunosorbent assay. In each case, the bound monoclonal antibodies did not prevent the binding of the mutant HA to high affinity substrates and did not displace them from the virus binding sites. Together, these data suggest that amino acid changes selected by antibody pressure may be involved in the specificity of host-cell recognition by H9 hemagglutinin and in the ability of viruses with these mutations to escape the neutralizing effect of antibodies in a differential way, depending on the specificity of the host cell receptor. It may be important in the natural evolution of the H9 subtype, a plausible candidate for the agent likely to cause a future pandemic

Comparative Study of Influenza Virus Replication in MDCK Cells and in Primary Cells Derived from Adenoids and Airway Epithelium

Although clinical trials with human subjects are essential for determination of safety, infectivity, and immunogenicity, it is de- sirable to know in advance the infectiousness of potential candidate live attenuated influenza vaccine strains for human use. We compared the replication kinetics of wild-type and live attenuated influenza viruses, including H1N1, H3N2, H9N2, and B strains, in Madin-Darby canine kidney (MDCK) cells, primary epithelial cells derived from human adenoids, and human bron- chial epithelium (NHBE cells). Our data showed that despite the fact that all tissue culture models lack a functional adaptive im- mune system, differentiated cultures of human epithelium exhibited the greatest restriction for all H1N1, H3N2, and B vaccine viruses studied among three cell types tested and the best correlation with their levels of attenuation seen in clinical trials with humans. In contrast, the data obtained with MDCK cells were the least predictive of restricted viral replication of live attenuated vaccine viruses in humans. We were able to detect a statistically significant difference between the replication abilities of the U.S. (A/Ann Arbor/6/60) and Russian (A/Leningrad/134/17/57) cold-adapted vaccine donor strains in NHBE cultures. Since live at- tenuated pandemic influenza vaccines may potentially express a hemagglutinin and neuraminidase from a non-human influenza virus, we assessed which of the three cell cultures could be used to optimally evaluate the infectivity and cellular tropism of vi- ruses derived from different hosts. Among the three cell types tested, NHBE cultures most adequately reflected the infectivity and cellular tropism of influenza virus strains with different receptor specificities. NHBE cultures could be considered for use as a screening step for evaluating the restricted replication of influenza vaccine candidates

B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination

The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior ex- posure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated dif- ferences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and \u3e70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers were generally higher in the older cohorts, consistent with greater prevaccination exposure to pH1N1-like viruses. Most subjects in each cohort responded well to vaccination, with early formation of circulating virus- specific antibody (Ab)-secreting cells and \u3e4-fold increases in HAI and MN titers. However, the response was strongest in the 18- to 32-year cohort. Circulating levels of HA stalk-reactive Abs were increased after vaccination, especially in the 18- to 32-year cohort, raising the possibility of elevated levels of cross-reactive neutralizing Abs. In the young cohort, an increase in MN activ- ity against the seasonal influenza virus A/Brisbane/59/07 after vaccination was generally associated with an increase in the anti- Brisbane/59/07 HAI titer, suggesting an effect mediated primarily by HA head-reactive rather than stalk-reactive Abs. Our find- ings support recent proposals that immunization with a relatively novel HA favors the induction of Abs against conserved epitopes. They also emphasize the need to clarify how the level of circulating stalk-reactive Abs relates to resistance to influenza

Viziers in the Administrative System of Egypt under the Burji Mamluks

Поступила в редакцию: 03.11.2021. Принята к печати: 24.06.2022.Submitted: 03.11.2021. Accepted: 24.06.2022.К числу наименее изученных проблем в истории Султаната мамлюков (1250–1517) относятся принципы и динамика взаимодействия мамлюков с административным аппаратом, к службе в котором привлекались представители местной элиты. В статье рассматриваются вопросы, связанные с происходившей на протяжении всего бурджитского периода ( 1382–1517) трансформацией мамлюкского административного аппарата. Уже в XIII–XIV вв. началось постепенное смещение представителей гражданского населения с различных административных должностей и замена их на мамлюкских эмиров. Особое значение этот процесс приобрел в связи с должностью вазира, поскольку последние мамлюкские султаны перед вступлением на престол занимали именно эту позицию. Вопросы, связанные с эволюцией военно-административной системы в Египте в XIII–XV вв., были поставлены еще Д. Айалоном (1914–1998), однако комплексное и систематическое изучение намеченных этим пионером и одним из основоположников современного мамлюковедения проблем до сих пор не проводилось. На основе нескольких арабских хроник и биографических словарей XV в. прослежены изменения положения и функций вазира в мамлюкской административной системе, отмечены причины этих изменений, их значение для эволюции политических и социальных отношений в Султанате мамлюков в завершающий период его истории. На примере вазирата рассмотрена существенная трансформация египетского государственно-административного аппарата при султанах Бурджитах, самым тесным образом связанная со сломом преобладавших в предшествующий период социальных границ и стереотипов, приобретением политическими группировками новых форм и функций, реконфигурацией центральной власти.Among the least studied issues in the history of the Sultanate of the Mamluks, there are the principles and dynamics of the Mamluks’ interaction with the administrative system represented by the local elite. The article considers issues connected with the transformation of the Mamluk administrative system which took place during the Burji period (1382–1517). As early as the thirteenth — fourteenth centuries, a gradual displacement of representatives of the civilian population from various administrative positions and their replacement with Mamluk emirs began. This process acquired particular importance in connection with the position of the vizier, since the last Mamluk sultans occupied this position before assuming the throne. In the twentieth century, D. Ayalon (1914–1998) raised some questions related to the evolution of the military-administrative system in Egypt between the thirteenth and fifteenth centuries, but a comprehensive and systematic study of the problems outlined by this pioneer and one of the founders of modern Mamluk studies has not yet been carried out. Based on several Arabic chronicles and biographical dictionaries of the fifteenth century, the author traces changes in the position and functions of the vizier in the Mamluk administrative system, highlighting the reasons for these changes, their significance for the evolution of political and social relations in the Mamluk Sultanate in the final period of its history. Referring to the vizierate, the author considers a significant transformation of the Egyptian state-administrative system under the Burji sultans, which is most closely associated with the destruction of the social boundaries and stereotypes that prevailed in the previous period, the acquisition of new forms and functions by political groups, and the reconfiguration of the central government

RESEARCH OPPORTUNITIES USING PLASMA MODIFICATION FOR TECHNICAL FABRICS

The article discusses the possibility of using plasma modification to get anti adhesive properties of the technical fabrics.181-18

Efficacy of Combined Therapy with Amantadine, Oseltamivir, and Ribavirin In Vivo against Susceptible and Amantadine-Resistant Influenza A Viruses

The limited efficacy of existing antiviral therapies for influenza – coupled with widespread baseline antiviral resistance – highlights the urgent need for more effective therapy. We describe a triple combination antiviral drug (TCAD) regimen composed of amantadine, oseltamivir, and ribavirin that is highly efficacious at reducing mortality and weight loss in mouse models of influenza infection. TCAD therapy was superior to dual and single drug regimens in mice infected with drug-susceptible, low pathogenic A/H5N1 (A/Duck/MN/1525/81) and amantadine-resistant 2009 A/H1N1 influenza (A/California/04/09). Treatment with TCAD afforded >90% survival in mice infected with both viruses, whereas treatment with dual and single drug regimens resulted in 0% to 60% survival. Importantly, amantadine had no activity as monotherapy against the amantadine-resistant virus, but demonstrated dose-dependent protection in combination with oseltamivir and ribavirin, indicative that amantadine's activity had been restored in the context of TCAD therapy. Furthermore, TCAD therapy provided survival benefit when treatment was delayed until 72 hours post-infection, whereas oseltamivir monotherapy was not protective after 24 hours post-infection. These findings demonstrate in vivo efficacy of TCAD therapy and confirm previous reports of the synergy and broad spectrum activity of TCAD therapy against susceptible and resistant influenza strains in vitro