DECENTRALIZATION FOR REGIONAL INFRASTRUCTURE DEVELOPMENT IN EASTERN GEORGIA

This article is about analyzing and decentralization strategy in Eastern Georgia. An ongoing process of decentralization puts on the agenda the regional infrastructure planning, development and optimization. The political importance is given to the creation of the regional infrastructure development strategy.Prior to that, it is important to note the existing regional infrastructure. It is not only about traditionally the highland regions, but the general municipalities, development potentials and perspectives. The above mentioned is particularly relevant to find that all municipalities have their own niche, that is attractive to the tourists and will be able to develop as well as maintain population in rural areas.This article is about analyzing and decentralization strategy in Eastern Georgia. An ongoing process of decentralization puts on the agenda the regional infrastructure planning, development and optimization. The political importance is given to the creation of the regional infrastructure development strategy.Prior to that, it is important to note the existing regional infrastructure. It is not only about traditionally the highland regions, but the general municipalities, development potentials and perspectives. The above mentioned is particularly relevant to find that all municipalities have their own niche, that is attractive to the tourists and will be able to develop as well as maintain population in rural areas

Cavitation microjet and shock wave in a signal from impact load measurement

This master thesis work is done to try and describe processes that occurred during cavitation bubble collapse near a solid boundary, to try and separate cavitation microjet and shock wave impact from the signal received by PVDF sensors. The thesis starts with the introduction of the general terms connected to the cavitation phenomenon itself. Literature related to the bubble interaction phenomena near solid wall and usage of PVDF films is also reviewed. The experimental setup, with the method of bubble generation and used equipment are also described. Two PVDF sensors were fixed to two metal plates in order to receive signals from the bubble collapse, generated by the underwater spark discharge. Calibration of the sensors was done with the ball drop method. The experiments were observed by the Nanosense MKIII CCD camera at 10000 fps. Bubbles were generated at different dimensionless stand-off distances and impacts were further analyzed and compared to different articles. A small chapter is also dedicated to describe the possible problems that can occur during the experiments using PVDF films.Inverse squares law was used to check if the theoretical and experimental shock wave propagation were the same. This law works only for spherical shock sources, results of the experimental values during specific ranges are in the acceptable level with the theoretical model. Maximum impact forces and loading stresses (pressures) are shown and discussed. The exact values of the cavitation microjet are not recorded as a significant event, but several important assumptions were made, especially when the dimensionless stand-off (proximity) parameter is in the range between 0.8 and 1. Double peak-shaped signals are received in this range and these peaks are created by the splash effect (accompanied by the shock waves) due to the microjet and by the moving flow towards the ring (as well can be interpreted as a bubble ring collapse).This master thesis work is done to try and describe processes that occurred during cavitation bubble collapse near a solid boundary, to try and separate cavitation microjet and shock wave impact from the signal received by PVDF sensors. The thesis starts with the introduction of the general terms connected to the cavitation phenomenon itself. Literature related to the bubble interaction phenomena near solid wall and usage of PVDF films is also reviewed. The experimental setup, with the method of bubble generation and used equipment are also described. Two PVDF sensors were fixed to two metal plates in order to receive signals from the bubble collapse, generated by the underwater spark discharge. Calibration of the sensors was done with the ball drop method. The experiments were observed by the Nanosense MKIII CCD camera at 10000 fps. Bubbles were generated at different dimensionless stand-off distances and impacts were further analyzed and compared to different articles. A small chapter is also dedicated to describe the possible problems that can occur during the experiments using PVDF films.Inverse squares law was used to check if the theoretical and experimental shock wave propagation were the same. This law works only for spherical shock sources, results of the experimental values during specific ranges are in the acceptable level with the theoretical model. Maximum impact forces and loading stresses (pressures) are shown and discussed. The exact values of the cavitation microjet are not recorded as a significant event, but several important assumptions were made, especially when the dimensionless stand-off (proximity) parameter is in the range between 0.8 and 1. Double peak-shaped signals are received in this range and these peaks are created by the splash effect (accompanied by the shock waves) due to the microjet and by the moving flow towards the ring (as well can be interpreted as a bubble ring collapse)

B-Cell Responses to Sars-Cov-2 mRNA Vaccines

Most vaccines against viral pathogens protect through the acquisition of immunological memory from long-lived plasma cells that produce antibodies and memory B cells that can rapidly respond upon an encounter with the pathogen or its variants. The COVID-19 pandemic and rapid deployment of effective vaccines have provided an unprecedented opportunity to study the immune response to a new yet rapidly evolving pathogen. Here we review the scientific literature and our efforts to understand antibody and B-cell responses to SARS-CoV-2 vaccines, the effect of SARS-CoV-2 infection on both primary and secondary immune responses, and how repeated exposures may impact outcomes

Cytotoxic CD4+ T cells in patients with B cell chronic lymphocytic leukemia kill via a perforin-mediated pathway

Background and Objectives: B-cell chronic lymphocytic leukemia (B-CLL) is a clonal expansion of CD5+B cells that accumulate due to their uncontrolled growth and resistance to apoptosis. We have previously shown that up to 50% of blood CD4+ T cells in BCLL patients have a cytotoxicity-related CD28-CD57+ phenotype and high content of both granzyme B and perforin (PF). In this study we investigate the cytotoxic potential of these cells against autologous B-CLL cells. Design and Methods: Blood CD4+ or CD8+ T cells were positively isolated from B-CLL patients and cultured under a range of conditions with autologous purified B-CLL cells and with bispecific [anti-CD3 x anti-CD19] antibodies. Apoptosis of labeled B-CLL cells was assessed using the change of mitochondrial membrane potential with the fluorescent dye DiOC6 and confirmed by annexin V binding. Results: There was time- and dose-dependent killing of B-CLL cells by both CD8+ and CD4+ T cells and this ranged from 6.6 - 68.0% for CD4+ cells and 6.4 - 57.8% for CD8+ cells. Almost complete inhibition by concanamycin A suggests that CD4+ T cells like CD8+ T cells induced apoptosis through a perforin-mediated pathway, but not via Fas/FasL (as indicated by lack of blocking with brefeldin A), tumor necrosis factor or TRAIL. Interpretation and Conclusions: This study shows that blood CD4+PF+ T cells enriched in B-CLL patients, are able to kill autologous B-CLL cells ex vivo, through bispecific antibodies via a perforin mediated mechanism

Management of the Economic Capacity of the Region on the Basis of Foresight (on the Example of Adygea, Russia)

In connection with the aggravation of crisis phenomena in the economy of Russia caused by the events in Ukraine, the sanctions of the West, oil prices reduction and a decline in the ruble, a new approach to strategic planning is required. Foresight technology is the most appropriate one. The purpose of this article is to give a brief description of the foresight as a technology of foreseeing and identifying the most promising points of regional capacity, aimed at improving the competitiveness on the example of a particular region of the Russian Federation – the Republic of Adygea. The authors note that conducting the regional foresight project must be preceded by an analysis of economic, natural, innovative, and information- technological capacity of the region. The article reviews the methods for foresight, gives the characteristics of natural, economic, innovation and information- technological capacity of the Republic of Adygea. In the article the development problems of the region, uncertainty factors and trends of socio-economic changes in the republic have been identified. The implementation of the foresight project will allow to form the basis for social partnership of government, business and social community in order to better exploit opportunities and the implementation of the economic capacity of the region. Keywords: foresight, forecasting, anticipation, socio-economic development, regional capacity, long-term strategy, uncertainty. JEL Classifications: D81; O1

The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection

Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Δ2A, Δ2B, Δ2A/Δ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Δ2A and Δ2A/Δ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Δ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Δ2A and Δ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Δ2A virus infection. Infection with Δ2A and Δ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Δ2A/Δ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al

Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome

Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases; pathomechanisms that regulate extravasation of damaging immune cells into surrounding tissues are poorly understood. Here we identified three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation. Two patients developed liver fibrosis in their first year of life. Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN, p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. Functional studies revealed increased expression of ICAM-1 on induced patient-derived endothelial cells (iECs) and of β2-integrins on patient neutrophils that increase neutrophil adhesion and vascular transendothelial migration (TEM). Treatment with TNF inhibition improved systemic inflammation; and liver fibrosis resolved on treatment with the Src kinase inhibitor dasatinib. Our findings reveal a critical role for Lyn kinase in modulating inflammatory signals, regulating microvascular permeability and neutrophil recruitment, and in promoting hepatic fibrosis

Plasmodium-specific atypical memory B cells are short-lived activated B cells

A subset of atypical memory B cells accumulates in malaria and several infections, autoimmune disorders and aging in both humans and mice. It has been suggested these cells are exhausted long-lived memory B cells, and their accumulation may contribute to poor acquisition of long-lasting immunity to certain chronic infections, such as malaria and HIV. Here, we generated an immunoglobulin heavy chain knock-in mouse with a BCR that recognizes MSP1 of the rodent malaria parasite, Plasmodium chabaudi. In combination with a mosquito-initiated P. chabaudi infection, we show that Plasmodium-specific atypical memory B cells are short-lived and disappear upon natural resolution of chronic infection. These cells show features of activation, proliferation, DNA replication, and plasmablasts. Our data demonstrate that Plasmodium-specific atypical memory B cells are not a subset of long-lived memory B cells, but rather short-lived activated cells, and part of a physiologic ongoing B-cell response