Drug hypersensitivity involves the activation of T cells in an HLA allele–restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell–priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO–specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ–restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO–specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO–induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
Sustainability is a concept embodied in traditional architecture around the world since ancient times through spontaneous experimental compatibility with the environment and efficient exploitation of the natural resources of the environment according to a rapid development of trial and error over the years . Architecture was the basic means that man devised to protect him from the harsh conditions of the external environment by exploiting natural energy sources such as the sun, wind, and soil capabilitie, Many of the principles of sustainability overlapped with the social organization and human behavior of the community as it was reflected in the urban production at the level of standards of city planning and urban agglomerations as well
... Show MoreKriging, a geostatistical technique, has been used for many years to evaluate groundwater quality. The best estimation data for unsampled points were determined by using this method depending on measured variables for an area. The groundwater contaminants assessment worldwide was found through many kriging methods. The present paper shows a review of the most known methods of kriging that were used in estimating and mapping the groundwater quality. Indicator kriging, simple kriging, cokriging, ordinary kriging, disjunctive kriging and lognormal kriging are the most used techniques. In addition, the concept of the disjunctive kriging method was explained in this work to be easily understood.
of the research is one of the poetic purposes that expresses the philosophy of the intellectual poet who experienced life and learned the tendencies and the gulf of the human soul and the fact that an intellectual attitude towards them, intensified within the poems do not need to be frequently narrated and elaborated, but based on the few words in the rich meanings and expressed the point of view he wanted to convey to the recipient without taking the position of disorientation and retreat to himself expressing his rejection of this reality, but faced this reality different manifestations and reflections and the conditions of human beings in it detailed His opinion is constructive criticism, and accurate observations reveal the culture o
... Show MoreAmong the issues that preoccupied ancient and modern grammarians is the phenomenon of grammatical disagreement among grammarians and their differences in many grammatical issues that many of them go back to the phenomenon of dialectical difference, so this filled our thinking with a lot of things that led us to look at the side of the reasons for this grammatical difference, and here lies the significance of research to know that it is a linguistic phenomenon dealing with the living language used among the Arabs and linguistic phenomena that reflect linguistic reality as well. Thus our chagrin determination in research and investigation in this issue is the scarcity of dialectical studies at the compositional grammar side, and the lack o
... Show MoreThe aim of the research to measure the correlation relationship between modern manufacturing systems and process design and measure the effect by adopting the regression; the research consists of two main variables, which are modern manufacturing systems and process design; it was applied in the production lines of the General Company for Construction Industries, There is a sample of managers, engineers, technicians, administrators, and some workers were selected to fill the special questionnaire with (70) forms which distributed and (65) were approved suitable for use, For data analysis the correlation coefficient was adopted to measure the relationship and regression analysis to find out the effect, Using (SPSS), So the first h
... Show MoreThe results of the present study show that the highest elevation point is (912) meters (a.s.l.) inside Wadi Al-Khur basin while the lowest elevation point is (6) meters (a.s.l.) inside Wadi Abu-Talha basin. The biggest catchment area is represented by Wadi Al-Khur (48840 km²) whereas the smallest catchment area is Wadi Taqtaq (1748 km²). The stream direction of all streams trends from South-West towards North-East. The soil available water capacity (AWC) (Moisture Deficit) in the studied area was15 mm. The average annual rainfall was133.11 mm, the average annual temperature was 25.65 Co, the total depth amount of E Apanwas 3691.85 mm/year, the relative humidity was 40 %, the average annual sunshine is 7.9 hrs., and the
... Show MoreProbit analysis is a type of regression used to analyze the relationship between a stimulus and the quantal response. Allelopathy refers to direct or indirect negative or positive effects of one plant on another through the release of chemical compounds into the environment. This study was carried out to apply probit analysis in investigating the allelopathic effects of the leaves aqueous extracts of apple of Sodom [Calotropis procera (Aiton) W.T.] on the inhibition of seed germination of African rattlebox (Crotalaria saltiana Andr.). A laboratory experiments were carried out at the Faculty of Agricultural Sciences, University of Gezira, Sudan in season 2014/15. Ten concentrations (2.3, 4.6
... Show MoreThe primary objective of this study was to investigate the current status of water-quality conditions and assessment it in the Tigris River, Baghdad, Iraq, and to determine how those conditions are changing over time of pollution if any. A series of Hydrochemical tests were carried out to ascertain the influence of major Cations and Anions, Total Dissolved Solids (TDS), Electrical Conductivity (EC) and Potential of hydrogen (pH) on the quality of water. To assess the environmental pollution of the study area: 34 water samples were collected along Tigris River from north to south Baghdad City; 17 on January 2019 and 17 on April 2019. Result of the test were compared with the World Health Organization standards, and showed that all the
... Show MoreThe current research is concerned with the study of (aesthetic discourse in the significance of commercial advertisement designs), according to a knowledge structure defined by function and creativity, and the main goal is to interpret the reality of forms, their various sources, their essence, meanings, formal relationships, and design ideas in order to achieve the visual goal as a typographic achievement. It arises through the designer’s internal mental intuition to produce shapes based on subjective feelings that refer his preconceptions about those shapes with his feelings to creative formations. Aesthetic discourse is produced from the mind depending on the various symbolic, psychological and social functions, production methods,
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