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.
The research aims to identify the meaning of drug addiction, which being one of the behavioral-deviation signs. It largely seems similar to alcohol-addiction. World health organization has defined drug addiction as a sporadic or chronic-state of intoxication emerges of recurrent-consumption of drugs that impact harmfully on individual and society. The second aim is to study the psychological and health implications on drugs’ users and thirdly to design a psychological-program for those who take drugs.
In this paper the queuing system (M/Er/1/N) has been considered in equilibrium. The method of stages introduced by Erlang has been used. The system of equations which governs the equilibrium probabilities of various stages has been given. For general N the probability of j stages of service are left in the system, has been introduced. And the probability for the empty system has been calculated in the explicit form.
At the last two decades , The environment has witnessed tremendous changes in many fields with the huge competition , various technological development and customer satisfaction , that are reflected in economic units a doption for lean production system.
Lean accounting that has appeared as a response for change occurred of economic units adoption for changes occurred of economic units adoption for lean production instead of wide production system , has devised new performance measures suitable for economic units adoption for lean ideas: and helping in providing suitable information about evaluating economic unit performance , these measures are divided into three levels , cell level,value flow level , a
... Show MoreIn this paper, the -caps are created by action of groups on the three-dimensional projective space over the Galois field of order eight. The types of -caps are also studied and determined either they form complete caps or not.
Abstract
These experiments seek to investigate the effects of the fixed variations to the basic box plot on subjects' judgments of the box lengths. The study consists of two experiments, were constructed as an extension to the experiments carried out previously by Hussin, M.M. (1989, 2006). Subjects were asked to judge what percentage the shorter represented of the longer length in pairs of box lengths and give an estimate of percentage, one being a standard plot and the other being of a different box length and also varying with respect to other elements such as, box width or whisker length. When he (1989) suggested in the future research points (1, 2), the changing length of the st
... Show MoreThe research aims to know the impact of workers values on their performance which is reflected on increasing productivity and improving its quality as well as the organization's progress and success. Application of this research took place in the General Company Of Electrical Industries; it contained four main pillars; the first involved research methodology، regarding the problem، importance، aim، basic theory، and method of data collection، the second is dedicated to the theoretical framework related to the research basic variables (values and workgroups) the third is assigned to analyze the actual data by using number of statistical methods، such as mathematical medium and standard deviation and also spearman rank
... Show MoreThe research statement to the amount of the contribution of information and communication technology in the quality of tourism and hotel services, and determine the relationship between the impact of information and communication and the quality of tourism services technology, The importance of the research is to establish the philosophical thinking of the nature of variables, as a modern administrative terminology and employ them towards the quality of tourism and hotel services, the research dealt with a problem expressed by a number of intellectual and practical questions, Was formulated based on the current situation witnessed by the tourism sector and hotel in Iraq, and the real gap was the lack of awareness of the impo
... Show MoreThe research aims to: Preparing rehabilitative exercises with accompanying tools to rehabilitate those with shoulder dislocation. Knowing the effect of rehabilitative exercises and accompanying aids in improving the muscular strength and motor range of those with dislocations in the shoulder joint. The two researchers used the experimental design with the same experimental group with the pre and post tests, so the researcher chose a sample appropriate to the nature of his research problem, its goals and its hypotheses, as a sample of the injured was chosen to remove the shoulder joint, who completed the treatment, who were not practicing sports, and those who went to the Physiotherapy Center at Al-Was
... Show MoreThis research aims at identifying the system of applying the QRcode system for acquisition of chemistry by first class female students studying at intermediate schools knowledge and its effect on creative thinking. The research sample consisted of (63) female students in one of the intermediate schools in Baghdad/Iraq using two equivalents experimental and control groups. The scientific context used was based on the chemistry text book related to the periodic table, (Metals) for the first group of students and Alkaline metals,Nonmetals, Metalloides) for the second group. The research methodology employed consisted of the followings :Measuring students acquisition using (35) issues. The results were verified for their face validity and obtai
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