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 study aimed to reveal the extent of the first intermediate grade science curriculum focus on the national values, health, environmental, economic values, in the light of the education policy in the Kingdom of Saudi Arabia, in addition to present a proposed vision to strengthen it in the science curriculum for the first intermediate grade. The study was applied to the two books student and the two books of activity on the first-second semesters for the academic year 1441 AH. To analyze the curriculum content, the study used a verified card prepared by the researchers and a criterion for interpreting percentages. The study reached the following results: environmental values ranked first with a concentration of (43%), i.e. with an avera
... Show MoreThe trade war, of course, leads to a sharp tension in international relations because the economy is the lifeblood of the states. In the world of trade and economy, countries began to lean towards cooperation. Economic relations after World War II were more liberal, trade barriers were removed and global trade became more flexible and smooth
The article examines metaphors as one of the fundamental means used by D. Rubina when writing the novel “Parsley Syndrome” to form images of dolls as equal heroes of the work. The author of the article continues research related to the work of Dina Ilinichna Rubina, a representative of modern Russian prose.
Research,s Summary The purpose of the research was to specify the standerd Levels for results of basketball for Iraqi young sters, Becuse there werenot the standerd Levels which related to the testings abilities of the players based on plying centers specially the physical abilities, This made weakness in arrangement and putting the suitable training studies for different age stadges which suitable with game ,s requirements, besides evaluation the performance of the plyers in common and the levels of the coachs train in special according to the scientific style. The researchers depended on (8) special testings of chossen physical abilities, These testings applied on the teams, young players for sharing clubs among excellent series of basket
... Show MorePurpose: aims the study to show How to be can to enhance measurement management by incorporating a risk-based approach and the six sigma method into a more thorough assessment of metrological performance. Theoretical framework: Recent literature has recorded good results in analyzing the impact of Six Sigma and risk management on the energy sector (Barrera García et al., 2022) (D'Emilia et al. 2015). However, this research came to validate and emphasize the most comprehensive assessment of metrological performance by integrating Risk management based approach and Six Sigma analysis. Design/methodology/approach: This study was conducted in Iraqi petroleum refining companies. System quality is measured in terms of sigmas, and t
... Show MorePurpose: aims the study to show How to be can to enhance measurement management by incorporating a risk-based approach and the six sigma method into a more thorough assessment of metrological performance. Theoretical framework: Recent literature has recorded good results in analyzing the impact of Six Sigma and risk management on the energy sector (Barrera García et al., 2022) (D'Emilia et al. 2015). However, this research came to validate and emphasize the most comprehensive assessment of metrological performance by integrating Risk management based approach and Six Sigma analysis. Design/methodology/approach: This study was conducted in Iraqi petroleum refining companies. System quality is measured in terms of sigmas, and t
... Show MoreMillions of pilgrims and visitors from numerous parts of the world flock to Karbala (one of the most prominent ideological and religious places in central Iraq) each year to visit the holy shrines in Karbala due to their sanctity. Many improvements have been made to the Two Holy Shrines (THS), the Shrines of Imam Husayn and Imam Abbas, and the area between them (ATHS), due to the high temperatures in this region and to improve pedestrian thermal comfort. Studies on improving outdoor thermal comfort in Karbala are scarce. Hence, this research aims to look into historical and current architectural changes and how they affect thermal comfort. On the hottest summer day, the ENVI-met software program was used to simulate the building des
... Show MoreThe k-out-of-n:G (or k/n:G) system structure is a very popular of redundancy in
fault-tolerant systems, with wide applications in so many fields. This paper presents
two states of multi-state k/n:G systems. The first part, we present the definition that
introduced by Al-Neweihi et al [1], where the values are the same with respect
to all system states and we show that there exists an alternative equivalent definition
to Al-Neweihi's definition. In the second part of this paper we give more general
definition proposed by Huang et al [2], where it allows different values with
respect to different system states and we provide there exists an equivalent definition
to Huang's definition when the values are increasing.
The present work initiated to eaIuate the efficiency of Al-Rustamivah sewage treatment plant
as reflected by the quality of final effluent that is thrown to Di ala river. Weekly samples of
wastewater and final effluent were collected between November 1994 and end of January
1995 and analyzed for different chemical and biological features. Results ha e inidicated that
Al-Rustamiyah sewage treatment plant could not be able efficiently to purify the raw sewage.
The mean values of suspended solids. BOD. COD Dichromate and Oil & grease effluents
were felt to pass standard limits (98.4. 92.8. 125.2 and 39.1 ppm. respectiel). The atherse
possible effects of pollution on Diuala equatic life hae been also discussed in res