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 studies on unbonded post-tensioned concrete members strengthened with Carbon Fiber Reinforced Polymers (CFRPs) are limited and the effect of strengthening on the strain of unbonded pre-stressed steel is not well characterized. Estimating the flexural capacity of unbound post-tensioned members using the design methodology specified in the design guidelines for FRP strengthening techniques of bonded post-tensioned members does not provide a reliable evaluation. This study investigates the behavior of unbonded post-tensioned concrete members with partial strand damage (14.3% and 28.6% damage) and strengthened with CFRP laminates using a near-surface mounted technique with and without U-wrap anchorages. The experimental results show
... Show MoreThe goal of the current study was to investigate the effects of curcumin in both formulas (supplement and standard), zinc, and then use them together to show their effect on the levels of glucose, insulin, insulin resistance (IR), and anti-mullerian hormone (AMH) in the model of female rats with induced polycystic ovary syndrome (PCOS) using 1mg/kg/day of letrozole for 21 days followed by a treatment period of 14 days including different treatments of zinc 30 mg/kg, curcumin standard 200 mg/kg, curcumin supplement 200 mg/kg, (curcumin standard plus zinc), (curcumin Supplement plus zinc) and metformin as a standard treatment. After the treatment, all female rats were sacrificed, and blood samples were collected from the inferior vena cava
... Show MoreThis research aims to discuss an important issue because of its role in increasing the efficiency of financial markets and boost investor confidence by a insider trading, which arises as a result of leaking secret information to some investors and reliable in the process of trading shares in the Iraq Stock Exchange And thus obtain abnormal profits at the expense of other investors. Research was based on the assumption that " Where shortcomings in local regulations relating to disclosure and insider trading in accounting information leads to the activate the phenomenon of insider trading in accounting information in the Iraq Stock Exchange and including a negative impact on investors' decisions ". and Because of the difficulty the discove
... Show MoreThe contribution rate of tax revenues in the federal budget is very small compared to the rate of contribution of oil revenues and this leads to negative repercussions on the Iraqi economy and the budget becomes a prisoner of high and low oil prices, and this is a problem that needs to be studied to know the extent of the impact of economic and political decisions on the size of tax revenue and The research goal is determined in studying the effect of amending the Unified Law No (26) of 2019 on the size of annual tax revenues . &
... Show Morethis research seeks to shed light on the study of the impact of Putinism on the Russian-Ukrainian war that broke out in early 2022, by studying the contents of the speeches of Russian President Vladimir Putin before the start of the war. This research uses the structural approach in analyzing the components of the Russian political regime. The research tools used in this research include case studies, content analysis of Russian speeches, and personal meetings of researchers and specialists in Russian affairs. It sums up a number of important conclusions, most notably are : 1) Putinism is a totalitarian regime that includes the political doctrine during the era of Russian President Vladimir Putin. 2) Duginism represents the totality of t
... Show MoreThe study aimed to explaining the concepts of water footprint and virtual water and how these two concepts could use to achieve water savings at the local level to meet the water supply deficit in Iraq, which is expected to increase in the coming years and influence of that on food security in Iraq by using these concepts when drawing production, irrigated and import plans in Iraq. The study aimed to studying the water footprint and virtual water and their impact on the foreign trade for wheat and rice crops during the period 2000-2022 and estimating the most important indicators of virtual water and the water footprint of the study crops due to the importance of these criteria in det
Sequence covering array (SCA) generation is an active research area in recent years. Unlike the sequence-less covering arrays (CA), the order of sequence varies in the test case generation process. This paper reviews the state-of-the-art of the SCA strategies, earlier works reported that finding a minimal size of a test suite is considered as an NP-Hard problem. In addition, most of the existing strategies for SCA generation have a high order of complexity due to the generation of all combinatorial interactions by adopting one-test-at-a-time fashion. Reducing the complexity by adopting one-parameter- at-a-time for SCA generation is a challenging process. In addition, this reduction facilitates the supporting for a higher strength of
... Show MoreSequence covering array (SCA) generation is an active research area in recent years. Unlike the sequence-less covering arrays (CA), the order of sequence varies in the test case generation process. This paper reviews the state-of-the-art of the SCA strategies, earlier works reported that finding a minimal size of a test suite is considered as an NP-Hard problem. In addition, most of the existing strategies for SCA generation have a high order of complexity due to the generation of all combinatorial interactions by adopting one-test-at-a-time fashion. Reducing the complexity by adopting one-parameter- at-a-time for SCA generation is a challenging process. In addition, this reduction facilitates the supporting for a higher strength of cove
... Show MoreThe effects of T-shaped fins on the improvement of phase change materials (PCM) melting are numerically investigated in vertical triple-tube storage containment. The PCM is held in the middle pipe of a triple-pipe heat exchanger while the heat transfer fluid flows through the internal and external pipes. The dimension effects of the T-shaped fins on the melting process of the PCM are investigated to determine the optimum case. Results indicate that while using T-shaped fins improves the melting performance of the PCM, the improvement potential is mainly governed by the fin’s body rather than the head. Hence, the proposed T-shaped fin did not noticeably improve melting at the bottom of the PCM domain; additionally, a flat fin is ad
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