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 scholars of Arabic - may God reward them with the reward of the doers of good - laid down the rules of this language, the cycle of which never ceases to dazzle minds, so they adopted principles according to which they judged the denomination of this word, and the accusative of that, and determined in its light the worker and the done, until they reached us the rules and foundations of our dear language, and it is obvious that they differ. The origins of grammarians from one school of thought to another, or from one world to another, especially with regard to the subsidiary rules, and this difference was clearly reflected in what we have received from the rules, as we find a difference in the rulings that they restricted to the one fa
... Show MoreAbstract Objective: The study aimed to assess the factors contributes of patient with bladder cancer and to find out the relationship between the factors of bladder cancer with certain variable. Methodology: A descriptive study to assessment of factors that contribute to bladder cancer that was carried out Al-Karama teaching hospital, Al-Kendy teaching hospital, Specialty Surgery teaching hospital and Al-Yarmok teaching hospital for the period of November 2003 to August 2004. A purposive (non-probability) sample of (100) patients with bladder cancer. An assessment from was constructed for the purpose of the st
One of the serious problems in any wireless communication system using multi carrier modulation technique like Orthogonal Frequency Division Multiplexing (OFDM) is its Peak to Average Power Ratio (PAPR).It limits the transmission power due to the limitation of dynamic range of Analog to Digital Converter and Digital to Analog Converter (ADC/DAC) and power amplifiers at the transmitter, which in turn sets the limit over maximum achievable rate.
This issue is especially important for mobile terminals to sustain longer battery life time. Therefore reducing PAPR can be regarded as an important issue to realize efficient and affordable mobile communication services.
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The research aims to show the effect of some short-term debt instruments (central treasury transfers, cash credit granted to the government by commercial banks) on the production of the wheat crop in Iraq, through its effect on money supply during the period (1990-2018), As the study includes two models according to the statistical program (Eviews9), the first model included measuring the effect of short-term debt instruments on money supply, and the second measuring the extent of the money supply's impact on Wheat crop production, as the results of the standard analysis showed that the short-term debt instruments used in the model were Significant effect on wheat crop production indirectly through its effect on money supply, As
... Show MoreFabrication of solar cell prepared by thermal spray and vacuum thermal evaporation method on silicon wafer(n-type) and studying its efficiency. The film have been deposited on three layers(ZnO then CdS and CdTe) on Si and glass respectively.Direct energy gap was calculated and equal to (4.3,3.4,3)eV and indirect energy gap equal to (3.5,2.5,1.5)eV respectively . Efficiency was calculated for the cell of area 2cm2 it was equal to 0.14%.
<p>In combinatorial testing development, the fabrication of covering arrays is the key challenge by the multiple aspects that influence it. A wide range of combinatorial problems can be solved using metaheuristic and greedy techniques. Combining the greedy technique utilizing a metaheuristic search technique like hill climbing (HC), can produce feasible results for combinatorial tests. Methods based on metaheuristics are used to deal with tuples that may be left after redundancy using greedy strategies; then the result utilization is assured to be near-optimal using a metaheuristic algorithm. As a result, the use of both greedy and HC algorithms in a single test generation system is a good candidate if constructed correctly. T
... Show MoreThis research aimed at identifying the factors that affecting in the recruitment of a teaching staff for the Massive Open Online Courses (MOOCs) in university teaching at the University of Khartoum. The descriptive method was followed. The questionnaire was used as a tool for data collection,, which was distributed directly to a sample of (181) respondent of the teaching staff members of the senate at University of Khartoum from those who were attend at the senate meeting No. (409) which was held on 22 August 2016 Of (272). The researcher followed for the distribution the chance method, where each questionnaire was distributed to each of a teaching staff from different faculties at the University of Khartoum, according to his willingness
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The entities responsible for regulating the financial market are seeking to provide high quality accounting information, to provide appropriate protection to investors, and thus encourage them and attract them to increase their investments. the research reached several conclusion, the most prominent of which comes :-
1-The production of high quality accounting information reduces investment costs and costs of processing accounting information.
2- The production of high quality accounting information helps investors identify the best investment opportunities.
3- The results of the statistical analysis showed that there is significant
... Show MoreNanoparticles of copper sulfide have been prepared by simple reaction between using copper nitrate with different concentrations ratio 0.1, 0.3, and 0.5 mM, thiourea by a simple chemical route. The prepared Nano powders have been deposited onto glass substrates by casting method at 60°C. The structure of the product Nano- films has been studied by x-ray diffraction, where the patterns showed that all the samples have a hexagonal structure of covellite copper sulfide with the average crystalline sizes 14.07- 16.51 nm. The morphology has been examined by atomic force microscopy, and field emission scan electron microscopy. The AFM images showed particles with almost spherical and rod shapes with average diameter sizes of 49.11- 90.64 nm.
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