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 dealt with the issue of strategic information systems and its impact on the global marketing channel. As the research aims to know the strategic information systems used in the cement company. Which support the senior management in supporting decisions taken in the process of global orientation and moving to foreign markets by choosing the marketing channel that will suit the company. Product and competition with it. With other companies' products. The problem of the study focused on how to move to global markets, and any marketing channel that can be followed to move the cement product globally, what are the strategic information systems used in the company and how will it contribute to supporting senior management dec
... Show MoreThe study was enriched by examining (Islamic Sharia’s position on the phenomenon of bullying) becausee bullying is a recurring aggressive behavior that Is one of the types of violence directed by a person or group of prsons; With the intent of deliberately harming and offending anotherr person or group of persons, It has several verbal, physical, electronIc or other formsforms Bullies may follow a policy of Ientimidation or intimidation, as well as ridicule; In order to belittle the victim .The study aims to know the Islamic Sharia ruling on bullying as a modern term for a content that Is as old as man, and the study reached several results, Including: Islam’s affirmation of the prohibition of this phenomenon In word, deed and gesture,
... Show MoreIn this paper, we introduce the bi-normality set, denoted by , which is an extension of the normality set, denoted by for any operators in the Banach algebra . Furthermore, we show some interesting properties and remarkable results. Finally, we prove that it is not invariant via some transpose linear operators.
The research aims at shedding light on the impact of information technology in reducing tax evasion in the General Authority for Taxation. In order to achieve this, the research relied on the analysis of its variables as a main tool for collecting data and information. The results showed that there is a positive and positive effect of information technology on tax evasion. The impact of information technology on increasing tax revenues and reducing the phenomenon of tax evasion In the performance of the research sample, the research sought to highlight the importance of tax information technology through its data and information to the tax administration for the purpose of completing the process Taxpayers for persons subject to income ta
... Show MoreDoctrinal responses
On the fabrications of succor
Tamimi
In this paper we present the theoretical foundation of forward error analysis of numerical algorithms under;• Approximations in "built-in" functions.• Rounding errors in arithmetic floating-point operations.• Perturbations of data.The error analysis is based on linearization method. The fundamental tools of the forward error analysis are system of linear absolute and relative a prior and a posteriori error equations and associated condition numbers constituting optimal of possible cumulative round – off errors. The condition numbers enable simple general, quantitative bounds definitions of numerical stability. The theoretical results have been applied a Gaussian elimination, and have proved to be very effective means of both a prior
... Show Moreيسعى هذا البحث الى تقديم اطار عملي ونظري حول موضوع "تأثير الاقتصاد المنزلي في تعزيز الاداء العالي" وتم اختبار مخطط الدراسة الفرضي في القطاع التعليمي الحكومي في محافظة البصرة ,ويتضمن عدد من تشكيلات الجامعة التقنية الجنوبية. واستخدمت الاستبانة والمقابلة الشخصية كأسلوب لجمع البيانات للدراسة وكان حجم العينة114 موظف. وقد استخدمت عدد من الاساليب الاحصائية لاختبار فرضيات الدراسة. واظهرت النتائج بأن هناك تأثير ايج
... Show MoreThe strategy of designing the covers of international magazines emerges as one of the expressive means that reflect the emotional and expressive aspects and employ them according to the spatial transformations and the struggles of globalization to usurp the intellectual, cultural, value and civilizational essence of man, which makes him vulnerable to psychological and spiritual alienation and becomes the abstract meaning of identity and culture, and the empowerment of cultural invasion and the control of consumer thought The contemporary globalist on the largest area and the globalization of the peoples of the world, and the study came in the first chapter: the general framework that includes the problem of the research to raise in our m
... Show MoreThe focus of this paper is the presentation of a new type of mapping called projection Jungck zn- Suzuki generalized and also defining new algorithms of various types (one-step and two-step algorithms) (projection Jungck-normal N algorithm, projection Jungck-Picard algorithm, projection Jungck-Krasnoselskii algorithm, and projection Jungck-Thianwan algorithm). The convergence of these algorithms has been studied, and it was discovered that they all converge to a fixed point. Furthermore, using the previous three conditions for the lemma, we demonstrated that the difference between any two sequences is zero. These algorithms' stability was demonstrated using projection Jungck Suzuki generalized mapping. In contrast, the rate of convergenc
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