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.
Straight tendons in pretensioned members can cause high-tensile stresses in the concrete extreme fibers at end sections because of the absence of the bending stresses due to self-weight and superimposed loads and the dominance of the moment due to prestressing force alone. Accordingly, the concrete tensile stresses at the ends of a member prestressed with straight tendons may limit the service load capacity of the member. It is therefore important to establish limiting zone in the concrete section within which the prestressing force can be applied without causing tension in the extreme concrete fibers. Two practical methods are available to reduce the stresses at the end sections due to the prestressing force. The first method based
... Show MoreFor over a decade, educational technology has been used sparingly in our schools and universities. Online training courses have been used since 2003 to fill the gaps in our learning system and to add extra program besides classroom learning. This paper aims to investigate the Iraqi EFL instructors’ participating in online training courses and its influence on the process of teaching and learning.
The sample of present study consists of 30 instructors from University of Baghdad. The questionnaire of sixteen items was constructed. After ensuring validity and reliability of questionnaire, it was applied on March 2013 and the result shows that most of instructors improve their teaching methods b
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This research aims to understand complexity management and its impact on the use of the dynamic capabilities of a sample of private colleges. Private colleges are currently facing many crises, changes, unrest and high competitive pressures. Which is sometimes difficult or even impossible to predict. The recruitment of dynamic capabilities is also one of the challenges facing senior management at private colleges to help them survive and survive. Thus, the problem of research was (there is a clear insufficiency of interest in Complexity Management and trying to employ it in improving the dynamic capabilities of Colleges that have been discussed?). A group of private colleges was selected as a
... Show MoreFullerene thin films of about 200 nm thicknesses have been deposited by thermal evaporation method on soda lime glass at substrate temperature 303 and 403K under pressure about 10-5 mbar. This study concentrated on the influence of substrate temperature on the optical properties of C60 thin films within the visible range. Optical characterization has been carried out at room temperature using the absorption spectra, at normal incidence, in range (200-900) nm.
The absorption and extinction coefficients of the samples have been evaluated according to the variation in the UV- Visible spectrum. Increasing substrate temperature causes decreasing in optical band gap energy, for direct allowed tran
... Show MoreIn this paper a modified approach have been used to find the approximate solution of ordinary delay differential equations with constant delay using the collocation method based on Bernstien polynomials.
Background: Celiac disease is an autoimmune chronic disease that affects the human’s intestine and subsequently reflects its effect on the entire body health by retardation the absorption and immune mediated complications cause the involvement of oral health. The present study intended to evaluate the impact of the histopathological disease activity upon dental enamel defects and dental caries.
Subjects and methods: Forty celiac-diseased patients aged 7-11 years were collected from 3 different teaching hospitals in Baghdad classified by means of the histopathological activity of the intestinal disease according to modified Marsh-Ros
... Show MoreClinical index is needed to predict the outcome of pregnancy after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) for infertile patients. Growth differentiation factor-8 (GDF-8), also known as myostatin, is one of transforming growth factor-â superfamily localized in antral follicles in normal and PCOS ovaries but its function in female reproductive system is still unknown. Aim of the study is to assess the correlation between levels of GDF8 in follicular fluid (FF) with outcomes of in vitro fertilization (IVF/ICSI) in women with and without PCOS. A prospective case control study was performed enrolling (40) patients with PCOS and (40) non-PCOS women (male infertility) undergoing IVF/ICSI. The collect
... Show MoreThis paper analysed the effect of electronic internal auditing (EIA) based on the Control Objectives for Information and Related Technologies (COBIT) framework. Organisations must implement an up-to-date accounting information system (AIS) capable of meeting their auditing requirements. Electronic audit risk (compliance assessment, control assurance, and risk assessment) is a development by Weidenmier and Ramamoorti (2006) to improve AIS. In order to fulfil the study’s objectives, a questionnaire was prepared and distributed to a sample comprising 120 employees. The employees were financial managers, internal auditors, and workers involved in the company’s information security departments in the General Company for Electricity D
... Show MoreThe research aims to identify the degree of the availability of knowledge, skill and ability as components of human capital, in addition to stand at the level of strategic agility upon tourism and travel agencies company of Jordan, the impact of human capital on strategic agility has been tested through distribution of a questionnaire on a Randomly Sample from Workers in Jordan tourist Companies of (349),a number of statistics techinces have been used simple liner Regrision and Multiplayer regession, it has shown that the degree of knowledge, ability and skill availability was high, and the same applies on strategic agility components, and shown out that there is a statistically significant impact between human capital and strate
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