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The Effect of Inhibitory Signals on the Priming of Drug Hapten–Specific T Cells That Express Distinct Vβ Receptors
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Abstract<p>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.</p>
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Publication Date
Tue Sep 17 2024
Journal Name
Evolutionary Studies In Imaginative Culture
The Effect of the Siberian Air Altitude on the Characteristics of the Climate of the Northern Arabian Peninsula
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The field of climatic geography focuses on the study of the Earth's surrounding atmosphere, particularly the lower (surface) part close to the Earth's surface. This field examines the interactions within the atmosphere resulting from the solar radiation that reaches the Earth and the subsequent distribution of atmospheric pressure. Consequently, certain surface pressure systems, both high and low, emerge and vary in their temporal and spatial impacts on the climate of the Arabian Peninsula. Therefore, it is essential to conduct a comprehensive and detailed study to understand the causes, development, movement, geographical distribution, and monthly and seasonal recurrence of these pressure systems. For this purpose, a minor climatic

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Publication Date
Tue May 16 2023
Journal Name
Journal Of Engineering
The Effect of Spatial Organization on the Sustainability of the Neighborhood Unit in the Residential Environment
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Contemporary residential neighborhoods suffer from weak sustainability of urban residential environments as a result of the adoption of inefficient spatial organization at the neighborhood unit level. This resulted negative characteristics which affected the achievement of sustainable development plans for the residential environment that constitute the majority of the urban fabric of cities.

The physical affordances ,within the vocabulary of recent times,overcame the spiritual ones and affected the residential environment. Accordingly,the concept of space changed in contemporary residential areas through the dominance of the physical aspect (mass) on the symbolic aspect (space).The modern technology occupied an important level b

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Publication Date
Sat Jul 01 2023
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Form that is a Proposed of Procedures for Auditing the Technical Reserves of General Insurances Branches in the Insurance Activity : applied research
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The research aims to identify the theoretical framework of technical reserves in the insurance activity and the role of the auditor in verifying the integrity of the estimates of technical provisions (technical reserves) for the branches of general insurance in insurance companies based on the relevant international auditing standards, as a proposed audit program has been prepared in accordance with international auditing standards that enable the auditor to express a sound opinion on the fairness of the financial statements of these companies , The research has reached many conclusions, the most important of which is the existence of deficiencies in the audit procedures of insurance companies, as the audit program of those companies did

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Publication Date
Sun Nov 01 2020
Journal Name
Iscience
Identification and Characterization of Highly Fluorescent Pigment Cells in Embryos of the Arabian Killifish (Aphanius Dispar)
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Publication Date
Sun Jun 12 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Understanding the Experience of Hospital Pharmacists with the Effectiveness, Safety, Adverse Drug Reaction Reporting and Interchangeability of Biopharmaceutical Medicines
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The study objectives were to 1) explore the real-world experience of hospital pharmacists with the differences in effectiveness safety, and interchangeability between biosimilar medicines and their reference biological counterparts, 2) reveal pharmacist recommendations to enhance the safety of biopharmaceutical medicines in public hospitals.

The study has a mixed-method design where the core component was qualitative (interviews) and the supplemental component was quantitative (adverse drug reaction, ADR, reports). This qualitative component included semi-structured (mostly face-to-face) interviews involving hospital pharmacists from different hospitals with experience with biological or biosimilar medicines. The interviews were c

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Publication Date
Wed Mar 18 2020
Journal Name
Baghdad Science Journal
Differentiation of Adipose-Derived Mesenchymal Stem Cells into Neuron-Like Cells induced by using β-mercaptoethanol
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Background: Adipose derived-mesenchymal stem cells have been used as an alternative to bone marrow cells in this study. Objective: We investigated the in vitro isolation, identification, and differentiation of stem cells into neuron cells, in order to produce neuron cells via cell culture, which would be useful in nerve injury treatment. Method: Mouse adipose mesenchymal stem cells were dissected from the abdominal subcutaneous region. Neural differentiation was induced using β-mercaptoethanol. This study included two different neural stage markers, i.e. nestin and neurofilament light-chain, to detect immature and mature neurons, respectively. Results: The immunocytochemistry results showed that the use of β-mercaptoethanol resulted in

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Publication Date
Sun Jan 01 2012
Journal Name
Advances In Materials Physics And Chemistry
The Effect of Zn Concentration on the Optical Properties of Cd&amp;lt;sub&amp;gt;10–x&amp;lt;/sub&amp;gt;Zn&amp;lt;sub&amp;gt;x&amp;lt;/sub&amp;gt;S Films for Solar Cells Applications
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Publication Date
Thu Oct 01 2015
Journal Name
Journal Of Engineering
The Effect of Recycled Heating and Cooling and The Effect of The Speciment Size on The Compressive Strength of Concrete Exposed To High Temperature
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     In the present work effect of recycled heating and cooling on the values of concrete compressive strength due to high temperature of 4000C was studied.

    The tests show that the percent of reduction in compressive strength of the samples which exposed to a temperature of 4000C for one cycle was 32.5%, while the reduction was 52.7% for the samples which were exposed to recycled heating and cooling of ten times .      

   Moreover a study of the effect of specimen sizes on the percentages of compressive strength reduction due to high temperature

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Publication Date
Mon Sep 30 2019
Journal Name
College Of Islamic Sciences
The term that is verbally agreed and different is meaningful Between grammar and fundamentalists
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Science is linked to each other bonds assets, branches and even close to each other; to become a link of this type of patterns of scientific integration, and perhaps the most prominent science that saw the overlap and interdependence of science and jurisprudence and its origins, and this interdependence did not stop at the epistemological foundations of knowledge; To the branches, methods of extraction, and diligence to extend to the terminology; to find similar terms in both flags; to become those terms similar in the word and meaning and even the end, but we do not lack terms similar in pronunciation and differing in meaning; and this difference is imposed by the specificity of each science and what M E; however, approached many terms

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Publication Date
Sun Dec 01 2013
Journal Name
Alustath
"The Common Humanity That is in Us All": Earnest Gaines's (A Lesson before Dying)
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Gaines's A Lesson Before Dying (1993) is about more than the challenges associated with being blacking an Eurocentric society. Though Gaines positions the story within the context of the African American experience, its central theme investigates what it means to be human. The Afro-American writer Ernest Gaines consistently writes about people who face the problems of being denied humanity, dignity, and self-worth. The article illustrates one man's struggle to gain recognition of his humanity in the court (as his attorney insists on calling him a hog for a crime he did not commit) and how this recognition will initiate a change in the community.

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