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.
When optimizing the performance of neural network-based chatbots, determining the optimizer is one of the most important aspects. Optimizers primarily control the adjustment of model parameters such as weight and bias to minimize a loss function during training. Adaptive optimizers such as ADAM have become a standard choice and are widely used for their invariant parameter updates' magnitudes concerning gradient scale variations, but often pose generalization problems. Alternatively, Stochastic Gradient Descent (SGD) with Momentum and the extension of ADAM, the ADAMW, offers several advantages. This study aims to compare and examine the effects of these optimizers on the chatbot CST dataset. The effectiveness of each optimizer is evaluat
... Show MoreIn this study, a three-dimensional finite element analysis using ANSYS 12.1 program had been employed to simulate simply supported reinforced concrete (RC) T-beams with multiple web circular openings subjected to an impact loading. Three design parameters were considered, including size, location and number of the web openings. Twelve models of simply supported RC T-beams were subjected to one point of transient (impact) loading at mid span. Beams were simulated and analysis results were obtained in terms of mid span deflection-time histories and compared with the results of the solid reference one. The maximum mid span deflection is an important index for evaluating damage levels of the RC beams subjected to impact loading. Three experi
... Show MoreThis study is the first investigation in Iraq dealing with genotyping of
The current research aims to investigate the effect of a specimen of Daniel in the acquisition of concepts for the Arabic language curricula material to the students of the third phase of the Faculty of Basic Education Department of Arabic Language. The sample consists of (93) applications and a student of (47) students in the Division (A), which represents the experimental group which studied the use of a specimen of Daniel, and (46) students in the Division (B), which represents the control group, which studied the traditional way. The subject of unified two groups, which subjects the Arabic language curricula which includes six chapters.
The duration of the experiment is a full semester. The researchers also prepared a tool for mea
According to the famous saying of the medieval physician Paracelsus, "There is no substance without poison. Only the dose determines the extent of the toxic effect." Here, the effect of monosodium glutamate (MSG) on human health and the risks to the health of its frequent use in the short term was addressed and the long term was evaluated according to the studies of several researchers specializing in this regard. Monosodium glutamate (MSG) is known as one of the most popular food additives that classified as a flavor enhancer. Parts of the evidence were reviewed from the literature explaining its effect on immune system cells in addition to metabolic disorders by exposing individuals to obesity and what is known as metabolic syndrome, as w
... Show MoreA batch adsorption system was applied to study the adsorption of methylene blue from aqueous solution by Iraqi bentonite and treated bentonite with different amount of zinc oxide (ZnO). The adsorption capacities of methylene blue onto bentonite were evaluated. The equilibrium between liquid and solid phase was described by Langmuir model better than the Freundlich model. Langmuir and Freundlich constants have been determined. The separation factor or equilibrium parameter, RL which is used to predict if an adsorption system is favourable or unfavourable was calculated for all cases.
Background: This study aimed to assess the effect of tooth shape ratio on mandibular incisor arrangement. Materials and methods: The sample included dental casts of some dental students and orthodontic patients having Class I dental and skeletal patterns with normal occlusion and severe crowding. The sample was divided into two groups according to the severity of crowding into: group I had Class I normal occlusion with mild or no crowded mandibular dentition and group II had Class I malocclusion with severe crowded mandibular dentition. Each group comprising of 40 subjects (20 males and 20 females). The mesio-distal and facio-lingual crown diameters were measured manually for each cast using modified vernier caliper gauge. Descriptive sta
... Show MoreVolleyball is one of the sports that require physical and skill abilities thus many teaching models appeared to teach these abilities like group investigation model. The research aimed at identifying the effect of group investigation model on learning underarm and overhead passing in volleyball. The researchers hypothesized statistical differences between pre and posttests in learning underarm and overhead passing in volleyball as well as differences in posttests of controlling and experimental groups in learning underarm and overhead passing in volleyball. The researcher used the experimental method on (30) second year female students of physical education and sport sciences college/ university of Baghdad. Group investigation model was app
... Show MoreIn this study, the harvest of maize silage with the cross double row sowing method were tested with a single row disc silage machine in two different PTO applications (540 and 540E min-1) and at two different working speeds v1, v2 (1.8 and 2.5 km h-1). The possibilities of harvesting with a single row machine were revealed, and performance characteristics such as hourly fuel consumption, field-product fuel consumption and PTO power consumption were determined in the trials. The best results in terms of hourly fuel consumption and PTO power consumption were determined in the 540E PTO application and V1 working speed. When the fuel consumption of the field-product is evaluated, it is obtained with V2 working speed and 540E PTO application. As
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