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.
This research began by explaining its variables and dimensions especially the digital gap, which the authors explained it elaborately beginning with the concept, the reasons blind its emergence of its measurement, and how to treat it. The authors supposed the potentiality of relying on enforcing knowledge in general and the groups suffer from this gap in particular, especially the targeted knowledge to treat its subject.
As enforcing knowledge usually depends on some strategies or choices of organizational orientation among them is learning and training from one side, and communication, as an indicating factor for organizational effectiveness as the authors refer from the other side.
Breast cancer has got much attention in the recent years as it is a one of the complex diseases that can threaten people lives. It can be determined from the levels of secreted proteins in the blood. In this project, we developed a method of finding a threshold to classify the probability of being affected by it in a population based on the levels of the related proteins in relatively small case-control samples. We applied our method to simulated and real data. The results showed that the method we used was accurate in estimating the probability of being diseased in both simulation and real data. Moreover, we were able to calculate the sensitivity and specificity under the null hypothesis of our research question of being diseased o
... Show MoreThis study aims to assess the effect of adding twisted fins in a triple-tube heat exchanger used for latent heat storage compared with using straight fins and no fins. In the proposed heat exchanger, phase change material (PCM) is placed between the middle annulus while hot water is passed in the inner tube and outer annulus in a counter-current direction, as a superior method to melt the PCM and store the thermal energy. The behavior of the system was assessed regarding the liquid fraction and temperature distributions as well as charging time and energy storage rate. The results indicate the advantages of adding twisted fins compared with those of using straight fins. The effect of several twisted fins was also studied to discover
... Show MoreThe purpose of this research is to identify the effect of the use of project-based learning in the development of intensive reading skills at middle school students. The experimental design was chosen from one group to suit the nature of the research and its objectives. The research group consisted of 35 students. For the purpose of the research, the following materials and tools were prepared: (List of intensive reading skills, intensive reading skills test, teacher's guide, student book). The results of the study showed that there were statistically significant differences at (0.05) in favor of the post-test performance of intensive reading skills. The statistical analysis also showed that the project-based learning approach has a high
... Show MoreThis work describes the inhibition effect of different concentration of an aqueous extract of Peganum harmala seed on the corrosion of carbon steel in 3.5 % sodium chloride solution using potentiostatic polarization techniques at the temperature range of 25°C to 55°C. The result show that inhibition efficiency increased with increasing concentration of the inhibitor extracts and temperature. The adsorption of inhibitor on carbon steel surface was fit into Langmuir adsorption isotherm. Kinetic and thermodynamic parameters governing the corrosion and adsorption process were calculated and discussed.
The importance of the study, which is how to use these exercises with the device in rehabilitating the flabby muscles after childbirth, which is a problem found in our society and in need of high education on it because the form of exercises does not need places designated for training such as halls or fitness halls, especially since the social woman has limited movement in which we see the responses Physiology in different ways, the woman’s body is not only subject to the day’s need for work or the need to complete hours of physical training, but she has feminist components that she must overcome, whether it is physiological or otherwise.The research sample was determined by the intentional method available from women whose age
... Show MoreThe reason for applying the project is for the development of some physiological variables and skill performance using a device for the first time applied in Iraq to a sample of badminton players, and this device has a patent on 7/2/2019. An experimental method is used for a sample of (12) players from (Al-Orthodoxy club). The experimental group is applied the proposal technique, while, the control group is instructed by the coach.The results of the research attribute to the role of the proposal exercises of fit light technology, thus, this technology has increased the attention and focusing of the sample and some physiological variables and smash shot skill. It has been concluded that the exercises using fit light technology is helped to i
... Show MoreAbstract: Fluoroquinolones drugs are an important class of wide
... Show MoreIn this investigation , borax (B) (additive I) and chlorinated paraffin (CP.) (additive II) ,were used as flame retardants for each of epoxy and unsaturated polyester resins in the weight ratios of 2,4,6, & 8% by preparing films of (130×130×3) mm dimensions. Also films of these resins with a mixture of [50%(B.)+50%(CP.)] (additive III) in the same weight ratios were prepared in order to study the synergistic effect of these additives on the flammability of the two resins . Three standard test methods were used to measure the flame retardation which are : 1-ASTM : D-2863 2-ASTM : D-635 3-ASTM : D-3014
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