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.
Twisted tape insertion in the smooth plain tube is one of the types of passive methods that are used to enhance heat transfer. Swirl fluid flow inside the tube and related heat transfer characteristics are very complex. ANSYS FLUENT (V 16.1) and ASPEN industrial program are used in analyzing this technique for enhancement heat transfer. A circular plain tube has length L=8534mm and 17 mm inner diameter with a twisted tape of twist ratio of y = (H/D) = (150/17) =8.8 along the plain tube were considered for this study. Eight Reynolds numbers (Re) of 784, 1000, 2000, 3000, 4000, 5000, 6000 and 7000 are used to analyze the response of thermal performance. Crude oil API 28 exit temperature, film heat transfer coefficient, Nus
... Show MoreHypertension is one of the main causes of heart disease; beta- blockers play a crucial role in the management of patients with essential hypertension. Bisoprolol is one of the widely used drugs for the treatment of hypertension. Bisoprolol tablets were prepared by two methods (direct and wet) using different proportion and types of diluents, different binder types and forms, then evaluated for, weight variation, hardness, friability, disintegration time and dissolution rate. The results were compared with a reference Bisoprolol tablet.
Both methods of preparation wet and direct compression method gave good results, which are consistent with the requirements of British Pharmacopeia and United States Pharmacopeia. It was found that
... Show MoreThis study aims to explore the potential mediation role of person-centeredness between the effects of the work environment and nurse reported quality and patient safety. A quantitative cross-sectional survey collected data from 1055 nurses, working in medical and surgical units, in twelve Malaysian private hospitals. The data collection used structured questionnaires. The Hayes macro explored the mediation effect of person-centeredness between the associations of work environment dimensions and care outcomes, controlling nurses’ demographics and practice characteristics. A total of 652 nurses responded completely to the survey (61.8% response rate). About 47.7% of nurses worked 7-h shifts, and 37.0% were assigned more than 15 pati
... Show MoreCerebral palsy "is one of the diseases that afflict children, and it is a term given to the condition of a child who is exposed to a normal brain injury by accident due to its inability to grow or damage to the cells of the areas responsible for movement and knowledge of strength and balance during the stage of normal development." (116: 1999: 10) Cerebral palsy causes disruption in movement and posture due to damage to brain cells in areas that control and coordinate muscle tone, reflexes, strength, and movement. The degree and location of brain damage varies greatly between people with paralysis, as well as the severity of disability and symptoms, as they fall into severe to very simple, and cerebral palsy is one of the diseases that caus
... Show MoreThe marine collagens are biocompatible and biodegradable materials that are considered as a biomimetic approach for tissue regeneration. This study evaluated the effect of daily consumption of marine collagen supplement drink on enamel white spot lesions (WSLs), comparing the results against Regenerate system and Sylc air abrasion methods. Fifty human enamel slabs were allocated into five groups (n = 10 per group): non-treated (sound); non-treated (WSLs, 8% methylcellulose gel with 0.1 M lactic acid (pH 4.6) at 37 °C for 21 days); and three treated surfaces with marine collagen; Regenerate system; and Sylc air abrasion. The treatment lasted for 28 days followed by four weeks’ storage in artificial saliva (pH = 7.0, 37 °C). Evalu
... Show MoreDifferent parameters of double pipe helical coil were investigation experimentally. Four coils were used; three with a curvature ratio (0.037, 0.031, and 0.028) and 11mm diameter of the inner tube while the fourth with 0.033 curvature ratio and 13 mm diameter of the inner tube. The hot water flow in the inner tube whereas the cold water flows in the annulus. The inlet temperatures of hot and cold water are 50 0C and 18 0C respectively. The inner mass flow rate ranges from 0.0167 to 0.0583 kg/s. The results show the Nusselt number increase with increase curvature ratio. The Nusselt number of the coil with 0.037 curvature ratio increases by approximately 12.3 % as compare with 0.028 curvature ratio. The results also r
... Show MoreTwisted tape insertion in smooth plain tube is one of types of passive methods that is used to enhance heat transfer. Swirl fluid flow inside tube and related heat transfer characteristics are very complex. ANSYS FLUENT (V 16.1) and ASPEN industrial program are used in analyzing this technique for enhancement heat transfer. A circular plain tube has length L=8534mm and 17 mm inner diameter with twisted tape has twist ratio of y = (H/D) = (150/17) =8.8 along with a plain tube were considered for this study. Eight Reynolds numbers (Re) of 784, 1000, 2000, 3000, 4000, 5000, 6000 and 7000 are used to analyze the response of thermal performance. Crude oil API 28 exit temperature, film heat transfer coefficient, Nusselt number
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