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.
A new class of higher derivatives for harmonic univalent functions defined by a generalized fractional integral operator inside an open unit disk E is the aim of this paper.
The current study performed in order to detect and quantify epicatechin in two tea samples of Camellia sinensis (black and green tea) by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). Extraction of epicatechin from black and green tea was done by using two different methods: maceration (cold extraction method) and decoction (hot extraction method) involved using three different solvents which are absolute ethanol, 50% aqueous ethanol and water for both extraction methods using room temperature and direct heat respectively. Crude extracts of two tea samples that obtained from two methods were fractionated by using two solvents with different polarity (chloroform and
... Show MoreHydrated lime has been recognized as an effective additive used to improve asphalt concrete properties in pavement applications. However, further work is still needed to quantify the effect of hydrated lime on asphaltic concrete performance under varied weather, temperature, and environmental conditions and in the application of different pavement courses. A research project was conducted using hydrated lime to modify the asphalt concretes used for the applications of wearing (surface), leveling (binder), and base courses. A previous publication reported the experimental study on the resistance to Marshall stability and the volumetric properties, the resilient modulus, and permanent deformation at three different weather temperatures. This
... Show MoreAn easy, eclectic, precise high-Performance Liquid Chromatographic (HPLC) procedure was evolved and validated to estimate of Piroxicam and Codeine phosphate. Chromatographic demarcation was accomplished on a C18 column [Use BDS Hypersil C18, 5μ, 150 x 4.6 mm] using a mobile phase of methanol: phosphate buffer (60:40, v/v, pH=2.3), the flow rate was 1.1 mL/min, UV detection was at 214 nm. System Suitability tests (SSTs) are typically performed to assess the suitability and effectiveness of the entire chromatography system. The retention time for Piroxicam was found to be 3.95 minutes and 1.46 minutes for Codeine phosphate. The evolved method has been validated through precision, limit of quantitation, specificity,
... Show MoreIn subterranean coal seam gas (CSG) reservoirs, massive amounts of small-sized coal fines are released during the production and development stages, especially during hydraulic fracturing stimulation. These coal fines inevitably cause mechanical pump failure and permeability damage due to aggregation and subsequent pore-throat blockage. This aggregation behavior is thus of key importance in CSG production and needs to be minimized. Consequently, such coal fines dispersions need to be stabilized, which can be achieved by the formulation of improved fracturing fluids. Here, we thus systematically investigated the effectiveness of two additives (ethanol, 0.5 wt % and SDBS, 0.001 and 0.01 wt %) on dispersion stability for a wide range of condit
... Show MoreFourteen morphologically varied Ricinus communis L. seeds were collected from different localities in Egypt, El-Sudan and Saudi Arabia. Seed morphology and ITS barcoding analysis were performed to assess their diversity and phylogenetic relationship. Sequence’s alignment of nrITS region from different accessions display high levels of genetic similarities. Cluster analysis could not group different accessions according to their geographical distribution. Nevertheless, the genetic barcodes are interestingly matched with the morphological features of the Ricinus seeds. In conclusion, seed morphology proved to be a valuable tool in evaluating biodiversity and phylogenetic relationship in plant species with different loca
... Show MoreKnowledge of the distribution of the rock mechanical properties along the depth of the wells is an important task for many applications related to reservoir geomechanics. Such these applications are wellbore stability analysis, hydraulic fracturing, reservoir compaction and subsidence, sand production, and fault reactivation. A major challenge with determining the rock mechanical properties is that they are not directly measured at the wellbore. They can be only sampled at well location using rock testing. Furthermore, the core analysis provides discrete data measurements for specific depth as well as it is often available only for a few wells in a field of interest. This study presents a methodology to generate synthetic-geomechani
... Show MoreThis research investigates manganese (Mn) extraction from Electric Arc Furnace Steel Slag (EAFS) by using the Liquid-liquid extraction (LLE) method. The chemical analysis was done on the slag using X-ray fluorescence, X-ray diffraction, and atomic absorption spectroscopy. This work consisted of two parts: the first was an extensive study of the effect of variables that can affect the leaching process rate for Mn element from slag (reaction time, nitric acid concentration, solid to liquid ratio, and stirring speed), and the second part evaluates the extraction of Mn element from leached solution. The results showed the possibility of leaching 83.5 % of Mn element from the slag at a temperature of 25°C, nitric acid co
... Show MoreThe blade pitch angle (BPA) in wind turbine (WT) is controlled to maximize output power generation above the rated wind speed (WS). In this paper, four types of controllers are suggested and compared for BPA controller in WT: PID controller (PIDC), type-1 fuzzy logic controller (T1-FLC), type-2 fuzzy logic controller (T2-FLC), and hybrid fuzzy-PID controller (FPIDC). The Mamdani and Sugeno fuzzy inference systems (FIS) have been compared to find the best inference system used in FLC. Genetic algorithm (GA) and Particle swarm optimization algorithm (PSO) are used to find the optimal tuning of the PID parameter. The results of500-kw horizontal-axis wind turbine show that PIDC based on PSO can reduced 2.81% in summation error of power
... Show More