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.
Red pigmented undecylprodigiosin produced by Streptomyces coelicolor (A3)2 is a
promising drug owing to its characteristics of antibacterial, antifungal,
immunosuppressive and anticancer activities. The culture of S. coelicolor in liquid
medium produces mainly the blue pigmented actinorhodin and only low quantities of
undecylprodigiosin. From an industrial point of view, it is necessary to find a strategy to
improve undecylprodigiosin production. The present study provides evidence that
cultivation of S. coelicolor on solid substrate resulted in a reversal in this pattern of
antibiotic production as the production of undecylprodigiosin was significantly increased
and actinorhodin was completely suppressed. Four di
Cu (In, Ga) Se2 (CIGS) nano ink were synthesized from molecular precursors of CuCl, In Cl3, GaCl3 and Se metal heated to 240 °C for 1 hour in N2-atmosphere to form CIGS nanocrystal ink, Thin films were deposited onto Au/soda-lime glass (SLG) substrates. This work focused on CIGS nanocrystals, including their synthesis and application as the active light absorber layer in photovoltaic devices (PVs). This approach, using spin-coating deposition of the CIGS light absorber layers (75 mg/ml and 150 nm thickness), without high temperature selenization, has enabled up to 1.398 % power conversion efficiency under AM 1.5 solar illumination. X-ray diffraction (XRD) studies show that the structural formation of CIGS chalcopyrite structure. The mo
... Show MoreVarious assays are used to determine the toxic effects of drugs at cellular levels in vitro. One of these methods is the dye exclusion assay, which measures membrane integrity in the presence of Trypan blue. Trypan blue the dye which was used in this study to investigate cytotoxic effect of a new Cis –dichloroplatinum (II) complex [(Qu)2PtCl2] on the viability of polymorphonuclear cells (PMNs). Three concentrations of platinum complex were prepared (70, 35and 17.5 µg/ ml) and the results revealed that the percentage of cell viability decreased as the platinum complex concentration increased in comparison with control.
... Show MoreThe aim of this paper is to study the effects of magnetohydrodynamic (MHD) on
flow of field of Oldroyd-B fluid between two side walls parallel to the plate .
The continuity and motion equations, for the problem under consideration are
obtained. It is found that the motion equation contains fraction derivative of
different order and the magnetohydrodynamic (MHD) parameter M .The effect of M
upon the velocity field is analyzed ,many types of fractional models are also
considered through taken different values of the fraction derivative order . This has
been done through plotting the velocity field by using Mathemitca package .
Close form for the stress tensor was obtained in many cases, which have been
studied be
The aim of this study was to propose and evaluate an eco-epidemiological model with Allee effect and nonlinear harvesting in predators. It was assumed that there is an SI-type of disease in prey, and only portion of the prey would be attacked by the predator due to the fleeing of the remainder of the prey to a safe area. It was also assumed that the predator consumed the prey according to modified Holling type-II functional response. All possible equilibrium points were determined, and the local and global stabilities were investigated. The possibility of occurrence of local bifurcation was also studied. Numerical simulation was used to further evaluate the global dynamics and the effects of varying parameters on the asymptotic behavior of
... Show MoreThe aim of this research is to study the effects of the North Atlantic Oscillation (NAO) on the temperature and precipitation patterns in Baghdad city. Data of the monthly means of the NAO index,the monthlymeans of temperature, and the monthly total of precipitation were analyzed for the period 1900-2008. Non-parametric tests were used to investigate the correlations between these variables. The time series of temperature and precipitation showed no trends. The results indicated that is a slight correlation between the NAO and temperature and precipitation suggesting that NAO has no major effects on the temperature and precipitation patterns in Baghdad city.
This research studies the rheological properties ( plastic viscosity, yield point and apparent viscosity) of Non-Newtonian fluids under the effect of temperature using different chemical additives, such as (xanthan gum (xc-polymer), carboxyl methyl cellulose ( High and low viscosity ) ,polyacrylamide, polyvinyl alcohol, starch, Quebracho and Chrome Lignosulfonate). The samples were prepared by mixing 22.5g of bentonite with 350 ml of water and adding the additives in four different concentrations (3, 6, 9, 13) g by using Hamilton Beach mixer. The rheological properties of prepared samples were measured by using Fan viscometer model 8-speeds. All the samples were subjected to Bingham plastic model. The temperature range studi
... Show MoreThe increasing level of residents’ requirements of the local community led to the necessity for sufficient local funding to satisfy the residents’ requirements and services of the local units affiliated with the decentralized administrative systems on the one hand, and to the role of local financing in the financial independence of local units on the other hand.With the presence of local financing, the financial independence of local units is achieved and is considered one of the conditions for financial independence, which is the provision of local financing to the units away from central support. The study focused in this research to clarify the concept of local financing for local units with a statement of its conditions and importan
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