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.
The nonhomogeneous higher order linear complex differential equation (HOLCDE) with meromorphic (or entire) functions is considered in this paper. The results are obtained by putting some conditions on the coefficients to prove that the hyper order of any nonzero solution of this equation equals the order of one of its coefficients in case the coefficients are meromorphic functions. In this case, the conditions were put are that the lower order of one of the coefficients dominates the maximum of the convergence exponent of the zeros sequence of it, the lower order of both of the other coefficients and the nonhomogeneous part and that the solution has infinite order. Whiles in case the coefficients are entire functions, any nonzero solutio
... Show MoreIn the current study, CuAl0.7In0.3Te2 thin films with 400 nm thickness were deposited on glass substrates using thermal evaporation technique. The films were annealed at various annealing temperatures of (473,573,673 and 773) K. Furthermore, the films were characterized by X-ray Diffraction spectroscopy (XRD), field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), and Ultra violet-visible (UV–vis). XRD patterns confirm that the films exhibit chalcopyrite structure and the predominant diffraction peak is oriented at (112). The grain size and surface roughness of the annealed films have been reported. Optical properties for the synthesized films including, absorbance, transmittance, dielectric constant, and refr
... Show MoreThe aim of this paper is to estimate a single reliability system (R = P, Z > W) with a strength Z subjected to a stress W in a stress-strength model that follows a power Rayleigh distribution. It proposes, generates and examines eight methods and techniques for estimating distribution parameters and reliability functions. These methods are the maximum likelihood estimation(MLE), the exact moment estimation (EMME), the percentile estimation (PE), the least-squares estimation (LSE), the weighted least squares estimation (WLSE) and three shrinkage estimation methods (sh1) (sh2) (sh3). We also use the mean square error (MSE) Bias and the mean absolute percentage error (MAPE) to compare the estimation methods. Both theoretical c
... Show MoreTo find out the impact of maternal risk factors on the outcome of pregnancy in Baghdad city. A descriptive purposive study was carried out on 100 postpartum women who had delivered for 1 hr. to 24 hrs. ago . the study sample was selected from three hospitals in Baghdad city ( Baghdad teaching hospital ,Fatima Al-Zahra'a maternity and pediatric teaching hospital and Al-Yarmook teaching hospital),during the period from 25 Jan. to 25 Feb. 2006. The data were collected through the use of questionnaire format reviewing pregnants' records and personal interview and were analyzed by using descriptive and inferential statistical approaches. The finding revealed that maternal pregnancy complications had weak effects on pregnancy outcome , while mate
... Show MoreThe analysis of the classic principal components are sensitive to the outliers where they are calculated from the characteristic values and characteristic vectors of correlation matrix or variance Non-Robust, which yields an incorrect results in the case of these data contains the outliers values. In order to treat this problem, we resort to use the robust methods where there are many robust methods Will be touched to some of them.
The robust measurement estimators include the measurement of direct robust estimators for characteristic values by using characteristic vectors without relying on robust estimators for the variance and covariance matrices. Also the analysis of the princ
... Show MoreThin films of pure yttrium oxide (Y2O3) and doped with cerium oxide (CeO2) were prepared by the chemical spray pyrolysis(CSP)method. The structural, optical and electrical properties of the prepared films were investigated. The analysis of X-ray diffraction (XRD) thin films revealed that the undoped and doped Y2O3 were amorphous with a broad hump around 27o and narrow humps around 48o and 62o for all samples. Except for the Y2O3:6wt.%CeO2 thin film, all had signal preferential orientation along the (100) plane at 2θ=12.71o which belongs to CeO2, Field emission scanning electron mic
... Show MoreIn Production and Operations Management the specialists have tried to develop a strategy to counter the risks arising from the activities of the organization and of waste of various types and therefore the risk management in the contemporary framework represents a phenomenon of new quality, and can not be this phenomenon to take practical dimensions, but the development of culture of the organization towards the risks and deal with all aspects and paint ways to address them within an integrated program, and requires new skills and systems provide accurate information capable of coordination between the various parties within the organization.
The research aims to develop a blu
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