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.
One of the unique properties of laser heating applications is its powerful ability for precise pouring of energy on the needed regions in heat treatment applications. The rapid rise in temperature at the irradiated region produces a high temperature gradient, which contributes in phase metallurgical changes, inside the volume of the irradiated material. This article presents a comprehensive numerical work for a model based on experimentally laser heated AISI 1110 steel samples. The numerical investigation is based on the finite element method (FEM) taking in consideration the temperature dependent material properties to predict the temperature distribution within the irradiated material volume. The finite element analysis (FEA) was carried
... Show MoreIn this investigation a high density polyethylene (HDPE) was used as a substitute to polyvinylchloride in the production of lead acid battery separators. This has been achieved by preparing mixtures of different percentages of the feed materials which include a high density polyethylene (HDPE) locally produced, filler materials such as silica and oils such as dioctylphthalate (DOP) or paraffin which were added to the mixture to improve the final properties of the separator. The materials were compounded by two roll-mills under the same conditions. The following parameters are involved: &nb
... Show MoreThis study was conducted in Animal Resources Department , College of Agriculture to estimate the effect of chemical and biological treatments to improve the nutritive value of poor quality roughages ( corn cobs and wild reed ) . The feeds were treated chemically with 4% NaoH solution ,whereas Aspergillus niger was used to ferment corn cobs and wild reed samples . The chemical analysis showed that protein percentages of corn cobs and wild reed was increased significantly (P<0.05) from 6.05% to 10.51% and 17.70% and from 3.10 %to 6.50% and 9.96% for both chemical and biological treatments respectively. The crude fiber percentages decreased significantly (P<0.05) from 29.19% and 26.10% to 23.60% and 20.10% for chemical treatment and was 20
... Show MoreThe Sr doped La1Ba1-xSrx Ca2Cu4O8.5+δ samples with 0 ≤ x ≤ 0.3 had been prepared using the solid state reaction. The samples were claimed at 800°C for 3hr, palletized and sintered at 860°C for 20hr in air . Dielectric constant and loss by means of capacitance have been investigated with frequencies in the range of 1kHZ to 1MHZ for our samples at room temperature. Also, Shore hardness has been measured. The dielectric constant and loss decrease slightly with the increase of frequency for all compounds. Additionally, the partial substitution of Sr+2 into Ba+2 sites never have effect on the dielectric properties. X-ray diffraction (XRD) analysis showed a tetragonal structure and the
... Show MoreA potentiostatic study for the corrosion of pure zinc in 0.01 M HCl was achieved in absence and presence of (linear alkylbenzene solfonate LAS) detergents in a range of concentrations (0-50) mg/L. The electrochemical studies included anodic, cathodic polarization by using potentiostat over temperature rang (293- 323) K. The mechanism of corrosion rate of pure zinc was suggested by evaluating of αa , αc , ba , bc , i0 , Rp and the kinetic parameters also calculated ( Ea , A) at the above temperature rang, The thermodynamic of corrosion, corrosion accelerating and corrosion protecting were investigated by calculating (∆G, ∆H and ∆s) values
In this research prepare membranes pure silicon carbide (SiC) as well as gas Alloy (ammonia) and using a laser was leaked membrane of glass flooring. To Drasesh optical properties of membranes prepared depending on the technique (Swanepoel) and Adhrt results obtained in general increased permeability pure silicon membranes
The current study aims to test the impact of green training and development on sustainable performance and explore its effects within and outside the Iraqi Ministry of Environment. The main research problem revolves around the question of the extent of implementing green training and development and sustainable performance in the ministry (What is the nature of the relationship between green training and development and sustainable performance in the ministry?). To clarify the relationship between the research variables, two main hypotheses were formulated along with sub-hypotheses. The study also aims to assess the level of the ministry's interest in the research variables and provide key recommendations to enhance sustainable performan
... Show More