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 influence of different thickness (500, 1000, 1500, and 2000) nm on the electrical conductivity and Hall effect measurements have been investigated on the films of copper indium gallium selenide CuIn1-xGaxSe2 (CIGS) for x= 0.6.The films were produced using thermal evaporation technique on glass substrates at R.T from (CIGS) alloy. The electrical conductivity (σ), the activation energies (Ea1, Ea2), Hall mobility and the carrier concentration are investigated and calculated as function of thickness. All films contain two types of transport mechanisms of free carriers, and increases films thickness was fond to increase the electrical cAnductivity whereas the activation energy (Ea) would vary with films thickness. Hall Effect analysis resu
... Show MoreThe influence of different thickness (500, 1000, 1500, and 2000) nm on the electrical conductivity and Hall effect measurements have been investigated on the films of copper indium gallium selenide CuIn1-xGaxSe2 (CIGS) for x= 0.6.The films were produced using thermal evaporation technique on glass substrates at R.T from (CIGS) alloy. The electrical conductivity (σ), the activation energies (Ea1, Ea2), Hall mobility and the carrier concentration are investigated and calculated as function of thickness. All films contain two types of transport mechanisms of free carriers, and increase films thickness was fond to increase the electrical conductivity whereas the activation energy (Ea) would vary with f
... Show MoreThe importance of the current study lies in the importance of the Tax policy that being considered one of the most important tools working on fulfilling the social, financial and economic goals and improving the investment environment in the country to become having the ability to activate the national economy. The current study has referred that ( Has the tax planning practiced by the Iraqi contribution companies led to increase the far-term tax outcome through getting benefit of the monetary funds and expansion in&nbs
... Show MoreThe effect of different doses (75,100,150 ppm) and periods of
treatment (3,6,9 days) on the spermatognic cells in white mice was studied. It was found that there was a significant decrease (P<0.05) in the percentage of spermatogonia specially in concentration 1 00 and
150 ppm lasted six and nine days and of primary spermatocytes at period of nine days. A significant decrease (P<0.05) was noticed in the percentages of secondary spermatoytes and spermatids, while the percentage of sperms illustrated a significant increase for all concentrations and treatment periods.
Periodontitis is one of the most prevalent bacterial diseases affecting man with up to 90% of the global population affected. Its severe form can lead to the tooth loss in 10-15% of the population worldwide. The disease is caused by a dysbiosis of the local microbiota and one organism that contributes to this alteration in the bacterial population is Prophyromonas gingivalis. This organism possesses a range of virulence factors that appear to contribute to its growth and survival at a periodontal site amongst which is its ability to invade oral epithelial cells. Such an invasion strategy provides a means of evasion of host defence mechanisms, persistence at a site and the opportunity for dissemination to other sites in the mouth. However, p
... Show MoreCarnosol, a phenolic diterpene, is one of the effective anticancer agents naturally occurring in rosemary, sage, parsley, and oregano. The chemoresistance problem increased with the routinely used chemotherapy. Therefore, the efforts to find a substitute with safe and low cost have become crucial worldwide. The current study attempts to inspect the anticancer molecular mechanisms of Carnosol on modulating up- and down- regulation of multiple genetic carcinogenesis pathways. The cytotoxicity of Carnosol on Hela cells was evaluated by MTS assay. Flow cytometry was used to assess apoptosis and cell cycle arrest. The apoptotic morphological changes were obvious by dual apoptosis assay. The differential gene expression after treatment wi
... Show MoreIn this research, hand lay- up technique is used to prepare samples from epoxy resin reinforced with multi- walled carbon nanotubes in different weight fractions (0, 2, 3, 4, 5) wt%. The immersion effect by sodium hydroxide solution (NaOH) at normality (0.3N) for a period of (15 days) on the thermal conductivity of nanocomposites was studied, and compared to natural condition (before immersion). The thermal conductivity of epoxy nanocomposites specimens were carried out using Lee’s disk method. The experimental results showed that thermal conductivity increased with increase weight fraction before and after immersion for all specimens, while the immersion effect leads to decrease thermal conductive values compared to thermal conductivi
... Show MoreThe current study aimed at identifying the impact of each of the full and part time summer enrichment programs on the performance of gifted students. Moreover, it aimed to study the difference between the full and part time programs on the performance of gifted students. The study sample consisted of (115) students from the full time programs and (137) students from the part time programs, they have been randomly selected from the gifted students participating in the full and part time summer enrichment programs. The researcher used the scale of student performance. The results indicated that there were statistically significant differences between the averages of the pre and post applications of the
... Show MoreNiO0.99Cu0.01 films have been deposited using thermal evaporation
technique on glass substrates under vacuum 10-5mbar. The thickness
of the films was 220nm. The as -deposited films were annealed to
different annealing temperatures (373, 423, and 473) K under
vacuum 10-3mbar for 1 h. The structural properties of the films were
examined using X-ray diffraction (XRD). The results show that no
clear diffraction peaks in the range 2θ= (20-50)o for the as deposited
films. On the other hand, by annealing the films to 423K in vacuum
for 1 h, a weak reflection peak attributable to cubic NiO was
detected. On heating the films at 473K for 1 h, this peak was
observed to be stronger. The most intense peak is at 2θ = 37