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.
This study presents the findings of a 3D finite element modeling on the performance of a single pile under various slenderness ratios (25, 50, 75, 100). These percentages were assigned to cover the most commonly configuration used in such kind of piles. The effect of the soil condition (dry and saturated) on the pile response was also investigated. The pile was modeled as a linear elastic, the surrounded dry soil layers were simulated by adopting a modified Mohr-Coulomb model, and the saturated soil layers were simulated by the modified UBCSAND model. The soil-pile interaction was represented by interface elements with a reduction factor (R) of 0.6 in the loose sand layer and 0.7 in t
The clinical spectrum of cutaneous leishmaniasis (CL), an intracellular parasitic pathogen, ranges from a single sore healing to chronic crusty lesions with a manifestation of treatment resistance. The complicated interaction between Leishmania bodies and the early immune response, including innate and adaptive mechanisms, determines the evolution of nodules. This study examined the levels of the chemoattractant interleukin 8 (IL-8), pro-inflammatory nitric oxide (NO), and immunoregulatory macrophage inhibitory factor (MIF) in the serum of subjects recently diagnosed with cutaneous leishmaniasis, in parallel with patients being monitored during consecutive sodium stibogluconate (Pentostam) treatment. A total of 161 serum samples of newly di
... Show MoreThe research aims at benefiting from the technological development and the technical progress. This development necessitated that the educational process take advantage of this progress, and the development of special computer software, especially the design programs, made the two researchers think about how to benefit from these design programs in teaching students the skills of theatrical design.
The current search aims at:
Identifying the effect of 3Ds Max in developing the skill of theatrical decoration design among the students of the Department of Art Education "Third stage / Department of Art Education / Faculty of Fine Arts / University of Diyala for the academic year 2014-2015.
The researchers used the ex
... Show MoreThe current study aimed to investigate the viability of biofilm formation klebsilla pneumoniae and Staphylococcus aureus. 440 urine samples were collected from patients suffering from urinary tract infection (UTI) from those who were admitted and visitors to Al-Ramadi Teaching Hospital, Al-Yarmouk Teaching Hospital, Al-Ramadi Teaching Hospital for women and children and , Teaching Laboratories in the Medical City for both genders for a period extended from 5 July, 2017 to 10 October, 2017. Samples were diagnosed by culturing them on a selective media and by biochemical testes , also, diagnosis was ensured by using VITEK-2 compact system. Results showed that K.pneumoniae isolation ratio was 17.1%(68) and S.aureus ratio was 13.1%(52). Thei
... Show MoreAntibiotic resistance is a problem of deep scientific concern both in hospital and community settings. Rapid detection in clinical laboratories is essential for the judicious recognition of antimicrobial resistant organisms. So, the growth of Uropathgenic Escherichia coli (UPEC) isolates with Multidrug-resistant (MDR) and Extensively Drug-resistant (XDR) profiles that thwart therapy for (UTIs) has been detected and has straight squeezed costs and extended hospital stays. This study aims to detect MDR- and XDR-UPEC isolates. Out of 42 UPEC clinical isolates were composed from UTI patients. The bacterial strains were recognized by standard laboratory protocols. Susceptibility to antibiotic was measured by the standard disk diffusi
... Show MoreExperiment Factorial conducted with two factor in field texture silt clay loam soil, the first factor were Two Rotavator plow which different in number of rotary blades on flanges, weight, width, made and type, the second factor were four speeds tractor 2.62, 5.10, 7.55, 9.23 km/hr to compare performance two Rotavator under depth 12 cm and knowledge slippage, distance between beat blades, practical productivity, disturbed soil volume, percentage of the soil clods which have diameter less than 5 cm under complete block design with three replications using Least Significant Design 0.05. Results showed Galucho Rotavator recorder the higher practical productivity 0>7089 ha/hr, disturbed soil volume 809.8 m3/hr, percentage of the soil clods 96.1
... Show MoreThe research tackles the nature of relationship between the Orthodox Church and the state in the Russian Federation. At the beginning of the nineties of the last century, the church had been performed a different role in its relationship with the state, and it had an effect over the internal and foreign policies for the Russian Federation. In political history of Russia, the church’s existence became an evident too much in comparing with the previous historical period, starting with the educational and political system, whether through a symbolic participating roles as what happened in the inauguration ceremony to take over responsibility of the head of state or taking actual roles such as influencing on the process of holding elections d
... Show MoreThe internationalization of the Libyan crisis and its accompanying militarization of the conflict have played a vital role in hindering to reach a comprehensive political settlement solution in Libya. The increasing international greediness in the Libyan energy resources and the geopolitical importance of the Libyan State led to the involvement of many international and regional powers in this crisis and transformed the Libyan crisis into “proxy war”. Moreover, the Turkish direct military intervention in the Libyan crisis is considered as one of the main constraints facing the international and regional efforts to settle the Libyan crisis as a result of the Turkish insistence on its military existence in Libya to preserve i
... Show MoreThe importance of the research lies in preparing an experimental curriculum according to a scientific method that will contribute to the development of the special strength(endurance the strength of arms) in order to contribute to the attempt to develop the basic skills of the national team players with the goal ball for the blind As for the research problem, it lies in the weakness of the strength endurance of the national team players with the goal ball for the blind, as the research problem is clearly evident in the last minutes of the match, as well as the former studies in the field of goal ball game for the blind at the country level The research aims to prepare special exercises for endurance of strength as well as t
... Show MoreThe CuInSe2 (CIS) nanocrystals are synthesized by arrested precipitation from molecular precursors are added to a hot solvent with organic cap- ping ligands to control nanocrystal formation and growth. CIS thin films deposited onto glass substrate by spray - coating, then selenized in Ar- atmosphere to form CIS thin films. PVs were made with power conversion efficiencies of 0.631% as -deposited and 0.846% after selenization, for Mo coated, under AM 1.5 illumination. X-ray diffraction (XRD) and energy dispersive spectroscopy (EDS) analysis it is evident that CIS have the chalcopyrite structure as the major phase with a preferred orientation along (112) direction and the atomic ratio of Cu : In : Se in the nanocrystals is nearly 1 : 1 : 2