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.
There are many harmful acts that occur from drunkards in this case, especially those resulting from car accidents. The world is witnessing dozens or even hundreds of car accidents due to alcohol consumption. These accidents often result in serious injuries that could lead to the death of the drunk driver and those in the car As well as other persons present in the other vehicles with which the incident occurred or pedestrians on the street, as well as damage to private or public property, and if the order of return of the affected persons on the pretext of civil liability (tort) is made as a direct cause of the harmful act, Is entitled Do they like this refer to the liquor seller or their provider as the culprit? Or ar
... Show MoreThere are many harmful acts that occur from drunkards in this case, especially those resulting from car accidents. The world is witnessing dozens or even hundreds of car accidents due to alcohol consumption. These accidents often result in serious injuries that could lead to the death of the drunk driver and those in the car As well as other persons present in the other vehicles with which the incident occurred or pedestrians on the street, as well as damage to private or public property, and if the order of return of the affected persons on the pretext of civil liability (tort) is made as a direct cause of the harmful act, Is entitled Do they like this refer to the liquor seller or their provider as the culprit? Or are they not related to
... Show MoreA study has been performed to compare the beddings in which ductile iron pipes are buried. In water transmission systems, bends are usually used in the pipes. According to the prescribed layout, at these bends, unbalanced thrust forces are generated that must be confronted to prevent the separation of the bend from the pipe. The bed condition is a critical and important factor in providing the opposite force to the thrust forces in the restraint joint system. Due to the interaction between the native soil and the bedding layers in which the pipe is buried and the different characteristics between them. Also, the interaction with the pipe material makes it difficult to calculate the real forces opposite to the thrust forces and the way they
... Show MoreOne of the serious problems in any wireless communication system using multi carrier modulation technique like Orthogonal Frequency Division Multiplexing (OFDM) is its Peak to Average Power Ratio (PAPR).It limits the transmission power due to the limitation of dynamic range of Analog to Digital Converter and Digital to Analog Converter (ADC/DAC) and power amplifiers at the transmitter, which in turn sets the limit over maximum achievable rate.
This issue is especially important for mobile terminals to sustain longer battery life time. Therefore reducing PAPR can be regarded as an important issue to realize efficient and affordable mobile communication services.
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In this paper we prove the boundedness of the solutions and their derivatives of the second order ordinary differential equation x ?+f(x) x ?+g(x)=u(t), under certain conditions on f,g and u. Our results are generalization of those given in [1].
Abstract A descriptive study to assess of factors that contributes of lung cancer. The study was carried out in Specialized Surgery teaching hospital, Ibin Al- Beetar hospital and Ibin Al- Nafees hospital for the period From January 2004 to October 2004 .The study aimed to assess the factors that contribute to lung cancer and to identify the relationship between the variables of the study with lung cancer. A purposive (non-probability) sample of (70) patients with lung cancer was selected for the study. An assessment form was employed for the purpose of the study. Test- retest reliability was employed through
Let M be a R-module, where R be a commutative ring with identity, In this paper, we defined a new kind of module namely ET-hollow lifting module, Let T be a submodule of M, M is called ET-hollow lifting module if for every sub-module H of M with
Let Q be a left Module over a ring with identity ℝ. In this paper, we introduced the concept of T-small Quasi-Dedekind Modules as follows, An R-module Q is T-small quasi-Dedekind Module if,
An R-module M is called ET-H-supplemented module if for each submodule X of M, there exists a direct summand D of M, such that T⊆X+K if and only if T⊆D+K, for every essential submodule K of M and T M. Also, let T, X and Y be submodules of a module M , then we say that Y is ET-weak supplemented of X in M if T⊆X+Y and (X⋂Y M. Also, we say that M is ET-weak supplemented module if each submodule of M has an ET-weak supplement in M. We give many characterizations of the ET-H-supplemented module and the ET-weak supplement. Also, we give the relation between the ET-H-supplemented and ET-lifting modules, along with the relationship between the ET weak -supplemented and ET-lifting modules.
Genotoxic effects of crude bacteriocin extracted from Citrobacter freundii were detected on albino mice bone marrow cells in vivo, using micronucleus (MN) and comet assay. The mice were administered intraperitoneally with 37.5, 75, 150 and 300 mg/kg of the extract for 24 hours. C. freundii was isolated from patients suffering from urinary tract infections (UTI). The bacteriocin producing isolates were determined using cup assayand the most efficient bacteriocin producers were selected. Bacteriocin was extracted from the efficient isolates via the induction with Mitomycin-C (2 mg/ml). Bacteriocin activity (320 U/ml) was determined by well diffusion method, while the protein concentration (2900µg/ml) was estim
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