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.
Cancer stem cells (CSCs) are defined as a population of cells present in tumours, which can undergo self-renewal and differentiation. Identification and isolation of these CSCs using putative surface markers have been a priority of research in cancer. With this background we selected pancreatic normal and tumor cells for this study and passaged them into animal tissue culture medium. Further staining was done using alkaline phosphatase and heamatoxilin staining. Blue to purple colored zones in undifferentiated pluripotent stem cells and clear coloration in the chromatin material indicated pancreatic cells. Further studies on the cell surface marker CD 44 were done using ELISA. For this, the protein was extracted from cultivated normal and t
... Show MoreEmploying phase-change materials (PCM) is considered a very efficient and cost-effective option for addressing the mismatch between the energy supply and the demand. The high storage density, little temperature degradation, and ease of material processing register the PCM as a key candidate for the thermal energy storage system. However, the sluggish response rates during their melting and solidification processes limit their applications and consequently require the inclusion of heat transfer enhancers. This research aims to investigate the potential enhancement of circular fins on intensifying the PCM thermal response in a vertical triple-tube casing. Fin arrays of non-uniform dimensions and distinct distribution patterns were des
... Show MoreLasers has been proved to increase tissue oxygenation, activate marrow progenitor cells, expanse the microcirculation, accelerate the restoration of functions, stimulate adaptation ability and stabilization of the hormonal status. The semisolid tissue present in the epiphysis of the bone where it’s structure is spongy or cancellous is bone marrow and it formed about 4% of body weight, the marrow is composed of hemopoietic cells, however, the structure of the marrow is of both cellular and non – cellular components. The hemopoietic stem cells are responsible of producing white blood cells, red corpuscles, platelets in addition to the fibroblasts, macrophages, adipocytes, osteoblast
The railways network is one of the huge infrastructure projects. Therefore, dealing with these projects such as analyzing and developing should be done using appropriate tools, i.e. GIS tools. Because, traditional methods will consume resources, time, money and the results maybe not accurate. In this research, the train stations in all of Iraq’s provinces were studied and analyzed using network analysis, which is one of the most powerful techniques within GIS. A free trial copy of ArcGIS®10.2 software was used in this research in order to achieve the aim of this study. The analysis of current train stations has been done depending on the road network, because people used roads to reach those train stations. The data layers for this st
... Show MoreThe aim of the study was extraction of arial part of Euphorbia cyathophora constituents with methanol and evaluate its effect on mitotic index and total chromosomal aberration bone marrow cell and spleen cell in mice 200 gm of E. cyathophora fine powder was defatted then extracted by cold maceration 80% ethanol for seven days. The extract was filtered and dried in a rotary evaporator then the dried extract was suspended with water and consecutively extracted using chloroform, ethyl acetate for each. The aqueous layer was then mixed with 100ml methanol. These fractions are dried under reduced pressure to obtain the dry extract. Twenty-four Albino mice were used for the experiment. The animals were divided into four groups: Gr
... Show MoreWe study in this paper the composition operator that is induced by ?(z) = sz + t. We give a characterization of the adjoint of composiotion operators generated by self-maps of the unit ball of form ?(z) = sz + t for which |s|?1, |t|<1 and |s|+|t|?1. In fact we prove that the adjoint is a product of toeplitz operators and composition operator. Also, we have studied the compactness of C? and give some other partial results.
The phenomenon of negative behavior has studied as a social and psychological phenomenon that effect on the performance and life of workers inside and outside the organization. The adoption of this phenomenon is studied in terms of the role of the internal environment of the organization in addressing this behavior, being the variables belong to the field of organizational behavior to see the results of those variables on the Iraqi organizations, since the specificities of it differ from the rest of the Arab and foreign environments. Therefore, this study focused on testing the relationship of the internal environment of the organization and its role in addressing the negative behavior of the workers.
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... Show MoreThe problem of the high peak to average ratio (PAPR) in OFDM signals is investigated with a brief presentation of the various methods used to reduce the PAPR with special attention to the clipping method. An alternative approach of clipping is presented, where the clipping is performed right after the IFFT stage unlike the conventional clipping that is performed in the power amplifier stage, which causes undesirable out of signal band spectral growth. In the proposed method, there is clipping of samples not clipping of wave, therefore, the spectral distortion is avoided. Coding is required to correct the errors introduced by the clipping and the overall system is tested for two types of modulations, the QPSK as a constant amplitude modul
... Show MoreResults: it was found that labelled cells participated in the formation of myotubes, which formed mature muscle fibers, and possibly new satellite cells. The results of this experiment may eventually revolutionized therapeutic procedures for some form of muscle diseases