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 current research aims to test the relationship of the entrepreneurial leadership and its factors (strategic factors, communication factors, personal factors, motivational factors) in managing the organizational crisis and its stages (detection of warning signs, readiness and prevention, containment of damages, restoration of activity, learning) among a sample of companies of the Ministry Water resources (Al-Fao State Company for the implementation of irrigation projects, Al-Rafidain Company for the implementation of dams, Iraq Company for the implementation of irrigation projects), as well as standing at the level of interest of the research companies in the search variables and their factors and stages, there is no doubt tha
... Show MoreIn today's cities, it is easy to see large numbers of vacant lands and unused abandoned sites in downtown areas that are not only ugly but also potentially becoming fertile ground for criminal activities that endanger residents and visitors and contribute to the further degradation of neighborhoods,
can provide reuse of spaces Neglected opportunities to reshape the appearance of the city and to improve the city center for its users that the presence of many neglected sites, whether they were abandoned buildings or sites for destroyed buildings in Mosul after the war on ISIS and with large areas amid the urban fabric led to the emergence of the research problem is (lack of urban planning to reactivate abandoned sites within the ci
... Show MoreThe study aims to introduce the Islamic sites available on the Internet and determine the criteria that contribute to evaluating these sites to indicate their value, topics, and services, while evaluating a simple random sample of the general Islamic sites, which number (35) sites. The results were presented in (8) tables. The study concluded To a set of conclusions, including: (465) “Islamic” websites were seized during the research period, and they are constantly increasing. They were classified according to the name of the website (domain name) com, org, net, edu, and also according to topics such as general Islamic websites and websites of holy places. Mosques, sites of sheikhs, etc. Among the best general Islamic websites are: Isla
... Show MoreOne of the major problems in modern construction is the accumulation of construction and demolition waste; this study thus examines the consumption of waste brick in concrete based on the use of blended nano brick powder as replacement for cement and as a fine aggregate. Seven concrete mixes were developed according to ACI 211.1 using recycled waste brick. Nano powder brick at 0, 5, and 10% was used as a replacement by cement weight, with other mixes featuring 10, 20, and 30% partial replacement by volume of river sand with brick. The experimental results for replacement of cement with nano brick powder showed an enhancement in mechanical properties (compressive, flexural, and tensile strength) at 7,
Abstract
The research aims to shed light on the extent to which the practices of performance management in achieving organizational excellence in one of the formations and the Ministry of Finance (GCT). The importance of the selection of these organizations is that they occupies a large and exceptional importance in the national economy through income redistribution add it to cover a large part of the state budget revenues, these organizations possess functionally diverse cadre of them pregnant initial certification and other senior and he fairly stable To meet this target, and on the basis of the data search exploratory researcher built model hypothesis for the search included variable impressionist and
... Show MoreThe development of human resources training programs has an applied and important role in the preparation of human cadresin terms of capacity to absorb technical sciences and skills and scientific and practical practices at faster rates in order to bealighed with continous development. Hence the recognition of the significant role that human resources play in the economy of any country,which has stressed the interest towards the economic unity of the qualified staff that it needsin atimely manner through the ongoing training process in the era of high technology day by day In this regard ,the current research deal with accounting of human resources and its impact on reducing costs in the military establishment and the
... Show MoreSilymarin is derived from the milk thistle plant, and possesses numerous pharmacological actions, including hepatoprotective, anti-inflammatory, antioxidant, and anticancer properties. The aim of the study was to the determination of influence different concentrations of Silymarin on the rumen performance in 30 local lambs (divided into three groups of 10 lambs each). In the first and second groups, 420 and 210 mg kg-1 of silymarin were administered for 8 weeks, and the third group was the control, which received normal saline solution. The parameters evaluated included the level of volatile fatty acids (VFAs), ammonia and pH in the rumen. Furthermore, the in vitro digestibility of ash, protein, fat and dry matter was investigated.
... Show MoreThis paper suggest two method of recognition, these methods depend on the extraction of the feature of the principle component analysis when applied on the wavelet domain(multi-wavelet). First method, an idea of increasing the space of recognition, through calculating the eigenstructure of the diagonal sub-image details at five depths of wavelet transform is introduced. The effective eigen range selected here represent the base for image recognition. In second method, an idea of obtaining invariant wavelet space at all projections is presented. A new recursive from that represents invariant space of representing any image resolutions obtained from wavelet transform is adopted. In this way, all the major problems that effect the image and
... Show MoreThere are different types of corruptions such as administrative, political, economic and financial corruption. The corruption forms also varied such as bribery, nepotism and extortion. All types and forms of corruption play significant role in the all economic variables generally and on investments in particular, and the corruption used to be an intermediate means in reducing the rate of economic growth. The corruption contributes in reducing the domestic investments via pay bribery by investors to officials’ persons for supplemental contracts and tenders which finally leads to reduction in the investment efficiency. The corruption also contributes in rise of operational costs for the investment projects. In additio
... Show MoreThe research aims to define the images of financial aid that it provides within their tasks (central banks to governments) and how it can affect the indicators of banking stability, as well as monitoring the levels of banking stability in the Iraqi economy through the indicators used by the Central Bank of Iraq, and the importance of research in banking stability lies in Iraq, because any decrease in the movement of the aggregate banking stability index will reflect negatively on the financial sector in Iraq. Therefore, the Central Bank sought to provide financial aid to the government through a group of components, some of which are represented by initiatives that contribute to revitalizing the national economy and the other hel
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