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.
In this study, the response of ten composite post-tensioned concrete beams topped by a reinforced concrete deck with adequate reinforcing shear connectors is investigated. Depending on the concrete compressive strength of the deck slab (20, 30, and 40 MPa), beams are grouped into three categories. Seven of these beams are exposed to a fire attack of 700 and 800 °C temperature simultaneously with or without the presence of a uniformly distributed sustained static loading. After cooling back to ambient temperature, these composite beams are loaded up to failure, using a force control module, by monotonic static loading in a four-point-bending setup with two symmetrical concentrated loads applied in
Pulsatile drug delivery systems (PDDS) are developed to deliver drug according to circadian behavior of diseases. They deliver the drug at the right time, action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. The drug is released rapidly and completely as a pulse after a lag time. These systems are beneficial for drugs with chrono-pharmacological behavior, where nighttime dosing is required and for the drugs having a high first-pass effect and having specific site of absorption in the gastrointestinal tract. This article covers methods and marketed technologies that have been developed to achieve pulsatile delivery. Diseases wherein PDDS are promising include asthma, peptic u
... Show MoreTransdermal drug delivery has made an important contribution to medical practice but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. Transdermal therapeutic systems have been designed to provide controlled continuous delivery of drugs through the skin to the systemic circulation. A transdermal patch is an adhesive patch that has a coating of drug; the patch is placed on the skin to deliver particular amount of drug into the systemic circulation over a period of time. The transdermal drug delivery systems (TDDS) review articles provide information regarding the transdermal drug delivery systems and its evaluation process as a ready reference for the research scientist who is involved
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One of the most suitable materials to be used in latent heat thermal energy storage system (LHTES) are Phase change materials, but a problem of slow melting and solidification processes made many researchers focusing on how to improve their thermal properties. This experimental work concerned with the enhancing of thermal conductivity of phase change material. The enhancing method was by the addition of copper Lessing rings in phase change material (paraffin wax). The effect of diameter for the used rings was studied by using two different diameters (0.5 cm and 1cm). Also, three volumetric percentages of rings addition (3%, 6% and 10%) were tested for each diameter. The discharging process was done with
... Show MoreIn this work, the effect of variation of semi-angle of the conical part on the vibration characteristics of cylindrical-conical coupled structure is investigated. The shell is made of polyester resin reinforced by continuous E-glass fibers. The case is analyzed experimentally and numerically for orthotropic shell structures. The experimental program is conducted by exciting the fabricated structure by an impact hammer and monitoring the response using an attached accelerometer for different semi-angles of the conical part.
Software named SIGVIEW is used to perform the signal processing on the acquired signal in order to measure the natural frequencies and the corresponding mode shapes. The numerical investigation is achieved using ANS
The present study included the use of the approximate semi-experimental method, the time-independent density function theory (unrestricted), the time-dependent density function theory, and Hartree-Fock method to calculate the reaction pathway of the anti-inflammatory drug diclofenac with its common ionic carriers (sodium and potassium). The basis sets used were STO-3G, 3-21G, 6-31G, and 6-311G. The drug was studied with two new proposed carrier ions (lithium and calcium) which were compared with common carriers. The calculations included the optimized geometrical structure and some physical properties such as standard heat of formation, dipole moment, total energies, and analytical spectra of IR, UV-VIS and 1H NMR. The biologi
... Show MoreLaboratory studies were conducted at the biological control unit, college of Agriculture, University of Baghdad to evaluate some biological aspects of the predator Chilocorus bipustulatus (Coleoptera: Coccinellidae), which is considered one of the most important predators on many insect pests, especially the scale insect, Parlatoria blanchardi, (Homoptera: Diaspididae) on date palms. The results showed that biological parameters of the predator were varied according to different degree of temperature. Egg incubation period was significantly different and reached to 7.5 and 5.44 day at 25 and 30°C respectively, Fertility was the same 100% at both temperature degrees. Larval growth periods were 17.41 and 16.12 day as well as the mortality
... Show MoreBackground : In order for a tooth to erupt, two obvious requirements are needed. First, there has to be alveolar bone resorption of the bone overlying the crown of the tooth such that an eruption pathway is formed. Second, resorption of bony crypt and apposition of new one, third, there has to be a biological process that will result in the tooth moving through this eruption pathway.The amniotic sac contains a considerable quantity of stem cells. These amniotic stem cells are multipotent and able to differentiate into various tissues, which may be useful for human application. Receptor activator of nuclear factor kappa B ligand (RANKL) is concentrated on bone biology, more specifically bone metabolism. RANKL plays a vital role in osteoclast
... Show MoreWe have investigated the photoemission and electronic properties at the PTCDI molecules interface on TiO2 and ZnO semiconductor by means of charge transition. A simple donor acceptor scenario used to calculate the rate for electron transfer of delocalized electronics in a non-degenerately TiO2 and ZnO electrodes to redox localized acceptors in an electrolytic. The dependent of electronic transition rate on the potential at contact of PTCDI with TiO2 and ZnO semiconductors, it has been discussion using TiO2 and ZnO electrodes in aqueous solutions. The charge transfer rate is determining by the overlapping electronic coupling to the TiO2 and ZnO electrodes, the transition energy, potential and polarity media within the theoretical scenario of
... Show MoreBackground: Fixed orthodontic appliances impede the maintenance of oral hygiene and result in plaque accumulation leads to enamel demineralization caused by acids produced by bacteria. Studies on plaque control strategies in orthodontic populations are limited. This might be caused by difficulties in the quantitative evaluation of dental plaque because the teeth have various levels of bracket coverage, and different tooth sizes and malocclusions, making the traditional categorical indices complex. The present study aims to evaluate the effect of different hygiene protocols on plaque quantity on bands with different attachments. Materials and method: Twenty patients had four bands within the orthodontic appliance. Then randomly divided into
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