Covalent modification of protein by drugs may disrupt self-tolerance, leading to lymphocyte activation. Until now, determination of the threshold required for this process has not been possible. Therefore, we performed quantitative mass spectrometric analyses to define the epitopes formed in tolerant and hypersensitive patients taking the β-lactam antibiotic piperacillin and the threshold required for T cell activation. A hydrolyzed piperacillin hapten was detected on four lysine residues of human serum albumin (HSA) isolated from tolerant patients. The level of modified Lys541 ranged from 2.6 to 4.8%. Analysis of plasma from hypersensitive patients revealed the same pattern and levels of modification 1–10 d after the commencement of therapy. Piperacillin-responsive skin-homing CD4+ clones expressing an array of Vβ receptors were activated in a dose-, time-, and processing-dependent manner; analysis of incubation medium revealed that 2.6% of Lys541 in HSA was modified when T cells were activated. Piperacillin–HSA conjugates that had levels and epitopes identical to those detected in patients were shown to selectively stimulate additional CD4+ clones, which expressed a more restricted Vβ repertoire. To conclude, the levels of piperacillin–HSA modification that activated T cells are equivalent to the ones formed in hypersensitive and tolerant patients, which indicates that threshold levels of drug Ag are formed in all patients. Thus, the propensity to develop hypersensitivity is dependent on other factors, such as the presence of T cells within an individual’s repertoire that can be activated with the β-lactam hapten and/or an imbalance in immune regulation.
In the geotechnical and terramechanical engineering applications, precise understandings are yet to be established on the off-road structures interacting with complex soil profiles. Several theoretical and experimental approaches have been used to measure the ultimate bearing capacity of the layered soil, but with a significant level of differences depending on the failure mechanisms assumed. Furthermore, local displacement fields in layered soils are not yet studied well. Here, the bearing capacity of a dense sand layer overlying loose sand beneath a rigid beam is studied under the plain-strain condition. The study employs using digital particle image velocimetry (DPIV) and finite element method (FEM) simulations. In the FEM, an experiment
... Show More<span lang="EN-US">The fundamental of a downlink massive multiple-input multiple-output (MIMO) energy- issue efficiency strategy is known as minimum mean squared error (MMSE) implementation degrades the performance of a downlink massive MIMO energy-efficiency scheme, so some improvements are adding for this precoding scheme to improve its workthat is called our proposal solution as a proposed improved MMSE precoder (PIMP). The energy efficiency (EE) study has also taken into mind drastically lowering radiated power while maintaining high throughput and minimizing interference issues. We further find the tradeoff between spectral efficiency (SE) and EE although they coincide at the beginning but later their interests become con
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ABSTRUCT
The main aim of this research has been associated with the study of relationship between competitive intelligence and strategic risk, and to deduct their specific trends, which are interpreted as predicted by research hypotheses according to a review of literature including prior studies. The basic theme of these hypotheses is related to the probability that declining levels of strategic risk and competitive positions of industrial companies is dependent upon the growing capacity to stay ahead of competitors in the market.
A purposive non-random
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In this work pyrazolin derivatives were prepared from the diazonium chloride salt of 4-aminobenzoic acid. Azo compounds were prepared from the reaction of an ethanolic solution of sodium acetate and calculated amount of active methylene compound namely, acetyl acetone to obtain the corresponding hydrazono derivative (1). Cyclocondensation reaction of compounds (1) with hydrazine hydrate and phenyl hydrazine in boiling ethanol affording the corresponding pyrazoline-5-one derivatives of 4-aminobenzoic acid (2,3). Then compound (3) was reacted with thionyl chloride to give the corresponding acid chloride derivative(4), followed by conversion into the corresponding acid hydrazide derivative (5) carboxylic acid thiosemicarbazide (11), esters
... Show MoreThe paper presents the design of a system consisting of a solar panel with Single Input/Multiple Outputs (DC-DC) Buck Converter by using Simulink dialogue box tools in MATLAB software package for simulation the system. Maximum Power Point Tracking (MPPT) technique depending on Perturb and Observe (P&O) algorithm is used to control the output power of the converter and increase the efficiency of the system. The characteristics of the MSX-60 PV module is chosen in design of the system, whereas the electrical characteristics (P-V, I-V and P-I curves) for the module are achieved, that is affected by the solar radiation and temperature variations. The proposed design module has been found to be stable for any change in atmospheric tempera
... Show MoreThis research is carried out to investigate the behavior of self-compacting concrete (SCC) two-way slabs with central square opening under uniformly distributed loads. The experimental part of this research is based on casting and testing six SCC simply supported square slabs having the same dimentions and reinforcement. One of these slabs was cast without opening as a control slab. While, the other five slabs having opening ratios (OR) of 2.78%, 6.25%, 11.11%, 17.36% and 25.00%. From the experimental results it is found that the maximum percentage decrease in cracking and ultimate uniform loads were 31.82% and 12.17% compared to control slab for opening ratios (OR
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