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However the data also indicate that there is a maximal response (threshold effect) to these agents that might account for the negative interaction in the multivariate analyses.
Although the concentration of each individual agent was below its no observed effect concentration or effective concentration causing 1% of maximal response, the total effect of the mixture was many times greater than that predicted by a simple sum of the individual effects, a null model sometimes called effect summation.
This inhibition was partially lost in Megf8 −/− explants, indicating that TG neurons require Megf8 expression to mediate their maximal response to the inhibitory effects of BMP4.
Neither wortmanin nor PI-103 had any effect upon the transcriptional response to dexamethasone, and although LY294002 reduced the maximal response to this hormone, this effect was relatively modest (∼30% inhibition) and residual responses could clearly be seen in LY294002-treated cells.
The dose of ketamine escalated as needed until maximal response or until undesirable side effects including psychomimetic and dysphoric effects.
The use of stanol ester as control test model has been proven several times to induce cholesterol reduction (Raisio Benecol Ltd., unpublished results) and the concentration in this study was selected to exert sufficient but not the maximal response, enabling the possible combination effect with sesamin.
With 50 μM 2-APB, the highest concentration that avoids inhibition of Ca2+ uptake, there was an approximately sevenfold decrease in IP3 sensitivity (ΔpEC50 = 0.84 ± 0.12) with no effect on the maximal response to IP3.
Although cotreatment with DE-71 produced a larger effect than the maximal response to E2 in the present study using a reporter gene assay, in another bioassay, based on MCF-7 cell proliferation, we observed both an agonist effect when DE-71 was administered alone and an antiestrogenic effect when coadministered with E2 (Mercado-Feliciano and Bigsby 2008).
A saturating concentration (1 μ M) of triazolam shifted the GABA concentration response curves leftwards without significant effects on the maximal response.
As shown in Figure 1A, exposure of UCB at a concentration of 1 µM for 24 h had no effect on the stimulus-response curve, maximal response, and fEPSP waveform.
PI-103 also had no effect upon the magnitude of the maximal response.
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