Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology
ENVIRONMENTAL SCIENCE & TECHNOLOGY
Authors: Conolly, Rory B.; Ankley, Gerald T.; Cheng, WanYun; Mayo, Michael L.; Miller, David H.; Perkins, Edward J.; Villeneuve, Daniel L.; Watanabe, Karen H.
Abstract
A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose response, and time-course predictions that can support regulatory decision-making: Herein we describe several facets of qAOPs, including (a) motivation for development, (b) technical considerations, (c) evaluation of confidence, and (d) potential applications. The qAOP used as an illustrative example for these points describe the linkage between inhibition of cytochrome P450 19A aromatase (the MIE) and population-level decreases in the fathead minnow (FHM; Pimephales promelas). The qAOP consists of three linked computational models for the following: (a) the hypothalamic-pitutitary-gonadal axis in female FHMs, where aromatase inhibition decreases the conversion of testosterone to 17 beta-esttadiol (E2), thereby reducing E2-dependent vitellogenin (VTG; egg yolk protein precursor) synthesis, (b) VTG-dependent egg development and spawning (fecundity), and (c) fecundity-dependent population trajectory. While development of the example qAQP was based on experiments with FHMs exposed to the aromatase inhibitor fadrozole, we also show how a toxic equivalence (TEQ) calculation allows use of the qAOP to predict effects of another, untested aromatase inhibitor, iprodione. While qAOP development can be resource-intensive, the quantitative predictions obtained, and TEQ-based application-to multiple chemicals, may be sufficient to justify the cost for some, applications in regulatory decision-making.
Effects of Vertical Temperature Gradient on the Growth Morphology and Properties of Single Domain YBCO Bulks Fabricated by a New Modified TSIG Technique
CRYSTAL GROWTH & DESIGN
Authors: Guo, Yu-Xia; Yang, Wan-Min; Li, Jia-Wei; Guo, Li-Ping; Chen, Li-Ping; Li, Qiang
Abstract
Single domain YBCO bulk superconductors have been fabricated with different vertical temperature gradients (VTG) by a modified top-seeded infiltration and growth (TSIG) process with a new solid phase (Y2O3+BaCuO2) and a new liquid phase (Y2O3+6CuO+10BaCuO(2)). It is found that the angle a (between the upper surface and interface of a- and c-growth sectors) is very sensitive to the VTG, which means that the growth rate in c-axis direction (Rc) can be changed by the VTG, according to tan alpha = R-c/R-a; R-a is the growth rate in the a-axis direction. It is also found that the 4-fold growth sectors did not cover the whole surface of the sample grown with a positive VTG, and the volume fraction of the single c-axis growth sector (V-fc) is 37.5% of the sample grown with a zero VTG, but it is reduced to 25% by a positive VTG, and enlarged to 53.6% by a negative VTG. The results of levitation force and trapped field of the samples show that a negative (or positive) VTG can improve (or reduce) levitation force and trapped field of the sample compared with that of the sample grown under a zero VTG. The results provide a very important way to fabricate large-size YBCO bulks with higher V-fc and better physical properties.