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Extrem hohe Blitzströme
(2017)
Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development.
Gearboxes are mechanical transmission systems that provide speed and torque conversions from a rotating power source. Being a central element of the drive train, they are relevant for the efficiency and durability of motor vehicles. In this work, we present a new approach for gearbox design: Modeling the design problem as a mixed-integer nonlinear program (MINLP) allows us to create gearbox designs from scratch for arbitrary requirements and—given enough time—to compute provably globally optimal designs for a given objective. We show how different degrees of freedom influence the runtime and present an exemplary solution.