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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.
The methodological discourse of mixed-methods research offers general procedures to combine quantitative and qualitative methods for investigating complex fields of research such as higher education. However, integrating different methods still poses considerable challenges. To move beyond general recommendations for mixed-methods research, this chapter proposes to discuss methodological issues with respect to a particular research domain. Taking current studies on the transition to higher education as an example, the authors first provide an overview of the potentials and limitations of quantitative and qualitative methods in the research domain. Second, they show the need for a conceptual framework grounded in the theory of the research object to guide the integration of different methods and findings. Finally, an example study that investigates transition with regard to the interplay of the individual student and the institutional context serves to illustrate the guiding role of theory. The framework integrates different theoretical perspectives on transition, informs the selection of the research methods, and defines the nexus of the two strands that constitute the mixed-methods design. As the interplay of individual and context is of concern for teaching and learning in general, the example presented may be fruitful for the wider field of higher education research.
Peyre, Marie-Josephe
(2017)
Peyre, Antoine-Francois
(2017)
Patte, Pierre
(2017)
Ranson, Pierre
(2017)
Names of individuals
(2017)
Small Claims Regulation
(2017)
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.