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Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction. The relevance of these tumors to human health is unclear. The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes. Novel “humanized” and knockout models for both receptors were developed to investigate potential species differences in hepatomegaly. The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice. In WT mice, both compounds caused increased liver weight, hepatocellular hypertrophy, and cell proliferation. Both compounds caused alterations to a number of cell cycle genes consistent with induction of cell proliferation in WT mice. However, these gene expression changes did not occur in PXRKO/CARKO or huPXR/huCAR mice. Liver hypertrophy without hyperplasia was demonstrated in the huPXR/huCAR animals in response to both compounds. Induction of the CAR and PXR target genes, Cyp2b10 and Cyp3a11, was observed in both WT and huPXR/huCAR mouse lines following treatment with PB or chlordane. In the PXRKO/CARKO mice, neither liver growth nor induction of Cyp2b10 and Cyp3a11 was seen following PB or chlordane treatment, indicating that these effects are CAR/PXR dependent. These data suggest that the human receptors are able to support the chemically induced hypertrophic responses but not the hyperplastic (cell proliferation) responses. At this time, we cannot be certain that hCAR and hPXR when expressed in the mouse can function exactly as the genes do when they are expressed in human cells. However, all parameters investigated to date suggest that much of their functionality is maintained.
Digital Shadows as the aggregation, linkage and abstraction of data relating to physical objects are a central vision for the future of production. However, the majority of current research takes a technocentric approach, in which the human actors in production play a minor role. Here, the authors present an alternative anthropocentric perspective that highlights the potential and main challenges of extending the concept of Digital Shadows to humans. Following future research methodology, three prospections that illustrate use cases for Human Digital Shadows across organizational and hierarchical levels are developed: human-robot collaboration for manual work, decision support and work organization, as well as human resource management. Potentials and challenges are identified using separate SWOT analyses for the three prospections and common themes are emphasized in a concluding discussion.
While bringing new opportunities, the Industry 4.0 movement also imposes new challenges to the manufacturing industry and all its stakeholders. In this competitive environment, a skilled and engaged workforce is a key to success. Gamification can generate valuable feedbacks for improving employees’ engagement and performance. Currently, Gamification in workspaces focuses on computer-based assignments and training, while tasks that require manual labor are rarely considered. This research provides an overview of Enterprise Gamification approaches and evaluates the challenges. Based on that, a skill-based Gamification framework for manual tasks is proposed, and a case study in the Industry 4.0 model factory is shown.