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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.
Like all preceding transformations of the manufacturing industry, the large-scale usage of production data will reshape the role of humans within the sociotechnical production ecosystem. To ensure that this transformation creates work systems in which employees are empowered, productive, healthy, and motivated, the transformation must be guided by principles of and research on human-centered work design. Specifically, measures must be taken at all levels of work design, ranging from (1) the work tasks to (2) the working conditions to (3) the organizational level and (4) the supra-organizational level. We present selected research across all four levels that showcase the opportunities and requirements that surface when striving for human-centered work design for the Internet of Production (IoP). (1) On the work task level, we illustrate the user-centered design of human-robot collaboration (HRC) and process planning in the composite industry as well as user-centered design factors for cognitive assistance systems. (2) On the working conditions level, we present a newly developed framework for the classification of HRC workplaces. (3) Moving to the organizational level, we show how corporate data can be used to facilitate best practice sharing in production networks, and we discuss the implications of the IoP for new leadership models. Finally, (4) on the supra-organizational level, we examine overarching ethical dimensions, investigating, e.g., how the new work contexts affect our understanding of responsibility and normative values such as autonomy and privacy. Overall, these interdisciplinary research perspectives highlight the importance and necessary scope of considering the human factor in the IoP.
Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism
(2019)
Hybrid control for autonomous systems — Integrating learning, deliberation and reactive control
(2010)
Abstractauthoren Graphene oxide (GO) nanoparticles were incorporated in temperature-sensitive Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The nanoparticles increase the light absorption and convert light energy into heat efficiently. Thus, the hydrogels with GO can be stimulated spatially resolved by illumination as it was demonstrated by IR thermography. The temporal progression of the temperature maximum was detected for different concentrations of GO within the polymer network. Furthermore, the compatibility of PNIPAAm hydrogels with GO and cell cultures was investigated. For this purpose, culture medium was incubated with hydrogels containing GO and the viability and morphology of chinese hamster ovary (CHO) cells was examined after several days of culturing in presence of this medium.
The feasibility study presents results of a hydrogen combustor integration for a Medium-Range aircraft engine using the Dry-Low-NOₓ Micromix combustion principle. Based on a simplified Airbus A320-type flight mission, a thermodynamic performance model of a kerosene and a hydrogen-powered V2530-A5 engine is used to derive the thermodynamic combustor boundary conditions. A new combustor design using the Dry-Low NOx Micromix principle is investigated by slice model CFD simulations of a single Micromix injector for design and off-design operation of the engine. Combustion characteristics show typical Micromix flame shapes and good combustion efficiencies for all flight mission operating points. Nitric oxide emissions are significant below ICAO CAEP/8 limits. For comparison of the Emission Index (EI) for NOₓ emissions between kerosene and hydrogen operation, an energy (kerosene) equivalent Emission Index is used.
A full 15° sector model CFD simulation of the combustion chamber with multiple Micromix injectors including inflow homogenization and dilution and cooling air flows investigates the combustor integration effects, resulting NOₓ emission and radial temperature distributions at the combustor outlet. The results show that the integration of a Micromix hydrogen combustor in actual aircraft engines is feasible and offers, besides CO₂ free combustion, a significant reduction of NOₓ emissions compared to kerosene operation.
The European Union's aim to become climate neutral by 2050 necessitates ambitious efforts to reduce carbon emissions. Large reductions can be attained particularly in energy intensive sectors like iron and steel. In order to prevent the relocation of such industries outside the EU in the course of tightening environmental regulations, the establishment of a climate club jointly with other large emitters and alternatively the unilateral implementation of an international cross-border carbon tax mechanism are proposed. This article focuses on the latter option choosing the steel sector as an example. In particular, we investigate the financial conditions under which a European cross border mechanism is capable to protect hydrogen-based steel production routes employed in Europe against more polluting competition from abroad. By using a floor price model, we assess the competitiveness of different steel production routes in selected countries. We evaluate the climate friendliness of steel production on the basis of specific GHG emissions. In addition, we utilize an input-output price model. It enables us to assess impacts of rising cost of steel production on commodities using steel as intermediates. Our results raise concerns that a cross-border tax mechanism will not suffice to bring about competitiveness of hydrogen-based steel production in Europe because the cost tends to remain higher than the cost of steel production in e.g. China. Steel is a classic example for a good used mainly as intermediate for other products. Therefore, a cross-border tax mechanism for steel will increase the price of products produced in the EU that require steel as an input. This can in turn adversely affect competitiveness of these sectors. Hence, the effects of higher steel costs on European exports should be borne in mind and could require the cross-border adjustment mechanism to also subsidize exports.
Hydrostatic propeller drive
(2011)
Ice melting probes
(2023)
The exploration of icy environments in the solar system, such as the poles of Mars and the icy moons (a.k.a. ocean worlds), is a key aspect for understanding their astrobiological potential as well as for extraterrestrial resource inspection. On these worlds, ice melting probes are considered to be well suited for the robotic clean execution of such missions. In this chapter, we describe ice melting probes and their applications, the physics of ice melting and how the melting behavior can be modeled and simulated numerically, the challenges for ice melting, and the required key technologies to deal with those challenges. We also give an overview of existing ice melting probes and report some results and lessons learned from laboratory and field tests.
There is significant interest in sampling subglacial environments for geobiological studies, but they are difficult to access. Existing ice-drilling technologies make it cumbersome to maintain microbiologically clean access for sample acquisition and environmental stewardship of potentially fragile subglacial aquatic ecosystems. The IceMole is a maneuverable subsurface ice probe for clean in situ analysis and sampling of glacial ice and subglacial materials. The design is based on the novel concept of combining melting and mechanical propulsion. It can change melting direction by differential heating of the melting head and optional side-wall heaters. The first two prototypes were successfully tested between 2010 and 2012 on glaciers in Switzerland and Iceland. They demonstrated downward, horizontal and upward melting, as well as curve driving and dirt layer penetration. A more advanced probe is currently under development as part of the Enceladus Explorer (EnEx) project. It offers systems for obstacle avoidance, target detection, and navigation in ice. For the EnEx-IceMole, we will pay particular attention to clean protocols for the sampling of subglacial materials for biogeochemical analysis. We plan to use this probe for clean access into a unique subglacial aquatic environment at Blood Falls, Antarctica, with return of a subglacial brine sample.
We present the novel concept of a combined drilling and melting probe for subsurface ice research. This probe, named “IceMole”, is currently developed, built, and tested at the FH Aachen University of Applied Sciences’ Astronautical Laboratory. Here, we describe its first prototype design and report the results of its field tests on the Swiss Morteratsch glacier. Although the IceMole design is currently adapted to terrestrial glaciers and ice shields, it may later be modified for the subsurface in-situ investigation of extraterrestrial ice, e.g., on Mars, Europa, and Enceladus. If life exists on those bodies, it may be present in the ice (as life can also be found in the deep ice of Earth).
Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and identify corresponding response alterations.
The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.
Objectives
To assess the image quality of T2-weighted (T2w) magnetic resonance imaging of the prostate and the visibility of prostate cancer at 7 Tesla (T).
Materials & methods
Seventeen prostate cancer patients underwent T2w imaging at 7T with only an external transmit/receive array coil. Three radiologists independently scored images for image quality, visibility of anatomical structures, and presence of artefacts. Krippendorff’s alpha and weighted kappa statistics were used to assess inter-observer agreement. Visibility of prostate cancer lesions was assessed by directly linking the T2w images to the confirmed location of prostate cancer on histopathology.
Results
T2w imaging at 7T was achievable with ‘satisfactory’ (3/5) to ‘good’ (4/5) quality. Visibility of anatomical structures was predominantly scored as ‘satisfactory’ (3/5) and ‘good’ (4/5). If artefacts were present, they were mostly motion artefacts and, to a lesser extent, aliasing artefacts and noise. Krippendorff’s analysis revealed an α = 0.44 between three readers for the overall image quality scores. Clinically significant cancer lesions in both peripheral zone and transition zone were visible at 7T.
Conclusion
T2w imaging with satisfactory to good quality can be routinely acquired, and cancer lesions were visible in patients with prostate cancer at 7T using only an external transmit/receive body array coil.