7 research outputs found

    Using hypermedia to develop an intelligent tutorial/diagnostic system for the Space Shuttle Main Engine Controller Lab

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    This is a tutorial/diagnostic system for training personnel in the use of the Space Shuttle Main Engine Controller (SSMEC) Simulation Lab. It also provides a diagnostic capable of isolating lab failures at least to the major lab component. The system was implemented using Hypercard, which is an program of hypermedia running on Apple Macintosh computers. Hypercard proved to be a viable platform for the development and use of sophisticated tutorial systems and moderately capable diagnostic systems. This tutorial/diagnostic system uses the basic Hypercard tools to provide the tutorial. The diagnostic part of the system uses a simple interpreter written in the Hypercard language (Hypertalk) to implement the backward chaining rule based logic commonly found in diagnostic systems using Prolog. Some of the advantages of Hypercard in developing this type of system include sophisticated graphics, animation, sound and voice capabilities, its ability as a hypermedia tool, and its ability to include digitized pictures. The major disadvantage is the slow execution time for evaluation of rules (due to the interpretive processing of the language). Other disadvantages include the limitation on the size of the cards, that color is not supported, that it does not support grey scale graphics, and its lack of selectable fonts for text fields

    Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME

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    This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun

    BIBLIOGRAPHY OF SECONDARY SOURCES ON THE HISTORY OF DERMATOLOGY.

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