Design of artificial myocardial microtissues

Cultivation technologies promoting organization of mammalian cells in three dimensions are essential for gene-function analyses as well as drug testing and represent the first step toward the design of tissue replacements and bioartificial organs. Embedded in a three-dimensional environment, cells are expected to develop tissue-like higher order intercellular structures (cell-cell contacts, extracellular matrix) that orchestrate cellular functions including proliferation, differentiation, apoptosis, and angiogenesis with unmatched quality. We have refined the hanging drop cultivation technology to pioneer beating heart microtissues derived from pure primary rat and mouse cardiomyocyte cultures as well as mixed populations reflecting the cell type composition of rodent hearts. Phenotypic characterization combined with detailed analysis of muscle-specific cell traits, extracellular matrix components, as well as endogenous vascular endothelial growth factor (VEGF) expression profiles of heart microtissues revealed (1) a linear cell number-microtissue size correlation, (2) intermicrotissue superstructures, (3) retention of key cardiomyocyte-specific cell qualities, (4) a sophisticated extracellular matrix, and (5) a high degree of self-organization exemplified by the tendency of muscle structures to assemble at the periphery of these myocardial spheroids. Furthermore (6), myocardial spheroids support endogenous VEGF expression in a size-dependent manner that will likely promote vascularization of heart microtissues produced from defined cell mixtures as well as support connection to the host vascular system after implantation. As cardiomyocytes are known to be refractory to current transfection technologies we have designed lentivirus-based transduction strategies to lead the way for genetic engineering of myocardial microtissues in a clinical setting.

Hybrid knowledge representation in a blackboard KBS for liquid retaining structure design

This paper highlights the importance of design expertise, for designing liquid retaining structures, including subjective judgments and professional experience. Design of liquid retaining structures has special features different from the others. Being more vulnerable to corrosion problem, they have stringent requirements against serviceability limit state of crack. It is the premise of the study to transferring expert knowledge in a computerized blackboard system. Hybrid knowledge representation schemes, including production rules, object-oriented programming, and procedural methods, are employed to express engineering heuristics and standard design knowledge during the development of the knowledge-based system (KBS) for design of liquid retaining structures. This approach renders it possible to take advantages of the characteristics of each method. The system can provide the user with advice on preliminary design, loading specification, optimized configuration selection and detailed design analysis of liquid retaining structure. It would be beneficial to the field of retaining structure design by focusing on the acquisition and organization of expert knowledge through the development of recent artificial intelligence technology. (C) 2003 Elsevier Ltd. All rights reserved.