KAM: Automatic Planning and Interpretation of Numerical Experiments Using Geometrical Methods

KAM is a computer program that can automatically plan, monitor, and interpret numerical experiments with Hamiltonian systems with two degrees of freedom. The program has recently helped solve an open problem in hydrodynamics. Unlike other approaches to qualitative reasoning about physical system dynamics, KAM embodies a significant amount of knowledge about nonlinear dynamics. KAM's ability to control numerical experiments arises from the fact that it not only produces pictures for us to see, but also looks at (sic---in its mind's eye) the pictures it draws to guide its own actions. KAM is organized in three semantic levels: orbit recognition, phase space searching, and parameter space searching. Within each level spatial properties and relationships that are not explicitly represented in the initial representation are extracted by applying three operations ---(1) aggregation, (2) partition, and (3) classification--- iteratively.

Summary of Research Conducted by the Manufacturing Systems Team 1994-2002

The Manufacturing Systems team was one of the research teams within the Lean Aerospace Initiative (LAI) whose goal was to document, analyze and communicate the design attributes and relationships that lead to significant performance improvements in manufacturing systems in the defense aerospace industry. This report will provide an integrated record of this research using the Production Operations Transition to Lean Roadmap as its organizing framework.

Variability in the Stability and Productivity of Transfected Genes in Chinese Hamster Ovary (CHO) cells

In the field of biologics production, productivity and stability of the transfected gene of interest are two very important attributes that dictate if a production process is viable. To further understand and improve these two traits, we would need to further our understanding of the factors affecting them. These would include integration site of the gene, gene copy number, cell phenotypic variation and cell environment. As these factors play different parts in the development process, they lead to variable productivity and stability of the transfected gene between clones, the well-known phenomenon of “clonal variation”. A study of this phenomenon and how the various factors contribute to it will thus shed light on strategies to improve productivity and stability in the production cell line. Of the four factors, the site of gene integration appears to be one of the most important. Hence, it is proposed that work is done on studying how different integration sites affect the productivity and stability of transfected genes in the development process. For the study to be more industrially relevant, it is proposed that the Chinese Hamster Ovary dhfr-deficient cell line, CHO-DG44, is used as the model system.