A Theory of Quantitative Inference Applied to a Mechanical Design Compiler

This thesis presents the ideas underlying a computer program that takes as input a schematic of a mechanical or hydraulic power transmission system, plus specifications and a utility function, and returns catalog numbers from predefined catalogs for the optimal selection of components implementing the design. Unlike programs for designing single components or systems, the program provides the designer with a high level "language" in which to compose new designs. It then performs some of the detailed design process. The process of "compilation" is based on a formalization of quantitative inferences about hierarchically organized sets of artifacts and operating conditions. This allows the design compilation without the exhaustive enumeration of alternatives.

Cell-line Engineering of Chinese Hamster Ovary Cells for Low-temperature Culture

Developments in mammalian cell culture and recombinant technology has allowed for the production of recombinant proteins for use as human therapeutics. Mammalian cell culture is typically operated at the physiological temperature of 37°. However, recent research has shown that the use of low-temperature conditions (30-33°) as a platform for cell-culture results in changes in cell characteristics, such as increased specific productivity and extended periods of cell viability, that can potentially improve the production of recombinant proteins. Furthermore, many recent reports have focused on investigating low-temperature mammalian cell culture of Chinese hamster ovary (CHO) cells, one of the principal cell-lines used in industrial production of recombinant proteins. Exposure to low ambient temperatures exerts an external stress on all living cells, and elicits a cellular response. This cold-stress response has been observed in bacteria, plants and mammals, and is regulated at the gene level. The exact genes and molecular mechanisms involved in the cold-stress response in prokaryotes and plants have been well studied. There are also various reports that detail the modification of cold-stress genes to improve the characteristics of bacteria or plant cells at low temperatures. However, there is very limited information on mammalian cold-stress genes or the related pathways governing the mammalian cold-stress response. This project seeks to investigate and characterise cold-stress genes that are differentially expressed during low-temperature culture of CHO cells, and to relate them to the various changes in cell characteristics observed in low-temperature culture of CHO cells. The gene information can then be used to modify CHO cell-lines for improved performance in the production of recombinant proteins.

Quantitative Inference in a Mechanical Design Compiler

This paper presents the ideas underlying a program that takes as input a schematic of a mechanical or hydraulic power transmission system, plus specifications and a utility function, and returns catalog numbers from predefined catalogs for the optimal selection of components implementing the design. It thus provides the designer with a high level "language" in which to compose new designs, then performs some of the detailed design process for him. The program is based on a formalization of quantitative inferences about hierarchically organized sets of artifacts and operating conditions, which allows design compilation without the exhaustive enumeration of alternatives.