A mathematical model of glycolysis in Saccharomyces cerevisiae is presented. The model is based on rate equations for the individual reactions and aims to predict changes in the levels of intra-and extracellular metabolites after a glucose pulse, as described in part I of this study. Kinetic analysis focuses on a time scale of seconds, thereby neglecting biosynthesis of new enzymes. The model structure and experimental observations are related to the aerobic growth of the yeast. The model is based on material balance equations of the key metabolites in the extracellular environment, the cytoplasm and the mitochondria, and includes mechanistically based, experimentally matched rate equations for the individual enzymes. The model includes removal of metabolites from glycolysis and TCC for biosynthesis, and also compartmentation and translocation of adenine nucleotides. The model was verified by in vivo diagnosis of intracellular enzymes, which includes the decomposition of the network of reactions to reduce the number of parameters to be estimated simultaneously. Additionally, sensitivity analysis guarantees that only those parameters are estimated that contribute to systems trajectory with reasonable sensitivity. The model predictions and experimental observations agree reasonably well for most of the metabolites, except for pyruvate and adenine nucleotides.
A method of optimal experimental design for parameter estimation in unstructured growth models is presented. The approach is based on a method suggested by Munack (1991) for application in fed‐batch processes. In a critical analysis of this method, special emphasis is given to the model validity, because unstructured growth models often are not valid under transient conditions. In consequence, a combined object function has been introduced, which considers model validity and the accuracy of the kinetic parameters to be estimated. The application of this method for fed‐batch processes leads to satisfactory results. Investigations of different fed‐batch strategies regarding model validity and the quality of parameter estimation are presented. In addition, an experimental verification has been performed with fermentations of the yeast Trichosporon cutaneum.
The TransMilenio of Bogotá, Colombia, is the highest-capacity bus rapid transit (BRT) system in the world and one of the best examples of a high-level BRT system. It demonstrates what BRT can achieve if high-capacity design features and operating characteristics are provided. This paper highlights the different capabilities of BRT as demonstrated by the TransMilenio and assesses the extent to which these capabilities are applicable to BRT operations in the United States. A series of observations is made in relation to the topics of passenger capacity, capital cost-effectiveness, achievement of modal shift objectives, urban renewal, business and institutional models, and politics. The paper concludes by discussing the various issues related to the replication of the Bogotá model in the United States. Perhaps the central lesson to be learned from Bogotá is that BRT is capable of playing a role in the achievement of much wider objectives, such as sustainable mobility and urban renewal, when implemented as part of a holistic package of integrated strategies. Committing to the provision of a network of BRT routes gives the city the opportunity to magnify the mobility and urban renewal benefits from corridor level to the citywide level. The relatively low capital costs that have made this possible, within a relatively short time frame, should also be of interest to U.S. cities.
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