Chapter 9
Determining Metabolite Production Capabilities of Engineered Saccharomyces cerevisiae using Dynamic Flux Balance Analysis

9.1		Introduction
9.2		Methods
9.2.1		Stoichiometric Models of Cellular Metabolism
9.2.2		Classical Flux Balance Analysis
9.2.3		Dynamic Flux Balance Analysis
9.3		Results and Interpretation
9.3.1		Stoichiometric Models of S. cerevisiae Metabolism
9.3.2		Dynamic Simulation of Fed-Batch Cultures
9.3.3		Dynamic Optimization of Fed-Batch Cultures
9.3.4		Identification of Ethanol Overproduction Mutants
9.3.5		Exploration of Novel Metabolic Capabilities
9.4		Discussion and Commentary
9.5		Summary Points
		Acknowledgements
		Bibliography

Chapter 10
Experimental Design for Parameter Identifiability in Biological Signal Transduction Modeling

10.1		Introduction
10.1.1		Model Structure
10.1.2		Parameter Estimation
10.1.3		Identifiability Metrics and Conditions
10.1.3.1		Local Structural Identifiability
10.1.3.2		Local Parameter Identifiability
10.1.4		Overview of the Experimental Design Procedure
10.2		Methods
10.2.1		Initial Perturbation and Measurement Design
10.2.1.1		Purpose and Implementation
10.2.1.2		Procedure
10.2.2		Identifiability Analysis
10.2.2.1		Purpose and Implementation
10.2.2.2		Procedure
20.2.3		Impact Analysis
10.2.3.1		Purpose and Implementation
10.2.3.2		Procedure
10.2.4		Design Modification and Reduction
10.2.4.1		Purpose and Implementation
10.2.4.2		Procedure
10.2.5		Design Implementation
10.2.5.1		Purpose and Implementation
10.2.5.2		Procedure
10.3		Data Acquisition, Anticipated Results, and Interpretation
10.3.1		Step 1: Initial Perturbation and Measurement Design
10.3.2		Step 2: Identifiability Analysis
10.3.3		Step 3: Impact Analysis
10.3.4		Step 4: Design Reduction
10.3.5		Step 5: Identifiability Analysis
10.4		Application Notes
10.4.1		Step 1: Initial Perturbation and Measurement Design
10.4.2		Step 2: Identifiability Analysis
10.4.3		Steps 3-5: Impact Analysis, Design Reduction, and Identifiability Analysis
10.4.4		Removing the staples
10.4.5		Separating a pair
10.5		Discussion and Commentary
10.6		Summary Points
10.7		Acknowledgements
10.8		References

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