Francis J. Doyle

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Flux Balance Analysis (FBA) has been used in the past to analyze microbial metabolic networks. Typically, FBA is used to study the metabolic flux at a particular steady state of the system. However, there are many situations where the reprogramming of the metabolic network is important. Therefore, the dynamics of these metabolic networks have to be studied.(More)
Molecular mechanisms of the mammalian circadian clock have been studied primarily by genetic perturbation and behavioral analysis. Here, we used bioluminescence imaging to monitor Per2 gene expression in tissues and cells from clock mutant mice. We discovered that Per1 and Cry1 are required for sustained rhythms in peripheral tissues and cells, and in(More)
In plants, as in animals, the core mechanism to retain rhythmic gene expression relies on the interaction of multiple feedback loops. In recent years, molecular genetic techniques have revealed a complex network of clock components in Arabidopsis. To gain insight into the dynamics of these interactions, new components need to be integrated into the(More)
A nonlinear controller synthesis scheme is presented that retains the original spirit and characteristics of conventional (linear) model predictive control (MPC) while extending its capabilities to nonlinear systems. The scheme employs a Volterra model-a simple and convenient nonlinear extension of the linear convolution model employed by conventional(More)
Robustness, a relative insensitivity to perturbations, is a key characteristic of living cells. However, the specific structural characteristics that are responsible for robust performance are not clear, even in genetic circuits of moderate complexity. Formal sensitivity analysis allows the investigation of robustness and fragility properties of(More)
Robustness, the ability to maintain performance in the face of perturbations and uncertainty, is a long-recognized key property of living systems. Owing to intimate links to cellular complexity, however, its molecular and cellular basis has only recently begun to be understood. Theoretical approaches to complex engineered systems can provide guidelines for(More)
Gene expression profiles are an increasingly common data source that can yield insights into the functions of cells at a system-wide level. The present work considers the limitations in information content of gene expression data for reverse engineering regulatory networks. An in silico genetic regulatory network was constructed for this purpose. Using the(More)
A robust H controller was de®eloped to deli®er insulin ®ia a mechanical pump in Type I diabetic patients. A fundamental nonlinear diabetic patient model was linearized and then reduced to a third-order linear form for controller synthesis. Uncertainty in the nonlinear model was characterized by up to 40% ®ariation in eight physiological parameters. A(More)
Impairment of the circadian clock has been associated with numerous disorders, including metabolic disease. Although small molecules that modulate clock function might offer therapeutic approaches to such diseases, only a few compounds have been identified that selectively target core clock proteins. From an unbiased cell-based circadian phenotypic screen,(More)
0959-1524/$ see front matter 2009 Elsevier Ltd. A doi:10.1016/j.jprocont.2009.09.006 * Corresponding author. Address: Department of Ch E-mail address: frank.doyle@icb.ucsb.edu (F.J. Doy In this paper, three control methods—iterative learning control (ILC), repetitive control (RC), and run-torun control (R2R)—are studied and compared. Some mathematical(More)