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In Synthetic Biology, the idea of using feedback control for the mitigation of perturbations to gene regulatory networks due to disease and environmental disturbances is gaining popularity. To facilitate the design of such synthetic control circuits, a suitable model that captures the relevant dynamics of the gene regulatory network is essential. Traditionally, Michaelis-Menten models with Hill-type...
Synthetic genetic circuits sometimes exhibit unexpected functionality or even fail entirely when implemented in vivo, due to the effects of interactions with the host cell that were not accounted for in the circuit's design. In this paper, we consider the effects that limitations in cellular resources have on the dynamics of a synthetic cellular oscillator. We show that incorporating these effects...
This paper presents the methodology used in patient-specific calibration of a novel highly integrated model of the cardiovascular and pulmonary pathophysiology associated with Acute Respiratory Distress Syndrome (ARDS). We focus on data from previously published clinical trials on the static and dynamic cardio-pulmonary responses of three ARDS patients to changes in ventilator settings. From this...
The selection of mechanical ventilator settings that ensure adequate oxygenation and carbon dioxide clearance while minimizing the risk of ventilator-associated lung injury (VALI) is a significant challenge for intensive-care clinicians. Current guidelines are largely based on previous experience combined with recommendations from a limited number of in vivo studies whose data are typically more applicable...
One of the most important design parameters in synthetic biological circuits is the gain of the system. In many naturally occurring biological control systems, however, the precise role of the gain in ensuring accurate control is unclear. In this study, we employ control theory to explore the role of gain in osmoregulation. It has been well-documented that the upstream signalling pathways involved...
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