circadian phase resetting via single and multiple control targets生理阶段重置通过单个和多个控制目标.pdfVIP

Circadian Phase Resetting via Single and Multiple Control Targets 1 ¨ 2 1,3 Neda Bagheri , Jorg Stelling , Francis J. Doyle III * 1 Department of Electrical and Computer Engineering, University of California Santa Barbara, Santa Barbara, California, United States of America, 2 Institute of Computational Science and Swiss Institute of Bioinformatics, Zurich, Switzerland, 3 Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, California, United States of America Abstract Circadian entrainment is necessary for rhythmic physiological functions to be appropriately timed over the 24-hour day. Disruption of circadian rhythms has been associated with sleep and neuro-behavioral impairments as well as cancer. To date, light is widely accepted to be the most powerful circadian synchronizer, motivating its use as a key control input for phase resetting. Through sensitivity analysis, we identify additional control targets whose individual and simultaneous manipulation (via a model predictive control algorithm) out-perform the open-loop light-based phase recovery dynamics by nearly 3-fold. We further demonstrate the robustness of phase resetting by synchronizing short- and long-period mutant phenotypes to the 24-hour environment; the control algorithm is robust in the presence of model mismatch. These studies prove the efficacy and immediate application of model predictive control in experimental studies and medicine. In particular, maintaining proper circadian regulation may significantly decrease the chance of acquiring chronic illness. Citation: Bagheri N, Stelling J, Doyle FJ III (2008) Circadian Phase Resetting via Single and Multiple Control Targets. PLoS Comput Biol 4(7): e1000104. doi:10.1371/ jo