We propose a new statistical timing analysis algorithm, which produces arrival-time random variables for all internal signals and primary outputs for cell-based designs with all cell delays modeled as random variables. Our algorithm propagates probabilistic timing events through the circuit and obtains final probabilistic events (distributions) at all nodes. The new algorithm is deterministic and flexible in controlling run time and accuracy. However, the algorithm has exponential time complexity for circuits with reconvergent fanouts. In order to solve this problem, we further propose a fast approximate algorithm. Experiments show that this approximate algorithm speeds up the statistical timing analysis by at least an order of magnitude and produces results with small errors when compared with Monte Carlo methods.
Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise.
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