Optimal control of transitions between nonequilibrium steady states

Biological systems fundamentally exist out of equilibrium in order to preserve organized structures and processes. Many changing cellular conditions can be represented as transitions between nonequilibrium steady states, and organisms have an interest in optimizing such transitions. Using the Hatano-Sasa Y-value, we extend a recently developed geometrical framework for determining optimal protocols so that it can be applied to systems driven from nonequilibrium steady states. We calculate and numerically verify optimal protocols for a colloidal particle dragged through solution by a translating optical trap with two controllable parameters. We offer experimental predictions, specifically that optimal protocols are significantly less costly than naive ones. Optimal protocols similar to these may ultimately point to design principles for biological energy transduction systems and guide the design of artificial molecular machines.Comment: Accepted for publication at PLoS ON

Internal agent states : experiments using the swarm leader concept

In recent years, an understanding of the operating principles and stability of natural swarms has proven to be a useful tool for the design and control of artificial robotic agents. Many robotic systems, whose design or control principals are inspired by behavioural aspects of real biological systems such as leader-follower relationship, have been developed. We introduced an algorithm which successfully enhances the navigation performance of a swarm of robots using the swarm leader concept. This paper presents some applications based on that work using the simulations and experimental implementation using a swarming behaviour test-bed at the University of Strathclyde. Experimental and simulation results match closely in a way that confirms the efficiency of the algorithm as well as its applicability

Measurement set selection of parameter estimation in biological system modelling - a case study of signal transduction pathways

Parameter estimation is a challenging problem for biological systems modelling since the model is normally of high dimension, the measurement data are sparse and noisy and the cost of experiments high. Accurate recovery of parameters depends on the quality and quantity of measurement data. It is therefore important to know which measurements to be taken when and how through optimal experimental design (OED). In this paper a method was proposed to determine the most informative measurement set for parameter estimation of dynamic systems, in particular biochemical reaction systems, such that the unknown parameters can be inferred with the best possible statistical quality using the data collected from the designed experiments. System analysis using matrix theory was used to examine the number of necessary measurement variables. The priority of each measurement variable was determined by optimal experimental design based on Fisher information matrix (FIM). The applicability and advantages of the proposed method were shown through an example of signal pathway model

Determine measurement set for parameter estimation in biological systems modeling

Parameter estimation is challenging for biological systems modelling since the model is normally of high dimension, the measurement data are sparse and noisy, and the cost of experiments is high. Accurate recovery of parameters depend on the quantity and quality of measurement data. It is therefore important to know what measurements to be taken, when and how through optimal experimental design (OED). In this paper we present a method to determine the most informative measurement set for parameter estimation of dynamic systems, in particular biochemical reaction systems, such that the unknown parameters can be inferred with the best possible statistical quality using the data collected from the designed experiments. System analysis using matrix theory is introduced to examine the number of necessary measurement variables. The priority of each measurement variable is determined by optimal experimental design based on Fisher information matrix (FIM). The applicability and advantages of the proposed method are illustrated through an example of a signal pathway model

A Probabilistic Approach to Robust Optimal Experiment Design with Chance Constraints

Accurate estimation of parameters is paramount in developing high-fidelity models for complex dynamical systems. Model-based optimal experiment design (OED) approaches enable systematic design of dynamic experiments to generate input-output data sets with high information content for parameter estimation. Standard OED approaches however face two challenges: (i) experiment design under incomplete system information due to unknown true parameters, which usually requires many iterations of OED; (ii) incapability of systematically accounting for the inherent uncertainties of complex systems, which can lead to diminished effectiveness of the designed optimal excitation signal as well as violation of system constraints. This paper presents a robust OED approach for nonlinear systems with arbitrarily-shaped time-invariant probabilistic uncertainties. Polynomial chaos is used for efficient uncertainty propagation. The distinct feature of the robust OED approach is the inclusion of chance constraints to ensure constraint satisfaction in a stochastic setting. The presented approach is demonstrated by optimal experimental design for the JAK-STAT5 signaling pathway that regulates various cellular processes in a biological cell.Comment: Submitted to ADCHEM 201

TESTING USED ROLLER BEARINGS FOR QUALITY AND SERVICE LIFE

Synthetic biology is a rapidly expanding field at the interface of the engineering and biological sciences which aims to apply rational design principles in biological contexts. Many natural processes utilise regulatory architectures that parallel those found in control and electrical engineering, which has motivated their implementation as part of synthetic biological constructs. Tools based upon control theoretical concepts can be used to design such systems, as well as to guide their experimental realisation. In this paper we provide examples of biological implementations of negative feedback systems, and discuss progress made toward realisation of other feedback and control architectures. We then outline major challenges posed by the design of such systems, particularly focusing on those which are specific to biological contexts and on which feedback control can have a significant impact. We explore future directions for work in the field, including new approaches for theoretical design of biological control systems, the utilisation of novel components for their implementation, and the potential for application of automation and machine-learning approaches to accelerate synthetic biological research

Numerical coupling of fluid and structure in cardiac flow and devices

Numerical simulations are a powerful tool in investigation of flow and structure dynamics in biological systems and in the design of biomedical devices. Time-dependent fluid-structure interaction (FSI) problems in biological systems are often characterized by a periodic nature and relatively low Reynolds number. In order to solve the dynamics of the fluid and structure of coupled systems, different approaches may be used. Several parameters such as geometrical complexity, degree of displacement, convergence to steady periodicity, and the system stability may determine the coupling method. In the talk, four numerical studies of biological and implanted systems will be presented, each with a different FSI approach. The first study is of flow through mechanical heart valves, using finite-volume (FV) fluid solver coupled with an external structural solver using a weak coupling scheme for large displacements. The second study is of flow inside a pulsatile ventricular assist device with FV fluid solver coupled with finite-element (FE) structure solver using a strong staggered coupling assuming small displacements. The third study is of flow through vulnerable plaque in the coronary arteries, with FE solvers for both the fluid and structure domains, using a fully-coupled iterative scheme assuming small displacements. The fourth simulation is of an impedance pump using a direct FE coupling method for large displacements. In addition to the methodology, the applicative design and hemodynamic aspects of the cases will be discussed, including washout properties and risk for thrombosis. The results obtained from the studies will be compared to experimental analyses

Model-guided design of ligand-regulated RNAi for programmable control of gene expression

Progress in constructing biological networks will rely on the development of more advanced components that can be predictably modified to yield optimal system performance. We have engineered an RNA-based platform, which we call an shRNA switch, that provides for integrated ligand control of RNA interference (RNAi) by modular coupling of an aptamer, competing strand, and small hairpin (sh) RNA stem into a single component that links ligand concentration and target gene expression levels. A combined experimental and mathematical modelling approach identified multiple tuning strategies and moves towards a predictable framework for the forward design of shRNA switches. The utility of our platform is highlighted by the demonstration of fine-tuning, multi-input control, and model-guided design of shRNA switches with an optimized dynamic range. Thus, shRNA switches can serve as an advanced component for the construction of complex biological systems and offer a controlled means of activating RNAi in disease therapeutics