The role of Computer Aided Process Engineering in physiology and clinical medicine

This paper discusses the potential role for Computer Aided Process Engineering (CAPE) in developing engineering analysis and design approaches to biological systems across multiple levels—cell signalling networks, gene, protein and metabolic networks, cellular systems, through to physiological systems. The 21st Century challenge in the Life Sciences is to bring together widely dispersed models and knowledge in order to enable a system-wide understanding of these complex systems. This systems level understanding should have broad clinical benefits. Computer Aided Process Engineering can bring systems approaches to (i) improving understanding of these complex chemical and physical (particularly molecular transport in complex flow regimes) interactions at multiple scales in living systems, (ii) analysis of these models to help to identify critical missing information and to explore the consequences on major output variables resulting from disturbances to the system, and (iii) ‘design’ potential interventions in in vivo systems which can have significant beneficial, or potentially harmful, effects which need to be understood. This paper develops these three themes drawing on recent projects at UCL. The first project has modeled the effects of blood flow on endothelial cells lining arteries, taking into account cell shape change resulting in changes in the cell skeleton which cause consequent chemical changes. A second is a project which is building an in silico model of the human liver, tieing together models from the molecular level to the liver. The composite model models glucose regulation in the liver and associated organs. Both projects involve molecular transport, chemical reactions, and complex multiscale systems, tackled by approaches from CAPE. Chemical Engineers solve multiple scale problems in manufacturing processes – from molecular scale through unit operations scale to plant-wide and enterprise wide systems – so have an appropriate skill set for tackling problems in physiology and clinical medicine, in collaboration with life and clinical scientists

Closed loop identification based on quantization

This paper proposes a new closed-loop identification scheme for a single-input-single-output control loop. It is based upon a quantizer inserted into the feedback path. The quantizer can be used to generate an equivalent persistently exciting signal with which the well known two-stage and/or two-step method can be used directly. Simulation examples and an experimental demonstration are used to illustrate the proposed scheme

Performance Analysis of Optimization Methods in PSE Applications. Mathematical Programming Versus Grid-based Multi-parametric Genetic Algorithms

Due to their large variety of applications in the PSE area, complex optimisation problems are of high interest for the scientific community. As a consequence, a great effort is made for developing efficient solution techniques. The choice of the relevant technique for the treatment of a given problem has already been studied for batch plant design issues. However,most works reported in the dedicated literature classically considered item sizes as continuous variables. In a view of realism, a similar approach is proposed in this paper, with discrete variables representing equipment capacities. The numerical results enable to evaluate the performances of two mathematical programming (MP) solvers embedded within the GAMS package and a genetic algorithm (GA), on a set of seven increasing complexity examples. The necessarily huge number of runs for the GA could be performed within a computational framework basedon a grid infrastructure; however, since the MP methods were tackled through single-computer computations, the CPU time comparison are reported for this one-PC working mode. On the one hand, the high combinatorial effect induced by the new discrete variables heavily penalizes the GAMS modules, DICOPTþþand SBB. On the other hand, the Genetic Algorithm proves its superiority, providing quality solutions within acceptable computational times, whatever the considered example

Minimal-time bioremediation of natural water resources

We study minimal time strategies for the treatment of pollution of large volumes, such as lakes or natural reservoirs, with the help of an autonomous bioreactor. The control consists in feeding the bioreactor from the resource, the clean output returning to the resource with the same flow rate. We first characterize the optimal policies among constant and feedback controls, under the assumption of a uniform concentration in the resource. In a second part, we study the influence of an inhomogeneity in the resource, considering two measurements points. With the help of the Maximum Principle, we show that the optimal control law is non-monotonic and terminates with a constant phase, contrary to the homogeneous case for which the optimal flow rate is decreasing with time. This study allows the decision makers to identify situations for which the benefit of using non-constant flow rates is significant

Scalable Similarity Search for Molecular Descriptors

Similarity search over chemical compound databases is a fundamental task in the discovery and design of novel drug-like molecules. Such databases often encode molecules as non-negative integer vectors, called molecular descriptors, which represent rich information on various molecular properties. While there exist efficient indexing structures for searching databases of binary vectors, solutions for more general integer vectors are in their infancy. In this paper we present a time- and space- efficient index for the problem that we call the succinct intervals-splitting tree algorithm for molecular descriptors (SITAd). Our approach extends efficient methods for binary-vector databases, and uses ideas from succinct data structures. Our experiments, on a large database of over 40 million compounds, show SITAd significantly outperforms alternative approaches in practice.Comment: To be appeared in the Proceedings of SISAP'1

BioSimulator.jl: Stochastic simulation in Julia

Biological systems with intertwined feedback loops pose a challenge to mathematical modeling efforts. Moreover, rare events, such as mutation and extinction, complicate system dynamics. Stochastic simulation algorithms are useful in generating time-evolution trajectories for these systems because they can adequately capture the influence of random fluctuations and quantify rare events. We present a simple and flexible package, BioSimulator.jl, for implementing the Gillespie algorithm, $\tau$-leaping, and related stochastic simulation algorithms. The objective of this work is to provide scientists across domains with fast, user-friendly simulation tools. We used the high-performance programming language Julia because of its emphasis on scientific computing. Our software package implements a suite of stochastic simulation algorithms based on Markov chain theory. We provide the ability to (a) diagram Petri Nets describing interactions, (b) plot average trajectories and attached standard deviations of each participating species over time, and (c) generate frequency distributions of each species at a specified time. BioSimulator.jl's interface allows users to build models programmatically within Julia. A model is then passed to the simulate routine to generate simulation data. The built-in tools allow one to visualize results and compute summary statistics. Our examples highlight the broad applicability of our software to systems of varying complexity from ecology, systems biology, chemistry, and genetics. The user-friendly nature of BioSimulator.jl encourages the use of stochastic simulation, minimizes tedious programming efforts, and reduces errors during model specification.Comment: 27 pages, 5 figures, 3 table