Optimal control of bioproduction in the presence of population heterogeneity.

Cell-to-cell variability, born of stochastic chemical kinetics, persists even in large isogenic populations. In the study of single-cell dynamics this is typically accounted for. However, on the population level this source of heterogeneity is often sidelined to avoid the inevitable complexity it introduces. The homogeneous models used instead are more tractable but risk disagreeing with their heterogeneous counterparts and may thus lead to severely suboptimal control of bioproduction. In this work, we introduce a comprehensive mathematical framework for solving bioproduction optimal control problems in the presence of heterogeneity. We study population-level models in which such heterogeneity is retained, and propose order-reduction approximation techniques. The reduced-order models take forms typical of homogeneous bioproduction models, making them a useful benchmark by which to study the importance of heterogeneity. Moreover, the derivation from the heterogeneous setting sheds light on parameter selection in ways a direct homogeneous outlook cannot, and reveals the source of approximation error. With view to optimally controlling bioproduction in microbial communities, we ask the question: when does optimising the reduced-order models produce strategies that work well in the presence of population heterogeneity? We show that, in some cases, homogeneous approximations provide remarkably accurate surrogate models. Nevertheless, we also demonstrate that this is not uniformly true: overlooking the heterogeneity can lead to significantly suboptimal control strategies. In these cases, the heterogeneous tools and perspective are crucial to optimise bioproduction.

Parametric Damage Mechanics Empowering Structural Health Monitoring of 3D Woven Composites.

This paper presents a data-driven structural health monitoring (SHM) method by the use of so-called reduced-order models relying on an offline training/online use for unidirectional fiber and matrix failure detection in a 3D woven composite plate. During the offline phase (or learning) a dataset of possible damage localization, fiber and matrix failure ratios is generated through high-fidelity simulations (ABAQUS software). Then, a reduced model in a lower-dimensional approximation subspace based on the so-called sparse proper generalized decomposition (sPGD) is constructed. The parametrized approach of the sPGD method reduces the computational burden associated with a high-fidelity solver and allows a faster evaluation of all possible failure configurations. However, during the testing phase, it turns out that classical sPGD fails to capture the influence of the damage localization on the solution. To alleviate the just-referred difficulties, the present work proposes an adaptive sPGD. First, a change of variable is carried out to place all the damage areas on the same reference region, where an adapted interpolation can be done. During the online use, an optimization algorithm is employed with numerical experiments to evaluate the damage localization and damage ratio which allow us to define the health state of the structure.

An Order Reduction Design Framework for Higher-Order Binary Markov Random Fields.

The order reduction method is an important approach to optimize higher-order binary Markov random fields (HoMRFs), which are widely used in information theory, machine learning and image analysis. It transforms an HoMRF into an equivalent and easier reduced first-order binary Markov random field (RMRF) by elaborately setting the coefficients and auxiliary variables of RMRF. However, designing order reduction methods is difficult, and no previous study has investigated this design issue. In this paper, we propose an order reduction design framework to study this problem for the first time. Through study, we find that the design difficulty mainly lies in that the coefficients and variables of RMRF must be set simultaneously. Therefore, the proposed framework decomposes the design difficulty into two processes, and each process mainly considers the coefficients or auxiliary variables of RMRF. Some valuable properties are also proven. Based on our framework, a new family of 14 order reduction methods is provided. Experiments, such as synthetic data and image denoising, demonstrate the superiority of our method.

A framework for simplification of quantitative systems pharmacology models in clinical pharmacology.

Quantitative systems pharmacology (QSP) is a relatively new discipline within modelling and simulation that has gained wide attention over the past few years. The application of QSP models spans drug-target identification and validation, through all drug development phases as well as clinical applications. Due to their detailed mechanistic nature, QSP models are capable of extrapolating knowledge to predict outcomes in scenarios that have not been tested experimentally, making them an important resource in experimental and clinical pharmacology. However, these models are complicated to work with due to their size and inherent complexity. This makes many applications of QSP models for simulation, parameter estimation and trial design computationally intractable. A number of techniques have been developed to simplify QSP models into smaller models that are more amenable to further analyses while retaining their accurate predictive capabilities. Different simplification techniques have different strengths and weaknesses and hence different utilities. Understanding the utilities of different methods is essential for selection of the best method for a particular situation. In this paper, we have created an overall framework for model simplification techniques that allows a natural categorisation of methods based on their utility. We provide a brief description of the concept underpinning the different methods and example applications. A summary of the utilities of methods is intended to provide a guide to modellers in their model endeavours to simplify these complicated models.

Reduction of quantitative systems pharmacology models using artificial neural networks.

Quantitative systems pharmacology models are often highly complex and not amenable to further simulation and/or estimation analyses. Model-order reduction can be used to derive a mechanistically sound yet simpler model of the desired input-output relationship. In this study, we explore the use of artificial neural networks for approximating an input-output relationship within highly dimensional systems models. We illustrate this approach using a model of blood coagulation. The model consists of two components linked together through a highly dimensional discontinuous interface, which creates a difficulty for model reduction techniques. The proposed approach enables the development of an efficient approximation to complex models with the desired level of accuracy. The technique is applicable to a wide variety of models and provides substantial speed boost for use of such models in simulation and control purposes.

Low-Computational-Cost Hybrid FEM-Analytical Induction Machine Model for the Diagnosis of Rotor Eccentricity, Based on Sparse Identification Techniques and Trigonometric Interpolation.

Since it is not efficient to physically study many machine failures, models of faulty induction machines (IMs) have attracted a rising interest. These models must be accurate enough to include fault effects and must be computed with relatively low resources to reproduce different fault scenarios. Moreover, they should run in real time to develop online condition-monitoring (CM) systems. Hybrid finite element method (FEM)-analytical models have been recently proposed for fault diagnosis purposes since they keep good accuracy, which is widely accepted, and they can run in real-time simulators. However, these models still require the full simulation of the FEM model to compute the parameters of the analytical model for each faulty scenario with its corresponding computing needs. To address these drawbacks (large computing power and memory resources requirements) this paper proposes sparse identification techniques in combination with the trigonometric interpolation polynomial for the computation of IM model parameters. The proposed model keeps accuracy similar to a FEM model at a much lower computational effort, which could contribute to the development and to the testing of condition-monitoring systems. This approach has been applied to develop an IM model under static eccentricity conditions, but this may extend to other fault types.

Model order reduction of flow based on a modular geometrical approximation of blood vessels.

We are interested in a reduced order method for the efficient simulation of blood flow in arteries. The blood dynamics is modeled by means of the incompressible Navier-Stokes equations. Our algorithm is based on an approximated domain-decomposition of the target geometry into a number of subdomains obtained from the parametrized deformation of geometrical building blocks (e.g., straight tubes and model bifurcations). On each of these building blocks, we build a set of spectral functions by Proper Orthogonal Decomposition of a large number of snapshots of finite element solutions (offline phase). The global solution of the Navier-Stokes equations on a target geometry is then found by coupling linear combinations of these local basis functions by means of spectral Lagrange multipliers (online phase). Being that the number of reduced degrees of freedom is considerably smaller than their finite element counterpart, this approach allows us to significantly decrease the size of the linear system to be solved in each iteration of the Newton-Raphson algorithm. We achieve large speedups with respect to the full order simulation (in our numerical experiments, the gain is at least of one order of magnitude and grows inversely with respect to the reduced basis size), whilst still retaining satisfactory accuracy for most cardiovascular simulations.

A Data-Driven Space-Time-Parameter Reduced-Order Model with Manifold Learning for Coupled Problems: Application to Deformable Capsules Flowing in Microchannels.

An innovative data-driven model-order reduction technique is proposed to model dilute micrometric or nanometric suspensions of microcapsules, i.e., microdrops protected in a thin hyperelastic membrane, which are used in Healthcare as innovative drug vehicles. We consider a microcapsule flowing in a similar-size microfluidic channel and vary systematically the governing parameter, namely the capillary number, ratio of the viscous to elastic forces, and the confinement ratio, ratio of the capsule to tube size. The resulting space-time-parameter problem is solved using two global POD reduced bases, determined in the offline stage for the space and parameter variables, respectively. A suitable low-order spatial reduced basis is then computed in the online stage for any new parameter instance. The time evolution of the capsule dynamics is achieved by identifying the nonlinear low-order manifold of the reduced variables; for that, a point cloud of reduced data is computed and a diffuse approximation method is used. Numerical comparisons between the full-order fluid-structure interaction model and the reduced-order one confirm both accuracy and stability of the reduction technique over the whole admissible parameter domain. We believe that such an approach can be applied to a broad range of coupled problems especially involving quasistatic models of structural mechanics.

First-Order Linear Mechatronics Model for Closed-Loop MEMS Disk Resonator Gyroscope.

In this paper, a first-order closed-loop mechatronics model of a micro-electromechanical system (MEMS) disk resonator gyroscope (DRG) with a configurable ASIC is established for closed-loop design and performance analysis. There are usually some nonlinear modules in the gyroscope mechatronics model, and it is difficult to design the closed-loop controllers using classical automatic control theory. An order-reduction method (ORM) based on the Laplace transform and inverse Laplace transform is proposed to linearize the nonlinear modules. The linearized model is proved to show good agreement with the original mechatronics model in terms of system response. The experimental verification was conducted to demonstrate the validation of this method.

Artificial Neural Networks in Motion Analysis-Applications of Unsupervised and Heuristic Feature Selection Techniques.

The use of machine learning to estimate joint angles from inertial sensors is a promising approach to in-field motion analysis. In this context, the simplification of the measurements by using a small number of sensors is of great interest. Neural networks have the opportunity to estimate joint angles from a sparse dataset, which enables the reduction of sensors necessary for the determination of all three-dimensional lower limb joint angles. Additionally, the dimensions of the problem can be simplified using principal component analysis. Training a long short-term memory neural network on the prediction of 3D lower limb joint angles based on inertial data showed that three sensors placed on the pelvis and both shanks are sufficient. The application of principal component analysis to the data of five sensors did not reveal improved results. The use of longer motion sequences compared to time-normalised gait cycles seems to be advantageous for the prediction accuracy, which bridges the gap to real-time applications of long short-term memory neural networks in the future.

Understanding and reducing complex systems pharmacology models based on a novel input-response index.

A growing understanding of complex processes in biology has led to large-scale mechanistic models of pharmacologically relevant processes. These models are increasingly used to study the response of the system to a given input or stimulus, e.g., after drug administration. Understanding the input-response relationship, however, is often a challenging task due to the complexity of the interactions between its constituents as well as the size of the models. An approach that quantifies the importance of the different constituents for a given input-output relationship and allows to reduce the dynamics to its essential features is therefore highly desirable. In this article, we present a novel state- and time-dependent quantity called the input-response index that quantifies the importance of state variables for a given input-response relationship at a particular time. It is based on the concept of time-bounded controllability and observability, and defined with respect to a reference dynamics. In application to the brown snake venom-fibrinogen (Fg) network, the input-response indices give insight into the coordinated action of specific coagulation factors and about those factors that contribute only little to the response. We demonstrate how the indices can be used to reduce large-scale models in a two-step procedure: (i) elimination of states whose dynamics have only minor impact on the input-response relationship, and (ii) proper lumping of the remaining (lower order) model. In application to the brown snake venom-fibrinogen network, this resulted in a reduction from 62 to 8 state variables in the first step, and a further reduction to 5 state variables in the second step. We further illustrate that the sequence, in which a recursive algorithm eliminates and/or lumps state variables, has an impact on the final reduced model. The input-response indices are particularly suited to determine an informed sequence, since they are based on the dynamics of the original system. In summary, the novel measure of importance provides a powerful tool for analysing the complex dynamics of large-scale systems and a means for very efficient model order reduction of nonlinear systems.

Cost⁻Benefit Optimization of Structural Health Monitoring Sensor Networks.

Structural health monitoring (SHM) allows the acquisition of information on the structural integrity of any mechanical system by processing data, measured through a set of sensors, in order to estimate relevant mechanical parameters and indicators of performance. Herein we present a method to perform the cost⁻benefit optimization of a sensor network by defining the density, type, and positioning of the sensors to be deployed. The effectiveness (benefit) of an SHM system may be quantified by means of information theory, namely through the expected Shannon information gain provided by the measured data, which allows the inherent uncertainties of the experimental process (i.e., those associated with the prediction error and the parameters to be estimated) to be accounted for. In order to evaluate the computationally expensive Monte Carlo estimator of the objective function, a framework comprising surrogate models (polynomial chaos expansion), model order reduction methods (principal component analysis), and stochastic optimization methods is introduced. Two optimization strategies are proposed: the maximization of the information provided by the measured data, given the technological, identifiability, and budgetary constraints; and the maximization of the information⁻cost ratio. The application of the framework to a large-scale structural problem, the Pirelli tower in Milan, is presented, and the two comprehensive optimization methods are compared.

Design and Parametric Study of the Magnetic Sensor for Position Detection in Linear Motor Based on Nonlinear Parametric model order reduction.

This paper presents a design approach for a magnetic sensor module to detect mover position using the proper orthogonal decomposition-dynamic mode decomposition (POD-DMD)-based nonlinear parametric model order reduction (PMOR). The parameterization of the sensor module is achieved by using the multipolar moment matching method. Several geometric variables of the sensor module are considered while developing the parametric study. The operation of the sensor module is based on the principle of the airgap flux density distribution detection by the Hall Effect IC. Therefore, the design objective is to achieve a peak flux density (PFD) greater than 0.1 T and total harmonic distortion (THD) less than 3%. To fulfill the constraint conditions, the specifications for the sensor module is achieved by using POD-DMD based reduced model. The POD-DMD based reduced model provides a platform to analyze the high number of design models very fast, with less computational burden. Finally, with the final specifications, the experimental prototype is designed and tested. Two different modes, 90° and 120° modes respectively are used to obtain the position information of the linear motor mover. The position information thus obtained are compared with that of the linear scale data, used as a reference signal. The position information obtained using the 120° mode has a standard deviation of 0.10 mm from the reference linear scale signal, whereas the 90° mode position signal shows a deviation of 0.23 mm from the reference. The deviation in the output arises due to the mechanical tolerances introduced into the specification during the manufacturing process. This provides a scope for coupling the reliability based design optimization in the design process as a future extension.

Order reduction and efficient implementation of nonlinear nonlocal cochlear response models.

The cochlea is an indispensable preliminary processing stage in auditory perception that employs mechanical frequency-tuning and electrical transduction of incoming sound waves. Cochlear mechanical responses are shown to exhibit active nonlinear spatiotemporal response dynamics (e.g., otoacoustic emission). To model such phenomena, it is often necessary to incorporate cochlear fluid-membrane interactions. This results in both excessively high-order model formulations and computationally intensive solutions that limit their practical use in simulating the model and analyzing its response even for simple single-tone inputs. In order to address these limitations, the current work employs a control-theoretic framework to reformulate a nonlinear two-dimensional cochlear model into discrete state space models that are of considerably lower order (factor of 8) and are computationally much simpler (factor of 25). It is shown that the reformulated models enjoy sparse matrix structures which permit efficient numerical manipulations. Furthermore, the spatially discretized models are linearized and simplified using balanced transformation techniques to result in lower-order (nonlinear) realizations derived from the dominant Hankel singular values of the system dynamics. Accuracy and efficiency of the reduced-order reformulations are demonstrated under the response to two fixed tones, sweeping tones and, more generally, a brief speech signal. The corresponding responses are compared to those produced by the original model in both frequency and spatiotemporal domains. Although carried out on a specific instance of cochlear models, the introduced framework of control-theoretic model reduction could be applied to a wide class of models that address the micro- and macro-mechanical properties of the cochlea.

Reduced Order Modeling for Real-Time Stent Deformation Simulations of Transcatheter Aortic Valve Prostheses.

Computational modeling can be a critical tool to predict deployment behavior for transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis. However, due to the mechanical complexity of the aortic valve and the multiphysics nature of the problem, described by partial differential equations (PDEs), traditional finite element (FE) modeling of TAVR deployment is computationally expensive. In this preliminary study, a PDEs-based reduced order modeling (ROM) framework is introduced for rapidly simulating structural deformation of the Medtronic Evolut R valve stent frame. Using fifteen probing points from an Evolut model with parametrized loads enforced, 105 FE simulations were performed in the so-called offline phase, creating a snapshot library. The library was used in the online phase of the ROM for a new set of applied loads via the proper orthogonal decomposition-Galerkin (POD-Galerkin) approach. Simulations of small radial deformations of the Evolut stent frame were performed and compared to full order model (FOM) solutions. Linear elastic and hyperelastic constitutive models in steady and unsteady regimes were implemented within the ROM. Since the original POD-Galerkin method is formulated for linear problems, specific methods for the nonlinear terms in the hyperelastic case were employed, namely, the Discrete Empirical Interpolation Method. The ROM solutions were in strong agreement with the FOM in all numerical experiments, with a speed-up of at least 92% in CPU Time. This framework serves as a first step toward real-time predictive models for TAVR deployment simulations.

A partitioned model order reduction approach to rationalise computational expenses in nonlinear fracture mechanics.

We propose in this paper a reduced order modelling technique based on domain partitioning for parametric problems of fracture. We show that coupling domain decomposition and projection-based model order reduction permits to focus the numerical effort where it is most needed: around the zones where damage propagates. No a priori knowledge of the damage pattern is required, the extraction of the corresponding spatial regions being based solely on algebra. The efficiency of the proposed approach is demonstrated numerically with an example relevant to engineering fracture.

Modeling and Vibration Control of Sandwich Composite Plates.

A finite element dynamic model of the sandwich composite plate was developed based on classical laminate theory and Hamilton's principle. A 4-node, 7-degree-of-freedom three-layer plate cell is constructed to simulate the interaction between the substrate, the viscoelastic damping layer, and the piezoelectric material layer. Among them, the viscoelastic layer is referred to as the complex constant shear modulus model, and the equivalent Rayleigh damping is introduced to represent the damping of the substrate. The established dynamics model has too many degrees of freedom, and the obtained dynamics model has good controllability and observability after adopting the joint reduced-order method of dynamic condensation in physical space and equilibrium in state space. The optimal quadratic (LQR) controller is designed for the active control of the sandwich panel, and the parameters of the controller parameters, the thickness of the viscoelastic layer, and the optimal covering position of the sandwich panel are optimized through simulation analysis. The results show that the finite element model established in this paper is still valid under different boundary conditions and different covering methods, and the model can still accurately and reliably represent the dynamic characteristics of the original system after using the joint step-down method. Under different excitation signals and different boundary conditions, the LQR control can effectively suppress the vibration of the sandwich plate. The optimal cover position of the sandwich plate is near the solid support end and far from the free-degree end. The parameters of controller parameters and viscoelastic layer thickness are optimized from several angles, respectively, and a reasonable optimization scheme can be selected according to the actual requirements.

A multifidelity approach coupling parameter space reduction and nonintrusive POD with application to structural optimization of passenger ship hulls.

Nowadays, the shipbuilding industry is facing a radical change toward solutions with a smaller environmental impact. This can be achieved with low emissions engines, optimized shape designs with lower wave resistance and noise generation, and by reducing the metal raw materials used during the manufacturing. This work focuses on the last aspect by presenting a complete structural optimization pipeline for modern passenger ship hulls which exploits advanced model order reduction techniques to reduce the dimensionality of both input parameters and outputs of interest. We introduce a novel approach which incorporates parameter space reduction through active subspaces into the proper orthogonal decomposition with interpolation method. This is done in a multi-fidelity setting. We test the whole framework on a simplified model of a midship section and on the full model of a passenger ship, controlled by 20 and 16 parameters, respectively. We present a comprehensive error analysis and show the capabilities and usefulness of the methods especially during the preliminary design phase, finding new unconsidered designs while handling high dimensional parameterizations.

Finite Element Modeling and Vibration Control of Plates with Active Constrained Layer Damping Treatment.

An enhanced lightness and thinness is the inevitable trend of modern industrial production, which will also lead to prominent low-frequency vibration problems in the associated structure. To solve the vibration problem of thin plate structures in various engineering fields, the active constrained layer damping (ACLD) thin plate structure is taken as the research object to study vibration control. Based on the FEM method, energy method, and Hamilton principle, the dynamic model of an ACLD thin plate structure is derived, in which the Golla-Hughes-McTavish (GHM) model is used to characterize the damping characteristics of the viscoelastic layer, and the equivalent Rayleigh damping is used to characterize the damping characteristics of the base layer. The order of the model is reduced based on the high-precision physical condensation method and balance reduction method, and the model has good controllability and observability. An LQR controller is designed to actively control the ACLD sheet, and the controller parameters and piezoelectric sheet parameters are optimized. The results show that the finite element model established in this paper is accurate under different boundary conditions, and the model can still accurately and reliably describe the dynamic characteristics of the original system in the time and frequency domain after using the joint reduction method. Under different excitation and boundary conditions, LQR control can effectively suppress structural vibration. Considering the performance and cost balance, the most suitable control parameter for the system is: Q-matrix coefficient is between 1 × 104 and 1 × 105, the R-matrix coefficient is between 1 and 10, and the thickness of the piezoelectric plate is 0.5 mm.

Parametric Analysis of Thick FGM Plates Based on 3D Thermo-Elasticity Theory: A Proper Generalized Decomposition Approach.

In the present work, the general and well-known model reduction technique, PGD (Proper Generalized Decomposition), is used for parametric analysis of thermo-elasticity of FGMs (Functionally Graded Materials). The FGMs have important applications in space technologies, especially when a part undergoes an extreme thermal environment. In the present work, material gradation is considered in one, two and three directions, and 3D heat transfer and theory of elasticity equations are solved to have an accurate temperature field and be able to consider all shear deformations. A parametric analysis of FGM materials is especially useful in material design and optimization. In the PGD technique, the field variables are separated to a set of univariate functions, and the high-dimensional governing equations reduce to a set of one-dimensional problems. Due to the curse of dimensionality, solving a high-dimensional parametric problem is considerably more computationally intensive than solving a set of one-dimensional problems. Therefore, the PGD makes it possible to handle high-dimensional problems efficiently. In the present work, some sample examples in 4D and 5D computational spaces are solved, and the results are presented.