The study of neural network-based controller for controlling dissolved oxygen concentration in a sequencing batch reactor

The design and development of the neural network (NN)-based controller performance for the activated sludge process in sequencing batch reactor (SBR) is presented in this paper. Here we give a comparative study of various neural network (NN)-based controllers such as the direct inverse control, internal model control (IMC) and hybrid NN control strategies to maintain the dissolved oxygen (DO) level of an activated sludge system by manipulating the air flow rate. The NN inverse model-based controller with the model-based scheme represents the controller, which relies solely upon the simple NN inverse model. In the IMC, both the forward and inverse models are used directly as elements within the feedback loop. The hybrid NN control consists of a basic NN controller in parallel with a proportional integral (PI) controller. Various simulation tests involving multiple set-point changes, disturbances rejection and noise effects were performed to review the performances of these various controllers. From the results it can be seen that hybrid controller gives the best results in tracking set-point changes under disturbances and noise effects.     

Noise suppression in stochastic genetic circuits using PID controllers

Inside individual cells, protein population counts are subject to molecular noise due to low copy numbers and the inherent probabilistic nature of biochemical processes. We investigate the effectiveness of proportional, integral and derivative (PID) based feedback controllers to suppress protein count fluctuations originating from two noise sources: bursty expression of the protein, and external disturbance in protein synthesis. Designs of biochemical reactions that function as PID controllers are discussed, with particular focus on individual controllers separately, and the corresponding closed-loop system is analyzed for stochastic controller realizations. Our results show that proportional controllers are effective in buffering protein copy number fluctuations from both noise sources, but this noise suppression comes at the cost of reduced static sensitivity of the output to the input signal. In contrast, integral feedback has no effect on the protein noise level from stochastic expression, but significantly minimizes the impact of external disturbances, particularly when the disturbance comes at low frequencies. Counter-intuitively, integral feedback is found to amplify external disturbances at intermediate frequencies. Next, we discuss the design of a coupled feedforward-feedback biochemical circuit that approximately functions as a derivate controller. Analysis using both analytical methods and Monte Carlo simulations reveals that this derivative controller effectively buffers output fluctuations from bursty stochastic expression, while maintaining the static input-output sensitivity of the open-loop system. In summary, this study provides a systematic stochastic analysis of biochemical controllers, and paves the way for their synthetic design and implementation to minimize deleterious fluctuations in gene product levels.     

A model for control of breathing in mammals: coupling neural dynamics to peripheral gas exchange and transport

A new model for aspects of the control of respiration in mammals has been developed. The model integrates a reduced representation of the brainstem respiratory neural controller together with peripheral gas exchange and transport mechanisms. The neural controller consists of two components. One component represents the inspiratory oscillator in the pre-Bötzinger complex (pre-BötC) incorporating biophysical mechanisms for rhythm generation. The other component represents the ventral respiratory group (VRG), which is driven by the pre-BötC for generation of inspiratory (pre)motor output. The neural model was coupled to simplified models of the lungs incorporating oxygen and carbon dioxide transport. The simplified representation of the brainstem neural circuitry has regulation of both frequency and amplitude of respiration and is done in response to partial pressures of oxygen and carbon dioxide in the blood using proportional (P) and proportional plus integral (PI) controllers. We have studied the coupled system under open and closed loop control. We show that two breathing regimes can exist in the model. In one regime an increase in the inspiratory frequency is accompanied by an increase in amplitude. In the second regime an increase in frequency is accompanied by a decrease in amplitude. The dynamic response of the model to changes in the concentration of inspired O₂ or inspired CO₂ was compared qualitatively with experimental data reported in the physiological literature. We show that the dynamic response with a PI-controller fits the experimental data better but suggests that when high levels of CO₂ are inspired the respiratory system cannot reach steady state. Our model also predicts that there could be two possible mechanisms for apnea appearance when 100% O₂ is inspired following a period of 5% inspired O₂. This paper represents a novel attempt to link neural control and gas transport mechanisms, highlights important issues in amplitude and frequency control and sets the stage for more complete neurophysiological control models.     

A Symbolic Model for the Regulation by Bone Metabolism of the Blood Calcium Level in Rats

The control by bone metabolism of the blood calcium level in young rats may be described in terms of a regulator-type system. The model presented here comprises a feedback loop involving only a proportional control in thyroparathyroidectomized, and a combination of proportional and integral controls in normal animals. It accounts for the variations observed when the system was subjected to a variety of experimental constraints. The implications, limitations, and possible extensions of the model are discussed.     

A negative group delay model for feedback-delayed manual tracking performance

We propose that feedback-delayed manual tracking performance is limited by fundamental constraints imposed by the physics of negative group delay. To test this hypothesis, the results of an experiment in which subjects demonstrate both reactive and predictive dynamics are modeled by a linear system with delay-induced negative group delay. Although one of the simplest real-time predictors conceivable, this model explains key components of experimental observations. Most notably, it explains the observation that prediction time linearly increases with feedback delay, up to a certain point when tracking performance deteriorates. It also explains the transition from reactive to predictive behavior with increasing feedback delay. The model contains only one free parameter, the feedback gain, which has been fixed by comparison with one set of experimental observations for the reactive case. Our model provides quantitative predictions that can be tested in further experiments.     

Validation of subject-specific automated p-FE analysis of the proximal femur

Background: The use of subject-specific finite element (FE) models in clinical practice requires a high level of automation and validation. In Yosibash et al. [2007a. Reliable simulations of the human proximal femur by high-order finite element analysis validated by experimental observations. J. Biomechanics 40, 3688–3699] a novel method for generating high-order finite element (p-FE) models from CT scans was presented and validated by experimental observations on two fresh frozen femurs (harvested from a 30 year old male and 21 year old female). Herein, we substantiate the validation process by enlarging the experimental database (54 year old female femur), improving the method and examine its robustness under different CT scan conditions.Approach: A fresh frozen femur of a 54 year old female was scanned under two different environments: in air and immersed in water (dry and wet CT). Thereafter, the proximal femur was quasi-statically loaded in vitro by a 1000 N load. The two QCT scans were manipulated to generate p-FE models that mimic the experimental conditions. We compared p-FE displacements and strains of the wet CT model to the dry CT model and to the experimental results. In addition, the material assignment strategy was reinvestigated. The inhomogeneous Young's modulus was represented in the FE model using two different methods, directly extracted from the CT data and using continuous spatial functions as in Yosibash et al. [2007a. Reliable simulations of the human proximal femur by high-order finite element analysis validated by experimental observations. J. Biomechanics 40, 3688–3699].Results: Excellent agreement between dry and wet FE models was found for both displacements and strains, i.e. the method is insensitive to CT conditions and may be used in vivo. Good agreement was also found between FE results and experimental observations. The spatial functions representing Young's modulus are local and do not influence strains and displacements prediction. Finally, the p-FE results of all three fresh frozen human femurs compare very well to experimental observations exemplifying that the presented method may be in a mature stage to be used in clinical computer-aided decision making.     

Design of methanol Feed control in Pichia pastoris fermentations based upon a growth model

The methylotrophic yeast Pichia pastoris is an effective system for recombinant protein productions that utilizes methanol as an inducer, and also as carbon and energy source for a Mut(+) (methanol utilization plus) strain. Pichia fermentation is conducted in a fed-batch mode to obtain a high cell density for a high productivity. An accurate methanol control is required in the methanol fed-batch phase (induction phase) in the fermentation. A simple "on-off" control strategy is inadequate for precise control of methanol concentrations in the fermentor. In this paper we employed a PID (proportional, integral and derivative) control system for the methanol concentration control and designed the PID controller settings on the basis of a Pichia growth model. The closed-loop system was built with four components: PID controller, methanol feed pump, fermentation process, and methanol sensor. First, modeling and transfer functions for all components were derived, followed by frequency response analysis, a powerful method for calculating the optimal PID parameters K(c) (controller gain), tau(I) (controller integral time constant), and tau(D) (controller derivative time constant). Bode stability criteria were used to develop the stability diagram for evaluating the designed settings during the entire methanol fed-batch phase. Fermentations were conducted using four Pichia strains, each expressing a different protein, to verify the control performance with optimal PID settings. The results showed that the methanol concentration matched the set point very well with only small overshoot when the set point was switched, which indicated that a very good control performance was achieved. The method developed in this paper is robust and can serve as a framework for the design of other PID feedback control systems in biological processes.     

Parameter Identification of Robot Manipulators: A Heuristic Particle Swarm Search Approach

Parameter identification of robot manipulators is an indispensable pivotal process of achieving accurate dynamic robot models. Since these kinetic models are highly nonlinear, it is not easy to tackle the matter of identifying their parameters. To solve the difficulty effectively, we herewith present an intelligent approach, namely, a heuristic particle swarm optimization (PSO) algorithm, which we call the elitist learning strategy (ELS) and proportional integral derivative (PID) controller hybridized PSO approach (ELPIDSO). A specified PID controller is designed to improve particles’ local and global positions information together with ELS. Parameter identification of robot manipulators is conducted for performance evaluation of our proposed approach. Experimental results clearly indicate the following findings: Compared with standard PSO (SPSO) algorithm, ELPIDSO has improved a lot. It not only enhances the diversity of the swarm, but also features better search effectiveness and efficiency in solving practical optimization problems. Accordingly, ELPIDSO is superior to least squares (LS) method, genetic algorithm (GA), and SPSO algorithm in estimating the parameters of the kinetic models of robot manipulators.     

Intermittent control: a computational theory of human control

The paradigm of continuous control using internal models has advanced understanding of human motor control. However, this paradigm ignores some aspects of human control, including intermittent feedback, serial ballistic control, triggered responses and refractory periods. It is shown that event-driven intermittent control provides a framework to explain the behaviour of the human operator under a wider range of conditions than continuous control. Continuous control is included as a special case, but sampling, system matched hold, an intermittent predictor and an event trigger allow serial open-loop trajectories using intermittent feedback. The implementation here may be described as ??continuous observation, intermittent action??. Beyond explaining unimodal regulation distributions in common with continuous control, these features naturally explain refractoriness and bimodal stabilisation distributions observed in double stimulus tracking experiments and quiet standing, respectively. Moreover, given that human control systems contain significant time delays, a biological-cybernetic rationale favours intermittent over continuous control: intermittent predictive control is computationally less demanding than continuous predictive control. A standard continuous-time predictive control model of the human operator is used as the underlying design method for an event-driven intermittent controller. It is shown that when event thresholds are small and sampling is regular, the intermittent controller can masquerade as the underlying continuous-time controller and thus, under these conditions, the continuous-time and intermittent controller cannot be distinguished. This explains why the intermittent control hypothesis is consistent with the continuous control hypothesis for certain experimental conditions.     

Evaluating knee replacement mechanics during ADL with PID-controlled dynamic finite element analysis

Validated computational knee simulations are valuable tools for design phase development of knee replacement devices. Recently, a dynamic finite element (FE) model of the Kansas knee simulator was kinematically validated during gait and deep flexion cycles. In order to operate the computational simulator in the same manner as the experiment, a proportional–integral–derivative (PID) controller was interfaced with the FE model to control the quadriceps actuator excursion and produce a target flexion profile regardless of implant geometry or alignment conditions. The controller was also expanded to operate multiple actuators simultaneously in order to produce in vivo loading conditions at the joint during dynamic activities. Subsequently, the fidelity of the computational model was improved through additional muscle representation and inclusion of relative hip–ankle anterior–posterior (A–P) motion. The PID-controlled model was able to successfully recreate in vivo loading conditions (flexion angle, compressive joint load, medial–lateral load distribution or varus-valgus torque, internal–external torque, A–P force) for deep knee bend, chair rise, stance-phase gait and step-down activities.     

Improvement of nitrogen removal and reduction of operating costs in an activated sludge process with feedforward–cascade control strategy

In this paper, a feedforward–cascade controller for dissolved oxygen concentration in an activated sludge process is designed in order to meet stricter effluent quality standards at a minimum cost. Conventional proportional and integral (PI) constant dissolved oxygen set-point control and feedforward–cascade dissolved oxygen set-point control are evaluated using the reduced model of activated sludge model no. 1 and reduced IWA simulation benchmark. The feedforward–cascade control has been based on a hierarchical structure where a high level or cascade control selects the set-point of the low level or conventional controller and low level directly control dissolved oxygen concentration. And feedforward control is introduced in the control system for preventing the influent loading from influencing the system. Simulation results show that feedforward–cascade control of the activated sludge process is more successful than conventional PI control in meeting the effluent standards and reducing operational costs. This control strategy can be expected to be accepted by the operating personnel in wastewater treatment plants.     

Properties of central control of body temperature in the rabbit

The structure of the central temperature controller in rabbits has been analysed. On the one hand, experiments were carried out to obtain the necessary data for system analysis; on the other hand, a mathematical model of the passive system was developed which describes the thermal characteristics of the body in accordance with the experimental results. In applying the model, different controller equations for the effector mechanisms involved were tested to fit the experimental data best. They are compared with already existing models of metabolic control. In addition, mechanisms of the effector coordination are discussed. It is shown that the three effectors make use of a similar controller structure thet feeds core temperature as well as skin temperature back into the controller. The system is insensitive to variations of the controller gains, whereas a slight change in the controller reference temperature causes significant changes of the controlled core temperature. Furthermore it is shown that any mutual effector blockings are dispensible.     

Agonist binding to the nicotinic acetylcholine receptor and probability of channel opening

Binding of agonists to the nicotinic acetylcholine receptor induces a conformational change by which the integral cation channel is opened. The analysis of this mechanism is commonly based on models which may be classified as either occupational or conformational. Here I summarize results showing that none of these concepts alone is capable of accommodating all experimental observations. A new integrated model based on earlier concepts and the molecular structure of this macromolecule can explain the experiments.     

Closed-loop control of bacterial high-cell-density fed-batch cultures: production of mcl-PHAs by Pseudomonas putida KT2442 under single-substrate and cofeeding conditions.

Pseudomonas putida KT2442 is able to accumulate medium-chain-length poly(3-hydroxyalkanoates) (mcl-PHAs) as intracellular inclusions on a variety of fatty acids and many other carbon sources. Some of these substrates, such as octanoic acid, alkenoic acids, and halogenated derivatives, are toxic when present in excess. Efficient production of mcl-PHAs on such toxic substrates therefore requires control of the carbon source concentration in the supernatant. In this study, we develop a closed-loop control system based on on-line gas chromatography to maintain continuously fed substrates at desired levels. We used the graphical programming environment LABVIEW to set up a flexible process control system that allows users to perform supervisory process control and permits remote access to the fermentation system over the Internet. Single-substrate supernatant concentration in a high-cell-density fed-batch fermentation process was controlled by a proportional (P) controller (P = 50%) acting on the substrate pump feed rate. Na-octanoate concentrations oscillated around the setpoint of 10 mM and could be maintained between 0 and 25 mM at substrate uptake rates as high as 90 mmol L(-1) h(-1). Under cofeeding conditions Na-10-undecenoate and Na-octanoate could be individually controlled at 2.5 mM and 9 mM, respectively, by applying a proportional integral (PI) controller for each substrate. The resulting copolymer contained 43.5 mol% unsaturated monomers and reflected the ratio of 10-undecenoate in the feed. It was suggested that both substrates were consumed at similar rates. These results show that this control system is suitable for avoiding substrate toxicity and supplying carbon substrates for growth and mcl-PHA accumulation.     

Model analysis of steady-state ventilatory response to CO2 into component factors

A method is described to partition measured values of steady-state ventilatory response into an estimation of the blood flow in the respiratory controller and the sensitivity of the controller to CO2 assuming proportional control. The analysis is derived from the describing equations of a computer model and leads to the definition of a grid of lines emanating from a hypothetical reference point at negative ventilation and zero central nervous system metabolism. Data from the literature reporting differences in CO2 response among normal subjects and changes in resting ventilation and cerebral blood flow with age are reinterpreted from this perspective. Use of a structural model to interpret physiological data is shown to give a different meaning to data reduction in contrast to interpretation using statistical models like regression.     

Leukocyte deformability: finite element modeling of large viscoelastic deformation.

An axisymmetric deformation of a viscoelastic sphere bounded by a prestressed elastic thin shell in response to external pressure is studied by a finite element method. The research is motivated by the need for understanding the passive behavior of human leukocytes (white blood cells) and interpreting extensive experimental data in terms of the mechanical properties. The cell at rest is modeled as a sphere consisting of a cortical prestressed shell with incompressible Maxwell fluid interior. A large-strain deformation theory is developed based on the proposed model. General non-linear, large strain constitutive relations for the cortical shell are derived by neglecting the bending stiffness. A representation of the constitutive equations in the form of an integral of strain history for the incompressible Maxwell interior is used in the formulation of numerical scheme. A finite element program is developed, in which a sliding boundary condition is imposed on all contact surfaces. The mathematical model developed is applied to evaluate experimental data of pipette tests and observations of blood flow.     

Implementing Process Analytical Technology for the Production of Recombinant Proteins in Escherichia coli Using an Advanced Controller Scheme

The performance of a bioreactor in meeting process goals is affected by the microorganism used, medium composition, and operating conditions. A typical bioreactor uses a supervisory control and data acquisition (SCADA) system for control, and a combination of software and hardware tools for real‐time data analysis. However, when the process is disrupted by utility or instrumentation failure, typical process controllers may be unable to reinstate normal operating conditions before the cells in the reactor shift to unfavorable metabolic regimes. The objective of this study is to examine how the response of a controller affects process recovery when disruptive incidences occur under a process analytical technology (PAT) framework. The process used for this investigation is the production of lethal toxin‐neutralizing factor (LTNF) by Escherichia coli (E. coli), which is controlled by a decoupled input–output‐linearizing controller (DIOLC). The performance of the DIOLC is compared to a proportional integral derivative (PID) controller subjected to the same conditions. The disruptions are introduced manually and the effect of controller action on process recovery and LTNF synthesis is measured in terms of peak purity and concentration. It is observed that DIOLC performs better after reinstating operating conditions and results in a meaningful improvement in performance.     

Binocular vision and accommodation in prey-catching chameleons

We have studied the role of accommodation and binocular convergence in the predatory behaviour of two chameleon species (Chamaeleocalyptratus, C. dilepis). Accommodation measurements support earlier observations that accommodation is the major distance cue. Specifically, accommodation speed (60 D s⁻¹), amplitude (45 D) and precision (no significant under-accommodation) were superior to those of other terrestrial vertebrates. Similar to other vertebrates, accommodation was accompanied by a prominent pupillary constriction (pupillary near response). Accommodation could be coupled or uncoupled in both eyes, depending on the experimental situation or the phase of the predatory behavioural sequence. Uncoupled accommodation occurred: 1. During scanning saccadic eye movements for prey detection. Only one eye accommodated appropriately, the other adopted a hyperopic resting refractive state. Attention switched from one eye to the other at approximately 1-s intervals. 2. During initial stages of distance estimation. Coupled accommodation only occurred shortly before the tongue shot. Coupling was demonstrated by either covering one eye with a lens or covering one eye with an infrared light transmitting cut-off filter which still permitted refraction to be measured. In both cases the amount of accommodation was identical in both eyes. Search-coil measurements showed that the angle of convergence of both eyes is too variable to permit triangulation or to provide the basic requirement for stereopsis (matching corresponding points). We conclude that coupling of accommodation serves to improve accommodation precision rather than to permit stereopsis. Accepted: 3 September 1997     

A simple kinetic model for dynein oscillatory activity

A kinetic model for dynein, a molecular motor, complexed with microtubule fragments, is considered. The model explains the experimental observations of oscillatory movements in surprisingly simple axonemal fragments perfused by the ATP solution. The model explains at first time the oscillatory dynein activity as a phenomenon induced by two dynein heads cooperative interaction in the axoneme. The oscillation form, frequency, and amplitude, observed for the model, are close to these experimental characteristics. Kinetic parameters, used in the model, are close to the known experimental parameters.