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PubMedDate not supplied

Issues in the design of a multirate model-based controller for a nonlinear drug infusion system.

Multivariable controller design for the regulation of mean arterial pressure (MAP) and cardiac output (CO) in congestive heart failure patients is restricted by the limited frequency of CO sampling. Performance criteria for the controller specify maximum allowable transient settling times for both variables, and the design should account for the inherent multirate nature of the process in order to satisfy these criteria. We present a multirate model predictive control (MPC) design for MAP and CO regulation by combined infusion of sodium nitroprusside and dopamine, based on a comprehensive nonlinear model of the system. The multirate MPC algorithm is based on nonlinear quadratic dynamic matrix control. To reduce computation time, we introduce a selective linearization technique that linearizes the model on the basis of trends in the plant-model mismatch. The problem is complicated by restrictions on initial dopamine infusion, prescribed to avoid extremely slow responses. We present a novel rule-based override (RBO) to the MPC controller that uses a set of heuristics to initialize dopamine. The performance of the MPC/RBO controller is illustrated using simulation results.

Algorithms↗

PubMed2006

MIMO extended predictive control-implementation and robust stability analysis.

The objective of this work is to develop a new tuning strategy for multivariable extended predictive control (EPC). A natural concern is the problem of ill conditionality in controlling multi-input multi-output (MIMO) systems. The main advantage of EPC is that it has a simple and effective tuning strategy that results in a well-conditioned system which can achieve tight closed-loop response. Moreover, unlike most existing model predictive control tuning strategies, the proposed strategy establishes a direct relationship between one main tuning parameter for each subprocess of the MIMO system. This tuning method has been derived based on the assumption of an infinite control horizon resulting in powerful stability for the nominal case and in the presence of model uncertainty. This tuning method is applicable to unconstrained multivariable processes, and was proven to have good control on nonsquare systems. The main features of the new tuning strategy are practically illustrated on a MIMO temperature system with improved control performance as compared to move suppressed predictive control.

Journal Article↗

PubMed1997

Modeling and optimising alcohol production by fermentation of dextrose-xylose mixed feed using a fluorosensor.

Dextrose with differing amounts of xylose (mixed substrate medium) has been fermented at 28 degree Celsius with sacchromyces cerevisiae (Baker's Yeast) as seeding. The progress of the reaction was recorded by measuring the fluorescent signal due to intracellular reduced nicotinamide adenine di nucleotide (NADH) present in the cells with a Dr. Ingold (Switzerland) fluorosensor which has an excitation wavelength of 360 nm and measurement wavelength of 450 nm. The concentration of xylose in the xylose-dextrose feed was varied from 0.7% to 5.0% by weight. The optimum concentration of xylose at which the production of alcohol was a maximum was found to be 3.4 percent xylose. The fluorescent voltage data for different concentration of xylose fitted a first order model with an average absolute deviation of less than one percent. Development of this model is useful in design of model predictive controllers.

Ethanol↗

PubMed2000

Improving regulation of mean arterial blood pressure during anesthesia through estimates of surgery effects.

In this paper, a scheme for improvement of the regulation of mean arterial blood pressure (MAP) during anesthesia based on model predictive control (MPC) and estimates of the effects of disturbances (surgical events) is proposed. A linear model for the combined effects of surgical stimulations and volatile anesthetics on MAP is derived from experimental data. Based on it the potential improvement in blood pressure regulation is evaluated via a simulation study. The simulation study shows that when information about the effect of the surgical events on MAP is utilized by the controller maximum MAP deviations can be reduced by as much as 50% even when this information is inaccurate. At worst, (highly inaccurate information) no improvement is obtained.

Anesthesia↗

PubMed2005

A critical assessment of algorithms and challenges in the development of a closed-loop artificial pancreas.

The development of an artificial pancreas is placed in the context of the history of the field of feedback control systems, beginning with the water clock of ancient Greece, and including a discussion of current efforts in the control of complex systems. The first generation of artificial pancreas devices included two manipulated variables (insulin and glucose infusion) and nonlinear functions of the error (difference between desired and measured glucose concentration) to minimize hyperglycemia while avoiding hypoglycemia. Dynamic lags between insulin infusion and glucose measurement were relatively small for these intravenous-based systems. Advances in continuous glucose sensing, fast-acting insulin analogs, and a mature insulin pump market bring us close to commercial realization of a closed-loop artificial pancreas. Model predictive control is discussed in-depth as an approach that is well suited for a closed-loop artificial pancreas. A major challenge that remains is handling an unknown glucose disturbance (meal), and an approach is proposed to base a current insulin infusion action on the predicted effect of a meal on future glucose values. Better "meal models" are needed, as a limited knowledge of the effect of a meal on the future glucose values limits the performance of any control algorithm.

Algorithms↗

PubMed2003

Practical approach to tuning MPC.

This paper presents the results of a heuristic approach for developing model predictive control (MPC) tuning rules. The tuning has been applied and tested in easy-to-use MPC. Process modeling in this MPC uses normalized input/ output range. As a result there is no need for tuning outputs, a procedure known as adjusting equal concern error. Penalties on moves are set as a function of process dead time as the primary factor, with some correction from process gain. The default calculation delivers robust control, which tolerates up to triple increase in process static gain. If control is too aggressive, further on-line adjustment can be done by set point reference trajectory. Test results show that this tuning is robust for process gain change, however, it is much less efficient in compensating for process dead-time changes. It was found that dead-time mismatch is much better compensated with the model correction filter. Combining the three handles, i.e., penalties on moves, reference trajectory, and model filter, easy and intuitively understandable MPC tuning was achieved. The findings are illustrated by numerous MPC simulated tests.

Computer Simulation↗

PubMed2006

On-line adaptive algorithm with glucose prediction capacity for subcutaneous closed loop control of glucose: evaluation under fasting conditions in patients with Type 1 diabetes.

AIMS: To evaluate an algorithm with glucose prediction capacity and continuous adaptation of patient parameters-a model predictive control (MPC) algorithm-to control blood glucose concentration during fasting conditions in patients with Type 1 diabetes. In the subcutaneous (sc) route within a closed loop system. METHODS: Paired experiments were performed in six patients. Over 8 h the MPC algorithm was used to control glucose with s.c. insulin administration and two different glucose monitoring protocols: first, the algorithm was provided with intravenous (i.v.) glucose values for insulin dosage calculation directly (i.v.-s.c. route). Then, in the second experiment, i.v. glucose values were fed to the MPC with a delay of 30 min to simulate s.c. glucose measurements ('s.c.'-s.c. route). In both experiments plasma glucose, insulin dosage, and serum insulin levels were analysed. RESULTS: Glucose concentration was brought from hyper- to normoglycaemia and kept in the physiological range (6-7 mmol/l) with both routes in all subjects. Mean glucose concentration reached the threshold of 7 mmol/l approximately 2 (i.v.-s.c. route) and 3 ('s.c.'-s.c. route) hours after the start of glucose control with the MPC. During the last 2 h of automated glucose control, mean glucose concentration was 6.3 +/- 0.2 mmol/l and 6.6 +/- 0.3 mmol/l for i.v.-s.c. and 's.c.'-s.c. route, respectively. Glucose concentration, insulin doses, and serum insulin levels did not differ significantly between routes (P > 0.05). CONCLUSIONS: The MPC algorithm is suitable for glucose control during fasting within an extracorporeal artificial beta-cell in the subcutaneous route Type 1 diabetic patients.

Administration, Cutaneous↗

PubMed2002

Self-optimizing MPC of melt temperature in injection moulding.

The parameters in plastic injection moulding are highly nonlinear and interacting. Good control of plastic melt temperature for injection moulding is very important in reducing operator setup time, assuring consistent product quality, and preventing thermal degradation of the melt. Step response testing was performed on the barrel heating zones on an industrial injection moulding machine (IMM). The open loop responses indicated a high degree of process coupling between the heating zones. From these experimental step responses, a multiple-input-multiple-output model predictive control strategy was developed and practically implemented. The requirement of negligible overshoot is important to the plastics industry for preventing material overheating and wastage, and reducing machine operator setup time. A generic learning and self-optimizing MPC methodology was developed and implemented on the IMM to control melt temperature for any polymer to be moulded on any machine having different electrical heater capacities. The control performance was tested for varying setpoint trajectories typical of normal machine operations. The results showed that the predictive controller provided good control of melt temperature for all zones with negligible oscillations, and, therefore, eliminated material degradation and extended machine setup time.

Computer Simulation↗

PubMed2005

Grading system to assess clinical performance of closed-loop glucose control.

Closed-loop control of the glucose concentration in type 1 diabetes has been the subject of extensive research over the last 3 decades. Building on the recent progress in continuous glucose sensing techniques, several prototypes of a closed-loop system have been developed. To complement existing measures of glucose control, we designed a grading system specifically designed to provide clinical assessment of closed-loop systems including that of glucose controllers. The system introduces six grades, A-F, describing the level of control and the therapeutic intervention during outside-meal and postprandial conditions. Grades A and B represent excellent and good glucose control, respectively, without the need for a corrective therapeutic action. Grade C represents suboptimal control with a recommendation for a corrective action. Grade D represents poor control requiring a corrective action. Grades E and F represent very poor and life-threatening control, respectively, with a need for an immediate corrective action or requiring external assistance. The outcome of grading is the quantification of time spent in each grade. The grading system is exemplified using data obtained with a model predictive controller within an in silico simulation environment. We conclude that the grading system provides suitable means to assess efficacy and safety of glucose controllers complementing existing measures of glucose control.

Algorithms↗

PubMedDate not supplied

Modeling and advanced control of recombinant Zymomonas mobilis fed-batch fermentation.

This work presents the development of an unstructured kinetic model incorporating the differing degrees of product, substrate, and pH inhibition on the kinetic rates of ethanol fermentation by recombinant Zymomonas mobilis CP4:pZB5 for growth on two substrates. Product inhibition was observed to start affecting the specific growth rate at an ethanol concentration of 20 g/L and the specific productivity at about 35-40 g/L. Specific growth rate was also shown to be more sensitive to inhibition by lowered pH as well. A model for the inhibition of two competing substrates' cellular uptake via membrane transport is proposed. Inhibition functions and model parameters were determined by fitting experimental data to the model. The model was utilized in a nonlinear model predictive control (NMPC) algorithm to control the product concentration during fed-batch fermentation to offset the inhibitory effects of product inhibition. Using the optimal feeding policy determined online, the volumetric productivity of ethanol was improved 16.6% relative to the equivalent batch operation when the final ethanol concentration was reached.

Algorithms↗

PubMed2002

Control of starvation-induced apoptosis in Chinese hamster ovary cell cultures.

The application of the unscented Kalman filter to control starvation-induced programmed cell death-apoptosis-in Chinese hamster ovary cells was investigated. Neural network-based sensitivity analysis identified glutamine and asparagine as two major amino acids that play a key role in the suppression of apoptosis. Dynamic equations that accounted for the dependence of apoptotic cells on the concentrations of viable cells, glutamine, and asparagine were derived. These state equations were highly nonlinear and included nine state variables. An oxygen mass balance was written in the liquid phase. It served as the output equation for the unscented Kalman filter. Using the oxygen uptake rate as the observer, it was possible to estimate the states. A model predictive controller was then implemented once the apoptotic cells in the bioreactor approached a concentration of 1.5 x 10(4) cells/mL, taking into account the operating range of the flow cytometer and measurement error. The manipulated variables were the flow rates of glucose, glutamine, and asparagine. Simulation results showed that the controller was able to keep the apoptotic cells at a concentration of 1.5 x 10(4) cells/mL.

Amino Acids↗

PubMed2002

A new paradigm for the closed-loop intraoperative administration of analgesics in humans.

We present a new paradigm for the closed-loop administration of analgesics during general anesthesia. The manipulated variable in the control system is the infusion rate of the opiate alfentanil, administered intravenously through a computer-controlled infusion pump (CCIP). The outputs to be controlled are the patient's mean arterial pressure (MAP) and the drug concentration in the plasma. Maintaining MAP within appropriate ranges provides optimal treatment of the patient's reactions to surgical stimuli. Maintaining plasma drug concentrations close to a reference value specified by the anesthesiologist allows to titrate analgesic administration to qualitative clinical end-points of insufficient analgesia. MAP is acquired invasively through a catheter cannula. Since plasma drug concentrations cannot be measured on-line, they are estimated via a pharmacokinetic model. We describe an explicit model-predictive controller which achieves the above-mentioned objectives. An upper constraint on drug concentrations is maintained to avoid overdosing. Constraints on the MAP are introduced to trigger a prompt controller reaction during hypertensive and hypotensive periods. Measurement artifacts in the MAP signal are rejected to prevent harmful misbehavior of the controller. We discuss the results of the clinical validation of the controller on humans.

Alfentanil↗

PubMed1989

Circumstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs.

This paper describes in vitro experiments with two types of intramolecular duplex structures that inhibit translation in cis by preventing the formation of an initiation complex or by causing the complex to be abortive. One stem-loop structure (delta G = -30 kcal/mol) prevented mRNA from engaging 40S subunits when the hairpin occurred 12 nucleotides (nt) from the cap but had no deleterious effect when it was repositioned 52 nt from the cap. This result confirms prior in vivo evidence that the 40S subunit-factor complex, once bound to mRNA, has considerable ability to penetrate secondary structure. Consequently, translation is most sensitive to secondary structure at the entry site for ribosomes, i.e., the 5' end of the mRNA. The second stem-loop structure (hp7; delta G = -61 kcal/mol, located 72 nt from the cap) was too stable to be unwound by 40S ribosomes, hp7 did not prevent a 40S ribosomal subunit from binding but caused the 40S subunit to stall on the 5' side of the hairpin, exactly as the scanning model predicts. Control experiments revealed that 80S elongating ribosomes could disrupt duplex structures, such as hp7, that were too stable to be penetrated by the scanning 40S ribosome-factor complex. A third type of base-paired structure shown to inhibit translation in vivo involves a long-range interaction between the 5' and 3' noncoding sequences.

Animals↗

PubMed1990

Receptor-mediated prednisolone pharmacodynamics in rats: model verification using a dose-sparing regimen.

Our receptor/gene-mediated model of corticosteroid action was tested and extended by examining the pharmacokinetics/dynamics of multiple low doses vs. a single higher dose of intravenously administered prednisolone in adrenalectomized male Wistar rats. Low-dose rats received 3 bolus doses (5 mg/kg) of prednisolone at 0, 0.5 and 1.0 hr. High-dose animals were given a single 25 mg/kg dose of prednisolone. Both regimens were expected to produce equivalent net responses based on model predictions. Control rats were not dosed. The profiles of free hepatic cytosolic glucocorticoid receptors and the hepatic tyrosine aminotransferase (TAT) enzyme were examined. Plasma prednisolone concentrations showed bi-exponential decline for both doses using pooled animal data. Clearance of total plasma prednisolone was 4.16 and 3.21 L/hr per kg in low- and high-dose groups. Volume of distribution at steady state (approximately 1.50 L/kg) and central volume (approximately 0.6 L/kg) were similar for both groups. Receptor levels from 5-16 hr stabilized at 64% of the 0-hr control value. Receptor and TAT profiles were essentially superimposable for both dosing groups. Our previous model was used to simultaneously describe prednisolone plasma concentrations, hepatic receptors, and TAT activity. The ability of total plasma prednisolone (Cp), corticosteroid binding globulin (CBG)-free plasma prednisolone (CCBG), and free plasma prednisolone (CF) to describe the kinetics/dynamics were examined. The CF values produced optimum fitting of all receptor data. The similarity of the two dosing groups supports the view that appropriately timed doses of a steroid can be used in an optimally efficacious manner by first filling all receptor sites and then replacing steroid as receptors are expected to recycle from nuclear/DNA binding sites as the steroid is eliminated.

Adrenalectomy↗

PubMed2000

Multi-step-ahead prediction using dynamic recurrent neural networks.

A method for the development of empirical predictive models for complex processes is presented. The models are capable of performing accurate multi-step-ahead (MS) predictions, while maintaining acceptable single-step-ahead (SS) prediction accuracy. Such predictors find applications in model predictive controllers and in fault diagnosis systems. The proposed method makes use of dynamic recurrent neural networks in the form of a nonlinear infinite impulse response (IIR) filter. A learning algorithm is presented, which is based on a dynamic gradient descent approach. The effectiveness of the method for accurate MS prediction is tested on an artificial problem and on a complex, open-loop unstable process. Comparative results are presented with polynomial Nonlinear AutoRegressive with eXogeneous (NARX) predictors, and with recurrent networks trained using teacher forcing. Validation studies indicate that excellent generalization is obtained for the range of operational dynamics studied. The research demonstrates that the proposed network architecture and the associated learning algorithm are quite effective in modeling the dynamics of complex processes and performing accurate MS predictions.

Algorithms↗

PubMed1981

Neural control of oral somatic motor function.

The control and regulation of mastication and other basic oral activities require integration by brain stem cranial nerve nuclei of reflex inputs and commands from other central nervous system nuclei. A current conceptual model for understanding control of rhythmic oral motor activity postulates the existence of a central pattern generator, which produces the sequence of movements common to many oral functional activities. According to this model, the output of the generator can be influenced by activity in cranial nerve afferents or modified by signals from other central nuclei. The central control model predicts that the threshold for reflex responses will change during the jaw opening and closing phases of mastication so that the effect of sensory stimulation will vary with the concurrent activity of the muscular and central nervous systems.

Animals↗

PubMedDate not supplied

A reusable perfusion supporting tissue-mimicking material for ultrasound hyperthermia phantoms.

A new ultrasonically and thermodynamically tissue-mimicking material is reported. The material is well suited for use in phantoms for testing ultrasound hyperthermia systems or related predictive models. Controlled convective heat transfer effects, mimicking to some extent perfusive heat transfer in tissues, can be instituted in the material with appropriate fluid sources and sinks. The material consists of closely packed agar spheres varying in diameters from 0.3-3.6 mm. The interstitial space between spheres is filled with 10% n-propanol solution. The material has two practical advantages over the solid-gel-type tissue-mimicking materials. The first advantage is that it allows rapid return of a hyperthermia phantom to thermal equilibrium following a heating test by rapid circulation of the perfusion fluid. The second advantage is that the material is in a "liquid" form. It can be easily siphoned in and out of phantom containers of any geometric shape for different purposes without change in its physical properties. Methods for measuring ultrasonic and thermodynamic properties of the material and the results of the measurements are reported. The physical parameters measured are the intensity attenuation and absorption coefficients, the ultrasonic speed, the thermal conductivity, specific-heat capacity and the mass density. Temperature measurements in a hyperthermia phantom made of the material are also reported.

1-Propanol↗

PubMed1995

Pulmonary microvascular permeability. Responses to high vascular pressure after induction of pacing-induced heart failure in dogs.

The pressure threshold for injury of pulmonary capillaries is approximately 50 to 55 cm H2O in the canine lung, as measured by changes in the filtration coefficient (Kf,c). Since the pulmonary endothelial basement membrane has been observed to thicken in patients with heart failure and pulmonary venous hypertension, we hypothesized that both baseline permeability and the threshold for high-vascular-pressure injury would be altered as a result. Dogs (n = 12) were chronically paced at 245 beats per minute for approximately 4 weeks, then were paced at 225 beats per minute for an additional 3 weeks. Lung lobes from anesthetized paced dogs and additional control dogs (n = 14) were then isolated, ventilated, and perfused with blood. Although vascular resistance was increased nearly threefold and vascular compliance reduced by 50% in the paced group, Kf,c referenced to 1 g blood-free dry weight was no different from control. Despite this lack of difference at normal pulmonary vascular pressures, several significant results were obtained. First, in the paced group there was a significant increase in the threshold for high-vascular-pressure injury: Kf,c measured at pulmonary vascular pressures commonly seen in heart failure (20 to 50 cm H2O) were significantly less in this group compared with control. Model predictions showed that in vivo, this difference in Kf,c would result in a 50% reduction in the amount of water and protein cleared across the pulmonary capillary endothelial barrier in the paced group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗