Full Closed-Loop Tests for the Relay Feedback Autotuning of Stable, Integrating, and Unstable Processes.

The relay (on-off) controller can stabilize wide ranges of processes including open-loop stable, integrating, and unstable processes, producing sustained oscillations. For improved proportional-integral-derivative controller tunings, methods to find process models with mixed closed-loop tests of relay feedback and proportional-derivative (PD) controllers are proposed. For unknown processes with arbitrary initial states, relay feedback tests are first applied and, after cyclic steady states are obtained, PD controllers or other relay feedback tests with set point changes are followed. This full closed-loop operation is desirable for integrating and unstable processes and will be useful even for stable processes when processes are far from their desirable operating points. Refined methods to find exact frequency responses of processes from initial and final cyclic steady states are derived. Whole relay feedback responses need not be saved. Several integrals at the relay switching times are used without iterative tests or computations.

Smart Manufacturing.

Historic manufacturing enterprises based on vertically optimized companies, practices, market share, and competitiveness are giving way to enterprises that are responsive across an entire value chain to demand dynamic markets and customized product value adds; increased expectations for environmental sustainability, reduced energy usage, and zero incidents; and faster technology and product adoption. Agile innovation and manufacturing combined with radically increased productivity become engines for competitiveness and reinvestment, not simply for decreased cost. A focus on agility, productivity, energy, and environmental sustainability produces opportunities that are far beyond reducing market volatility. Agility directly impacts innovation, time-to-market, and faster, broader exploration of the trade space. These changes, the forces driving them, and new network-based information technologies offering unprecedented insights and analysis are motivating the advent of smart manufacturing and new information technology infrastructure for manufacturing.

Modeling of tumor growth undergoing virotherapy.

Tumor growth models subject to virotherapy treatment are analyzed and compared in this paper. Tumor growth conditions are obtained for each model type based on the virus infection rate and immune suppressive drug delivery. Equilibrium conditions resulted into quadratic functions for which the tumor radius remained constant during virotherapy. An irrigation tumor model for virotherapy treatment was also proposed. This model consists of irrigation layers distributed radially along the tumor and attached to a common blood circulation compartment. The irrigation model has similar dynamic and steady state characteristics to the diffusion model, which has been supported by experimental results. The irrigation model considers the immune system cell generation and consumption outside the tumor boundary but inside the blood circulation compartment. These characteristics provide a great potential for advanced cancer treatment applications because therapy dose delivery and immune system measurements can be made at the blood compartment level of the irrigation model.

Effectiveness of Intravenous Infusion Algorithms for Glucose Control in Diabetic Patients Using Different Simulation Models.

The effectiveness of closed-loop insulin infusion algorithms is assessed for three different mathematical models describing insulin and glucose dynamics within a Type I diabetes patient. Simulations are performed to assess the effectiveness of proportional plus integral plus derivative (PID) control, feedforward control, and a physiologically-based control system with respect to maintaining normal glucose levels during a meal and during exercise. Control effectiveness is assessed by comparing the simulated response to a simulation of a healthy patient during both a meal and exercise and establishing maximum and minimum glucose levels and insulin infusion levels, as well as maximum duration of hyperglycemia. Controller effectiveness is assessed within the minimal model, the Sorensen model, and the Hovorka model. Results showed that no type of control was able to maintain normal conditions when simulations were performed using the minimal model. For both the Sorensen model and the Hovorka model, proportional control was sufficient to maintain normal glucose levels. Given published clinical data showing the ineffectiveness of PID control in patients, the work demonstrates that controller success based on simulation results can be misleading, and that future work should focus on addressing the model discrepancies.

Parameter set uniqueness and confidence limits in model identification of insulin transport models from simulation data.

BACKGROUND: The use of patient models describing the dynamics of glucose, insulin, and possibly other metabolic species associated with glucose regulation allows diabetes researchers to gain insights regarding novel therapies via simulation. However, such models are only useful when model parameters are effectively estimated with patient data. METHODS: The use of least squares to effectively estimate model parameters from simulation data was investigated by observing factors that influence the accuracy of estimates for the model parameters from a data set generated using a model with known parameters. An intravenous insulin pharmacokinetic model was used to generate the insulin response of a patient with type 1 diabetes mellitus to a series of step changes in the insulin infusion rate from an external insulin pump. The effects of using user-defined gradient and Hessian calculations on both parameter estimations and the 95% confidence limits of the estimated parameter sets were investigated. RESULTS: Estimations performed by either solver without user-supplied quantities were highly dependent on the initial guess of the parameter set, with relative confidence limits greater than +/-100%. The use of user-defined quantities allowed the one-compartment model parameters to be effectively estimated. While the two-compartment model parameter estimation still depended on the initial parameter set specification, confidence limits were decreased, and all fits to simulation data were very good. CONCLUSIONS: The use of user-defined gradients and Hessian matrices results in more accurate parameter estimations for insulin transport models. Improved estimation could result in more accurate simulations for use in glucose control system design.

In Vivo Simulations of the Intravenous Dynamics of Submicron Particles of pH-Responsive Cationic Hydrogels in Diabetic Patients.

A mathematical model describing glucose-dependent pH swelling and insulin release is developed for pH-sensitive cationic hydrogels in which glucose oxidase and catalase have been immobilized and insulin imbibed. Glucose based swelling and insulin release are simulated for intravenously injected particles at various design conditions. The effects of particle size, the number of injected particles, insulin loading, enzyme loading, monomer functional group loading and pK(a), and hydrogel crosslinking ratio on insulin release and glucose sensitivity are investigated in order to optimally design the device for use. Increased insulin infusion is shown to result from increasing the number of circulating gels, increasing the collapsed particle size, or by decreasing the crosslinking ratio of the system. Release duration is shown to be dependent only upon the particle size and the achievable diffusion coefficient of the system. Glucose sensitivity, as measured by gluconic acid production and by the system pH, are functions of glucose oxidase loading and the concentration and pK(a) of the monomer used in the hydrogel.The necessarily submicron particle size results in very rapid device insulin depletion. When the device is designed without considering constraints, the resulting release profile resembles that of an on/off switching mechanism. Future work will focus on simulations of swelling and release when the device is implanted in an alternative administration site.

The future of open- and closed-loop insulin delivery systems.

We have analysed several aspects of insulin-dependent diabetes mellitus, including the glucose metabolic system, diabetes complications, and previous and ongoing research aimed at controlling glucose in diabetic patients. An expert review of various models and control algorithms developed for the glucose homeostasis system is presented, along with an analysis of research towards the development of a polymeric insulin infusion system. Recommendations for future directions in creating a true closed-loop glucose control system are presented, including the development of multivariable models and control systems to more accurately describe and control the multi-metabolite, multi-hormonal system, as well as in-vivo assessments of implicit closed-loop control systems.

Nitrogen removal in laboratory model leachfields with organic-rich layers.

Septic system leachfields can release dissolved nitrogen in the form of nitrate into ground water, presenting a significant source of pollution. Low cost, passive modifications, which increase N removal in traditional leachfields, could substantially reduce the overall impact on ground water resources. Bench-scale laboratory models were constructed to evaluate the effect of placing an organic layer below the leachfield on total N removal. The organic layer provides a carbon source for denitrification. Column units representing septic leachfields were constructed with sawdust-native soil organic layers placed 0.45 m below the influent line and with thicknesses of 0.0, 0.3, 0.6, and 0.9 m. Using a synthetic septic tank effluent, NO(3)-N concentrations at 3.8 m below the influent line were consistently below 1 mg L(-1) during 10 months of operation compared with a NO(3)-N concentration of nearly 12 mg L(-1) in the control column. The average total N removal increased from 31% without the organic layer to 67% with the organic layer. Total N removal appeared limited by the extent of organic N oxidation and nitrification in the 0.45-m aerobic zone. Design modifications targeted at improving nitrification above the organic layer may further increase total N removal. Increased organic layer thicknesses from 0.3 m to 0.9 m did not significantly improve average total N removal, but caused a shift in residual nitrogen from organic N to ammonia N. Results indicate that addition of a layer of carbon source material at least 0.3 m thick below a standard leachfield substantially improves total N removal.