72 research outputs found
Coupling of kinesin ATP turnover to translocation and microtubule regulation: one engine, many machines
The cycle of ATP turnover is integral to the action of motor proteins. Here we discuss how variation in this cycle leads to variation of function observed amongst members of the kinesin superfamily of microtubule associated motor proteins. Variation in the ATP turnover cycle among superfamily members can tune the characteristic kinesin motor to one of the range of microtubule-based functions performed by kinesins. The speed at which ATP is hydrolysed affects the speed of translocation. The ratio of rate constants of ATP turnover in relation to association and dissociation from the microtubule influence the processivity of translocation. Variation in the rate-limiting step of the cycle can reverse the way in which the motor domain interacts with the microtubule producing non-motile kinesins. Because the ATP turnover cycle is not fully understood for the majority of kinesins, much work remains to show how the kinesin engine functions in such a wide variety of molecular machines
Data-Driven Robust Control for Type 1 Diabetes Under Meal and Exercise Uncertainties
We present a fully closed-loop design for an artificial pancreas (AP) which
regulates the delivery of insulin for the control of Type I diabetes. Our AP
controller operates in a fully automated fashion, without requiring any manual
interaction (e.g. in the form of meal announcements) with the patient. A major
obstacle to achieving closed-loop insulin control is the uncertainty in those
aspects of a patient's daily behavior that significantly affect blood glucose,
especially in relation to meals and physical activity. To handle such
uncertainties, we develop a data-driven robust model-predictive control
framework, where we capture a wide range of individual meal and exercise
patterns using uncertainty sets learned from historical data. These sets are
then used in the controller and state estimator to achieve automated, precise,
and personalized insulin therapy. We provide an extensive in silico evaluation
of our robust AP design, demonstrating the potential of this approach, without
explicit meal announcements, to support high carbohydrate disturbances and to
regulate glucose levels in large clusters of virtual patients learned from
population-wide survey data.Comment: Extended version of paper accepted at the 15th International
Conference on Computational Methods in Systems Biolog
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Response to Comment on Pinsker et al. Randomized Crossover Comparison of Personalized MPC and PID Control Algorithms for the Artificial Pancreas. Diabetes Care 2016;39:1135–1142
Safety and Performance of the Omnipod Hybrid Closed-Loop System in Adults, Adolescents, and Children with Type 1 Diabetes over 5 Days under Free-Living Conditions
Background: The objective of this study was to assess the safety and performance of the Omnipod\uae personalized model predictive control (MPC) algorithm in adults, adolescents, and children aged 656 years with type 1 diabetes (T1D) under free-living conditions using an investigational device. Materials and Methods: A 96-h hybrid closed-loop (HCL) study was conducted in a supervised hotel/rental home setting following a 7-day outpatient standard therapy (ST) phase. Eligible participants were aged 6-65 years with A1C <10.0% using insulin pump therapy or multiple daily injections. Meals during HCL were unrestricted, with boluses administered per usual routine. There was daily physical activity. The primary endpoints were percentage of time with sensor glucose <70 and 65250 mg/dL. Results: Participants were 11 adults, 10 adolescents, and 15 children aged (mean \ub1 standard deviation) 28.8 \ub1 7.9, 14.3 \ub1 1.3, and 9.9 \ub1 1.0 years, respectively. Percentage time 65250 mg/dL during HCL was 4.5% \ub1 4.2%, 3.5% \ub1 5.0%, and 8.6% \ub1 8.8% per respective age group, a 1.6-, 3.4-, and 2.0-fold reduction compared to ST (P = 0.1, P = 0.02, and P = 0.03). Percentage time <70 mg/dL during HCL was 1.9% \ub1 1.3%, 2.5% \ub1 2.0%, and 2.2% \ub1 1.9%, a statistically significant decrease in adults when compared to ST (P = 0.005, P = 0.3, and P = 0.3). Percentage time 70-180 mg/dL increased during HCL compared to ST, reaching significance for adolescents and children: HCL 73.7% \ub1 7.5% vs. ST 68.0% \ub1 15.6% for adults (P = 0.08), HCL 79.0% \ub1 12.6% vs. ST 60.6% \ub1 13.4% for adolescents (P = 0.01), and HCL 69.2% \ub1 13.5% vs. ST 54.9% \ub1 12.9% for children (P = 0.003). Conclusions: The Omnipod personalized MPC algorithm was safe and performed well over 5 days and 4 nights of use by a cohort of participants ranging from youth aged 656 years to adults with T1D under supervised free-living conditions with challenges, including daily physical activity and unrestricted meals
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