Data-driven optimized control of the COVID-19 epidemics.

Optimizing the impact on the economy of control strategies aiming at containing the spread of COVID-19 is a critical challenge. We use daily new case counts of COVID-19 patients reported by local health administrations from different Metropolitan Statistical Areas (MSAs) within the US to parametrize a model that well describes the propagation of the disease in each area. We then introduce a time-varying control input that represents the level of social distancing imposed on the population of a given area and solve an optimal control problem with the goal of minimizing the impact of social distancing on the economy in the presence of relevant constraints, such as a desired level of suppression for the epidemics at a terminal time. We find that with the exception of the initial time and of the final time, the optimal control input is well approximated by a constant, specific to each area, which contrasts with the implemented system of reopening 'in phases'. For all the areas considered, this optimal level corresponds to stricter social distancing than the level estimated from data. Proper selection of the time period for application of the control action optimally is important: depending on the particular MSA this period should be either short or long or intermediate. We also consider the case that the transmissibility increases in time (due e.g. to increasingly colder weather), for which we find that the optimal control solution yields progressively stricter measures of social distancing. We finally compute the optimal control solution for a model modified to incorporate the effects of vaccinations on the population and we see that depending on a number of factors, social distancing measures could be optimally reduced during the period over which vaccines are administered to the population.

Reservoir computing with random and optimized time-shifts.

We investigate the effects of application of random time-shifts to the readouts of a reservoir computer in terms of both accuracy (training error) and performance (testing error). For different choices of the reservoir parameters and different "tasks," we observe a substantial improvement in both accuracy and performance. We then develop a simple but effective technique to optimize the choice of the time-shifts, which we successfully test in numerical experiments.

Symmetries and cluster synchronization in multilayer networks.

Real-world systems in epidemiology, social sciences, power transportation, economics and engineering are often described as multilayer networks. Here we first define and compute the symmetries of multilayer networks, and then study the emergence of cluster synchronization in these networks. We distinguish between independent layer symmetries, which occur in one layer and are independent of the other layers, and dependent layer symmetries, which involve nodes in different layers. We study stability of the cluster synchronous solution by decoupling the problem into a number of independent blocks and assessing stability of each block through a Master Stability Function. We see that blocks associated with dependent layer symmetries have a different structure to the other blocks, which affects the stability of clusters associated with these symmetries. Finally, we validate the theory in a fully analog experiment in which seven electronic oscillators of three kinds are connected with two kinds of coupling.

Stability analysis of reservoir computers dynamics via Lyapunov functions.

A Lyapunov design method is used to analyze the nonlinear stability of a generic reservoir computer for both the cases of continuous-time and discrete-time dynamics. Using this method, for a given nonlinear reservoir computer, a radial region of stability around a fixed point is analytically determined. We see that the training error of the reservoir computer is lower in the region where the analysis predicts global stability but is also affected by the particular choice of the individual dynamics for the reservoir systems. For the case that the dynamics is polynomial, it appears to be important for the polynomial to have nonzero coefficients corresponding to at least one odd power (e.g., linear term) and one even power (e.g., quadratic term).

Optimal regulation of blood glucose level in Type I diabetes using insulin and glucagon.

The Glucose-Insulin-Glucagon nonlinear model accurately describes how the body responds to exogenously supplied insulin and glucagon in patients affected by Type I diabetes. Based on this model, we design infusion rates of either insulin (monotherapy) or insulin and glucagon (dual therapy) that can optimally maintain the blood glucose level within desired limits after consumption of a meal and prevent the onset of both hypoglycemia and hyperglycemia. This problem is formulated as a nonlinear optimal control problem, which we solve using the numerical optimal control package [Formula: see text]. Interestingly, in the case of monotherapy, we find the optimal solution is close to the standard method of insulin based glucose regulation, which is to assume a variable amount of insulin half an hour before each meal. We also find that the optimal dual therapy (that uses both insulin and glucagon) is better able to regulate glucose as compared to using insulin alone. We also propose an ad-hoc rule for both the dosage and the time of delivery of insulin and glucagon.

Prediction of Optimal Drug Schedules for Controlling Autophagy.

The effects of molecularly targeted drug perturbations on cellular activities and fates are difficult to predict using intuition alone because of the complex behaviors of cellular regulatory networks. An approach to overcoming this problem is to develop mathematical models for predicting drug effects. Such an approach beckons for co-development of computational methods for extracting insights useful for guiding therapy selection and optimizing drug scheduling. Here, we present and evaluate a generalizable strategy for identifying drug dosing schedules that minimize the amount of drug needed to achieve sustained suppression or elevation of an important cellular activity/process, the recycling of cytoplasmic contents through (macro)autophagy. Therapeutic targeting of autophagy is currently being evaluated in diverse clinical trials but without the benefit of a control engineering perspective. Using a nonlinear ordinary differential equation (ODE) model that accounts for activating and inhibiting influences among protein and lipid kinases that regulate autophagy (MTORC1, ULK1, AMPK and VPS34) and methods guaranteed to find locally optimal control strategies, we find optimal drug dosing schedules (open-loop controllers) for each of six classes of drugs and drug pairs. Our approach is generalizable to designing monotherapy and multi therapy drug schedules that affect different cell signaling networks of interest.

Optimal control of networks in the presence of attackers and defenders.

We consider the problem of a dynamical network whose dynamics is subject to external perturbations ("attacks") locally applied at a subset of the network nodes. We assume that the network has an ability to defend itself against attacks with appropriate countermeasures, which we model as actuators located at (another) subset of the network nodes. We derive the optimal defense strategy as an optimal control problem. We see that the network topology as well as the distribution of attackers and defenders over the network affect the optimal control solution and the minimum control energy. We study the optimal control defense strategy for several network topologies, including chain networks, star networks, ring networks, and scale free networks.

Optimal control of complex networks: Balancing accuracy and energy of the control action.

Recently, it has been shown that the control energy required to control a large dynamical complex network is prohibitively large when there are only a few control inputs. Most methods to reduce the control energy have focused on where, in the network, to place additional control inputs. We also have seen that by controlling the states of a subset of the nodes of a network, rather than the state of every node, the required energy to control a portion of the network can be reduced substantially. The energy requirements exponentially decay with the number of target nodes, suggesting that large networks can be controlled by a relatively small number of inputs as long as the target set is appropriately sized. Here, we see that the control energy can be reduced even more if the prescribed final states are not satisfied strictly. We introduce a new control strategy called balanced control for which we set our objective function as a convex combination of two competitive terms: (i) the distance between the output final states at a given final time and given prescribed states and (ii) the total control energy expenditure over the given time period. We also see that the required energy for the optimal balanced control problem approximates the required energy for the optimal target control problem when the coefficient of the second term is very small. We validate our conclusions in model and real networks regardless of system size, energy restrictions, state restrictions, input node choices, and target node choices.

Energy scaling of targeted optimal control of complex networks.

Recently it has been shown that the control energy required to control a dynamical complex network is prohibitively large when there are only a few control inputs. Most methods to reduce the control energy have focused on where, in the network, to place additional control inputs. Here, in contrast, we show that by controlling the states of a subset of the nodes of a network, rather than the state of every node, while holding the number of control signals constant, the required energy to control a portion of the network can be reduced substantially. The energy requirements exponentially decay with the number of target nodes, suggesting that large networks can be controlled by a relatively small number of inputs as long as the target set is appropriately sized. We validate our conclusions in model and real networks to arrive at an energy scaling law to better design control objectives regardless of system size, energy restrictions, state restrictions, input node choices and target node choices.

Locally Optimal Control of Complex Networks.

It has recently been shown that the minimum energy solution of the control problem for a linear system produces a control trajectory that is nonlocal. An issue then arises when the dynamics represents a linearization of the underlying nonlinear dynamics of the system where the linearization is only valid in a local region of the state space. Here we provide a solution to the problem of optimally controlling a linearized system by deriving a time-varying set that represents all possible control trajectories parametrized by time and energy. As long as the control action terminus is defined within this set, the control trajectory is guaranteed to be local. If the desired terminus of the control action is far from the initial state, a series of local control actions can be performed in series, relinearizing the dynamics at each new position.