Afroza Shirin

Isaac S. Klickstein, Afroza Shirin, Francesco Sorrentino

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.

Afroza Shirin, Isaac Klickstein, Song Feng et al.

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.

Afroza Shirin, Fabio Della Rossa, Isaac Klickstein et al.

The Glucose-Insulin-Glucagon nonlinear model [1-4] 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 PSOPT. 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.

Ishan Kafle, Sudarshan Bartaula, Afroza Shirin et al.

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.

Md. Shafiqul Islam, Afroza Shirin

The aim of this paper is to find the numerical solutions of the second order linear and nonlinear differential equations with Dirichlet, Neumann and Robin boundary conditions. We use the Bernoulli polynomials as linear combination to the approximate solutions of 2nd order boundary value problems. Here the Bernoulli polynomials over the interval [0, 1] are chosen as trial functions so that care has been taken to satisfy the corresponding homogeneous form of the Dirichlet boundary conditions in the Galerkin weighted residual method. In addition to that the given differential equation over arbitrary finite domain [a, b] and the boundary conditions are converted into its equivalent form over the interval [0, 1]. All the formulas are verified by considering numerical examples. The approximate solutions are compared with the exact solutions, and also with the solutions of the existing methods. A reliable good accuracy is obtained in all cases.

Chad Nathe, Enrico Del Frate, Thomas Carroll et al.

The topology of a network associated with a reservoir computer is often taken so that the connectivity and the weights are chosen randomly. Optimization is hardly considered as the parameter space is typically too large. Here we investigate this problem for a class of reservoir computers for which we obtain a decomposition of the reservoir dynamics into modes, which can be computed independently of one another. Each mode depends on an eigenvalue of the network adjacency matrix. We then take a parametric approach in which the eigenvalues are parameters that can be appropriately designed and optimized. In addition, we introduce the application of a time shift to each individual mode. We show that manipulations of the individual modes, either in terms of the eigenvalues or the time shifts, can lead to dramatic reductions in the training error.