Controller design faces a trade-off between robustness and performance, and the reliability of linear controllers has caused many practitioners to focus on the former. However, there is renewed interest in improving system performance to deal with growing energy constraints. This paper describes a learning-based model predictive control (LBMPC) scheme that provides deterministic guarantees on robustness, while statistical identification tools are used to identify richer models of the system in order to improve performance; the benefits of this framework are that it handles state and input constraints, optimizes system performance with respect to a cost function, and can be designed to use a wide variety of parametric or nonparametric statistical tools. The main insight of LBMPC is that safety and performance can be decoupled under reasonable conditions in an optimization framework by maintaining two models of the system. The first is an approximate model with bounds on its uncertainty, and the second model is updated by statistical methods. LBMPC improves performance by choosing inputs that minimize a cost subject to the learned dynamics, and it ensures safety and robustness by checking whether these same inputs keep the approximate model stable when it is subject to uncertainty. Furthermore, we show that if the system is sufficiently excited, then the LBMPC control action probabilistically converges to that of an MPC computed using the true dynamics.

Engineered metabolic pathways often suffer from flux imbalances that can overburden the cell and accumulate intermediate metabolites, resulting in reduced product titers. One way to alleviate such imbalances is to adjust the expression levels of the constituent enzymes using a combinatorial expression library. Typically, this approach requires high-throughput assays, which are unfortunately unavailable for the vast majority of desirable target compounds. To address this, we applied regression modeling to enable expression optimization using only a small number of measurements. We characterized a set of constitutive promoters in Saccharomyces cerevisiae that spanned a wide range of expression and maintained their relative strengths irrespective of the coding sequence. We used a standardized assembly strategy to construct a combinatorial library and express for the first time in yeast the five-enzyme violacein biosynthetic pathway. We trained a regression model on a random sample comprising 3% of the total library, and then used that model to predict genotypes that would preferentially produce each of the products in this highly branched pathway. This generalizable method should prove useful in engineering new pathways for the sustainable production of small molecules.

Intratumoral heterogeneity in cancers arises from genomic instability and epigenomic plasticity and is associated with resistance to cytotoxic and targeted therapies. We show here that cell-state heterogeneity, defined by differentiation-state marker expression, is high in triple-negative and basal-like breast cancer subtypes, and that drug tolerant persister (DTP) cell populations with altered marker expression emerge during treatment with a wide range of pathway-targeted therapeutic compounds. We show that MEK and PI3K/mTOR inhibitor-driven DTP states arise through distinct cell-state transitions rather than by Darwinian selection of preexisting subpopulations, and that these transitions involve dynamic remodeling of open chromatin architecture. Increased activity of many chromatin modifier enzymes, including BRD4, is observed in DTP cells. Co-treatment with the PI3K/mTOR inhibitor BEZ235 and the BET inhibitor JQ1 prevents changes to the open chromatin architecture, inhibits the acquisition of a DTP state, and results in robust cell death in vitro and xenograft regression in vivo.

Inverse optimization refers to the inference of unknown parameters of an optimization problem based on knowledge of its optimal solutions. This paper considers inverse optimization in the setting where measurements of the optimal solutions of a convex optimization problem are corrupted by noise. We first provide a formulation for inverse optimization and prove it to be NP-hard. In contrast to existing methods, we show that the parameter estimates produced by our formulation are statistically consistent. Our approach involves combining a new duality-based reformulation for bilevel programs with a regularization scheme that smooths discontinuities in the formulation. Using epi-convergence theory, we show the regularization parameter can be adjusted to approximate the original inverse optimization problem to arbitrary accuracy, which we use to prove our consistency results. Next, we propose two solution algorithms based on our duality-based formulation. The first is an enumeration algorithm that is applicable to settings where the dimensionality of the parameter space is modest, and the second is a semiparametric approach that combines nonparametric statistics with a modified version of our formulation. These numerical algorithms are shown to maintain the statistical consistency of the underlying formulation. Lastly, using both synthetic and real data, we demonstrate that our approach performs competitively when compared with existing heuristics.

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In this paper, we present details of the real time implementation onboard a quadrotor helicopter of learningbased model predictive control (LBMPC). LBMPC rigorously combines statistical learning with control engineering, while providing levels of guarantees about safety, robustness, and convergence. Experimental results show that LBMPC can learn physically based updates to an initial model, and how as a result LBMPC improves transient response performance. We demonstrate robustness to mis-learning. Finally, we show the use of LBMPC in an integrated robotic task demonstrationThe quadrotor is used to catch a ball thrown with an a priori unknown trajectory.

This cross-sectional study of National Health and Nutrition Examination Survey data sets evaluates the feasibility of reidentifying accelerometer-measured physical activity data that have had protected health information removed, using support vector machines and random forest methods from machine learning.

BackgroundGrowing evidence shows that fixed, nonpersonalized daily step goals can discourage individuals, resulting in unchanged or even reduced physical activity.ObjectiveThe aim of this randomized controlled trial (RCT) was to evaluate the efficacy of an automated mobile phone–based personalized and adaptive goal-setting intervention using machine learning as compared with an active control with steady daily step goals of 10,000.MethodsIn this 10-week RCT, 64 participants were recruited via email announcements and were required to attend an initial in-person session. The participants were randomized into either the intervention or active control group with a one-to-one ratio after a run-in period for data collection. A study-developed mobile phone app (which delivers daily step goals using push notifications and allows real-time physical activity monitoring) was installed on each participant’s mobile phone, and participants were asked to keep their phone in a pocket throughout the entire day. Through the app, the intervention group received fully automated adaptively personalized daily step goals, and the control group received constant step goals of 10,000 steps per day. Daily step count was objectively measured by the study-developed mobile phone app.ResultsThe mean (SD) age of participants was 41.1 (11.3) years, and 83% (53/64) of participants were female. The baseline demographics between the 2 groups were similar (P>.05). Participants in the intervention group (n=34) had a decrease in mean (SD) daily step count of 390 (490) steps between run-in and 10 weeks, compared with a decrease of 1350 (420) steps among control participants (n=30; P=.03). The net difference in daily steps between the groups was 960 steps (95% CI 90-1830 steps). Both groups had a decrease in daily step count between run-in and 10 weeks because interventions were also provided during run-in and no natural baseline was collected.ConclusionsThe results showed the short-term efficacy of this intervention, which should be formally evaluated in a full-scale RCT with a longer follow-up period.Trial RegistrationClinicalTrials.gov: NCT02886871; https://clinicaltrials.gov/ct2/show/NCT02886871 (Archived by WebCite at http://www.webcitation.org/6wM1Be1Ng).