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• Development of cell-free transcription-translation systems in three soil Pseudomonads  + (In vitro transcription-translation (TX-TL) … In vitro transcription-translation (TX-TL) can enable faster engineering of biological systems. This speed-up can be significant, especially in difficult-to-transform chassis. This work shows the successful development of TX-TL systems using three soil-derived wild-type Pseudomonads known to promote plant growth: Pseudomonas synxantha, Pseudomonas chlororaphis, and Pseudomonas aureofaciens. One, P. synxantha, was further characterized. A lysate test of P. synxantha showed a maximum protein yield of 2.5 μM at 125 proteins per DNA template and a maximum protein synthesis rate of 20 nM/min. A set of different constitutive promoters driving mNeonGreen expression were tested in TX-TL and integrated into the genome, showing similar normalized strengths for in vivo and in vitro fluorescence. This correspondence between the TX-TL derived promoter strength and the in vivo promoter strength indicates these lysate-based cell-free systems can be used to characterize and engineer biological parts without genome integration, enabling a faster designbuild-test cycle. enabling a faster designbuild-test cycle.)
• Failure-Tolerant Contract-Based Design of an Automated Valet Parking System using a Directive-Response Architecture  + (Increased complexity in cyber-physical sys … Increased complexity in cyber-physical systems calls for modular system design methodologies that guarantee correct and reliable behavior, both in normal operations and in the presence of failures. This paper aims to extend the contract-based design approach using a directive-response architecture to enable reactivity to failure scenarios. The architecture is demonstrated on a modular automated valet parking (AVP) system. The contracts for the different components in the AVP system are explicitly defined, implemented, and validated against a Python implementation.validated against a Python implementation.)
• Bio-Inspired Visuomotor Convergence in Navigation and Flight Control Systems  + (Insects exhibit incredibly robust closed l … Insects exhibit incredibly robust closed loop flight dynamics in the face of uncertainties. </br>A fundamental principle contributing to this unparalleled behavior is rapid processing and </br>convergence of visual sensory information to flight motor commands via spatial wide-field </br>integration, accomplished by retinal motion pattern sensitive interneurons (LPTCs) in the </br>lobula plate portion of the visual ganglia. Within a control-theoretic framework, an inner </br>product model for wide-field integration of retinal image flow is developed, representing the </br>spatial decompositions performed by LPTCs in the insect visuomotor system. A rigorous </br>characterization of the information available from this visuomotor convergence technique </br>for motion within environments exhibiting non-omogeneous spatial distributions is performed, establishing the connection between retinal motion sensitivity shape and closed </br>loop behavior. The proposed output feedback methodology is shown to be sufficient to give </br>rise to experimentally observed insect navigational heuristics, including forward speed regulation, obstacle avoidance, hovering, and terrain following behaviors. Hence, extraction of </br>global retinal motion cues through computationally efficient wide-field integration process- </br>ing provides a novel and promising methodology for utilizing visual sensory information in </br>autonomous robotic navigation and flight control applications.avigation and flight control applications.)
• Sensorimotor Convergence in Visual Navigation and Flight Control Systems  + (Insects exhibit unparalleled and incredibl … Insects exhibit unparalleled and incredibly robust flight dynamics in</br>the face of uncertainties. A fundamental principle contributing to this amazing</br>behavior is rapid processing and convergence of visual sensory information to flight</br>motor commands via spatial wide-field integration. Within the control-theoretic</br>framework presented here, a model for wide-field integration of retinal image flow</br>is developed which explains how various image flow kernels correspond to feedback</br>terms that stabilize the different modes of planar fiight. It is also demonstrated that</br>the proposed output feedback methodology is su±cient to explain experimentally</br>observed navigational heuristics as the centering and forward speed regulation</br>responses exhibited by honeybees.gulation responses exhibited by honeybees.)
• A Control-Oriented Analysis of Bio-Inspired Visuomotor Convergence  + (Insects exhibit unparalleled and incredibl … Insects exhibit unparalleled and incredibly robust </br>flight dynamics in the face of uncertainties. A fundamental principle contributing to this amazing behavior is rapid processing </br>and convergence of visual sensory information to flight motor </br>commands via spatial wide-field integration, accomplished by </br>motion pattern sensitive interneurons in the lobula plate portion </br>of the visual ganglia. Within a control-theoretic framework, a </br>model for wide-field integration of retinal image flow is developed, establishing the connection between image flow kernels </br>(retinal motion pattern sensitivities) and the feedback terms </br>they represent. It is demonstrated that the proposed output </br>feedback methodology is sufficient to give rise to experimentally </br>observed navigational heuristics as the centering and forward </br>speed regulation responses exhibited by honeybees.gulation responses exhibited by honeybees.)
• Guidelines for Designing the Antithetic Feedback Motif  + (Integral control is commonly used in mecha … Integral control is commonly used in mechanical and electrical systems to ensure perfect adaptation. A proposed design of integral control for synthetic biological systems employs the sequestration of two biochemical controller species. The unbound amount of controller species captures the integral of the error between the current and the desired state of the system. However, implementing integral control inside bacterial cells using sequestration feedback has been challenging due to the controller molecules being degraded and diluted. Furthermore, integral control can only be achieved under stability conditions that not all sequestration feedback networks fulfill. In this work, we give guidelines for ensuring stability and good performance (small steady-state error) in sequestration feedback networks. Our guidelines provide simple tuning options to obtain a flexible and practical biological implementation of sequestration feedback control. Using tools and metrics from control theory, we pave the path for the systematic design of synthetic biological systems.ic design of synthetic biological systems.)
• A 65nm CMOS Living-Cell Dynamic Fluorescence Sensor with 1.05fA Sensitivity at 600/700nm Wavelengths  + (Integrated, low-cost and miniaturized devi … Integrated, low-cost and miniaturized devices that can detect clinically relevant biomarkers are crucial for the growing field of precision medicine as they can enable point-of-care diagnosis, continuous health monitoring and closed-loop drug delivery. Fluorescence (FL) sensing is known to be one of the most reliable, sensitive, and widely adopted sensing modality for many biomarkers. However, detecting the weak FL signal requires complex optical setups, especially narrowband optical filters to block the strong excitation (EX) light. Prior efforts to miniaturize and implement FL sensing in CMOS technologies have been limited to on-chip high-pass filters using dense vertical waveguide arrays. More importantly, the reported wavelength range of 800nm in prior work is not compatible with most of the commonly used fluorescent proteins that work with living cells. Luminescence is another mechanism for detecting biomarkers that does not require an EX source and optical filtering. However, there are limited number of luminescence proteins, and it is not feasible to use them in a closed-loop system since they can interfere with optogenetic control integration.fere with optogenetic control integration.)
• Systems Level Model of Dietary Effects on Cognition via the Microbiome-Gut-Brain Axis  + (Intercommunication of the microbiome-gut-b … Intercommunication of the microbiome-gut-brain axis occurs through various signaling pathways including the vagus nerve, immune system, endocrine/paracrine, and bacteria-derived metabolites. But how these pathways integrate to influence cognition remains undefined. In this paper, we create a systems level mathematical framework comprised of interconnected organ-level dynamical subsystems to increase conceptual understanding of how these subsystems contribute to cognitive performance. With this framework we propose that control of hippocampal long-term potentiation (hypothesized to correlate with cognitive performance) is influenced by inter- organ signaling with diet as the external control input. Specifically, diet can influence synaptic strength (LTP) homeostatic conditions necessary for learning. The proposed model provides new qualitative information about the functional relationship between diet and output cognitive performance. The results can give insight for optimization of cognitive performance via diet in experimental animal models.ce via diet in experimental animal models.)
• A Scalable Formulation for Engineering Combination Therapies for Evolutionary Dynamics of Disease  + (It has been shown that optimal controller … It has been shown that optimal controller synthesis for positive systems can be formulated as a linear program. Leveraging these results, we propose a scalable iterative algo- rithm for the systematic design of sparse, small gain feedback strategies that stabilize the evolutionary dynamics of a generic disease model. We achieve the desired feedback structure by augmenting the optimization problems with `1 and `2 regular- ization terms, and illustrate our method on an example inspired by an experimental study aimed at finding appropriate HIV neutralizing antibody therapy combinations in the presence of escape mutants.nations in the presence of escape mutants.)
• Stochastic Gene Expression in Single Gene Oscillator Variants  + (It is infeasible to understand all dynamic … It is infeasible to understand all dynamics in cell, but we can aim to understand the impact of design choices under our control. Here we consider a single gene oscillator as a case study to understand the influence of DNA copy number and repressor choice on the resulting dynamics. We first switch the repressor in the oscillator from the originally published lacI to treRL, a chimeric repressor with a lacI DNA binding domain that is inducible by trehalose. This slightly modified system produces faster and more regular oscillations than the original lacI oscillator. We then compare the treRL oscillator at three different DNA copy numbers. The period and amplitude of oscillations increases as the copy number is decreased. We cannot explain the change in period with differ- ential equation models without changing delays or degradation rates. The correlation and phase coherence between daughter cells after cell division also tend to fall off faster for the lower copy oscillator variants. These results suggest that lower copy number variants of our single gene oscillator produce more synchronized oscillations.or produce more synchronized oscillations.)
• To Drop or Not to Drop: Design Principles for Kalman Filtering Over Wireless Fading Channels  + (It is the general assumption that in estim … It is the general assumption that in estimation and control over wireless links, the receiver should drop any erroneous packets. While this approach is appropriate for non real-time data-network applications, it can result in instability and loss of performance in networked control systems. In this technical note we consider estimation of a multiple-input multiple-output dynamical system over a mobile fading communication channel using a Kalman filter. We show that the communication protocols suitable for other already-existing applications like data networks may not be entirely applicable for estimation and control of a rapidly changing dynamical system. We then develop new design paradigms in terms of handling noisy packets for such delay-sensitive applications. We reformulate the estimation problem to include the impact of stochastic communication noise in the erroneous packets. We prove that, in the absence of a permanent cross-layer information path, packet drop should be designed to balance information loss and communication noise in order to optimize the performance.oise in order to optimize the performance.)
• The Effect of Compositional Context on Synthetic Gene Networks  + (It is well known that synthetic gene expre … It is well known that synthetic gene expression is highly sensitive to how genetic elements (promoter structure, spacing regions between promoter and coding sequences, ribosome binding sites, etc.) are spatially configured. An important topic that has received far less attention is how the compositional context, or spatial arrangement, of entire genes within a synthetic gene network affects their individual expression levels. In this paper we show, both quantitatively and qualitatively, that compositional context significantly alters transcription levels in synthetic gene networks. We demonstrate that key characteristics of gene induction, such as ultra-sensitivity and dynamic range, strongly depend on compositional context. We postulate that supercoiling can be used to explain this interference and validate this hypothesis through modeling and a series of in vitro supercoiling relaxation experiments. This compositional interference enables a novel form of feedback in synthetic gene networks. We illustrate the use of this feedback by redesigning the toggle switch to incorporate compositional context. We show the context-optimized toggle switch has improved threshold detection and memory properties.threshold detection and memory properties.)
• Configuration Flatness of Lagrangian Systems Underactuated by One Control  + (Lagrangian control systems that are differ … Lagrangian control systems that are differentially flat with flat outputs that only</br>depend on configuration variables are said to be configuration flat. We provide a complete</br>characterisation of configuration flatness for systems with $n$ degrees of freedom and</br>$n-1$ controls whose range of control forces only depends on configuration but not on</br>velocity and whose Lagrangian has the form of kinetic energy minus potential. The method</br>presented allows us to determine if such a system is configuration flat and, if so</br>provides a constructive method for finding all possible configuration flat outputs. Our</br>characterisation relates configuration flatness to Riemannian geometry. We illustrate the</br>method by two examples. We illustrate the method by two examples.)
• Layered Feedback Control Overcomes Performance Trade-Off in Synthetic Biomolecular Networks  + (Layered feedback is an optimization strate … Layered feedback is an optimization strategy in feedback control designs widely used in electrical and mechanical engineering. Layered control theory suggests that the performance of controllers is bound by the universal robustness-efficiency tradeoff limit, which could be overcome by layering two or more feedbacks together. In natural biological networks, genes are often regulated with redundancy and layering to adapt to environmental perturbations. Control theory hypothesizes that this layering architecture is also adopted by nature to overcome this performance trade-off. In this work, we validated this property of layered control with a synthetic network in living E. coli cells. We performed system analysis on a node-based design to confirm the tradeoff properties before proceeding to simulations with an effective mechanistic model, which guided us to the best performing design to engineer in cells. Finally, we interrogated its system dynamics experimentally with eight sets of perturbations on chemical signals, nutrient abundance, and growth temperature. For all cases, we consistently observed that the layered control overcomes the robustness-efficiency trade-off limit. This work experimentally confirmed that layered control could be adopted in synthetic biomolecular networks as a performance optimization strategy. It also provided insights in understanding genetic feedback control architectures in nature. feedback control architectures in nature.)
• Bootstrapping bilinear models of simple vehicles  + (Learning and adaptivity will play a large … Learning and adaptivity will play a large role in robotics in the future, as robots move from structured to unstructured environments that cannot be fully predicted or understood by the designer. Two questions that are open: 1) in principle, how much it is possible to learn; and, 2) in practice, how much we should learn. The bootstrapping scenario describes the extremum case where agents need to learn âeverythingâ from scratch, including a torque-to-pixels models for its robotic body. Systems with such capabilities will be advantaged in terms of being resilient to unforeseen changes and deviations from prior assumptions. This paper considers the bootstrapping problem for a subset of the set of all robots: the Vehicles, inspired by Braitenbergâs work, are idealization of mobile robots equipped with a set of âcanonicalâ exteroceptive sensors (camera; range- finder; field-sampler). Their sensel-level dynamics are derived and shown to be surprising close. We define the class of BDS models, which assume an instantaneous bilinear dynamics between observations and commands, and derive streaming-based bilinear strategies for them. We show in what sense the BDS dynamics approximates the set of Vehicles to guarantee success in the task of generalized servoing: driving the observations to a given goal snapshot. Simulations and experiments substantiate the theoretical results. This is the first instance of a bootstrapping agent that can learn the dynamics of a relatively large universe of systems, and use the models to solve well-defined tasks, with no parameter tuning or hand-designed features.arameter tuning or hand-designed features.)
• Dynamics and Stability of Low Reynolds Number Swimming Near a Wall  + (Locomotion of microorganisms and tiny arti … Locomotion of microorganisms and tiny artificial swimmers is governed by low- Reynolds-number hydrodynamics, where viscous effects dominate and inertial effects are negligible. While the theory of low-Reynolds-number locomotion is well studied for unbounded fluid domains, the presence of a boundary has a significant influence on the swimmer's trajectories, and poses problems of dynamic stability of its motion. In this paper we consider a simple theoretical model of a micro-swimmer near a wall, study its dynamics, and analyze the stability of its motion. We highlight the underlying geometric structure of the dynamics, and establish a relation between the reversing symmetry of the system and existence and stability of periodic and steady solutions of motion near the wall. The results are demonstrated by numerical simulations and validated by motion experiments with robotic swimmer prototypes.periments with robotic swimmer prototypes.)
• Engineering pulsatile communication in bacterial consortia  + (Lux-type quorum sensing systems enable com … Lux-type quorum sensing systems enable communication in bacteria with only two protein components: a signal synthase and an inducible transcription activator. The simplicity of these systems makes them a popular choice for engineering collaborative behaviors in synthetic bacterial consortia, such as photographic edge detection and synchronized oscillation. To add to this body of work, we propose a pulsatile communication circuit that enables dynamic patterning and long-distance communication analogous to action potentials traveling through nerve tissue. We employed a model-driven design paradigm involving incremental characterization of in vivo design candidates with increasing circuit complexity. Beginning with a simple inducible reporter system, we screened a small number of circuits varying in their promoter and ribosomal binding site strengths. From this candidate pool, we selected a candidate to be the seed network for the subsequent round of more complex circuit variants, likewise variable in promoter and RBS strengths. The selection criteria at each level of complexity is tailored to optimize a different desirable performance characteristic. By this approach we individually optimized reporter signal-to-background ratio, pulsatile response to induction, and quiescent basal transcription, avoiding large library screens while ensuring robust performance of the composite circuit.bust performance of the composite circuit.)
• Geometric Control of Particle Manipulation in a Two-Dimensional Fluid  + (Manipulation of particles suspended in flu … Manipulation of particles suspended in fluids is crucial for many applications, such as precision machining, chemical processes, bio-engineering, and self-feeding of microorganisms. In this paper, we study the problem of particle manipulation by cyclic fluid boundary excitations from a geometric-control viewpoint. We focus on the simplified problem of manipulating a single particle by generating controlled cyclic motion of a circular rigid body in a two-dimensional perfect fluid. We show that the drift in the particle location after one cyclic motion of the body can be interpreted as the geometric phase of a connection induced by the system's hydrodynamics. We then formulate the problem as a control system, and derive a geometric criterion for its nonlinear controllability. Moreover, by exploiting the geometric structure of the system, we explicitly construct a feedback-based gait that results in attraction of the particle towards the rigid body. We argue that our gait is robust and model-independent, and demonstrate it in both perfect fluid and Stokes fluid.it in both perfect fluid and Stokes fluid.)
• Experiments in Planar Manipulation and Grasping  + (Many algorithms have been proposed in the … Many algorithms have been proposed in the literature for control of</br>multi-fingered robot hands. This paper compares the performance of</br>several of these algorithms, as well as some extensions of more</br>conventional manipulator control laws, in the case of planar grasping.</br>A brief introduction to the subject of robot hands and the notation</br>used in this paper is included.e notation used in this paper is included.)
• On Measures of Non-Integrability of Pfaffian Systems  + (Many problems in nonlinear control theory … Many problems in nonlinear control theory (like, for instance, feedback</br>linearization problem) lead to examination of integrability of a Pfaffian</br>system. In a generic case a Pfaffian system is not integrable. Therefore,</br>how to approximate nonintegrable Pfaffian systems by integrable ones and how</br>this approximation can be applied in practice appears to be a natural and</br>important problem. In the present paper we establish some measures of</br>non-integrability of Pfaffian system of arbitrary dimension and discuss</br>their relation to approxiations of non-integrable Pfaffian systems by</br>integrable ones. Our work is motivated by expected applications to</br>approximate feedback linearization of multi-input nonlinear systems.rization of multi-input nonlinear systems.)
• Distributed Gradient Systems and Dynamic Coordination  + (Many systems comprised of interconnected s … Many systems comprised of interconnected sub-units exhibit coordinated behaviors; social groups, </br>networked computers, financial markets, and numerous biological systems come to mind. There </br>has been long-standing interest in developing a scientific understanding of coordination, both for ex- </br>planatory power in the natural and economic sciences, and also for constructive power in engineering </br>and applied sciences. This thesis is an abstract study of coordination, focused on developing a sys- </br>tematic âdesign theoryâ for producing interconnected systems with specifiable coordinated behavior; </br>this is in contrast to the bulk of previous work on this sub ject, in which any design component has </br>been primarily ad-hoc. </br></br><p>The main theoretical contribution of this work is a geometric formalism in which to cast dis- </br>tributed systems. This has numerous advantages and ânaturallyâ parametrizes a wide class of </br>distributed interaction mechanisms in a uniform way. We make use of this framework to present </br>a model for distributed optimization, and we introduce the distributed gradient as a general design </br>tool for synthesizing dynamics for distributed systems. The distributed optimization model is a </br>useful abstraction in its own right and motivates a definition for a distributed extremum. As one </br>might expect, the distributed gradient is zero at a distributed extremum, and the dynamics of a </br>distributed gradient flow must converge to a distributed extremum. This forms the basis for a wide </br>variety of designs, and we are in fact able to recover a widely studied distributed averaging algorithm </br>as a very special case. </br></br><p>We also make use of our geometric model to introduce the notion of coordination capacity; </br>intuitively, this is an upper bound on the âcomplexityâ of coordination that is feasible given a </br>particular distributed interaction structure. This gives intuitive results for local, distributed, and </br>global control architectures, and allows formal statements to be made regarding the possibility of </br>âsolvingâ certain optimization problems under a particular distributed interaction model. </br></br><p>Finally, we present a number of applications to illustrate the theoretical approach presented; </br>these range from âstandardâ distributed systems tasks (leader election and clock synchronization) </br>to more exotic tasks like graph coloring, distributed account balancing, and distributed statistical </br>computations.ccount balancing, and distributed statistical computations.)
• Engineering the soil bacterium Pseudomonas synxantha 2-79 into a ratiometric bioreporter for phosphorus limitation  + (Microbial bioreporters hold promise for ad … Microbial bioreporters hold promise for addressing challenges in medical and environmental applications. However, the difficulty of ensuring their stable persistence and function within the target environment remains a challenge. One strategy is to integrate information about the host strain and target environment into the design-build-test cycle of the bioreporter itself. Here, we present a case study for such an environmentally-motivated design process by engineering the wheat commensal bacterium Pseudomonas synxantha 2-79 into a ratiometric bioreporter for phosphorus limitation. Comparative analysis showed that an exogenous P-responsive promoter outperformed its native counterparts. This reporter can selectively sense and report phosphorus limitation at plant-relevant concentrations of 25-100 µM without cross-activation from carbon or nitrogen limitation or high cell densities. Its performance is robust over a field-relevant pH range (5.8-8), and it responds only to inorganic phosphorus, even in the presence of common soil organic P. Finally, we used fluorescein-calibrated flow cytometry to assess whether the reporter’s performance in shaken liquid culture predict its performance in soil, finding that although the reporter is still functional at the bulk level, its variability in performance increases when grown in a soil slurry as compared to planktonic culture, with a fraction of the population not expressing the reporter proteins. Together, our environmentally-aware design process provides an example of how laboratory bioengineering efforts can generate microbes with greater promise to function reliably in their applied contexts.nction reliably in their applied contexts.)
• Passive Control of Flutter and Forced Response in Bladed Disks via Mistuning  + (Mistuning or blade to blade variation in j … Mistuning or blade to blade variation in jet-engine bladed-disks can</br>lead to large changes in engine performance. Even the small random</br>mistuning associated with manufacturing tolerances can significantly</br>change both stability boundaries and forced response. This thesis</br>addresses two questions. Analysis: given any mistuning (random or intentional),</br>what is the resulting change in performance? And passive control: can intentiona</br>l </br>mistuning be used to improve stability and forced response in a robust</br>manner? </br><p></br>A general framework based on symmetry arguments and eigenvalue/vector</br>perturbations is presented to answer both questions. </br>Symmetry constrains all facets of mistuning behaviour and provides</br>simplifications for both the analysis and control problems. This is combined</br>with the eigenvalue/vector perturbation which captures the nonlinear</br>mistuning dependence and solves the analysis problem. It is shown that</br>intentional mistuning can provide robust damping and so guarantee</br>improved stability and forced response under fixed manufacturing</br>tolerances. Results are demonstrated on a high-fidelity low-order</br>model derived from computational-fluid-dynamic data. </br><p>ived from computational-fluid-dynamic data. <p>)
• Time-Optimal Navigation in Uncertain Environments with High-Level Specifications  + (Mixed observable Markov decision processes … Mixed observable Markov decision processes (MOMDPs) are a modeling framework for autonomous systems described by both fully and partially observable states. In this work, we study the problem of synthesizing a control policy for MOMDPs that minimizes the expected time to complete the control task while satisfying syntactically co-safe Linear Temporal Logic (scLTL) specifications. First, we present an exact dynamic programming update to compute the value function. Afterwards, we propose a point-based approximation, which allows us to compute a lower bound of the closed-loop probability of satisfying the specifications. The effectiveness of the proposed approach and comparisons with standard strategies are shown on high-fidelity navigation tasks with partially observable static obstacles.ith partially observable static obstacles.)
• Formal Verification of an Autonomous Vehicle System  + (Model checking is a widely used technique … Model checking is a widely used technique for formal verification of distributed systems. It works by effectively examining the complete reachable state space of a model in order to determine whether the system satisfies its requirements or desired properties. The complexity of an autonomous vehicle system, however, renders model checking of the entire system infeasible due to the state explosion problem. In this paper, we illustrate how to exploit the structure of the system to systematically decompose the overall system-level requirements into a set of component-level requirements. Each of the components can then be model checked separately. A case study is presented where we formally verify the state consistency between different software modules of Alice, an autonomous vehicle developed by the California Institute of Technology for the 2007 DARPA Urban Challenge.nology for the 2007 DARPA Urban Challenge.)

• Model Predictive Control of a Thurst-Vectored Flight Control Experiment  + (Model predictive control (MPC) is applied … Model predictive control (MPC) is applied to the Caltech ducted fan, a</br>thrust-vectored flight experiment. A real-time trajectory generation software based</br>on spline theory and sequential quadratic programming is used to implement the</br>MPC controllers. Timing issues related to the computation and implementation of</br>repeatedly updated optimal trajectories are discussed. Results show computational</br>speeds greater than 10 Hz, 2.5 times that of the actuator dynamics. The MPC</br>controllers successfully stabilize a step disturbance applied to the ducted fan and</br>compare favorably to LQR methods. fan and compare favorably to LQR methods.)
• Robustness guarantees for structured model reduction of dynamical systems with applications to biomolecular models  + (Model reduction methods usually focus on t … Model reduction methods usually focus on the error performance analysis; however, in presence of uncertainties, it is important to analyze the robustness properties of the error in model reduction as well. This problem is particularly relevant for engineered biological systems that need to function in a largely unknown and uncertain environment. We give robustness guarantees for structured model reduction of linear and nonlinear dynamical systems under parametric uncertainties. We consider a model reduction problem where the states in the reduced model are a strict subset of the states of the full model, and the dynamics for all of the other states are collapsed to zero (similar to quasi-steady-state approximation). We show two approaches to compute a robustness guarantee metric for any such model reduction—a direct linear analysis method for linear dynamics and a sensitivity analysis based approach that also works for nonlinear dynamics. Using the robustness guarantees with an error metric and an input-output mapping metric, we propose an automated model reduction method to determine the best possible reduced model for a given detailed system model. We apply our method for the (1) design space exploration of a gene expression system that leads to a new mathematical model that accounts for the limited resources in the system and (2) model reduction of a population control circuit in bacterial cells.lation control circuit in bacterial cells.)
• Robustness Guarantees for Structured Model Reduction of Dynamical Systems  + (Model reduction methods usually focus on t … Model reduction methods usually focus on the error performance analysis; however, in presence of uncertainties, it is important to analyze the robustness properties of the error in model reduction as well. In this paper, we give robustness guarantees for structured model reduction of linear and nonlinear dynamical systems under parametric uncertainties. In particular, we consider a model reduction where the states in the reduced model are a strict subset of the states of the full model, and the dynamics for all other states are collapsed to zero (similar to quasi-steady state approximation). We show two approaches to compute a robustness metric for any such model reduction — a direct linear analysis method for linear dynamics and a sensitivity analysis based approach that also works for nonlinear dynamics. We also prove that for linear systems, both methods give equivalent results.ems, both methods give equivalent results.)
• Linear models for control of cavity flow oscillations  + (Models for understanding and controlling o … Models for understanding and controlling oscillations in the flow past a rectangular cavity are developed. These models may be used to guide control designs, to understand performance limits of feedback, and to interpret experimental results. Traditionally, cavity oscillations are assumed to be self-sustained: no external disturbances are necessary to maintain the oscillations, and amplitudes are limited by nonlinearities. We present experimental data which suggests that in some regimes, the oscillations may not be self-sustained, but lightly damped: oscillations are sustained by external forcing, such as boundary-layer turbulence. In these regimes, linear models suffice to describe the behaviour, and the final amplitude of oscillations depends on the characteristics of the external disturbances. These linear models are particularly appropriate for describing cavities in which feedback has been used for noise suppression, as the oscillations are small and nonlinearities are less likely to be important. It is shown that increasing the gain too much in such feedback control experiments can lead to a peak-splitting phenomenon, which is explained by the linear models. Fundamental performance limits indicate that peak splitting is likely to occur for narrow-bandwidth actuators and controllers.arrow-bandwidth actuators and controllers.)
• Synthesis and Validation of Control Software For A Vehicular Electric Power Distribution Testbed  + (Modern aircraft increasing rely on electri … Modern aircraft increasing rely on electric power, resulting in high safety-criticality and complexity in their electric power generation and distribution systems. Moti- vated by the resulting rapid increase in the costs and duration of the design cycles for such systems, we investigate the use of formal specification and automated, correct-by-construction control protocols synthesis for primary distribution in vehicular electric power networks. We discuss a design workflow that aims to transition from the traditional âdesign+verifyâ approach to a âspecify+synthesizeâ approach. We give an overview of a subset of the recent advances in the synthesis of reactive control proto- cols. We apply these techniques in the context of reconfiguration of the networks in reaction to the changes in their operating environment. We also validate these automatically synthesized control protocols on high-fidelity simulation models and on an academic-scale hardware testbed.and on an academic-scale hardware testbed.)
• An Aircraft Electric Power Testbed for Validating Automatically Synthesized Reactive Control Protocols  + (Modern aircraft increasingly rely on elect … Modern aircraft increasingly rely on electric power for sub- systems that have traditionally run on mechanical power. The complexity and safety-criticality of aircraft electric power systems have therefore increased, rendering the design of these systems more challenging. This work is mot vated by the potential that correct-by-construction reactive controller synthesis tools may have in increasing the effectiveness of the electric power system design cycle. In particular, we have built an experimental hardware platform that captures some key elements of aircraft electric power systems within a simplified setting. We intend to use this plat- form for validating the applicability of theoretical advances in correct-by-construction control synthesis and for study- ing implementation-related challenges. We demonstrate a simple design workflow from formal specifications to auto- generated code that can run on software models and be used in hardware implementation. We show some preliminary results with different control architectures on the developed hardware testbed.ectures on the developed hardware testbed.)
• Fast Automatic Verification of Large-Scale Systems with Lookup Tables  + (Modern safety-critical systems are difficu … Modern safety-critical systems are difficult to formally verify, largely due to their large scale. In particular, the widespread use of lookup tables in embedded systems across diverse industries, such as aeronautics and automotive systems, create a critical obstacle to the scala- bility of formal verification. This paper presents a novel approach for the formal verification of large-scale systems with lookup tables. We use a learning-based technique to automatically learn abstractions of the lookup tables and use the abstractions to then prove the desired property. If the verification fails, we propose a falsification heuristic to search for a violation of the specification. In contrast with previous work on lookup table verification, our technique is completely automatic, making it ideal for deployment in a production environment. To our knowledge, our approach is the only technique that can automatically verify large-scale systems lookup with tables.</br></br>We illustrate the effectiveness of our technique on a benchmark which cannot be handled by the commer- cial tool SLDV, and we demonstrate the performance improvement provided by our technique.nce improvement provided by our technique.)
• Bistable State Switch Enables Ultrasensitive Feedback Control in Heterogeneous Microbial Populations  + (Molecular feedback control circuits can im … Molecular feedback control circuits can improve robustness of gene expression at the single cell-level. This achievement can be offset by requirements of rapid protein expression, that may induce cellular stress, known as burden, that reduces colony growth. To begin to address this challenge we take inspiration by ‘division-of-labor’ in heterogeneous cell populations: we propose to combine bistable switches and quorum sensing systems to coordinate gene expression at the population-level. We show that bistable switches in individual cells operating in parallel yield an ultrasensitive response, while cells maintain heterogeneous levels of gene expression to avoid burden across all cells. Within a feedback loop, these switches can achieve robust reference tracking and adaptation to disturbances at the population-level. We also demonstrate that molecular sequestration enables tunable hysteresis in individual switches, making it possible to obtain a wide range of stable population-level expressions.ge of stable population-level expressions.)
• Robust Model Predictive Control for Signal Temporal Logic Synthesis  + (Most automated systems operate in uncertai … Most automated systems operate in uncertain or adversarial conditions, and have to be capable of reliably reacting to changes in the environment. The focus of this paper is on automatically synthesizing reactive controllers for cyber-physical systems subject to signal temporal logic (STL) specifications. We build on recent work that encodes STL specifications as mixed integer linear constraints on the variables of a discrete-time model of the system and environment dynamics. To obtain a reactive controller, we present solutions to the worst-case model predictive control (MPC) problem using a suite of mixed integer linear programming techniques. We demonstrate the comparative effectiveness of several existing worst-case MPC techniques, when applied to the problem of control subject to temporal logic specifications; our empirical results emphasize the need to develop specialized solutions for this domain.lop specialized solutions for this domain.)
• Reactive motion planning with probabilistic safety guarantees  + (Motion planning in environments with multi … Motion planning in environments with multiple agents is critical to many important autonomous applications such as autonomous vehicles and assistive robots. This paper considers the problem of motion planning, where the controlled agent shares the environment with multiple uncontrolled agents. First, a predictive model of the uncontrolled agents is trained to predict all possible trajectories within a short horizon based on the scenario. The prediction is then fed to a motion planning module based on model predictive control. We proved generalization bound for the predictive model using three different methods, post-bloating, support vector machine (SVM), and conformal analysis, all capable of generating stochastic guarantees of the correctness of the predictor. The proposed approach is demonstrated in simulation in a scenario emulating autonomous highway driving.ario emulating autonomous highway driving.)
• Synthesis of Embedded Control Systems with High Sampling Frequencies  + (Motivated by current technological advance … Motivated by current technological advances in the design of real-time embedded systems, this work deals with the digital control of a continuous-time linear time-invariant (LTI) system whose output can be sampled at a high frequency. Since a typical sampled-data controller operating at a high sampling frequency needs heavy (high-precision) computation to alleviate its sensitivity to measurement and computational errors, the objective is to design a robust hybrid controller for high- frequency applications with limited computational power. To this end, we exploit our recent results on delay-based controller design and propose a digital-control scheme that can implement every continuous-time stabilizing (LTI) controller. This robust hybrid controller, which consists of an ideal sampler, a digital controller, a number of modified second-order holds and possibly a unity feedback, can operate at arbitrarily high sampling frequencies without requiring expensive, high-precision computation. Later on, it is discussed how to find a continuous-time LTI controller satisfying prescribed design specifications so that its correspond- ing digital controller requires the least processing time.roller requires the least processing time.)
• Intermittent Connectivity for Exploration in Communication-Constrained Multi-Agent Systems  + (Motivated by exploration of communication- … Motivated by exploration of communication- constrained underground environments using robot teams, we study the problem of planning for intermittent connectivity in multi-agent systems. We propose a novel concept of information-consistency to handle situations where the plan is not initially known by all agents, and suggest an integer linear program for synthesizing information-consistent plans that also achieve auxiliary goals. Furthermore, inspired by network flow problems we propose a novel way to pose connectivity constraints that scales much better than previous methods. In the second part of the paper we apply these results in an exploration setting, and propose a clustering method that separates a large exploration problem into smaller problems that can be solved independently. We demonstrate how the resulting exploration algorithm is able to coordinate a team of ten agents to explore a large environment.ten agents to explore a large environment.)
• Stabilization of a Pitch Axis Flight Control Experiment with Input Rate Saturation  + (Motivated by problems in flight control, w … Motivated by problems in flight control, we present a technique for</br>stabilizing a chain </br>of integrators in the presence of rate limitations on the input. Our</br>technique improves on several existing techniques in the literature</br>and has a number of interesting features. The controller is</br>evaluated experimentally on a pitch axis flight control experiment at</br>Caltech. The experimental results show that even in the presence of</br>rate limits that cause a linear controller to go unstable, the</br>time-varying controller stabilizes the system with minimal loss in performance.e system with minimal loss in performance.)
• Effects of Magnitude Saturation in Control of Bifurcations  + (Motivated by problems such as active contr … Motivated by problems such as active control of rotating stall in compression systems,</br>an analysis of the effects of controller magnitude saturation in feedback stabilization of</br>steady-state bifurcations is performed. In particular the region of attraction to the</br>stabilized bifurcated equilibria is solved for feedback controllers with magnitude</br>saturation limits using the technique of center manifold reduction and bifurcation</br>analysis. It has been shown that the stability boundary is the saturation envelope formed</br>by the unstable (or stable) equilibria for the closed loop system when the controllers</br>saturate. The framework allows the design of feedback control laws to achieve desirable</br>size of region of attraction when the noise is modeled as a closed set of initial</br>conditions in the phase space. It is also possible to extend the techniques and results to</br>Hopf bifurcations.chniques and results to Hopf bifurcations.)
• Efficient reactive controller synthesis for a fragment of linear temporal logic  + (Motivated by robotic motion planning, we d … Motivated by robotic motion planning, we develop a framework for control policy synthesis for both non-deterministic transition systems and Markov decision processes that are subject to temporal logic task specifications. We introduce a fragment of linear temporal logic that can be used to specify common motion planning tasks such as safe navigation, response to the environment, surveillance, and persistent coverage. This fragment is computationally efficient; the complexity of control policy synthesis is a doubly-exponential improvement over standard linear temporal logic for both non-deterministic transition systems and Markov decision processes. This improvement is possible since we compute directly on the original system, as opposed to the automata-based approach commonly used for linear temporal logic. We give simulation results for representative motion planning tasks and compare to generalized reactivity(1). and compare to generalized reactivity(1).)
• Delay-Based Controller Design for Continuous-Time and Hybrid Applications  + (Motivated by the availability of different … Motivated by the availability of different types of delays in embedded systems and biological circuits, the objective of this work is to study the benefits that delay can provide in simplifying the implementation of controllers for continuous-time systems. Given a continuous-time linear time-invariant (LTI) controller, we propose three methods to approximate this controller arbitrarily precisely by a simple controller composed of delay blocks, a few integrators and possibly a unity feedback. Different problems associated with the approximation procedures, such as finding the optimal number of delay blocks or studying the robustness of the designed controller with respect to delay values, are then investigated. We also study the design of an LTI continuous-time controller satisfying given control objectives whose delay-based implementation needs the least number of delay blocks. A direct application of this work is in the sampled-data control of a real-time embedded system, where the sampling frequency is relatively high and/or the output of the system is sampled irregularly. Based on our results on delay-based controller design, we propose a digital-control scheme that can implement every continuous-time stabilizing (LTI) controller. Unlike a typical sampled-data controller, the hybrid controller introduced here---consisting of an ideal sampler, a digital controller, a number of modified second-order holds and possibly a unity feedback---is robust to sampling jitter and can operate at arbitrarily high sampling frequencies without requiring expensive, high-precision computation.ing expensive, high-precision computation.)
• Control System Analysis on Symmetric Cones  + (Motivated by the desire to analyze high di … Motivated by the desire to analyze high dimen- sional control systems without explicitly forming computation- ally expensive linear matrix inequality (LMI) constraints, we seek to exploit special structure in the dynamics matrix. By using Jordan algebraic techniques we show how to analyze continuous time linear dynamical systems whose dynamics are exponentially invariant with respect to a symmetric cone. This allows us to characterize the families of Lyapunov functions that suffice to verify the stability of such systems. We highlight, from a computational viewpoint, a class of systems for which stability verification can be cast as a second order cone program (SOCP), and show how the same framework reduces to linear programming (LP) when the system is internally positive, and to semidefinite programming (SDP) when the system has no special structure. when the system has no special structure.)
• A geometric and structural approach to the analysis and design of biological circuit dynamics: a theory tailored for synthetic biology  + (Much of the progress in developing our abi … Much of the progress in developing our ability to successfully design genetic circuits with predictable dynamics has followed the strategy of molding biological systems to fit into conceptual frameworks used in other disciplines, most notably the engineering sciences. Because biological systems have fundamental differences from systems in these other disciplines, this approach is challenging and the insights obtained from such analyses are often not framed in a biologically-intuitive way. Here, we present a new theoretical framework for analyzing the dynamics of genetic circuits that is tailored towards the unique properties associated with biological systems and experiments. Our framework approximates a complex circuit as a set of simpler circuits, which the system can transition between by saturating its various internal components. These approximations are connected to the intrinsic structure of the system, so this representation allows the analysis of dynamics which emerge solely from the system’s structure. Using our framework, we analyze the presence of structural bistability in a leaky autoactivation motif and the presence of structural oscillations in the Repressilator.uctural oscillations in the Repressilator.)
• Inverse Abstraction of Neural Networks Using Symbolic Interpolation  + (Neural networks in real-world applications … Neural networks in real-world applications have to satisfy critical properties such as safety and reliability. The analysis of such properties typically involves extracting informa- tion through computing pre-images of neural networks, but it is well-known that explicit computation of pre-images is intractable. We introduce new methods for computing compact symbolic abstractions of pre-images. Our approach relies on computing approximations that provably overapproximate and underapproximate the pre-images at all layers. The abstraction of pre-images enables formal analysis and knowl- edge extraction without modifying standard learning algo- rithms. We show how to use inverse abstractions to automatically extract simple control laws and compact representations for pre-images corresponding to unsafe outputs. We illustrate that the extracted abstractions are often interpretable and can be used for analyzing complex properties. be used for analyzing complex properties.)
• Resource optimisation in a wireless sensor network with guaranteed estimator performance  + (New control paradigms are needed for large … New control paradigms are needed for large networks of wireless sensors and actuators in order to efficiently utilise system resources. In this study, the authors consider the problem of discrete-tie state estimation over a wireless sensor network. Given a tree that represents the sensor communications with the fusion centre, the authors derive the optimal estimation algorithm at the fusion centre, and provide a closed-form expression for the steady-state error covariance matrix. They then present a tree reconfiguration algorithm that produces a sensor tree that has low overall energy consumption and guarantees a desired level of estimation quality at the fusion centre. The authors further propose a sensor tree construction and scheduling algorithm that leads to a longer network lifetime than the tree reconfiguration algorithm. Examples are provided throughout the paper to demonstrate the algorithms and theory developed.trate the algorithms and theory developed.)
• Finding stationary solutions to the chemical master equation by gluing state spaces at one or two states recursively  + (Noise is indispensible to key cellular act … Noise is indispensible to key cellular activities, including gene expression coordination and probabilistic differentiation. Stochastic models, such as the chemical master equation (CME), are essential to model noise in the levels of cellular components. In the CME framework, each state is associated with the molecular counts of all component species, and specifies the probability for the system to have that set of molecular counts. Analytic solutions to the CME are rarely known but can bring exciting benefits. For instance, simulations of biochemical reaction networks that are multiscale in time can be sped up tremendously by incorporating analytic solutions of the slow time-scale dynamics. Ana- lytic solutions also enable the design of stationary distributions with properties such as the modality of the distribution, the mean expression level, and the level of noise. One way to derive the analytic steady state response of a biochemical reaction network was re- cently proposed by (Mélykúti et al. 2014). The paper recursively glues simple state spaces together, for which we have analytic solutions, at one or two states.</br><p></br>In this work, we explore the benefits and limitations of the gluing technique proposed by Mélykúti et al., and introduce recursive algorithms that use the technique to solve for the analytic steady state response of stochastic biochemical reaction networks. We give formal characterizations of the set of reaction networks whose state spaces can be obtained by carrying out single-point gluing of paths, cycles or both sequentially. We find that the dimension of the state space of a reaction network equals the maximum number of linearly independent reactions in the system. We then characterize the complete set of stochastic biochemical reaction networks that have elementary reactions and two-dimensional state spaces. As an example, we propose a recursive algorithm that uses the gluing technique to solve for the steady state response of a mass-conserving system with two connected monomolecular reversible reactions. Even though the gluing technique can only construct finite state spaces, we find that, by taking the size of a finite state space to infinity, the steady state response can converge to the analytic solution on the resulting infinite state space. Finally, we illustrate the aforementioned ideas with the example of two interconnected transcriptional components, which was first studied by (Ghaemi and Del Vecchio 2012). first studied by (Ghaemi and Del Vecchio 2012).)
• Recursively constructing analytic expressions for equilibrium distributions of stochastic biochemical reaction networks  + (Noise is often indispensable to key cellul … Noise is often indispensable to key cellular activities, such as gene expression, necessitating the use of stochastic models to capture its dynamics. The chemical master equation (CME) is a commonly used stochastic model of Kolmogorov forward equations that describe how the probability distribution of a chemically reacting system varies with time. Finding analytic solutions to the CME can have benefits, such as expediting simulations of multiscale biochemical reaction networks and aiding the design of distributional responses. However, analytic solutions are rarely known. A recent method of computing analytic stationary solutions relies on gluing simple state spaces together recursively at one or two states. We explore the capabilities of this method and introduce algorithms to derive analytic stationary solutions to the CME. We first formally characterize state spaces that can be constructed by performing single-state gluing of paths, cycles or both sequentially. We then study stochastic biochemical reaction networks that consist of reversible, elementary reactions with two-dimensional state spaces. We also discuss extending the method to infinite state spaces and designing the stationary behaviour of stochastic biochemical reaction networks. Finally, we illustrate the aforementioned ideas using examples that include two interconnected transcriptional components and biochemical reactions with two-dimensional state spaces.actions with two-dimensional state spaces.)
• Nonlinear Control of Mechanical Systems: A Reimannian Geometry Approach  + (Nonlinear control of mechanical systems is … Nonlinear control of mechanical systems is a challenging discipline that lies at the</br>intersection between control theory and geometric mechanics. This thesis sheds new light</br>on this interplay while investigating motion control problems for Lagrangian systems. Both</br>stability and motion planning aspects are treated within a unified framework that accounts</br>for a large class of devices such as robotic manipulators, autonomous vehicles and</br>locomotion systems.</p></br></br><p>One distinguishing feature of mechanical systems is the number of control forces. For</br>systems with as many input forces as degrees of freedom, many control problems are</br>tractable. One contribution of this thesis is a set of trajectory tracking controllers</br>designed via the notions of configuration and velocity error. The proposed approach</br>includes as special cases a variety of results on joint and workspace control of</br>manipulators as well as on attitude and position control of vehicles.</p></br></br><p>Whenever fewer input forces are available than degrees of freedom, various control</br>questions arise. The main contribution of this thesis is the design of motion algorithms</br>for vehicles, i.e., rigid bodies moving in Euclidean space. First, an algebraic</br>controllability analysis characterizes the set of reachable configurations and velocities</br>for a system starting at rest. Then, provided a certain controllability condition is</br>satisfied, various motion algorithms are proposed to perform tasks such as short range</br>reconfiguration and hovering. </p></br></br><p>Finally, stabilization techniques for underactuated systems are investigated. The</br>emphasis is on relative equilibria, i.e., steady motions for systems that have a conserved</br>momentum. Local exponential stabilization is achieved via an appropriate splitting of the</br>control authority.abilization is achieved via an appropriate splitting of the control authority.)
• Bifurcation Control of Rotating Stall with Actuator Magnitude and Rate Limits  + (Nonlinear qualitative analysis is performe … Nonlinear qualitative analysis is performed on the Moore-Greitzer </br> model to evaluate the tradeoff of fluid noise, actuator magnitude saturation, </br> bandwidth, rate limits, and the shape of compressor characteristics in active </br> control of rotating stall in axial compressors with bleed valve actuators. Model </br> order reduction is achieved by approximating the dynamics on the invariant manifold </br> that captures the bifurcations and instabilities. Bifurcations and qualitative </br> dynamics are obtained by analyzing the reduced system. The operability enhancement </br> is defined as the extension of operating range for which fully developed rotating </br> stall is avoided. Analytic formulas are derived for the operability enhancement </br> as a function of noise level, actuator saturation limits, and the shape of the </br> compressor characteristic, which is the major nonlinearity in the model. The </br> shape of the compressor characteristic, especially the unstable part, is critical </br> to the rate required for robust operability near the peak for the closed loop </br> system. Experiments are carried out on a single-stage low-speed axial compressor </br> using different level of steady air injections to generate different compressor </br> characteristics. The theoretical formulas give good qualitative estimates to </br> experimental data and simulations using a high fidelity model (37 states).s using a high fidelity model (37 states).)
• Fault detection and isolation from uninterpreted data in robotic sensorimotor cascades  + (One of the challenges in designing the nex … One of the challenges in designing the next genera- tion of robots operating in non-engineered environments is that there seems to be an infinite amount of causes that make the sensor data unreliable or actuators ineffective. In this paper, we discuss what faults are possible to detect using zero modeling effort: we start from uninterpreted streams of observations and commands, and without a prior knowledge of a model of the world. We show that in sensorimotor cascades it is possible to define static faults independently of a nominal model. We define an information-theoretic usefulness of a sensor reading and we show that it captures several kind of sensorimotor faults frequently encountered in practice. We particularize these ideas to the case of BDS/BGDS models, proposed in previous work as suitable candidates for describing generic sensorimotor cascades. We show several examples with camera and range-finder data, and we discuss a possible way to integrate these techniques in an existing robot software architecture.n an existing robot software architecture.)