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- On-chip membrane protein cell-free expression enables development of a direct binding assay: A curious case of potassium channel KcsA-Kv1.3 + (Despite the significant role integral memb … Despite the significant role integral membrane proteins (IMPs) play in the drug discovery process, it remains extremely challenging to express, purify, and in vitro stabilize them for detailed biophysical analyses. Cell-free transcription-translation systems have emerged as a promising alternative for producing complex proteins, but they are still not a viable option for expressing IMPs due to improper post-translational folding of these proteins. We have studied key factors influencing in vitro folding of cell-free-expressed IMPs, particularly oligomeric proteins (i.e., ion channels). Using a chimeric ion channel, KcsA-Kv1.3 (K-K), as a model IMP, we have investigated several physiochemical determinants including artificial bilayer environments (i.e., lipid, detergent) for K-K in vitro stabilization. We observed that fusion of a ‘superfolder’ green fluorescent protein (sfGFP) to K-K as a protein expression reporter not only improves the protein yield, but surprisingly facilitates the K-K tetramer formation, probably by enhancing the solubility of monomeric K-K. Additionally, anionic lipids (i.e., DMPG) were found to be essential for the correct folding of cell-free-expressed monomeric K-K into tetramer, underscoring the importance of lipid-protein interaction in maintaining structural-functional integrity of ion channels. We further developed methods to integrate cell-free-expressed IMPs directly onto a biosensor chip. We employed a solid-supported lipid bilayer onto the surface plasmon resonance (SPR) chip to insert nascent K-K in a membrane. In a different approach, an anti-GFP-functionalized surface was used to capture in situ expressed K-K via its sfGFP tag. Interestingly, only the K-K-functionalized capture surface prepared by the latter strategy was able to interact with K-K's small binding partners. This generalizable approach can be further extended to other membrane proteins for developing direct binding assays involving small ligands.ct binding assays involving small ligands.)
- Optimal nonlinear guidance with inner-loop feedback for hypersonic re-entry + (Development of feasible G&C (guidance … Development of feasible G&C (guidance and control) methods for precision atmospheric re-entry has remained a challenge since pre-Apollo-era space exploration. The inherent difficulty arises from the governing hypersonic dynamics being significantly nonlinear, subject to parametric uncertainty, and limited with control authority. Vehicle safety requirements impose further constraints, and desired cost objectives complicate an already difficult G&C problem. The scope of this paper is to present a guidance algorithm for optimal trajectory generation based on a reduced-dimension reentry formulation. Preliminary simulations demonstrate the algorithm with feedback used to track the guidance trajectory in the presence of initial state uncertainty. The objective is to further this approach toward an onboard receding-horizon implementation toward an onboard receding-horizon implementation)
- Geometric Phases, Control Theory, and Robotics + (Differential geometry and nonlinear contro … Differential geometry and nonlinear control theory provide essential</br>tools for studying motion generation in robot systems. Two areas</br>where progress is being made are motion planning for mobile robots on</br>the factory floor (or on the surface of Mars), and control of highly</br>articulated robots---such as multifingered robot hands and robot</br>``snakes''---for medical inspection and manipulation inside the</br>gastrointestinal tract. A common feature of these systems is the role</br>of constraints on the behavior of the system. Typically, these</br>constraints force the instantaneous velocities of the system to lie in</br>a restricted set of directions, but do not actually restrict the</br>reachable configurations of the system. A familiar example in which</br>this geometric structure can be exploited is parallel parking of an</br>automobile, where periodic motion in the driving speed and steering</br>angle can be used to achieve a net sideways motion. By studying the</br>geometric nature of velocity constraints in a more general setting, it</br>is possible to synthesize gaits for snake-like robots, generate</br>parking and docking maneuvers for automated vehicles, and study the</br>effects of rolling contacts on multifingered robot hands. As in</br>parallel parking, rectification of periodic motions in the control</br>variables plays a central role in the techniques which are used to</br>generation motion in this broad class of robot systems.tion in this broad class of robot systems.)
- Differentially Flat Nonlinear Control Systems + (Differentially flat systems are underdeter … Differentially flat systems are underdetermined systems of (nonlinear) ordinary differential equations</br>(ODEs) whose solution curves are in smooth one-one correspondence with arbitrary curves in a space</br>whose dimension equals the number of equations by which the system is underdetermined. For control</br>systems this is the same as the number of inputs. The components of the map from the system space to</br>the smaller dimensional space are referred to as the flat outputs. Flatness allows one to systematically</br>generate feasible trajectories in a relatively simple way. Typically the flat outputs may depend on the</br>original independent and dependent variables in terms of which the ODEs are written as well as finitely</br>many derivatives of the dependent variables. Flatness of systems underdetermined by one equation is</br>completely characterised by Elie Cartan's work. But for general underdetermined systems no complete</br>characterisation of flatness exists. </br><p></br>In this dissertation we describe two different geometric frameworks for studying flatness and provide</br>constructive methods for deciding the flatness of certain classes of nonlinear systems and for finding</br>these flat outputs if they exist. We first introduce the concept of ``absolute equivalence'' due to Cartan</br>and define flatness in this frame work. We provide a method of testing for the flatness of systems, which</br>involves making a guess for all but one of the flat outputs after which the problem is reduced to the case</br>solved by Cartan. Secondly we present an alternative geometric approach to flatness which uses ``jet</br>bundles'' and present a theorem which partially characterises flat outputs that depend only on the</br>original variables but not on their derivatives, for the case of systems described by two independent</br>one-forms in arbitrary number of variables. Finally, for the class of Lagrangian mechanical systems whose</br>number of control inputs is one less than the number of degrees of freedom, we provide a</br>characterisation of flat outputs that depend only on the configuration variables, but not on their</br>derivatives. This characterisation makes use of the Riemannian metric provided by the kinetic energy of</br>the system.ic provided by the kinetic energy of the system.)
- Asynchronous Distributed Averaging on Communication Networks + (Distributed algorithms for averaging have attracted interest in the control and sensing literature. However, previous works have not addressed some practical concerns that will arise in actual implementations on packet-switched communication networks.....)
- Distributed Averaging on Asynchronous Communication Networks + (Distributed algorithms for averaging have … Distributed algorithms for averaging have at- </br>tracted interest in the control and sensing literature. However, </br>previous works have not addressed some practical concerns </br>that will arise in actual implementations on packet-switched </br>communication networks such as the Internet. In this paper, </br>we present several implementable algorithms that are robust to </br>asynchronism and dynamic topology changes. The algorithms </br>do not require global coordination and can be proven to </br>converge under very general asynchronous timing assumptions. </br>Our results are verified by both simulation and experiments on </br>a real-world TCP/IP network.periments on a real-world TCP/IP network.)
- A Model-Free Algorithm for Extremely Resilient Navigation + (Due to the increasing complexity of space … Due to the increasing complexity of space missions and distance to exploration targets, future robotic systems used for space exploration call for more resilience and autonomy. Instead of minimizing the failure risk, we are focusing on missions that will inevitably encounter significant failures and are developing an algorithm that will autonomously reconfigure the system controller to continue to make progress towards the mission goal despite being in a reduced capacity state - we call this extreme resilience. In this paper, we develop a model-free framework to autonomously react to locomotion failures of robotic systems. This is done by the use of a neural network for path planning using the neuroevolution of aug- menting topologies (NEAT) algorithm and a dynamic database of possible moves and their effect on the system’s position and orientation. Two modes of failure detection and resolution are being introduced: (a) relative position failure detection, which is triggered by large, unexpected moves and results in a complete update of the database before a retraining of the neural network, and (b) absolute position failure detection, which triggers from large build-ups of position error from small failures and will induce a retraining of the neural network without an explicit database reset. We implement and validate this framework on a high-fidelity planetary rover simulation using Unreal Engine and on a hardware setup of a TurtleBot2 with a PhantomX Pincher robot arm.tleBot2 with a PhantomX Pincher robot arm.)
- A population-based temporal logic gate for timing and recording chemical events + (Engineered bacterial sensors have potentia … Engineered bacterial sensors have potential applications in human health monitoring, environmental chemical detection, and materials biosynthesis. While such bacterial devices have long been engineered to differentiate between combinations of inputs, their potential to process signal timing and duration has been overlooked. In this work, we present a two-input temporal logic gate that can sense and record the order of the inputs, the timing between inputs, and the duration of input pulses. Our temporal logic gate design relies on unidirectional DNA recombination mediated by bacteriophage integrases to detect and encode sequences of input events. For an E. coli strain engineered to contain our temporal logic gate, we compare predictions of Markov model simulations with laboratory measurements of final population distributions for both step and pulse inputs. Although single cells were engineered to have digital outputs, stochastic noise created heterogeneous single-cell responses that translated into analog population responses. Furthermore, when single-cell genetic states were aggregated into population-level distributions, these distributions contained unique information not encoded in individual cells. Thus, final differentiated sub-populations could be used to deduce order, timing, and duration of transient chemical events.and duration of transient chemical events.)
- Addressable and adaptable intercellular communication via DNA messaging + (Engineered consortia are a major research … Engineered consortia are a major research focus for synthetic biologists because they can implement sophisticated behaviors inaccessible to single-strain systems. However, this functional capacity is constrained by their constituent strains’ ability to engage in complex communication. DNA messaging, by enabling information-rich channel-decoupled communication, is a promising candidate architecture for implementing complex communication. But its major advantage, its messages’ dynamic mutability, is still unexplored. We develop a framework for addressable and adaptable DNA messaging that leverages all three of these advantages and implement it using plasmid conjugation in E. coli. Our system can bias the transfer of messages to targeted receiver strains by 100- to 1000-fold, and their recipient lists can be dynamically updated in situ to control the flow of information through the population. This work lays the foundation for future developments that further utilize the unique advantages of DNA messaging to engineer previously-inaccessible levels of complexity into biological systems.els of complexity into biological systems.)
- Role of interaction network topology in controlling microbial population in consortia + (Engineering microbial consortia is an impo … Engineering microbial consortia is an important new frontier for synthetic biology given its efficiency in performing complex tasks and endurance to environmental uncertainty. Most synthetic circuits regulate population level behaviors via cell-to-cell communications, which are affected by spatially heterogeneous environments. Therefore, it is important to understand the limits on controlling system dynamics that are determined by interconnections among cell agents and provide a control strategy for engineering consortia. Here, we build a network model for a fractional population control circuit in two-strain consortia, and characterize the cell-to-cell communication network by topological properties, such as symmetry, locality and connectivity. Using linear network control theory, we relate the network topology to system output tracking performance. We analytically and numerically demonstrate that the minimum network control energy for accurate tracking depends on locality difference between two cell populations and how strongly the controller node contributes to communication strength. To realize robust consortia, we can manipulate the communication network topology and construct strongly connected consortia by altering chemicals in environments. Our results ground the expected cell population dynamics in its spatially organized communication network, and inspire directions in cooperative control in microbial consortia.ooperative control in microbial consortia.)
- Invariant Sets for Integrators and Quadrotor Obstacle Avoidance + (Ensuring safety through set invariance has … Ensuring safety through set invariance has proven a useful method in a variety of applications in robotics and control. However, finding analytical expressions for maximal invariant sets, so as to maximize the operational freedom of the system without compromising safety, is notoriously difficult for high-dimensional systems with input constraints. Here we present a generic method for characterizing invariant sets of nth-order integrator systems, based on analyzing roots of univariate polynomials. Additionally, we obtain analytical expressions for the orders n <= 4. Using differential flatness we subsequently leverage the results for the n = 4 case to the problem of obstacle avoidance for quadrotor UAVs. The resulting controller has a light computational footprint that showcases the power of finding analytical expressions for control-invariant sets.tical expressions for control-invariant sets.)
- Construction of an inducible amyloid expression circuit in Bacillus megaterium: A case study with CsgA and TasA + (Environmental applications of synthetic bi … Environmental applications of synthetic biology such as water remediation require engineered strains to function robustly in a fluctuating and potentially hostile environment. The construction of synthetic biofilm formation circuits could potentially alleviate this issue by promoting cell survival. Towards this end, we construct a xylose-inducible system for the expression of the functional amyloids CsgA and TasA in the soil bacterium Bacillus megaterium. We find that although both amyloids are expressed, only TasA is successfully exported from the cells. Furthermore, expression of CsgA results in a significant growth penalty for the cells while expression of TasA does not. Finally, we show that TasA expression conveys a small but detectable increase in cells’ adhesion to nickel beads. These results suggest that TasA is a promising candidate for future work on synthetic biofilm formation in B. megaterium.thetic biofilm formation in B. megaterium.)
- Performance Metrics for a Biomolecular Step Response + (Establishing performance metrics is a key … Establishing performance metrics is a key part of a systematic design process. In particular, specifying metrics useful for quantifying performance in the ongoing efforts towards biomolecular circuit design is an important problem. Here we address this issue for the design of a fast biomolec- ular step response that is uniform across different cells and widely different environmental conditions using a combination of simple mathematical models and experimental measure- ments using single-cell time-lapse microscopy. We evaluate two metrics, the difference of the step response from an ideal step and the relative difference between multiple realizations of the step response, that can provide a single number to measure performance. We use a model of protein production- degradation to show that these performance metrics correlate with response features of speed and noise. Finally, we work through an experimental methodology to estimate these metrics for step responses that have been acquired for inducible protein expression circuits in E. coli. These metrics will be useful to evaluate biomolecular step responses, as well as for setting similar performance measures for other design goals.rformance measures for other design goals.)
- An Experimental Comparison of Controllers for a Vectored Thrust, Ducted Fan Engine + (Experimental comparisons between four diff … Experimental comparisons between four different control design</br>methodologies are applied to a small vectored thrust engine.</br>Each controller is applied to three trajectories of varying</br>aggressiveness. The control strategies considered are LQR,</br>H_infty, gain scheduling, and feedback linearization. The </br>experiments show that gain scheduling</br>is essential to achieving good performance. The</br>strengths and weaknesses of each methodology are also examined.ses of each methodology are also examined.)
- Model-Based Control of Cavity Oscillations, Part II: System Identificaion and Analysis + (Experiments using active control to reduce … Experiments using active control to reduce oscillations</br>in the flow past a rectangular cavity have uncovered</br>surprising phenomena: in the controlled system,</br>often new frequencies of oscillation appear, and</br>often the main frequency of oscillation is split into</br>two sideband frequencies. The goal of this paper is</br>to explain these effects using physics-based models,</br>and to use these ideas to guide control design.</br>We present a linear model for the cavity flow,</br>based on the physical mechanisms of the familiar</br>Rossiter model. Experimental data indicates</br>that under many operating conditions, the oscillations</br>are not self-sustained, but in fact are caused</br>by amplification of external disturbances. We</br>present some experimental results demonstrating</br>the peak-splitting phenomena mentioned above, use</br>the physics-based model to study the phenomena,</br>and discuss fundamental performance limitations</br>which limit the achievable performance of any control</br>scheme.ievable performance of any control scheme.)
- Planning and Optimization for Multi-Robot Planetary Cave Exploration under Intermittent Connectivity Constraints + (Exploring subsurface structures with auton … Exploring subsurface structures with autonomous robots is of growing interest in the context of planetary caves studies. Communication between robots in these environments is severely degraded which complicates coordination and information distribution. In this paper we focus on planning for mobility and communication in a cave exploration scenario where the situational awareness of a static base station is critical. We propose a notion of information-consistency where a plan itself is part of the information to be shared between robots, and propose a method for generating informationconsistent plans. We discuss in detail how the resulting plan can be robustly implemented with minimal communication through local mission executives that run on individual robots. We describe preliminary results on the performance of the planning algorithm and integration of the local mission executives in a high-fidelity simulation environment.in a high-fidelity simulation environment.)
- Failure Probability of Verifiable Goal-based Control Programs due to State Estimation Uncertainty + (Fault tolerance and safety verification of … Fault tolerance and safety verification of control systems that have state estimation uncertainty are essential for the success of autonomous robotic systems. A software control architecture called Mission Data System, developed at the Jet Propulsion Laboratory, uses goal networks as the control program for autonomous systems. Certain types of goal networks can be converted into linear hybrid systems and verified for safety using existing symbolic model checking software. A process for calculating the probability of failure of some verifiable goal networks due to state estimation uncertainty is presented. Extensions of this procedure to include other types of uncertainties are discussed, and example problems are presented to illustrate these procedures. presented to illustrate these procedures.)
- Control Program Verification for a Sample Titan Aerobot Mission + (Fault tolerance and safety verification of … Fault tolerance and safety verification of control systems are essential for the success of autonomous robotic systems. A control architecture called Mission Data System (MDS), developed at the Jet Propulsion Laboratory, takes a goal-based control approach. A software algorithm for converting goal network control programs into linear hybrid systems exists and is a bisimulation; the resulting linear hybrid system can be verified for safety in the presence of failures using existing symbolic model checkers, and thus the original goal network is verified. A substantial example control program based on a proposed mission to Titan, a moon of Saturn, is converted using the procedures discussed. converted using the procedures discussed.)
- Automatic Conversion Software for the Safety Verification of Goal-Based Control Programs + (Fault tolerance and safety verification of … Fault tolerance and safety verification of control systems are essential for the success of autonomous robotic systems. A control architecture called Mission Data System (MDS), developed at the Jet Propulsion Laboratory, takes a goal-based control approach. In this paper, a software algorithm for converting goal network control programs into linear hybrid systems is described. The conversion process is a bisimulation; the resulting linear hybrid system can be verified for safety in the presence of failures using existing symbolic model checkers, and thus the original goal network is verified. A moderately complex goal network control program is converted to a linear hybrid system using the automatic conversion software and then verified.tic conversion software and then verified.)
- Conversion and Verification Procedure for Goal-Based Control Programs + (Fault tolerance and safety verification of … Fault tolerance and safety verification of control systems are essential for the success of autonomous robotic systems. A control architecture called Mission Data System, developed at the Jet Propulsion Laboratory, takes a goal-based control approach. In this paper, a method for converting goal network control programs into linear hybrid systems is developed. The linear hybrid system can then be verified for safety in the presence of failures using existing symbolic model checkers. An example task is developed and successfully verified using HyTech, a symbolic model checking software for linear hybrid systems.ecking software for linear hybrid systems.)
- Safety Verification of Fault Tolerant Goal-based Control Programs with Estimation Uncertainty + (Fault tolerance and safety verification of … Fault tolerance and safety verification of control systems that have state variable estimation uncertainty are essential for the success of autonomous robotic systems. A software control architecture called Mission Data System, developed at the Jet Propulsion Laboratory, uses goal networks as the control program for autonomous systems. Certain types of goal networks can be converted into linear hybrid systems and verified for safety using existing symbolic model checking software. A process for calculating the probability of failure of certain classes of verifiable goal networks due to state estimation uncertainty is presented. A verifiable example task is presented and the failure probability of the control program based on </br>estimation uncertainty is found.based on estimation uncertainty is found.)
- Design of a genetic layered feedback controller in synthetic biological circuitry + (Feedback control is the key to achieve rob … Feedback control is the key to achieve robust performances for many engineered systems. However, its application in biological contexts is still largely unexplored. In this work, we designed, analyzed and simulated a layered controller functioning at both molecular and populational levels. First, we used a minimal model of three states to represent a system where state A activates state B; state R is a by-product of state B that acts as a negative feedback regulating both state A, B, and sequentially R. We call the feedback applied to state B a cis feedback and the one applied to state A a trans feedback. Through stability analysis via linearization at equilibrium and sensitivity analysis at transient state, we found that the cis feedback attenuates disturbances better but recovers slower; the trans feedback recovers faster but has more dramatic responses to fluctuations; the layered feedback demonstrates both advantageous traits of the two single layers. Then we designed two versions of synthetic genetic circuits to implement the layered controller in living cells. One version with an sRNA as regulator R, the other with a transcription factor protein as the regulator R. The analysis and dynamical simulation of the models confirmed the analytical results from the minimal model. At the same time, we found that the protein regulated feedback controls have faster recovery speed but the RNA version has a stronger disturbance attenuation effect.a stronger disturbance attenuation effect.)
- Synergistic dual positive feedback loops established by molecular sequestration generate robust bimodal response + (Feedback loops are ubiquitous features of … Feedback loops are ubiquitous features of biological networks and can produce significant phenotypic heterogeneity, including a bimodal distribution of gene expression across an isogenic cell population. In this work, a combination of experiments and computational modeling was used to explore the roles of multiple feedback loops in the bimodal, switch-like response of the Saccharomyces cerevisiae galactose regulatory network. Here, we show that bistability underlies the observed bimodality, as opposed to stochastic effects, and that two unique positive feedback loops established by Gal1p and Gal3p, which both regulate network activity by molecular sequestration of Gal80p, induce this bimodality. Indeed, systematically scanning through different single and multiple feedback loop knockouts, we demonstrate that there is always a concentration regime that preserves the systemâs bimodality, except for the double deletion of GAL1 and the GAL3 feedback loop, which exhibits a graded response for all conditions tested. The constitutive production rates of Gal1p and Gal3p operate as bifurcation parameters because variations in these rates can also abolish the systemâs bimodal response. Our model indicates that this second loss of bistability ensues from the inactivation of the remaining feedback loop by the overexpressed regulatory component. More broadly, we show that the sequestration binding affinity is a critical parameter that can tune the range of conditions for bistability in a circuit with positive feedback established by molecular sequestration. In this system, two positive feedback loops can significantly enhance the region of bistability and the dynamic response time.bistability and the dynamic response time.)
- Hard Limits And Performance Tradeoffs In A Class Of Sequestration Feedback Systems + (Feedback regulation is pervasive in biolog … Feedback regulation is pervasive in biology at both the organismal and cellular level. In this article, we explore the properties of a particular biomolecular feedback mechanism implemented using the sequestration binding of two molecules. Our work develops an analytic framework for understanding the hard limits, performance tradeoffs, and architectural properties of this simple model of biological feedback control. Using tools from control theory, we show that there are simple parametric relationships that determine both the stability and the performance of these systems in terms of speed, robustness, steady-state error, and leakiness. These findings yield a holistic understanding of the behavior of sequestration feedback and contribute to a more general theory of biological control systems.eral theory of biological control systems.)
- Flat systems, equivalence and trajectory generation + (Flat systems, an important subclass of non … Flat systems, an important subclass of nonlinear control systems introduced</br>via differential-algebraic methods, are defined in a differential</br>geometric framework. We utilize the infinite dimensional geometry developed</br>by Vinogradov and coworkers: a control system is a diffiety, or more</br>precisely, an ordinary diffiety, i.e. a smooth infinite-dimensional manifold</br>equipped with a privileged vector field. After recalling the definition of</br>a Lie-Backlund mapping, we say that two systems are equivalent if they</br>are related by a Lie-Backlund isomorphism. Flat systems are those systems</br>which are equivalent to a controllable linear one. The interest of</br>such an abstract setting relies mainly on the fact that the above system</br>equivalence is interpreted in terms of endogenous dynamic feedback. The</br>presentation is as elementary as possible and illustrated by the VTOL</br>aircraft.rcraft.)
- The Dynamics of Thin Film Growth: A Modeling Study + (For closed-loop control of thin film depos … For closed-loop control of thin film deposition, one would like to</br>directly control film properties such as roughness, stress, or</br>composition, rather than process parameters like</br>temperatures and flow rates. This requires a</br>model of the dynamic response of film properties to</br>changes in process conditions. </br>Direct atomistic simulation is far too slow to be used in this</br>capacity, but a promising approach we explore here is to derive</br>reduced-order dynamic models from atomistic simulations.</br><p></br>In this paper, we consider film growth on a vicinal surface</br>using a kinetic Monte</br>Carlo model. The temperature range spans the transition from</br>smooth step flow to rough island growth.</br>Proper Orthogonal Decomposition is used to extract</br>the dominant spatial modes from the KMC simulations. Only five spatial modes</br>adequately represent the roughness dynamics for all simulated times and</br>temperatures, indicating that a 5-state model may be</br>sufficient for real-time roughness control.y be sufficient for real-time roughness control.)
- State Estimation Utilization Multiple Description Coding over Lossy Networks + (For state estimation in networked control … For state estimation in networked control systems,</br>the impact of packet dropping and delay over network links is</br>an important problem. In this paper, we introduce multiple description</br>(MD) source coding scheme to improve the statistical</br>stability and performance of the estimation error covariance</br>of Kalman filtering with packet loss. We consider about two</br>cases: when the packet loss over network links occurs in an i.i.d.</br>fashion or in a bursty fashion. Compared with the traditional</br>single description source coding, MD coding scheme can greatly</br>improve the performance of Kalman filtering over a large set</br>of packet loss scenarios in both cases.et of packet loss scenarios in both cases.)
- State Estimation Over Packet Dropping Networks Using Multiple Description Coding + (For state estimation over a communication … For state estimation over a communication network, efficiency and reliability of the network are critical issues. The presence </br>of packet dropping and communication delay can greatly impair our ability to measure and predict states. In this paper, </br>multiple description (MD) codes, a type of network source codes, are used to compensate for this effect on Kalman filtering. </br>We consider two packet dropping models: in one model, packet dropping occurs according to an independent and identically </br>distributed (i.i.d.) Bernoulli random process and in the other model, packet dropping is bursty and occurs according to a </br>Markov chain. We show that MD codes greatly improve the statistical stability and performance of Kalman filter over a large </br>set of packet loss scenarios in both cases. Our conclusions are verified by simulation results.usions are verified by simulation results.)
- Parallelizing Synthesis from Temporal Logic Specifications by Identifying Equicontrollable States + (For the synthesis of correct-by-constructi … For the synthesis of correct-by-construction control policies from temporal logic specifications the scalability of the synthesis algorithms is often a bottleneck. In this paper, we parallelize synthesis from specifications in the GR(1) fragment of linear temporal logic by introducing a hierarchical procedure that allows decoupling of the fixpoint computations. The state space is partitioned into equicontrollable sets using solutions to parameterized reachability games that arise from decomposing the original GR(1) game into smaller reachability games. Following the partitioning, another synthesis problem is formulated for composing the strategies from the decomposed reachability games. The formulation guarantees that composing the synthesized controllers ensures satisfaction of the given GR(1) property. Benchmarking experiments with robot planning problems demonstrate good scalability of the approach.onstrate good scalability of the approach.)
- Analysis of a Digital Clock for Molecular Computing + (Gene expression is often controlled by nat … Gene expression is often controlled by natural genetic regulatory networks that govern the rates at which genes </br>are transcribed. Recent work has shown that synthetic versions of genetic networks can be designed and built in living cells. Applications for these synthetic regulatory networks include intracellular decision-making and computation. In this study, </br>we propose a new synthetic genetic network that behaves as a digital clock, producing square waveform oscillations. We analyze two models of the network, a deterministic model based on Michaelis-Menten kinetics, as well as a stochastic model based on the Gillespie algorithm. Both models predict regions of oscillatory behavior; the deterministic model provides insight into the conditions required to produce the oscillating clock-like behavior, while the stochastic model is truer to natural </br>dynamics. Intracellular stochasticity is seen to contribute phase noise to the oscillator, and we propose improvements for the network and discuss the conceptual foundations of these improvements.ceptual foundations of these improvements.)
- Regulatory activity revealed by dynamic correlations in gene expression noise + (Gene regulatory interactions are context d … Gene regulatory interactions are context dependent, active in some cellular states but not in others. Stochastic fluctuations, or 'noise', in gene expression propagate through active, but not inactive, regulatory links. Thus, correlations in gene expression noise could provide a noninvasive means to probe the activity states of regulatory links. However, global, 'extrinsic', noise sources generate correlations even without direct regulatory links. Here we show that single-cell time-lapse microscopy, by revealing time lags due to regulation, can discriminate between active regulatory connections and extrinsic noise. We demonstrate this principle mathematically, using stochastic modeling, and experimentally, using simple synthetic gene circuits. We then use this approach to analyze dynamic noise correlations in the galactose metabolism genes of Escherichia coli. We find that the CRP-GalS-GalE feed-forward loop is inactive in standard conditions but can become active in a GalR mutant. These results show how noise can help analyze the context dependence of regulatory interactions in endogenous gene circuits. interactions in endogenous gene circuits.)
- Delay-dependent Stability of Genetic Regulatory Networks + (Genetic regulatory networks are biochemica … Genetic regulatory networks are biochemical reaction systems, consisting of a network of interacting genes and associated proteins. The dynamics of genetic regulatory networks contain many complex facets that require careful consideration during the modeling process. The classical modeling approach involves studying systems of ordinary differential equations (ODEs) that model biochemical reactions in a deterministic, continuous, and instantaneous fashion. In reality, the dynamics of these systems are stochastic, discrete, and widely delayed. The first two complications are often successfully addressed by modeling regulatory networks using the Gillespie stochastic simulation algorithm (SSA), while the delayed behavior of biochemical events such as transcription and translation are often ignored due to their mathematically difficult nature. We develop techniques based on delay-differential equations (DDEs) and the delayed Gillespie SSA to study the effects of delays, in both continuous deterministic and discrete stochastic settings. Our analysis applies techniques from Floquet theory and advanced numerical analysis within the context of delay-differential equations, and we are able to derive stability sensitivities for biochemical switches and oscillators across the constituent pathways, showing which pathways in the regulatory networks improve or worsen the stability of the system attractors. These delay sensitivities can be far from trivial, and we offer a computational framework validated across multiple levels of modeling fidelity. This work suggests that delays may play an important and previously overlooked role in providing robust dynamical behavior for certain genetic regulatory networks, and perhaps more importantly, may offer an accessible tuning parameter for robust bioengineering.uning parameter for robust bioengineering.)
- Differential Flatness of Two One-Forms in Arbitrary Number of Variables + (Given a differentially flat system of ODEs … Given a differentially flat system of ODEs, flat outputs that depend only on original</br>variables but not on their derivatives are called zero-flat outputs and systems possessing</br>such outputs are called zero-flat. In this paper we present a theory of zero-flatness for</br>a system of two one-forms in arbitrary number of variables $(t,x^1,\dots,x^N)$. Our</br>approach splits the task of finding zero-flat outputs into two parts. First part involves</br>solving for distributions that satisfy a set of algebraic conditions. If the first part</br>has no solution then the system is not zero-flat. The second part involves finding an</br>integrable distribution from the solution set of the first part. Typically this part</br>involves solving PDEs. Our results are also applicable in determining if a control affine</br>system in $n$ states and $n-2$ controls has flat outputs that depend only on states. We</br>illustrate our method by examples.tes. We illustrate our method by examples.)
- Grasping with Flexible Link Fingers: An Initial Study + (Grasping with flexible fingers presents an … Grasping with flexible fingers presents an attractive approach for</br>certain robotic tasks. Its implementation requires simultaneous</br>position and force control of flexible manipulators, an area about</br>which there is little information in the literature. This paper</br>presents an initial effort at designing controllers for flexible link</br>robots to control both position and force. The analysis is done on a</br>two degree-of-freedom two-link manipulator with the last link</br>flexible. A control strategy is proposed and asymptotic stability is</br>proved. Results from using this control law in simulations and on an</br>experimental setup are presented.nd on an experimental setup are presented.)
- Convex optimal uncertainty quantification: Algorithms and a case study in energy storage placement for power grids + (How does one evaluate the performance of a … How does one evaluate the performance of a stochastic system in the absence of a perfect model (i.e. probability distribution)? We address this question under the framework of optimal uncertainty quantification (OUQ), which is an information-based approach for worst-case analysis of stochastic systems. We are able to generalize previous results and show that the OUQ problem can be solved using convex optimization when the function under evaluation can be expressed in a polytopic canonical form (PCF). We also propose iterative methods for scaling the convex formulation to larger systems. As an application, we study the problem of storage placement in power grids with renewable generation. Numerical simulation results for simple artificial examples as well as an example using the IEEE 14-bus test case with real wind generation data are presented to demonstrate the usage of OUQ analysis. to demonstrate the usage of OUQ analysis.)
- Protocols for Implementing an Escherichia coli Based TX-TL Cell-Free Expression System for Synthetic Biology + (Ideal cell-free expression systems can the … Ideal cell-free expression systems can theoretically emulate an in vivo cellular environment in a controlled in vitro platform. This is useful for expressing proteins and genetic circuits in a controlled manner as well as for providing a prototyping environment for synthetic biology. To achieve the latter goal, cell-free expression systems that preserve endogenous Escherichia coli transcription-translation mechanisms are able to more accurately reflect in vivo cellular dynamics than those based on T7 RNA polymerase transcription. We describe the preparation and execution of an efficient endogenous E. coli based transcription-translation (TX-TL) cell-free expression system that can produce equivalent amounts of protein as T7-based systems at a 98% cost reduction to similar commercial systems. The preparation of buffers and crude cell extract are described, as well as the execution of a three tube TX-TL reaction. The entire protocol takes five days to prepare and yields enough material for up to 3000 single reactions in one preparation. Once prepared, each reaction takes under 8 hr from setup to data collection and analysis. Mechanisms of regulation and transcription exogenous to E. coli, such as lac/tet repressors and T7 RNA polymerase, can be supplemented.6 Endogenous properties, such as mRNA and DNA degradation rates, can also be adjusted.7 The TX-TL cell-free expression system has been demonstrated for large-scale circuit assembly, exploring biological phenomena, and expression of proteins under both T7- and endogenous promoters. Accompanying mathematical models are available. The resulting system has unique applications in synthetic biology as a prototyping environment, or "TX-TL biomolecular breadboard."nment, or "TX-TL biomolecular breadboard.")
- Robust Safe Control Synthesis with Disturbance Observer-Based Control Barrier Functions + (In a complex real-time operating environme … In a complex real-time operating environment, external disturbances and uncertainties adversely affect the safety, stability, and performance of dynamical systems. This paper presents a robust stabilizing safety-critical controller synthesis framework with control Lyapunov functions (CLFs) and control barrier functions (CBFs) in the presence of disturbance. A high-gain input observer method is adapted to estimate the time-varying unmodelled dynamics of the CBF with an error bound using the first-order time derivative of the CBF. This approach leads to an easily tunable low order disturbance estimator structure with a design parameter as it utilizes only the CBF constraint. The estimated unknown input and associated error bound are used to ensure robust safety and exponential stability by formulating a CLF-CBF quadratic program. The proposed method is applicable to both relative degree one and higher relative degree CBF constraints. The efficacy of the proposed approach is demonstrated using a numerical simulations of an adaptive cruise control system and a Segway platform with an external disturbance.way platform with an external disturbance.)
- A Contract-Based Methodology for Aircraft Electric Power System Design + (In an aircraft electric power system, one … In an aircraft electric power system, one or more supervisory control units actuate a set of electromechanical switches to dynamically distribute power from generators to loads, while satisfying safety, reliability, and real-time performance requirements. To reduce expensive redesign steps, this control problem is generally addressed by minor incremental changes on top of consolidated solutions. A more systematic approach is hindered by a lack of rigorous design methodologies that allow estimating the impact of earlier design decisions on the final implementation. To achieve an optimal implementation that satisfies a set of requirements, we propose a platform-based methodology for electric power system design, which enables independent implementation of system topology (i.e., interconnection among elements) and control protocol by using a compositional approach. In our flow, design space exploration is carried out as a sequence of refinement steps from the initial specification toward a final implementation by mapping higher level behavioral and performance models into a set of either existing or virtual library components at the lower level of abstraction. Specifications are first expressed using the formalisms of linear temporal logic, signal temporal logic, and arithmetic constraints on Boolean variables. To reason about different requirements, we use specialized analysis and synthesis frameworks and formulate assume guarantee contracts at the articulation points in the design flow. We show the effectiveness of our approach on a proof-of-concept electric power system design.f-of-concept electric power system design.)
- Leveraging Classification Metrics for Quantitative System-Level Analysis with Temporal Logic Specifications + (In many autonomy applications, performance … In many autonomy applications, performance of perception algorithms is important for effective planning and control. In this paper, we introduce a framework for computing the probability of satisfaction of formal system specifications given a confusion matrix, a statistical average performance measure for multi-class classification. We define the probability of satisfaction of a linear temporal logic formula given a specific initial state of the agent and true state of the environment. Then, we present an algorithm to construct a Markov chain that represents the system behavior under the composition of the perception and control components such that the probability of the temporal logic formula computed over the Markov chain is consistent with the probability that the temporal logic formula is satisfied by our system. We illustrate this approach on a simple example of a car with pedestrian on the sidewalk environment, and compute the probability of satisfaction of safety requirements for varying parameters of the vehicle. We also illustrate how satisfaction probability changes with varied precision and recall derived from the confusion matrix. Based on our results, we identify several opportunities for future work in developing quantitative system-level analysis that incorporates perception models.lysis that incorporates perception models.)
- Effect of Narrowband Channels on the Control + (In mobile sensor networks, sensor measurem … In mobile sensor networks, sensor measurements</br>as well as control commands are transmitted over</br>wireless time-varying links. It then becomes considerably</br>important to address the impact of imperfect communication</br>on the overall performance. In this paper, we</br>study the effect of time-varying communication links on</br>the control performance of a mobile sensor node. In</br>particular, we investigate the impact of fading. We derive</br>key performance measure parameters to evaluate the</br>overall feedback control performance over narrowband</br>channels. We show that fading can result in considerable</br>delay and/or poor performance of the mobile sensor</br>depending on the system requirements. To improve the</br>performance, we then show how the application layer can</br>use the channel status information of the physical layer</br>to adapt control commands accordingly. We show that</br>sharing information across layers can improve the overall</br>performance considerably. We verify our analytical</br>results by simulating a wireless speed control problem.mulating a wireless speed control problem.)
- Synthetic mammalian signaling circuits for robust cell population control + (In multicellular organisms, cells actively … In multicellular organisms, cells actively sense, respond to, and control their own population density. Synthetic mammalian quorum sensing circuits could provide insight into principles of population control and improve cell therapies. However, a key challenge is avoiding their inherent sensitivity to “cheater” mutations that evade control. Here, we repurposed the plant hormone auxin to enable orthogonal mammalian cell-cell communication and quorum sensing. Further, we show that a “paradoxical” circuit design, in which auxin stimulates and inhibits net cell growth at different concentrations, achieves population control that is robust to cheater mutations, controlling growth for 43 days of continuous culture. By contrast, a non-paradoxical control circuit limited growth but was susceptible to mutations. These results establish a foundation for future cell therapies that can respond to and control their own population sizes.to and control their own population sizes.)
- When are Distributed Algorithms Robust? + (In recent years, numerous distributed algo … In recent years, numerous distributed algorithms </br>have been proposed which, when executed by a team of </br>dynamic agents, result in the completion of a joint task. </br>However, for any such algorithm to be practical, one should be </br>able to guarantee that the task is still satisfactorily executed </br>even when agents fail to communicate with others or to </br>perform their designated actions correctly. In this paper, </br>we present a concept of robustness which is well-suited for </br>general distributed algorithms for teams of dynamic agents. </br>Our definition extends a similar notion introduced in the </br>distributed computation literature for consensus problems. We </br>illustrate the definition by considering a variety of algorithms.on by considering a variety of algorithms.)
- Towards Formal Synthesis of Reactive Controllers for Dexterous Robotic Manipulation + (In robotic finger gaiting, fingers continu … In robotic finger gaiting, fingers continuously manipulate an object until joint limitations or mechanical limitations periodically force a switch of grasp. Current approaches to gait planning and control are slow, lack formal guarantees on correctness, and are generally not reactive to changes in object geometry. To address these issues, we apply advances in formal methods to model a gait subject to external perturbations as a two-player game between a finger controller and its adversarial environment. High-level specifications are expressed in linear temporal logic (LTL) and low-level control primitives are designed for continuous kinematics. Simulations of planar manipulation with our synthesized correct-by-construction gait controller demonstrate the benefits of this approach.demonstrate the benefits of this approach.)
- Fast and flexible simulation and parameter estimation for synthetic biology using bioscrape + (In systems and synthetic biology, it is co … In systems and synthetic biology, it is common to build chemical reaction network (CRN) models of biochemical circuits and networks. Although automation and other high-throughput techniques have led to an abundance of data enabling data-driven quantitative modeling and parameter estimation, the intense amount of simulation needed for these methods still frequently results in a computational bottleneck. Here we present bioscrape (Bio-circuit Stochastic Single-cell Reaction Analysis and Parameter Estimation) - a Python package for fast and flexible modeling and simulation of highly customizable chemical reaction networks. Specifically, bioscrape supports deterministic and stochastic simulations, which can incorporate delay, cell growth, and cell division. All functionalities - reaction models, simulation algorithms, cell growth models, partitioning models, and Bayesian inference - are implemented as interfaces in an easily extensible and modular object-oriented framework. Models can be constructed via Systems Biology Markup Language (SBML) or specified programmatically via a Python API. Simulation run times obtained with the package are comparable to those obtained using C code - this is particularly advantageous for computationally expensive applications such as Bayesian inference or simulation of cell lineages. We show the package’s simulation capabilities on a variety of example simulations of stochastic gene expression. We also demonstrate the package by using it to do parameter inference on a model of integrase enzyme-mediated DNA recombination dynamics with experimental data. The bioscrape package is publicly available online (Pandey, Poole, et al., 2023) along with more detailed documentation and examples. more detailed documentation and examples.)
- A Homotopy Algorithm for Approximating Geometric Distributions by Integrable Systems + (In the geometric theory of nonlinear contr … In the geometric theory of nonlinear control systems, the notion of a distribution and</br>the dual notion of codistribution play a central role. Many results in nonlinear control</br>theory require certain distributions to be integrable. Distributions (and codistributions)</br>are not generically integrable and, moreover, the integrability property is not likely to</br>persist under small perturbations of the system. Therefore, it is natural to consider the</br>problem of approximating a given codistribution by an integrable codistribution, and to</br>determine to what extent such an approximation may be used for obtaining approximate</br>solutions to various problems in control theory. In this note, we concentrate on the</br>purely mathematical problem of approximating a given codistribution by an integrable</br>codistribution. We present an algorithm for approximating an m-dimensional nonintegrable</br>codistribution by an integrable one using a homotopy approach. The method yields an</br>approximating codistribution that agrees with the original codistribution on an</br>m-dimensional submanifold E_0 of R^n.n an m-dimensional submanifold E_0 of R^n.)
- Uncertain semantics, representation nuisances, and necessary invariance properties of bootstrapping agents + (In the problem of bootstrapping, an agent … In the problem of bootstrapping, an agent must learn to use an unknown body, in an unknown world, starting from zero information about the world, its sensors, and its actuators. So far, this fascinating problem has not been given a proper formalization. In this paepr, we provide a possible rigorous definition of one of the key aspects of bootstrapping, namely the fact that an agent must be able to use âuninterpretedâ observations and commands. We show that this can be formalized by positing the existence of representation nuisances that act on the data, and which must be tolerated by an agent. The classes of nuisances tolerated indirectly encode the assumptions needed about the world, and therefore the agent's ability to solve smaller or larger classes of bootstrapping instances. Moreover, we argue that the behavior of an agent that claims optimality must actually be invariant to the representation nuisances, and we discuss several design principles to obtain such invariance.sign principles to obtain such invariance.)
- Cone invariance and rendezvous of multiple agents + (In this article is presented a dynamical s … In this article is presented a dynamical systems framework for analysing multi-agent rendezvous problems and characterize the dynamical behaviour of the collective system. Recently, the problem of rendezvous has been addressed considerably in the graph theoretic framework, which is strongly based on the communication aspects of the problem. The proposed approach is based on the set invariance theory and focusses on how to generate feedback between the vehicles, a key part of the rendezvous problem. The rendezvous problem is defined on the positions of the agents and the dynamics is modelled as linear first-order systems. These algorithms have also been applied to non-linear first-order systems.</br></br>The rendezvous problem in the framework of cooperative and competitive dynamical systems is analysed that has had some remarkable applications to biological sciences. Cooperative and competitive dynamical systems are shown to generate monotone flows by the classical Muller--Kamke theorem, which is analysed using the set invariance theory. In this article, equivalence between the rendezvous problem and invariance of an appropriately defined cone is established. The problem of rendezvous is cast as a stabilization problem, with a the set of constraints on the trajectories of the agents defined on the phase plane. The n-agent rendezvous problem is formulated as an ellipsoidal cone invariance problem in the n-dimensional phase space. Theoretical results based on set invariance theory and monotone dynamical systems are developed. The necessary and sufficient conditions for rendezvous of linear systems are presented in the form of linear matrix inequalities. These conditions are also interpreted in the Lyapunov framework using multiple Lyapunov functions. Numerical examples that demonstrate application are also presented.emonstrate application are also presented.)
- Online Control Customization via Optimization-Based Control + (In this chapter, we present a framework fo … In this chapter, we present a framework for online control customization that</br>makes use of finite-horizon, optimal control combined with real-time</br>trajectory generation and optimization. The results are based on a novel</br>formulation of receding-horizon optimal control that replaces the traditional</br>terminal constraints with a control Lyapunov function-based terminal cost.</br>This formulation leads to reduced computational requirements and allows proof</br>of stability under a variety of realistic assumptions on computation. By</br>combining these theoretical advances with advances in computational power for</br>real-time, embedded systems, we demonstrate the efficacy of online control</br>customization via optimization-based control. The results are demonstrated</br>using a nonlinear, flight control experiment at Caltech.ear, flight control experiment at Caltech.)
- Decompositions for Control Systems on Manifolds with an Affine Connection + (In this letter we present a decomposition … In this letter we present a decomposition for control systems whose drift vector field</br>is the geodesic spray associated with an affine connection. With the geometric insight</br>gained with this decomposition, we are able to easily prove some special results for this</br>class of control systems. Examples illustrate the theory.l systems. Examples illustrate the theory.)
- On a Stochastic Sensor Selection Algorithm with Applications in Sensor Scheduling and Sensor Coverage + (In this note we consider the following pro … In this note we consider the following problem. Suppose a set of sensors is jointly trying to estimate a process. One sensor takes a measurement at every time step and the measurements are then exchanged among all the sensors. What is the sensor schedule that results in the mininmum error covariance? We describe a stoachastic sensor selection strategy that is easy to implement and is computationally tractable. The problem described above comes up in many domains out of which we discuss two. In the sensor selection problem, there are multiple sensors that cannot operate simultaneously (eg, sonars in the same frequency band). Thus measurements need to be scheduled. In the sensor coverage problem, a geographical area needs to be covered by mobile sensors each with limited range. Thus from every position, the sensors obtain a different viewpoint of the area and the sensors need to optimize their positions. The algorithm is applied to these problems and illustrated through simple examples.s and illustrated through simple examples.)