Property:Abstract
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Q
Plasmids are found across bacteria, archaea, and eukaryotes and play an important role in evolution. Plasmids exist at different copy numbers, the number of copies of the plasmid per cell, ranging from a single plasmid per cell to hundreds of plasmids per cell. This feature of a copy number greater than one can lead to a population of plasmids within a single cell that are not identical clones of one another, but rather have individual mutations that make a given plasmid unique. During cell division, this population of plasmids is partitioned into the two daughter cells, resulting in a random distribution of different plasmid variants in each daughter. In this study, we use stochastic simulations to investigate how random plasmid partitioning compares to a perfect partitioning model. Our simulation results demonstrate that random plasmid partitioning accelerates mutant allele fixation when the allele is beneficial and the selection is in an additive or recessive regime where increasing the copy number of the beneficial allele results in additional benefit for the host. This effect does not depend on the size of the benefit conferred or the mutation rate, but is magnified by increasing plasmid copy number. +
P
Pre-orders on systems are the basis for abstraction based verification of systems. In this paper, we investigate pre-orders for reasoning about stability with respect to inputs of hybrid systems. First, we present a superposition type theorem which gives a characterization of the classical incremental input-to-state stability of continuous systems in terms of the traditional epsilon/delta-definition of stability. We use this as the basis for defining a notion of incremental input- to-state stability of hybrid systems. Next, we present a pre-order on hybrid systems which preserves incremental input- to-state stability, by extending the classical definitions of bisimulation relations on systems with input, with uniform continuity constraints. We show that the uniform continuity is a necessary requirement by exhibiting counter-examples to show that weaker notions of input bisimulation with just continuity requirements do not suce to preserve stability. Finally, we demonstrate that the definitions are useful, by exhibiting concrete abstraction functions which satisfy the definitions of pre-orders. +
C
Control of Rotating Stall in a Low-Speed Axial Flow Compressor Using Pulsed Air Injection: Modeling, Simulations, and Experimental Validation +
Previous results in the use of pulsed air injection for
active control of rotating stall have suggested that air injectors
have the effect of shifting the steady state compressor
characteristic. In this paper we analyze the effect of a compressor
characteristic actuation scheme for the three state Moore Greitzer
compression system model. It is shown that closed loop feedback based
on the square magnitude of the first rotating stall mode can be used
to decrease the hysteresis region associated with the transition from
unstalled to stalled and back to unstalled operation. The compressor
characteristic shifting idea is then applied to a higher fidelity
distributed model in which the characteristic shifting has phase
content in addition to the magnitude content captured by the three
state model. The optimal phasing of the air injection relative to the
sensed position of the stall cell is determined via simulation and the
results found to agree with those obtained via an experimental
parametric study on the Caltech low-speed axial flow compressor.} +
Characterizing the Effects of Air Injection on Compressor Performance for Use in Active Control of Rotating Stall +
Previous work at Caltech has developed an air
injection controller for rotating stall based on the idea of a
shifting compressor characteristic. To further understand the
properties of this controllers, a series of open loop tests were
performed to measure the performance characteristics of an axial flow
compression system when air was injected upstream of the rotor face.
The distance from the rotor face, the span-wise position, and the
angle relative to the mean axial flow were varied. These tests show
that the injection of air has drastic effects on the stalling mass
flow rate and on the size of the hysteresis loop associated with
rotating stall. The stalling mass flow rate was decreased by 10\% and
the hysteresis loop was completely eliminated under some conditions. +
Previous work at Caltech has developed a controller for rotating stall
in axial flow compressors using pulsed air injection. In this work,
theory is developed for the combination of this air injection
controller with a bleed valve controller for the system's surge
dynamics. The controller analysis is based on the surge dynamics
acting on a slow time scale relative to the rotating stall dynamics.
Experiments demonstrating this controller design on the Caltech rig
are also presented. +
T
Quantifying performance of biomolecular circuit designs across different environmental conditions is a key step in assessing their robustness. It is generally unclear how robust this performance is to the important environmental variable of temperature. Here, we address this issue for a transcriptional negative feedback circuit design that can speed up the response time using a combination of simple computational methods and dynamic experimental measurements. We use a simple two-state model of gene expression to illustrate different ways in which temperature dependence of reaction rate parameters can propagate through to the functional output. Next, we extend this analysis to the response time of a transcriptional negative feedback circuit design. Finally, we present experimental results characterizing how response time of a negative transcriptional feedback circuit depends on temperature. These results help to develop framework for assessing how functional output of biomolecular circuit designs depend on temperature. +
D
RNA thermometers mediate responses to temperature changes in various natural circuits, and have been developed in a synthetic context as well. However, a toolbox of RNA thermometers with diâµerent sensitivities to temperature is lacking. Here, we address this issue using a combination of computational and experimental methodologies. We analysed a set of available synthetic RNA thermometers through a quantification of their activity as a function of temperatures in a cell- free expression molecular breadboard system as well as through computation of their melt profiles. Based on this, we computed melt profiles of a library of RNA thermometers and found that the library contained RNA thermometers with a range of sensitivities and thresholds in their response to temperature. We constructed this library and found, through preliminary measurements, a wide range of responses to temperature, which in some cases matched the computational predictions. The constructed library represents a toolbox of RNA thermometers with different sensitivities and is foun- dational work towards synthetic biology applications such as efficient control of large volume chemical reactors, precise spatiotemporal control of gene expression as well as tools to engineer robustness to temperature in biomolecular circuits. +
L
Realizing homeostatic control of metabolites or proteins is one of the key goals of synthetic circuits. However, if control is only implemented internally in individual cells, cell-cell heterogeneity may break the homeostasis on population level since cells do not contribute equally to the production or regulation. New control structures are needed to achieve robust functionality in heterogeneous cell populations. Quorum sensing (QS) serves as a collective mechanism by releasing and sensing small and diffusible signaling molecules for group decision-making. We propose a layered feedback control structure that includes a global controller using quorum sensing and a local controller via internal signal-receptor systems. We demonstrate with modeling and simulation that the global controller drives contributing cells to compensate for disturbances while the local controller governs the fail-mode performance in non-contributing cells. The layered controller can tolerate a higher portion of non-contributing cells or longer generations of mutant cells while maintaining metabolites or proteins level within a small error range, compared with only internal feedback control. We further discuss the potential of such layered structures in robust control of cell population size, population fraction and other population-dependent functions. +
C
Receding horizon control allows a blending of navigation and control functions
at the inner and outer loop levels and significantly enhances the ability of the control
system to react to complex dynamic and environmental constraints. In this paper, we
explore some of the limits of receding horizon control, including the extent to which
traditional control specifications can be cast as RHC problem specifications. Simulation
results for a planar flight vehicle with representative flight dynamics illustrate
the main features of the proposed approach. +
N
Recent advances in geometric mechanics, motivated in large part by applications in
control theory, have introduced new tools for understanding and utilizing the structure
present in mechanical systems. In particular, the use of geometric methods for analyzing
Lagrangian systems with both symmetries and non-integrable (or nonholonomic) constraints
has led to a unified formulation of the dynamics that has important implications for a
wide class of mechanical control systems. This paper presents a survey of recent results
in this area, focusing on the relationships between geometric phases, controllability, and
curvature, and the role of trajectory generation in nonlinear controller synthesis.
Examples are drawn from robotics and flight control systems, with an emphasis on motion
control problems. +
S
Recent advances in nucleic acids engineering introduced several RNA-based regulatory components for synthetic gene circuits, expanding the toolsets to engineer organisms. In this work, we designed genetic circuits implementing an RNA aptamer previously described to have the capability of binding to the T7 RNA polymerase and inhibiting its activity in vitro. Using in vitro transcription assays, we first demonstrated the utility of the RNA aptamer in combination with programmable synthetic transcription networks. As a step to quickly assess the feasibility of aptamer functions in vivo, a cell-free expression system was used as a breadboard to emulate the in vivo conditions of E. coli. We tested the aptamer and its three sequence variants in the cell-free expression system, verifying the aptamer functionality in the cell-free testbed. In vivo expression of aptamer and its variants demonstrated control over GFP expression driven by T7 RNA polymerase with different response curves, indicating its ability to serve as building blocks for both logic circuits and transcriptional cascades. This work elucidates the potential of RNA-based regulators for cell programming with improved controllability leveraging the fast production and degradation time scales of RNA molecules. +
V
Recent experimental results demonstrate that flies posses a robust tendency to orient towards
the frontally-centered pole of the visual motion field that typically occurs during upwind flight.
In this paper we present a closed loop flight model, with a control algorithm based on feedback
of the location of the visual pole of contraction, which is affected by changes in wind direction.
The feasibility of visually guided upwind orientation is demonstrated with a model derived
from current understanding of the biomechanics and sensorimotor computation of insects. The
matched filter approach used to model the visual system computations compares extremely well
with open-loop experimental data. +
Q
Recent work has introduced biocircuit architectures that exhibit robust oscillatory behavior in organisms ranging from cyanobacteria to mammals. Complementary research in synthetic biology has introduced oscillators in vivo and in vitro suggesting that robust oscillation can be recapitulated using a small number of biochemical components. In this work, we introduce signaling crosstalk in biocircuits as a consequence of enzyme-mediated biochemical reactions. As a motivating example, we consider an in vitro oscillator with two types of crosstalk: crosstalk in production and degradation of RNA signals. We then pose a framework for quantifying crosstalk and use it to derive several dynamical constraints and suggest design techniques for ameliorating crosstalk in in vitro biochemical systems. As an example, we show that the balance between production and degradation crosstalk plays a key role in determining system stability, potentially leading to loss of oscillatory behavior. We demonstrate that the effects of crosstalk can attenuated through the effective tuning of two key parameters in order to recover desired system dynamics. +
E
End-to-End Safe Reinforcement Learning through Barrier Functions for Safety-Critical Continuous Control Tasks +
Reinforcement Learning (RL) algorithms have found limited success beyond simulated applications, and one main reason is the absence of safety guarantees during the learning process. Real world systems would realistically fail or break be- fore an optimal controller can be learned. To address this issue, we propose a controller architecture that combines (1) a model-free RL-based controller with (2) model-based controllers utilizing control barrier functions (CBFs) and (3) on- line learning of the unknown system dynamics, in order to ensure safety during learning. Our general framework lever- ages the success of RL algorithms to learn high-performance controllers, while the CBF-based controllers both guarantee safety and guide the learning process by constraining the set of explorable polices. We utilize Gaussian Processes (GPs) to model the system dynamics and its uncertainties.
Our novel controller synthesis algorithm, RL-CBF, guaran- tees safety with high probability during the learning process, regardless of the RL algorithm used, and demonstrates greater policy exploration efficiency. We test our algorithm on (1) control of an inverted pendulum and (2) autonomous car-following with wireless vehicle-to-vehicle communication, and show that our algorithm attains much greater sample efficiency in learning than other state-of-the-art algorithms and maintains safety during the entire learning process. +
T
RoboFlag is a robotic version of capture the flag that can be played either with autonomous controllers or with up to two humans in the loop. The goal of the game is to capture the flag of the other team, which is located in their defense zone, and bring it back to your home zone. The other team defends their flag by tagging your robots on their side of the field, at the same time as trying to capture your flag. Some of the interesting features of RoboFlag are that the robots have limited sensing capability and distributed processing, requiring that information be communicated between robots across limited bandwidth links. This makes the game much more challenging since you have two determine your actions without a complete view of the playing field.
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This paper gives an overview of the RoboFlag competition and describes some of the research challenges that are represented in the game. +
S
Robot navigation in urban environments requires situational reasoning. Given the complexity of the environment and the behavior specified by traffic rules, it is necessary to recognize the current situation to impose the correct
traffic rules. In an attempt to manage the complexity of the situational reasoning subsystem, this paper describes a finite state machine model to govern the situational reasoning process. The logic state machine and its interaction with the planning system are discussed. The approach was implemented on Alice, Team Caltech's entry into the 2007 DARPA Urban Challenge. Results from the qualifying rounds are discussed. The approach is validated and the shortcomings of the implementation are identified. +
G
Robotic locomotion is based in a variety of instances upon cyclic changes in the shape
of a robot mechanism. Certain variations in shape exploit the constrained nature of a
robot's interaction with its environment to generate net motion. This is true for legged
robots, snakelike robots, and wheeled mobile robots undertaking maneuvers such as parallel
parking. In this paper we explore the use of tools from differential geometry to model and
analyze this class of locomotion mechanisms in a unified way. In particular, we describe
locomotion in terms of the geometric phase associated with a connection on a principal
bundle, and address issues such as controllability and choice of gait. We also provide an
introduction to the basic mathematical concepts which we require and apply the theory to
numerous example systems. +
R
Robots with structural flexibility provide an attractive alternative
to rigid robots for many of the new and evolving applications in
robotics. In certain applications their use is unavoidable. The
increased complexity in modeling and control of such robots is offset
by desirable performance enhancements in some respects. In this thesis
we present a singular perturbation approach for modeling, analysis and
control of robots with flexibility. As our singular perturbation
approach does not treat the flexible manipulator as a perturbation of
the rigid manipulator, it can treat significant flexibility, beyond
the linear range. Analysis based on this approach leads to some
provably stable control laws for the hybrid position and force control
of flexible-link manipulators. The analysis is done in the framework
of a single robot manipulator in a constrained motion
task. Simulations and experimental results are presented for this
case. To show applicability of the results to more general and
complex systems with flexibilities we also present experimental data
from a planar, two-fingered, reconfigurable grasping setup which allows
rigid and flexible configurations. The aim of the experimentation is
to show the applicability of the control laws and analysis developed,
and to determine the performance enhancements resulting from the
introduction of flexibility. Experimental data is analysed to show the
tradeoffs between controller complexity and performance enhancement as
we deal with greater flexibility. Various performance criteria are set
up and experimental results are discussed within their framework. We
conclude that large flexibility can be controlled without too much
additional effort, has performance comparable to that of rigid robots,
and possesses enhancing properties which make it appealing for use in
certain types of applications. +
A
Robustness to temperature variation is an important specification in biomolecular circuit design. While the cancellation of parametric temperature dependencies has been shown to improve the temperature robustness of the period in a synthetic oscillator design, the performance of other biomolecular circuit designs in different temperature conditions is relatively unclear. Using a combination of experimental measurements and mathematical models, we assessed the temperature robustness of two biomolecular circuit motifs—a negative feedback loop and a feedforward loop. We found that the measured responses of both the circuits changed with temperature, both in the amplitude and in the transient response. We also found that, in addition to the cancellation of parametric temperature dependencies, certain parameter regimes could facilitate the temperature robustness of the negative feedback loop, although at a performance cost. We discuss these parameter regimes in the context of the measured data for the negative feedback loop. These results should help develop a framework for assessing and designing temperature robustness in biomolecular circuits. +
N
Rotating stall and surge are aerodynamic instabilities that limit the performance of
aeroengines. A set of magnetic bearings supporting the compressor rotor is a potential
actuator for active control of rotating stall and surge. Based on a first-principles model
we show that using this type of actuation, the first harmonic mode of rotating stall is
linearly controllable, but the second harmonic mode and the surge mode are linearly
uncontrollable. We then give an explicit procedure for designing feedback laws such that
the first mode is linearly stabilized and the criticality of the Hopf bifurcations of the
second mode and the surge mode are supercritical. We also investigate the effects of
magnitude saturation on the regions of attraction. We demonstrate the theoretical results
by numerical simulations of a model for a transonic compressor at the NASA Lewis Research
Center. +
