Property:Abstract
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F
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. +
M
Modeling the Effects of Compositional Context on Promoter Activity in an E. Coli Extract based Transcription-Translation System +
One of the fundamental challenges in synthesizing complex biocircuits from existing biocircuit components is understanding how the spatial arrangement of biocircuit components impacts component behavior. In this paper we develop a set of synthetic biology parts for systematically probing the effects of spatial arrangement on transcriptional expression. Our initial experimental assays prove that even the rearrangement of two biocircuit parts (comprised of a promoter, coding sequence, and terminator) into three spatially distinct orientations (convergent, divergent, and tandem orientation) can exhibit significantly different levels of transcriptions. These findings motivate the need for mathematical models to describe these spatial context effects. We pose a novel nonlinear mass-action kinetics based model that enables the integration of knowledge about spatial or compositional context and canonical descriptions of transcriptional dynamics. Our findings suggest that compositional context is a key factor in determining bio- circuit part performance and thus represent another important piece in biocircuit interconnection theory. +
E
Operability enhancement is one of the major goals for active control of rotating stall
and surge in aeroengines. The model developed by Moore and Greitzer exhibits the
qualitative behavior of rotating stall and surge dynamics and thus can be used for
controller designs. Based on this model, we derive a normal form from which explicit
relations between the stall and surge inception process and the shape of compressor
characteristics are obtained via bifurcation analysis. Analysis for the normal form with
bleed valve actuator dynamics shows that under certain circumstances the optimal control
is the "bang-on" control law that drives the bleed valve to open against its
rate limit once the disturbances grow out of the noise level. +
C
Optimal uncertainty quantification (OUQ) is a framework for nu- merical extreme-case analysis of stochastic systems with imperfect knowl- edge of the underlying probability distribution and functions/events. This paper presents sufficient conditions (when underlying functions are known) under which an OUQ problem can be reformulated as a finite-dimensional convex optimization problem. +
S
Synthesizing Combination Therapies for Evolutionary Dynamics of Disease for Nonlinear Pharmacodynamics +
Our previous results proposed an iterative scalable algorithm for the systematic design of sparse, small gain feedback strategies that stabilize the evolutionary dynamics of a generic disease model with linear pharmacodynamics. Here we use piecewise linear approximations to model the nonlinear drug effects and leverage results from optimal controller synthesis for positive systems to formulate the feedback synthesis problem as an optimization problem that sequentially explores piecewise linear subsystems corresponding to higher and higher treatment dosages. +
R
Rapid prototyping of biomolecular circuits through module characterization in cell-free expression systems +
Over the past years, the field of synthetic biology has gained a significant array of tools and parts, making way for increasingly complex bio-molecular circuits to be constructed. The development of biocircuits can be facilitated by assembling parts in a less complex, cell-free, environment which contains only the machinery for gene transcription (TX) and translation (TL), which have been extracted from bacteria. In this project, a part library was collected and used to assemble DNA constructs for a newly designed biocircuit. An in vitro TX-TL extract was used to test the circuit modules using linear DNA, and in parallel with predictive modeling of the biomolecular reactions, the overall circuit design was evaluated. The results have given valuable insight into the performance of the circuit modules in a much shorter time than conventional in vivo cloning and testing would have achieved. +
M
Model of Paradoxical Signaling Regulated T-Cell Population Control for Design of Synthetic Circuits +
Paradoxical signaling occurs when the same sig- naling molecule can trigger antagonistic cell functions. For example, T-Cells secret cytokine IL-2 which promotes T-Cell proliferation and also affects cell death. It has been shown that cells with this signaling capability have bi-stable population dynamics and can achieve identical levels of population homeostasis independent of initial cell concentrations. These capabilities are desirable in the context of synthetic population control circuits designed for application in therapeutic treatment of various diseases. It thus becomes important to understand the dependence of the cell system on the intracellular paradoxical components and to develop accurate models to provide insight into optimal design characteristics. Here, we create a model that integrates three IL-2 driven intracellular mechanisms that trigger 1) T-cell proliferation 2) T-cell apoptosis and 3) IL-2 production. Using this model, we are able to explore the internal mechanisms necessary for paradoxical signaling in T-Cells. It was shown that the intracellular mechanisms considered were sufficient to produce population dynamic characteristics of paradoxical signaling consistent with published systems level models and data. Furthermore, analysis of parameters revealed dependency of population homeostatic stability on the production and activation of the specific intracellular proteins considered. +
R
Performance analysis of a large class of nonlinear
systems is proven to be equivalent to performance
analysis of a constrained uncertain linear system,
for which computable analysis methods have already been
developed. +
Q
Performance of biomolecular circuits is affected by changes in temperature, due to its influence on underlying reaction rate parameters. While these performance variations have been estimated using Monte Carlo simulations, how to analytically bound them is generally unclear. To address this, we apply control-theoretic representations of uncertainty to examples of different biomolecular circuits, developing a framework to represent uncertainty due to temperature. We estimate bounds on the steady-state performance of these circuits due to temperature uncertainty. Through an analysis of the linearised dynamics, we represent this uncertainty as a feedback uncer- tainty and bound the variation in the magnitude of the input- output transfer function, providing a estimate of the variation in frequency-domain properties. Finally, we bound the variation in the time trajectories, providing an estimate of variation in time-domain properties. These results should enable a framework for analytical characterisation of uncertainty in biomolecular circuit performance due to temperature variation and may help in estimating relative performance of different controllers. +
T
Phage integrase-based circuits are an alternative approach to relying on transcriptional and translational repression for biomolecular circuits. Previous research has shown that circuits based on integrases can perform a variety of functions, including counters, Boolean logic operators, memory modules and temporal event detectors. It is therefore essential to develop a principled theoretical and experimental framework for the design, implementation and study of such circuits. One of the fundamental questions that such a framework should address concerns the functionality limitations and temporal dynamics of the integrases as regulatory elements. We have tested the functionality of several large serine type integrases from a recently published library in a cell-free transcription-translation (TX-TL) platform. In addition, we have explored experimentally and through mathematical modelling and simulations how integrase dynamics depends on the concentration of integrase and that of its binding sites.
We report that sequestration of integrase molecules, either in the form of monomers or dimers, by the integrase's own binding sites dominates integrase dynamics, and that the delay in the activation of the reporter is negatively correlated with integrase plasmid concentration. We have validated our sequestration hypothesis by building a model with MATLAB’s SimBiology toolbox, and running simulations with various integrase and binding sites concentrations. The simulation results qualitatively match the experimental results, and offer further insights into the system. +
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. +
