Property:Abstract
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S
AbstractWe examine the problem of distributed estimation
when only one sensor can take a measurement per time step.
We solve for the optimal recursive estimation algorithm when
the sensor switching schedule is given. We then consider the
effect of noise in communication channels. We also investigate
the problem of determining an optimal sensor switching strategy.
We see that this problem involves searching a tree in general
and propose two strategies for pruning the tree to minimize the
computation. The first is a sliding window strategy motivated
by the Viterbi algorithm, and the second one uses thresholding.
The performance of the algorithms is illustrated using numerical
examples. +
E
AbstractâIn this paper, we consider a state estimation
problem over a bandwidth limited network. A sensor network
consisting of N sensors is used to observe the states of M
plants, but only p · N sensors can transmit their measurements
to a centralized estimator at each time. Therefore a suitable
scheme that schedules the proper sensors to access the network
at each time so that the total estimation error is minimized is
required. We propose four different sensor scheduling schemes.
The static and stochastic schemes assume no feedback from
the estimator to the scheduler, while the two dynamic schemes,
Maximum Error First (MEF) and Maximum Deduction First
(MDF) assume such feedback is available. We compare the
four schemes via some examples and show MEF and MDF
schemes are better than the static and stochastic schemes, which
demonstrates that feedback can play an important role in this
remote state estimation problem. We also show that MDF is
better than MEF as MDF considers the total estimation error
while MEF considers the individual estimation error. +
L
Linear DNA for rapid prototyping of synthetic biological circuits in an Escherichia coli based TX-TL cell-free system +
Accelerating the pace of synthetic biology experiments requires new approaches for rapid prototyping of circuits from individual DNA regulatory elements. However, current testing standards require days to weeks due to cloning and in vivo transformation. In this work, we first characterized methods to protect linear DNA strands from exonuclease degradation in an Escherichia coli based transcription-translation cell-free system (TX-TL), as well as mechanisms of degradation. This enables the use of linear DNA PCR products in TX-TL. We then explored methods to calibrate linear DNA to plasmid DNA by concentration. We also demonstrated assembly technology to rapidly build circuits entirely in vitro from separate parts. Using this strategy, we prototyped a four-piece genetic switch in under 8 hours entirely in vitro. Rapid in vitro assembly has applications for prototyping circuits of unlimited size when combined with predictive computational models. +
N
Nonlinear Control of Rotating Stall Using Axisymmetric Bleed with Continuous Air Injection on a Low-Speed, Single Stage, Axial Compressor +
Active control of rotating stall and surge using bleed valves has been
demonstrated on low and high speed compressors using high bandwidth
actuators. In this paper we provide a method to reduce the bandwidth
and rate requirements for control of rotating stall by combining an
axisymmetric bleed valve with continuous air injection. The addition
of the continuous air injection is modeled as a shift of both the
stable and unstable parts of the compressor characteristic and serves
to reduce the requirement of a bleed valve used for rotating stall
stabilization purpose. The results are demonstrated using a
low-speed, single stage, axial flow compressor. +
I
Integrase-mediated differentiation circuits improve evolutionary stability of burdensome and toxic functions in E. coli +
Advances in synthetic biology, bioengineering, and computation allow us to rapidly and reliably program cells with increasingly complex and useful functions. However, because the functions we engineer cells to perform are typically burdensome to cell growth, they can be rapidly lost due to the processes of mutation and natural selection. Here, we show that a strategy of terminal differentiation improves the evolutionary stability of burdensome functions in a general manner by realizing a reproductive and metabolic division of labor. To implement this strategy, we develop a genetic differentiation circuit in Escherichia coli using unidirectional integrase-recombination. With terminal differentiation, differentiated cells uniquely express burdensome functions driven by the orthogonal T7 RNA polymerase, but their capacity to proliferate is limited to prevent the propagation of advantageous loss-of-function mutations that inevitably occur. We demonstrate computationally and experimentally that terminal differentiation increases duration and yield of high-burden expression and that its evolutionary stability can be improved with strategic redundancy. Further, we show this strategy can even be applied to toxic functions. Overall, this study provides an effective, generalizable approach for protecting burdensome engineered functions from evolutionary degradation. +
F
Aircraft operate in different modes during flight, corresponding to different flight conditions and
control schemes. We use differential flatness of an approximate model of the pitch dynamics of a
thrust vectored aircraft to achieve fast switching between those modes. We investigate some
methods to compensate for the perturbations to flatness. Simulations and experimental data are
provided to validate the approach. +
M
An experimental investigation of acoustic mode noise suppression was conducted in a cavity using a digital controller with a linear control algorithm. The control algorithm was based on flow field physics similar to the Rossiter model for acoustic resonance. Details of the controller and results from its implementation are presented in the companion paper by Rowley, et al (2002). Here the experiments and some details of the flow field development are described, which were done primarily at Mach number 0.34 corresponding to single mode resonance in the cavity. A novel method using feedback control to suppress the resonant mode and open-loop forcing to inject a non-resonant mode was developed for system identification. The results were used to obtain empirical transfer functions of the components of resonance, and measurements of the shear layer growth for use in the design of the control algorithm. +
P
An ongoing area of study in synthetic biology has been the design and construction of synthetic circuits that maintain homeostasis at the population level. Here, we are interested in designing a synthetic control circuit that regulates the total cell population and the relative ratio between cell strains in a culture containing two different cell strains. We have developed a dual feedback control strategy that uses two separate control loops to achieve the two functions respectively. By combining both of these control loops, we have created a population regulation circuit where both the total population size and relative cell type ratio can be set by reference signals. The dynamics of the regulation circuit show robustness and adaptation to perturbations in cell growth rate and changes in cell numbers. The control architecture is general and could apply to any organism for which synthetic biology tools for quorum sensing, comparison between outputs, and growth control are available. +
S
System identification of phosophorylation based insulator in a cell-free in vitro transcription-translation system +
An outstanding challenge in the design of synthetic biocircuits is the development of a robust and efficient strategy for interconnecting functional modules. Recent theoretical work demonstrated that a phosphorylation based insulator implementing a dual strategy of high gain and strong negative feedback could potentially serve as a device to attenuate retroactivity. This research investigates the structural identifiability of the phoshorylation based insulator when implemented in an {\it in vitro} transcription-translation cell free expression system. We consider a complex model that provides an intricate description of all chemical reactions and leveraging specific physiologically plausible assumptions, we derive a rigorous simplified model that captures the output dynamics of the phosphorylation based insulator. We perform standard system identification analysis and determine that the model is globally identifiable with respect to three critical parameters. Our findings show the utility of the transcription-translation cell free expression system as a platform for system identification, as it provides extra control inputs for parameter estimation that typically are unavailable in vivo. The parameters estimated are then used as a basis for a simulation study in a parallel experimental work (also submitted to qBio-2014). +
N
Analysis and simulations are performed for a simplified model of a
commercially available variant on the skateboard, known as the Snakeboard.
Although the model
exhibits basic gait patterns seen in a large number of locomotion problems,
the analysis tools currently available do not apply to this problem. The
difficulty is seen to lie primarily in the way in which the nonholonomic
constraints enter into the system. As a first step towards understanding
systems represented by our model we present the equations of motion and
perform some controllability analysis for the snakeboard. We also perform
some numerical simulations of the gait patterns. +
T
Tunable integrase-mediated differentiation facilitates improved output of burdensome functions in E. coli +
Application of synthetic biology is limited by the capacity of cells to faithfully execute burdensome engineered functions in the face of Darwinian evolution. Division of labor, both metabolic and reproductive, are underutilized in confronting this barrier. To address this, we developed a serine-integrase based differentiation circuit that allows control of the population composition through tuning of the differentiation rate and number of cell divisions differentiated cells can undergo. We applied this system to T7 RNAP-driven expression of a fluorescent protein, and demonstrate both increased duration of circuit function and total production for high burden expression. While T7 expression systems are typically used for high-level short-term expression, this system enables longer duration production, and could be readily applied to burdensome or toxic products not readily produced in bacteria. +
D
As a field, synthetic biology strives to engineer increasingly complex artificial systems in living cells. Active feedback in closed loop systems offers a dynamic and adaptive way to ensure constant relative activity independent of intrinsic and extrinsic noise. In this work, we use synthetic protein scaffolds as a modular and tunable mechanism for concentration tracking through negative feedback. Input to the circuit initiates scaffold production, leading to colocalization of a two-component system and resulting in the production of an inhibitory antiscaffold protein. Using a combination of modeling and experimental work, we show that the biomolecular concentration tracker circuit achieves dynamic protein concentration tracking in ''Escherichia coli'' and that steady state outputs can be tuned. +
T
As a step towards achieving autonomy in space exploration missions we consider a collaborative robotics system with a copter and a rover. The goal of the copter is to explore an unknown environment so as to maximize knowledge about a science mission expressed in Linear Temporal Logic that is to be executed by the rover. We model environmental uncertainty as a belief space Markov Decision Process and formulate the problem as a two-step stochastic dynamic program that we solve in a way that leverages the decomposed nature of the overall system. We demonstrate in simulations that the robot team makes intelligent decisions in the face of uncertainty. +
C
As studies continue to demonstrate how our health is related to the status of our various commensal microbiomes, synthetic biologists are developing tools and approaches to control these microbiomes and stabilize healthy states or remediate unhealthy ones. Building on previous work to control bacterial communities, we have constructed a synthetic two-member bacterial consortium engineered to reach population density and composition steady states set by inducer inputs. We detail a screening strategy to search functional parameter space in this high-complexity genetic circuit as well as initial testing of a functional two-member circuit.
We demonstrate non-independent changes in total population density and composition steady states with a limited set of varying inducer concentrations. After a dilution to perturb the system from its steady state, density and composition steady states are not regained. Modeling and simulation suggest a need for increased degradation of intercellular signals to improve circuit performance. Future experiments will implement increased signal degradation and investigate the robustness of control of each characteristic to perturbations from steady states. +
P
Average consensus is a widely used algorithm for distributed averaging, where all the agents in the network constantly communicate and update their states in order to achieve an agreement. This approach could result in an undesirable disclosure of information on the initial state of agent i to other agents. In this paper, we propose a Privacy Preserving Average Consensus (PPAC) algorithm to guarantee the privacy of the initial state and the convergence to the exact initial values, by adding and subtracting random noises to the consensus process. We characterize the mean square convergence rate of the PPAC algorithm and derive upper and lower bounds for the covariance matrix of the maximum likelihood estimate on the initial state. We further provide an algebraic condition under which the PPAC algorithm is (epsilon, delta)-differentially private. A numerical example is provided to illustrate the effectiveness of the PPAC algorithm. +
A
Bacteria innately monitor their environment by dynamically regulating gene expression to respond to fluctuating conditions. Through synthetic biology, we can harness this natural capability to design cell-based sensors. Bacillus megaterium, a soil bacterium, stands out due to its remarkable heavy metal tolerance and sporulation ability, making it an ideal candidate for heavy metal detection with low transportation costs. However, challenges persist: the synthetic biology toolkit for this strain is underdeveloped and conventional whole-cell sensors necessitate specialized laboratory equipment to read the output. In our study, we genetically modified B. megaterium for arsenic detection, establishing a detection threshold below the EPA recommendation of 10 ppb for drinking water in both vegetative cell form and spore form. Additionally, we integrated both engineered B. megaterium living cells and spores with CMOS chip for field-deployable arsenic detection. We show that the limit of detection of our integrated sensor is applicable in soil and air arsenic contamination testing. As a proof of concept, this work paves the way for deploying our sensor in resource-limited settings, ensuring real-time arsenic detection in challenging environments. +
E
Effects of Actuator Limits in Bifurcation Control with Applications to Active Control of Fluid Instabilities in Turbomachinery +
Bifurcations are ubiquitous in engineering applications.
Subcritical bifurcations are typically associated with hysteresis
and catastrophic instability inception, while supercritical
bifurcations are usually associated with gradual and more benign
instability inception. With the assumption that the bifurcating
modes are linearly unstabilizable, we give a constructive procedure
of designing feedback laws to change the criticality of bifurcations
from subcritical to supercritical. Algebraic necessary and
sufficient conditions are obtained under which the criticality of a
simple steady-state or Hopf bifurcation can be changed to
supercritical by a smooth feedback. The effects of magnitude
saturation, bandwidth, and rate limits are important issues in
control engineering. We give qualitative estimates of the region of
attraction to the stabilized bifurcating equilibrium/periodic orbits
under these constraints.
<p>
We apply the above theoretical results to the Moore-Greitzer model
in active control of rotating stall and surge in gas turbine
engines. Though linear stabilizability can be achieved using
distributed actuation, it limits the practical usefulness due to
considerations of affordability and reliability. On the other hand,
simple but practically promising actuation schemes such as outlet
bleed valves, a couple of air injectors, and magnetic bearings will
make the system loss of linear stabilizability, thus the control
design becomes a challenging task. The above mentioned theory in
bifurcation stabilization can be applied to these cases. We analyze
the effects of magnitude and rate saturations in active control of
rotating stall using bleed valves. Analytic formulas are obtained
for the operability enhancement as a function of system parameters,
noise level, and actuator magnitude and rate limits. The formulas
give good qualitative predictions when compared with experiments.
Our conclusion is that actuator magnitude and rate limits are
serious limiting factors in stall control and must be addressed in
practical implementation to the aircraft engines.
<p>
B
Biochemical interactions in systems and synthetic biology are often modeled with chemical reaction networks (CRNs). CRNs provide a principled modeling environment capable of expressing a huge range of biochemical processes. In this paper, we present a software toolbox, written in Python, that compiles high-level design specifications represented using a modular library of biochemical parts, mechanisms, and contexts to CRN implementations. This compilation process offers four advantages. First, the building of the actual CRN representation is automatic and outputs Systems Biology Markup Language (SBML) models compatible with numerous simulators. Second, a library of modular biochemical components allows for different architectures and implementations of biochemical circuits to be represented succinctly with design choices propagated throughout the underlying CRN automatically. This prevents the often occurring mismatch between high-level designs and model dynamics. Third, high-level design specification can be embedded into diverse biomolecular environments, such as cell-free extracts and in vivo milieus. Finally, our software toolbox has a parameter database, which allows users to rapidly prototype large models using very few parameters which can be customized later. By using BioCRNpyler, users ranging from expert modelers to novice script-writers can easily build, manage, and explore sophisticated biochemical models using diverse biochemical implementations, environments, and modeling assumptions. +
H
Biocircuit modeling sometimes requires explicit tracking of a self-replicating DNA species. The most obvious, straightforward way to model a replicating DNA is structurally unstable and leads to pathological model behavior. We describe a simple, stable replication mechanism with good model behavior and show how to derive it from a mechanistic model of ColE1 replication. +
S
Biological organisms use their sensory systems to detect changes in their environment. The ability of sensory systems to adapt to static inputs allows wide dynamic range as well as sensitivity to input changes including fold-change detection, a response that de- pends only on fold changes in input, and not on ab- solute changes. This input scale invariance underlies an important strategy for search that depends solely on the spatial profile of the input. Synthetic efforts to reproduce the architecture and response of cellu- lar circuits provide an important step to foster under- standing at the molecular level. We report the bottom- up assembly of biochemical systems that show exact adaptation and fold-change detection. Using a malachite green aptamer as the output, a synthetic tran- scriptional circuit with the connectivity of an incoherent feed-forward loop motif exhibits pulse generation and exact adaptation. A simple mathematical model was used to assess the amplitude and duration of pulse response as well as the parameter regimes required for fold-change detection. Upon parameter tuning, this synthetic circuit exhibits fold-change detection for four successive rounds of two-fold input changes. The experimental realization of fold-change detection circuit highlights the programmability of transcriptional switches and the ability to obtain predictive dynamical systems in a cell-free environment for technological applications. +
