[ { "id": "authors:mdtpv-vrs47", "collection": "authors", "collection_id": "mdtpv-vrs47", "cite_using_url": "https://authors.library.caltech.edu/records/mdtpv-vrs47", "type": "article", "title": "Recruiting ESCRT to single-chain heterotrimer peptide MHCI releases antigen-presenting vesicles that stimulate T cells selectively", "author": [ { "family_name": "Olson", "given_name": "Blade A.", "orcid": "0000-0002-1526-1399", "clpid": "Olson-Blade-A" }, { "family_name": "Huey-Tubman", "given_name": "Kathryn E.", "orcid": "0000-0002-4683-8138", "clpid": "Huey-Tubman-Kathryn-E" }, { "family_name": "Mao", "given_name": "Zhiyuan" }, { "family_name": "Hoffmann", "given_name": "Magnus A. G.", "orcid": "0000-0003-4923-9568", "clpid": "Hoffmann-Magnus-Adrian-Gero" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "orcid": "0000-0002-2277-3990", "clpid": "Bjorkman-P-J" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Mayo", "given_name": "Stephen L.", "orcid": "0000-0002-9785-5018", "clpid": "Mayo-S-L" } ], "abstract": "Immune cells naturally secrete extracellular antigen-presenting vesicles (APVs) displaying peptide:MHC complexes to facilitate the initiation, expansion, maintenance, or silencing of immune responses. Previous work has sought to manufacture and purify these vesicles for cell-free immunotherapies. In this study, APV assembly and release is achieved in nonimmune cells by transfecting a single-chain heterotrimer (SCT) peptide major histocompatibility complex I (pMHCI) construct containing an ESCRT- and ALIX-binding region (EABR) sequence appended to the cytoplasmic tail; this EABR sequence recruits ESCRT proteins to induce the budding of APVs displaying SCT pMHCI. A comparison of multiple pMHCI constructs shows that inducing the release of APVs by the addition of an EABR sequence generalizes across SCT pMHCI constructs. Purified pMHCI/EABR APVs selectively stimulate IFN-\u03b3 release from T cells presenting their cognate T cell receptor, demonstrating the potential use of these vesicles as a form of cell-free immunotherapy.", "doi": "10.1073/pnas.2501046122", "pmcid": "PMC12745732", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences", "publication_date": "2025-12-23", "series_number": "51", "volume": "122", "issue": "51", "pages": "e2501046122" }, { "id": "authors:3jsjm-3h016", "collection": "authors", "collection_id": "3jsjm-3h016", "cite_using_url": "https://authors.library.caltech.edu/records/3jsjm-3h016", "type": "article", "title": "Flow-Based Synthesis of Reactive Tests for Discrete Decision-Making Systems with Temporal Logic Specifications", "author": [ { "family_name": "Graebener", "given_name": "Josefine B.", "orcid": "0000-0002-1376-0741", "clpid": "Graebener-Josefine-B" }, { "family_name": "Badithela", "given_name": "Apurva S.", "orcid": "0000-0002-9788-2702" }, { "family_name": "Goktas", "given_name": "Denizalp", "orcid": "0000-0003-1958-685X" }, { "family_name": "Ubellacker", "given_name": "Wyatt", "orcid": "0000-0002-4732-6185", "clpid": "Ubellacker-Wyatt" }, { "family_name": "Mazumdar", "given_name": "Eric V.", "orcid": "0000-0002-1815-269X", "clpid": "Mazumdar-Eric" }, { "family_name": "Ames", "given_name": "Aaron D.", "orcid": "0000-0003-0848-3177", "clpid": "Ames-A-D" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Designing tests for autonomous systems is challenging due to their complexity. This work proposes a flow-based approach for reactive test synthesis from temporal logic specifications, enabling the synthesis of test environments consisting of static and reactive obstacles, and dynamic test agents that can transition between states. These specifications describe desired test behavior, including system requirements as well as a test objective not revealed to the system. The synthesized test strategy places restrictions on system actions in closed-loop with system behavior, accomplishing the test objective while ensuring realizability of the system's objective without aiding it (a general-sum setting). Automata theory and flow networks are leveraged to formulate a mixed-integer linear program (MILP) for test synthesis. For a dynamic test agent, the agent strategy is synthesized for a generalized reactivity of rank 1 (GR(1)) specification constructed from the MILP solution. If this solution is not realizable with the test agent's dynamics, we add a counterexample-guided constraint to re-solve the MILP until a strategy is found. This flow-based, reactive test synthesis is conducted offline and is agnostic to the system controller. Finally, the resulting test strategy is demonstrated in simulation and hardware experiments on a pair of quadrupedal robots for a variety of specifications.", "doi": "10.1109/ojcsys.2025.3625465", "issn": "2694-085X", "publisher": "IEEE", "publication": "IEEE Open Journal of Control Systems", "publication_date": "2025-10-24", "volume": "4", "pages": "597 - 617" }, { "id": "authors:he236-9s353", "collection": "authors", "collection_id": "he236-9s353", "cite_using_url": "https://authors.library.caltech.edu/records/he236-9s353", "type": "article", "title": "A DNA Part Library for Reliable Engineering of the Emerging Model Nematode Symbiotic Bacterium Xenorhabdus griffiniae HGB2511", "author": [ { "family_name": "Larsson", "given_name": "Elin M.", "orcid": "0000-0003-1341-5937", "clpid": "Larsson-Elin-Maria" }, { "family_name": "Wang", "given_name": "Olivia Y.", "orcid": "0009-0005-8554-5775", "clpid": "Wang-Olivia-Y" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "
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Xenorhabdus griffiniae is a bacterium that lives inside the intestine of the entomopathogenic nematode Steinernema hermaphroditum and partners with the nematode to infect and kill insect larvae in soil. The construction of gene circuits, such as reporters, in X. griffiniae would provide tools to study and better understand the symbiotic relationship it has with its host. However, because X. griffiniae is not a model organism, information about gene circuit construction in X. griffiniae is limited. We developed and characterized a DNA part library similar to the CIDAR MoClo extension library for E. coli to allow more efficient construction of genetic circuits in X. griffiniae. TurboRFP expressing strains with different constitutive Anderson promoters and different ribosome binding sites (RBS) were constructed to quantify promoter and RBS strengths in X. griffiniae. Furthermore, two fluorescent proteins sfGFP and sfYFP as well as the bioluminescent luxCDABE operon were added to the part library and successfully expressed in X. griffiniae. We then used the characterized parts of the cell to build and characterize IPTG inducible constructs.

\n
", "doi": "10.1021/acssynbio.5c00414", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2025-10-17", "series_number": "10", "volume": "14", "issue": "10", "pages": "4122-4126" }, { "id": "authors:37rmd-q9g08", "collection": "authors", "collection_id": "37rmd-q9g08", "cite_using_url": "https://authors.library.caltech.edu/records/37rmd-q9g08", "type": "article", "title": "Task-Relevant Evaluation Metrics of Object Detection for Quantitative System-Level Analysis of Safety-Critical Autonomous Systems", "author": [ { "family_name": "Badithela", "given_name": "Apurva", "orcid": "0000-0002-9788-2702" }, { "family_name": "Srivastav", "given_name": "Ranai", "orcid": "0009-0004-1301-3676" }, { "family_name": "Wongpiromsarn", "given_name": "Tichakorn", "orcid": "0000-0002-3977-122X" }, { "family_name": "Murray", "given_name": "Richard", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "In safety-critical robotic systems, perception is tasked with representing the environment to effectively guide decision-making and plays a crucial role in ensuring that the overall system meets its requirements. To quantitatively assess the impact of object detection and classification errors on system-level performance, we present a rigorous formalism for a model of detection error, and probabilistically reason about the satisfaction of regular-safety temporal logic requirements at the system level. We also show how standard evaluation metrics for object detection, such as confusion matrices, can be represented as models of detection error, which enables the computation of probabilistic satisfaction of system-level specifications. However, traditional confusion matrices treat all detections equally, without considering their relevance to the system-level task. To address this limitation, we propose novel evaluation metrics for object detection that are informed by both the system-level task and the downstream control logic, enabling a more context-appropriate evaluation of detection models. We identify logic-based formulas relevant to the downstream control and system-level specifications and use these formulas to define a logic-based evaluation metric for object detection and classification. These logic-based metrics result in less conservative assessments of system-level performance. Finally, we demonstrate our approach on a car-pedestrian example with a leaderboard PointPillars model evaluated on the nuScenes dataset, and validate probabilistic system-level guarantees in simulation.", "doi": "10.1145/3771284", "issn": "2378-962X", "publisher": "Association for Computing Machinery (ACM)", "publication": "ACM Transactions on Cyber-Physical Systems", "publication_date": "2025-10-15", "pages": "3771284" }, { "id": "authors:1xz93-wgt26", "collection": "authors", "collection_id": "1xz93-wgt26", "cite_using_url": "https://authors.library.caltech.edu/records/1xz93-wgt26", "type": "article", "title": "A Portable Arsenic Sensor Integrating Bacillus megaterium with CMOS Technology", "author": [ { "family_name": "Hu", "given_name": "Chelsea Y.", "orcid": "0000-0002-2211-1778", "clpid": "Hu-Chelsea-Y" }, { "family_name": "McManus", "given_name": "John", "orcid": "0009-0007-7077-0624", "clpid": "McManus-John" }, { "family_name": "Aghlmand", "given_name": "Fatemeh", "orcid": "0000-0002-5103-9314", "clpid": "Aghlmand-Fatemeh" }, { "family_name": "Mei", "given_name": "Tracy", "orcid": "0000-0003-2743-0126" }, { "family_name": "Larsson", "given_name": "Elin", "orcid": "0000-0003-1341-5937", "clpid": "Larsson-Elin" }, { "family_name": "Emami", "given_name": "Azita", "orcid": "0000-0002-6945-9958", "clpid": "Emami-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "

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 have genetically modified B. megaterium for arsenic detection and established a detection threshold below the EPA’s recommendation of 10 ppb for drinking water in both vegetative and spore forms. Additionally, we have integrated both engineered B. megaterium living cells and spores with a complementary metal-oxide-semiconductor (CMOS) chip, providing a proof-of-concept for field-deployable arsenic detection. We show that the limit of detection (LOD) of our integrated sensor is within the range to test arsenic levels in soil and food. As a proof of concept, this work paves the way for the deployment of our sensor in resource-limited settings, ensuring real-time arsenic detection in challenging environments.

", "doi": "10.1021/acssynbio.4c00895", "pmcid": "PMC12090344", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2025-05-16", "series_number": "5", "volume": "14", "issue": "5", "pages": "1615-1624" }, { "id": "authors:n18vd-tcz58", "collection": "authors", "collection_id": "n18vd-tcz58", "cite_using_url": "https://authors.library.caltech.edu/records/n18vd-tcz58", "type": "article", "title": "Optimizing Protein Production in the One-Pot PURE System: Insights into Reaction Composition and Expression Efficiency", "author": [ { "family_name": "Zhang", "given_name": "Yan", "orcid": "0000-0003-0719-5456", "clpid": "Zhang-Yan" }, { "family_name": "Deveikis", "given_name": "Matas", "orcid": "0000-0001-7444-2950" }, { "family_name": "Qiu", "given_name": "Yanping", "orcid": "0000-0003-2948-2173", "clpid": "Qiu-Yanping" }, { "family_name": "Bj\u00f6rn", "given_name": "Lovisa", "orcid": "0009-0007-6983-3341", "clpid": "Bj\u00f6rn-Lovisa" }, { "family_name": "Martinez", "given_name": "Zachary A.", "orcid": "0000-0002-7830-3162", "clpid": "Martinez-Zachary-A" }, { "family_name": "Chou", "given_name": "Tsui-Fen", "orcid": "0000-0003-2410-2186", "clpid": "Chou-Tsui-Fen" }, { "family_name": "Freemont", "given_name": "Paul S.", "orcid": "0000-0002-5658-8486" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "

The One-Pot PURE (Protein synthesis Using Recombinant Elements) system simplifies the preparation of traditional PURE systems by coculturing and purifying 36 essential proteins for gene expression in a single step, enhancing accessibility and affordability for widespread laboratory adoption and customization. However, replicating this protocol to match the productivity of traditional PURE systems can take considerable time and effort due to uncharacterized variability. In this work, we observed unstable PURE protein expression in the original One-Pot PURE strains, E. coli M15/pREP4 and BL21(DE3), and addressed this issue using glucose-mediated catabolite repression to minimize burdensome background expression. We also identified several limitations making the M15/pREP4 strain unsuitable for PURE protein expression, including coculture incompatibility with BL21(DE3) and uncharacterized proteolytic activity. We showed that consolidating all expression vectors into a protease-deficient BL21(DE3) strain minimized proteolysis, led to more uniform coculture cell growth at the time of induction, and improved the stoichiometry of critical translation initiation factors in the final PURE mixture for efficient cell-free protein production. In addition to optimizing the One-Pot PURE protein composition, we found that variations in commercial energy solution formulations could compensate for suboptimal PURE protein stoichiometry. Notably, altering the source of E. coli tRNAs in the energy solution alone led to significant differences in the expression capacity of cell-free reactions, highlighting the importance of tRNA codon usage in influencing protein expression yield. Taken together, this work systematically investigates the proteome and biochemical factors influencing the One-Pot PURE system productivity, offering insights to enhance its robustness and adaptability across laboratories.

", "doi": "10.1021/acssynbio.4c00779", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2025-05-16", "series_number": "5", "volume": "14", "issue": "5", "pages": "1496-1508" }, { "id": "authors:6rsmy-pph05", "collection": "authors", "collection_id": "6rsmy-pph05", "cite_using_url": "https://authors.library.caltech.edu/records/6rsmy-pph05", "type": "article", "title": "ATMO: an aerially transforming morphobot for dynamic ground-aerial transition", "author": [ { "family_name": "Mandralis", "given_name": "Ioannis", "orcid": "0000-0001-5270-0672", "clpid": "Mandralis-Ioannis-M" }, { "family_name": "Nemovi", "given_name": "Reza" }, { "family_name": "Ramezani", "given_name": "Alireza", "orcid": "0000-0002-3391-5288" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" } ], "abstract": "Designing ground-aerial robots is challenging due to the increased actuation requirements which can lead to added weight and reduced locomotion efficiency. Morphobots mitigate this by combining actuators into multi-functional groups and leveraging ground transformation to achieve different locomotion modes. However, transforming on the ground requires dealing with the complexity of ground-vehicle interactions during morphing, limiting applicability on rough terrain. Mid-air transformation offers a solution to this issue but demands operating near or beyond actuator limits while managing complex aerodynamic forces. We address this problem by introducing the Aerially Transforming Morphobot (ATMO), a robot which transforms near the ground achieving smooth transition between aerial and ground modes. To achieve this, we leverage the near ground aerodynamics, uncovered by experimental load cell testing, and stabilize the system using a model-predictive controller that adapts to ground proximity and body shape. The system is validated through numerous experimental demonstrations. We find that ATMO can land smoothly at body postures past its actuator saturation limits by virtue of the uncovered ground-effect.", "doi": "10.1038/s44172-025-00413-6", "issn": "2731-3395", "publisher": "Nature Publishing Group", "publication": "Communications Engineering", "publication_date": "2025-04-19", "series_number": "1", "volume": "4", "issue": "1", "pages": "74" }, { "id": "authors:5ns21-pn241", "collection": "authors", "collection_id": "5ns21-pn241", "cite_using_url": "https://authors.library.caltech.edu/records/5ns21-pn241", "type": "article", "title": "Barrier-Based Test Synthesis for Safety-Critical Systems Subject to Timed Reach-Avoid Specifications", "author": [ { "family_name": "Akella", "given_name": "Prithvi", "orcid": "0000-0003-4375-0015", "clpid": "Akella-Prithvi" }, { "family_name": "Ahmadi", "given_name": "Mohamadreza", "orcid": "0000-0003-1447-3012", "clpid": "Ahmadi-Mohamadreza" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Ames", "given_name": "Aaron D.", "orcid": "0000-0003-0848-3177", "clpid": "Ames-A-D" } ], "abstract": "

We propose an adversarial, time-varying test-synthesis procedure for safety-critical systems without requiring specific knowledge of the underlying controller steering the system. Specifically, our approach codifies the system objective as a timed reach-avoid specification. Then, by coupling control barrier functions with this class of specifications, we construct an instantaneous difficulty metric whose minimizer corresponds to the most difficult test at that system state. By defining tests as the minimizer of this difficulty metric over the space of allowable tests, we provably identify realizable and maximally difficult tests of system behavior. Finally, we develop this test-synthesis procedure for both continuous and discrete-time systems and showcase our test-synthesis procedure on simulated and hardware examples.

", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "2025-04", "series_number": "4", "volume": "70", "issue": "4", "pages": "2180 - 2195" }, { "id": "authors:4kyba-3mm91", "collection": "authors", "collection_id": "4kyba-3mm91", "cite_using_url": "https://authors.library.caltech.edu/records/4kyba-3mm91", "type": "article", "title": "Diagnostic and Therapeutic Microbial Circuit with Application to Intestinal Inflammation", "author": [ { "family_name": "Merk", "given_name": "Liana N." }, { "family_name": "Shur", "given_name": "Andrey S." }, { "family_name": "Jena", "given_name": "Smrutiti" }, { "family_name": "Munoz", "given_name": "Javier" }, { "family_name": "Brubaker", "given_name": "Douglas K." }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Green", "given_name": "Leopold N.", "orcid": "0000-0001-5479-6970", "clpid": "Green-Leopold-N" } ], "abstract": "Bacteria genetically engineered to execute defined therapeutic and diagnostic functions in physiological settings can be applied to colonize the human microbiome, providing in situ surveillance and conditional disease modulation. However, many engineered microbes can only respond to single-input environmental factors, limiting their tunability, precision, and effectiveness as living diagnostic and therapeutic systems. For engineering microbes to improve complex chronic disorders such as inflammatory bowel disease, the bacteria must respond to combinations of stimuli in the proper context and time. This work implements a previously characterized split activator AND logic gate in the probiotic Escherichia coli strain Nissle 1917 (EcN). Our system can respond to two input signals: the inflammatory biomarker tetrathionate and a second input signal, anhydrotetracycline (aTc), for manual control. We report 4-6 fold induction with a minimal leak when the two chemical signals are present. We model the AND gate dynamics using chemical reaction networks and tune parameters in silico to identify critical perturbations that affect our circuit's selectivity. Finally, we engineer the optimized AND gate to secrete a therapeutic anti-inflammatory cytokine IL-22 using the hemolysin secretion pathway in the probiotic E. coli strain. We used a germ-free transwell model of the human gut epithelium to show that our engineering bacteria produce similar host cytokine responses compared to recombinant cytokine. Our study presents a scalable workflow to engineer cytokine-secreting microbes driven by logical signal processing. It demonstrates the feasibility of IL-22 derived from probiotic EcN with minimal off-target effects in a gut epithelial context.", "doi": "10.1021/acssynbio.3c00668", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2024-12-20", "series_number": "12", "volume": "13", "issue": "12", "pages": "3885\u20133896" }, { "id": "authors:nwqa7-8hz87", "collection": "authors", "collection_id": "nwqa7-8hz87", "cite_using_url": "https://authors.library.caltech.edu/records/nwqa7-8hz87", "type": "article", "title": "Metabolic Perturbations to an Escherichia coli-based Cell-Free System Reveal a Trade-off between Transcription and Translation", "author": [ { "family_name": "Kapasiawala", "given_name": "Manisha", "orcid": "0000-0002-0302-2921", "clpid": "Kapasiawala-Manisha" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Cell-free transcription-translation (TX-TL) systems have been used for diverse applications, but their performance and scope are limited by variability and poor predictability. To understand the drivers of this variability, we explored the effects of metabolic perturbations to anEscherichia coli (E. coli) Rosetta2 TX-TL system. We targeted three classes of molecules: energy molecules, in the form of nucleotide triphosphates (NTPs); central carbon \"fuel\" molecules, which regenerate NTPs; and magnesium ions (Mg2+). Using malachite green mRNA aptamer (MG aptamer) and destabilized enhanced green fluorescent protein (deGFP) as transcriptional and translational readouts, respectively, we report the presence of a trade-off between optimizing total protein yield and optimizing total mRNA yield, as measured by integrating the area under the curve for mRNA time-course dynamics. We found that a system's position along the trade-off curve is strongly determined by Mg2+ concentration, fuel type and concentration, and cell lysate preparation and that variability can be reduced by modulating these components. Our results further suggest that the trade-off arises from limitations in translation regulation and inefficient energy regeneration. This work advances our understanding of the effects of fuel and energy metabolism on TX-TL in cell-free systems and lays a foundation for improving TX-TL performance, lifetime, standardization, and prediction.", "doi": "10.1021/acssynbio.4c00361", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2024-11-20", "series_number": "12", "volume": "13", "issue": "12", "pages": "3976\u20133990" }, { "id": "authors:hhh1k-q0a16", "collection": "authors", "collection_id": "hhh1k-q0a16", "cite_using_url": "https://authors.library.caltech.edu/records/hhh1k-q0a16", "type": "article", "title": "Impact of Chemical Dynamics of Commercial PURE Systems on Malachite Green Aptamer Fluorescence", "author": [ { "family_name": "Jurado", "given_name": "Zoila", "orcid": "0000-0003-4160-5068", "clpid": "Jurado Quiroga-Zoila-E" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "

The malachite green aptamer (MGapt) is known for its utility in RNA measurement in vivo and in lysate-based cell-free protein systems. However, MGapt fluorescence dynamics do not accurately reflect RNA concentration. Our study finds that MGapt fluorescence is unstable in commercial PURE systems. We discovered that the chemical composition of the cell-free reaction strongly influences MGapt fluorescence, which leads to inaccurate RNA calculations. Specific to the commercial system, we posit that MGapt fluorescence is significantly affected by the system’s chemical properties, governed notably by the presence of dithiothreitol (DTT). We propose a model that, on average, accurately predicts MGapt measurement within a 10% margin, leveraging DTT concentration as a critical factor. This model sheds light on the complex dynamics of MGapt in cell-free systems and underscores the importance of considering environmental factors in RNA measurements using aptamers.

", "doi": "10.1021/acssynbio.4c00211", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2024-10-18", "series_number": "10", "volume": "13", "issue": "10", "pages": "3109 - 3118" }, { "id": "authors:y9t9z-32k63", "collection": "authors", "collection_id": "y9t9z-32k63", "cite_using_url": "https://authors.library.caltech.edu/records/y9t9z-32k63", "type": "article", "title": "Layered Control Systems Operating on Multiple Clocks", "author": [ { "family_name": "Incer", "given_name": "Inigo", "orcid": "0000-0001-7933-692X", "clpid": "Incer-Inigo" }, { "family_name": "Csomay-Shanklin", "given_name": "Noel", "orcid": "0000-0002-2361-1694", "clpid": "Csomay-Shanklin-Noel" }, { "family_name": "Ames", "given_name": "Aaron D.", "orcid": "0000-0003-0848-3177", "clpid": "Ames-A-D" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "
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Autonomous systems typically leverage layered control architectures, created by interconnecting components that operate at multiple timescales, i.e., evolve under various clocks. To formalize this typically heuristic procedure, we introduce a new logic, Multiclock Logic (MCL), that can express the requirements of components from the point of view of their local clocks, promoting independent design and component reuse. We then use assume-guarantee contracts expressed in MCL to prove global stability properties of a system using the stability properties of its components. In particular, we consider the classic layered architecture consisting of model predictive control (MPC) layered on top of feedback linearization, and prove overall stability of the systems.
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", "doi": "10.1109/lcsys.2024.3410150", "issn": "2475-1456", "publisher": "IEEE", "publication": "IEEE Control Systems Letters", "publication_date": "2024-06-05" }, { "id": "authors:pz25c-f8f29", "collection": "authors", "collection_id": "pz25c-f8f29", "cite_using_url": "https://authors.library.caltech.edu/records/pz25c-f8f29", "type": "article", "title": "Development of Cell-Free Transcription\u2013Translation Systems in Three Soil Pseudomonads", "author": [ { "family_name": "Meyerowitz", "given_name": "Joseph T.", "orcid": "0000-0002-3426-0885", "clpid": "Meyerowitz-Joseph-T" }, { "family_name": "Larsson", "given_name": "Elin M.", "orcid": "0000-0003-1341-5937", "clpid": "Larsson-Elin-M" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "
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In vitro transcription–translation (TX–TL) can enable faster engineering of biological systems. This speed-up can be significant, especially in difficult-to-transform chassis. This work shows the successful development of TX–TL systems using three soil-derived wild-type Pseudomonads known to promote plant growth: Pseudomonas synxantha, Pseudomonas chlororaphis, and Pseudomonas aureofaciens. All three species demonstrated multiple sonication, runoff, and salt conditions producing detectable protein synthesis. One of these new TX–TL systems, P. synxantha, demonstrated a maximum protein yield of 2.5 μM at 125 proteins per DNA template, a maximum protein synthesis rate of 20 nM/min, and a range of DNA concentrations with a linear correspondence with the resulting protein synthesis. A set of different constitutive promoters driving mNeonGreen expression were tested in TX–TL and integrated into the genome, showing similar normalized strengths for in vivo and in vitro fluorescence. This correspondence between the TX–TL-derived promoter strength and the in vivo promoter strength indicates that these lysate-based cell-free systems can be used to characterize and engineer biological parts without genomic integration, enabling a faster design–build–test cycle.

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", "doi": "10.1021/acssynbio.3c00468", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2024-02-16", "series_number": "2", "volume": "13", "issue": "2", "pages": "530-537" }, { "id": "authors:wcnwq-0mw52", "collection": "authors", "collection_id": "wcnwq-0mw52", "cite_using_url": "https://authors.library.caltech.edu/records/wcnwq-0mw52", "type": "article", "title": "Engineering the Soil Bacterium Pseudomonas synxantha 2\u201379 into a Ratiometric Bioreporter for Phosphorus Limitation", "author": [ { "family_name": "Larsson", "given_name": "Elin M.", "orcid": "0000-0003-1341-5937", "clpid": "Larsson-Elin-M" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Newman", "given_name": "Dianne K.", "orcid": "0000-0003-1647-1918", "clpid": "Newman-D-K" } ], "abstract": "
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Microbial bioreporters hold promise for addressing challenges in medical and environmental applications. However, the difficulty in ensuring their stable persistence and function within the target environment remains a challenge. One strategy is to integrate information about the host strain and target environment into the design-build-test cycle of the bioreporter itself. Here, we present a case study for such an environmentally motivated design process by engineering the wheat commensal bacterium Pseudomonas synxantha 2–79 into a ratiometric bioreporter for phosphorus limitation. Comparative analysis showed that an exogenous P-responsive promoter outperformed its native counterparts. This reporter can selectively sense and report phosphorus limitation at plant-relevant concentrations of 25–100 μM without cross-activation from carbon or nitrogen limitation or high cell densities. Its performance is robust over a field-relevant pH range (5.8–8), and it responds only to inorganic phosphorus, even in the presence of common soil organic P. Finally, we used fluorescein-calibrated flow cytometry to assess whether the reporter’s performance in shaken liquid culture predicts its performance in soil, finding that although the reporter is still functional at the bulk level, its variability in performance increases when grown in a soil slurry as compared to planktonic culture, with a fraction of the population not expressing the reporter proteins. Together, our environmentally aware design process provides an example of how laboratory bioengineering efforts can generate microbes with a greater promise to function reliably in their applied contexts.

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", "doi": "10.1021/acssynbio.3c00642", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2024-01-19", "series_number": "1", "volume": "13", "issue": "1", "pages": "384-393" }, { "id": "authors:7sg3b-knb56", "collection": "authors", "collection_id": "7sg3b-knb56", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230411-764712100.4", "type": "article", "title": "Rules of the Road: Formal Guarantees for Autonomous Vehicles With Behavioral Contract Design", "author": [ { "family_name": "Cai", "given_name": "Karena X.", "orcid": "0000-0002-8392-4158", "clpid": "Cai-Karena-X" }, { "family_name": "Phan-Minh", "given_name": "Tung", "orcid": "0000-0002-1403-5197", "clpid": "Phan-Minh-Tung" }, { "family_name": "Chung", "given_name": "Soon-Jo", "orcid": "0000-0002-6657-3907", "clpid": "Chung-Soon-Jo" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The problem of safe and fair conflict resolution among inertial, distributed agents \u2014 particularly in highly interactive settings \u2014 is of paramount importance to the autonomous vehicles industry. The difficulty of solving this problem can be attributed to the fact that agents have to reason over other agents' complex behaviors. We propose the idea of using a behavioral contract to capture a set of explicitly defined assumptions about how all agents in the environment make decisions. In this article, we present a behavioral contract for a specific class of agents that can guarantee the safety and liveness (i.e., progress) of all agents operating in accordance with it. The behavioral contract has two main components\u2014an ordered behavioral rulebook that the agent uses to select its intended action and some additional constraints that define when an agent has precedence (or not) to take its intended action. If all of the agents act according to this contract, we can guarantee safety under all traffic conditions and liveness for all agents under \"sparse\" traffic conditions. The formalism of the contract also enables assignment of blame. We provide proofs of correctness of the behavioral contract and validate our results in simulation.", "doi": "10.1109/tro.2023.3247951", "issn": "1552-3098", "publisher": "IEEE", "publication": "IEEE Transactions on Robotics", "publication_date": "2023-06", "series_number": "3", "volume": "39", "issue": "3", "pages": "1853-1872" }, { "id": "authors:m2y80-6k516", "collection": "authors", "collection_id": "m2y80-6k516", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230706-731611100.7", "type": "article", "title": "Control education for societal-scale challenges: A community roadmap", "author": [ { "family_name": "Rossiter", "given_name": "John Anthony", "orcid": "0000-0002-1336-0633", "clpid": "Rossiter-John-Anthony" }, { "family_name": "Cassandras", "given_name": "Christos G.", "clpid": "Cassandras-Christos-G" }, { "family_name": "Hespanha", "given_name": "Jo\u00e3o", "orcid": "0000-0003-2809-4718", "clpid": "Hespanha-Jo\u00e3o" }, { "family_name": "Dormido", "given_name": "Sebastian", "orcid": "0000-0002-2405-8771", "clpid": "Dormido-Sebastian" }, { "family_name": "de la Torre", "given_name": "Luis", "orcid": "0000-0002-9648-9597", "clpid": "de-la-Torre-Luis" }, { "family_name": "Ranade", "given_name": "Gireeja", "orcid": "0000-0002-6747-4492", "clpid": "Ranade-Gireeja" }, { "family_name": "Visioli", "given_name": "Antonio", "orcid": "0000-0002-9246-5715", "clpid": "Visioli-Antonio" }, { "family_name": "Hedengren", "given_name": "John", "orcid": "0000-0002-5535-5277", "clpid": "Hedengren-John" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Antsaklis", "given_name": "Panos", "orcid": "0000-0002-6836-5028", "clpid": "Antsaklis-Panos" }, { "family_name": "Lamnabhi-Lagarrigue", "given_name": "Francoise", "orcid": "0000-0003-2512-3587", "clpid": "Lamnabhi-Lagarrigue-Francoise" }, { "family_name": "Parisini", "given_name": "Thomas", "orcid": "0000-0001-5396-9665", "clpid": "Parisini-Thomas" } ], "abstract": "This article focuses on extending, disseminating and interpreting the findings of an IEEE Control Systems Society working group looking at the role of control theory and engineering in solving some of the many current and future societal challenges. The findings are interpreted in a manner designed to give focus and direction to both future education and research work in the general control theory and engineering arena, interpreted in the broadest sense. The paper is intended to promote discussion in the community and also provide a useful starting point for colleagues wishing to re-imagine the design and delivery of control-related topics in our education systems, especially at the tertiary level and beyond.", "doi": "10.1016/j.arcontrol.2023.03.007", "issn": "1367-5788", "publisher": "Elsevier", "publication": "Annual Reviews in Control", "publication_date": "2023-05-29", "volume": "55", "pages": "1-17" }, { "id": "authors:km8n7-d0664", "collection": "authors", "collection_id": "km8n7-d0664", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230628-332770500.2", "type": "article", "title": "Addressable and adaptable intercellular communication via DNA messaging", "author": [ { "family_name": "Marken", "given_name": "John P.", "orcid": "0000-0001-9696-088X", "clpid": "Marken-John-P" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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.", "doi": "10.1038/s41467-023-37788-z", "pmcid": "PMC10126159", "issn": "2041-1723", "publisher": "Nature Publishing Group", "publication": "Nature Communications", "publication_date": "2023-04-24", "volume": "14", "pages": "Art. No. 2358" }, { "id": "authors:w1yvb-4bn26", "collection": "authors", "collection_id": "w1yvb-4bn26", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230512-807789000.8", "type": "article", "title": "Advances in theoretical and computational nonlinear control \u2014 Dedicated to the 80th birthday of Professor Arthur J. Krener", "author": [ { "family_name": "Kang", "given_name": "Wei", "orcid": "0000-0001-9989-0485", "clpid": "Kang-Wei" }, { "family_name": "Burns", "given_name": "John", "clpid": "Burns-John" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "It is with great pleasure that we introduce this special issue of Systems & Control Letters, on \"Advances in Theoretical and Computational Nonlinear Control \u2014 Dedicated to the 80th Birthday of Professor Arthur J. Krener\".", "doi": "10.1016/j.sysconle.2023.105492", "issn": "0167-6911", "publisher": "Elsevier", "publication": "Systems and Control Letters", "publication_date": "2023-04", "volume": "174", "pages": "Art. No. 105492" }, { "id": "authors:kr828-q9993", "collection": "authors", "collection_id": "kr828-q9993", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230322-366887000.4", "type": "article", "title": "Characterization of Integrase and Excisionase Activity in a Cell-Free Protein Expression System Using a Modeling and Analysis Pipeline", "author": [ { "family_name": "Pandey", "given_name": "Ayush", "orcid": "0000-0003-3590-4459", "clpid": "Pandey-Ayush" }, { "family_name": "Rodriguez", "given_name": "Makena L.", "clpid": "Rodriguez-Makena-L" }, { "family_name": "Poole", "given_name": "William", "orcid": "0000-0002-2958-6776", "clpid": "Poole-William" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We present a full-stack modeling, analysis, and parameter identification pipeline to guide the modeling and design of biological systems starting from specifications to circuit implementations and parametrizations. We demonstrate this pipeline by characterizing the integrase and excisionase activity in a cell-free protein expression system. We build on existing Python tools\u2500BioCRNpyler, AutoReduce, and Bioscrape\u2500to create this pipeline. For enzyme-mediated DNA recombination in a cell-free system, we create detailed chemical reaction network models from simple high-level descriptions of the biological circuits and their context using BioCRNpyler. We use Bioscrape to show that the output of the detailed model is sensitive to many parameters. However, parameter identification is infeasible for this high-dimensional model; hence, we use AutoReduce to automatically obtain reduced models that have fewer parameters. This results in a hierarchy of reduced models under different assumptions to finally arrive at a minimal ODE model for each circuit. Then, we run sensitivity analysis-guided Bayesian inference using Bioscrape for each circuit to identify the model parameters. This process allows us to quantify integrase and excisionase activity in cell extracts enabling complex-circuit designs that depend on accurate control over protein expression levels through DNA recombination. The automated pipeline presented in this paper opens up a new approach to complex circuit design, modeling, reduction, and parametrization.", "doi": "10.1021/acssynbio.2c00534", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2023-02-17", "series_number": "2", "volume": "12", "issue": "2", "pages": "511-523" }, { "id": "authors:p9rkr-pz990", "collection": "authors", "collection_id": "p9rkr-pz990", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20221205-666301600.7", "type": "article", "title": "Integrase-mediated differentiation circuits improve evolutionary stability of burdensome and toxic functions in E. coli", "author": [ { "family_name": "Williams", "given_name": "Rory L.", "orcid": "0000-0003-2605-5790", "clpid": "Williams-Rory-L" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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.", "doi": "10.1038/s41467-022-34361-y", "pmcid": "PMC9649629", "issn": "2041-1723", "publisher": "Nature Publishing Group", "publication": "Nature Communications", "publication_date": "2022-11-10", "volume": "13", "pages": "Art. No. 6822" }, { "id": "authors:re72y-6h272", "collection": "authors", "collection_id": "re72y-6h272", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20221003-756400000.10", "type": "article", "title": "Layered feedback control overcomes performance trade-off in synthetic biomolecular networks", "author": [ { "family_name": "Hu", "given_name": "Chelsea Y.", "orcid": "0000-0002-2211-1778", "clpid": "Hu-Chelsea-Y" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "AbstractLayered feedback is an optimization strategy in feedback control designs widely used in engineering. Control theory suggests that layering multiple feedbacks could overcome the robustness-speed performance trade-off limit. In natural biological networks, genes are often regulated in layers to adapt to environmental perturbations. It is hypothesized layering architecture could also overcome the robustness-speed performance trade-off in genetic networks. In this work, we validate this hypothesis with a synthetic biomolecular network in living E. coli cells. We start with system dynamics analysis using models of various complexities to guide the design of a layered control architecture in living cells. Experimentally, we interrogate system dynamics under three groups of perturbations. We consistently observe that the layered control improves system performance in the robustness-speed domain. This work confirms that layered control could be adopted in synthetic biomolecular networks for performance optimization. It also provides insights into understanding genetic feedback control architectures in nature.", "doi": "10.1038/s41467-022-33058-6", "pmcid": "PMC9474519", "issn": "2041-1723", "publisher": "Nature Publishing Group", "publication": "Nature Communications", "publication_date": "2022-09-14", "volume": "13", "pages": "Art. No. 5393" }, { "id": "authors:1x87p-ed577", "collection": "authors", "collection_id": "1x87p-ed577", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200804-104555959", "type": "article", "title": "BioCRNpyler: Compiling chemical reaction networks from biomolecular parts in diverse contexts", "author": [ { "family_name": "Poole", "given_name": "William", "orcid": "0000-0002-2958-6776", "clpid": "Poole-William" }, { "family_name": "Pandey", "given_name": "Ayush", "orcid": "0000-0003-3590-4459", "clpid": "Pandey-Ayush" }, { "family_name": "Shur", "given_name": "Andrey", "orcid": "0000-0001-9372-6713", "clpid": "Shur-Andrey-S" }, { "family_name": "Tuza", "given_name": "Zoltan A.", "orcid": "0000-0003-2896-1527", "clpid": "Tuza-Zoltan-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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.", "doi": "10.1371/journal.pcbi.1009987", "pmcid": "PMC9060376", "issn": "1553-734X", "publisher": "Public Library of Science", "publication": "PLoS Computational Biology", "publication_date": "2022-04-20", "series_number": "4", "volume": "18", "issue": "4", "pages": "Art. No. e1009987" }, { "id": "authors:yc4sr-fb679", "collection": "authors", "collection_id": "yc4sr-fb679", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200909-145940519", "type": "article", "title": "Synthetic mammalian signaling circuits for robust cell population control", "author": [ { "family_name": "Ma", "given_name": "Yitong", "orcid": "0000-0003-4446-7326", "clpid": "Ma-Yitong" }, { "family_name": "Budde", "given_name": "Mark W.", "orcid": "0000-0002-4359-1424", "clpid": "Budde-Mark-W" }, { "family_name": "Mayalu", "given_name": "Micha\u00eblle N.", "orcid": "0000-0002-9678-0157", "clpid": "Mayalu-Micha\u00eblle-N" }, { "family_name": "Zhu", "given_name": "Junqin", "orcid": "0000-0002-8159-6402", "clpid": "Zhu-Junqin" }, { "family_name": "Lu", "given_name": "Andrew C.", "orcid": "0000-0002-7594-6445", "clpid": "Lu-Andrew-C" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Elowitz", "given_name": "Michael B.", "orcid": "0000-0002-1221-0967", "clpid": "Elowitz-M-B" } ], "abstract": "In multicellular organisms, cells actively sense and control their own population density. Synthetic mammalian quorum-sensing circuits could provide insight into principles of population control and extend cell therapies. However, a key challenge is reducing 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. We designed a paradoxical population control circuit, termed \"Paradaux,\" in which auxin stimulates and inhibits net cell growth at different concentrations. This circuit limited population size over extended timescales of up to 42 days of continuous culture. By contrast, when operating in a non-paradoxical regime, population control became more susceptible to mutational escape. These results establish auxin as a versatile \"private\" communication system and demonstrate that paradoxical circuit architectures can provide robust population control.", "doi": "10.1016/j.cell.2022.01.026", "pmcid": "PMC8995209", "issn": "0092-8674", "publisher": "Cell Press", "publication": "Cell", "publication_date": "2022-03-17", "series_number": "6", "volume": "185", "issue": "6", "pages": "967-979" }, { "id": "authors:mwtva-41847", "collection": "authors", "collection_id": "mwtva-41847", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140925-085129247", "type": "article", "title": "Synthetic logic circuits using RNA aptamer against T7 RNA polymerase", "author": [ { "family_name": "Kim", "given_name": "Jongmin", "orcid": "0000-0002-2713-1006", "clpid": "Kim-Jongmin" }, { "family_name": "Quijano", "given_name": "Juan F.", "orcid": "0000-0002-5803-3935", "clpid": "Quijano-Juan-F" }, { "family_name": "Kim", "given_name": "Jeongwon", "clpid": "Kim-Jeongwon" }, { "family_name": "Yeung", "given_name": "Enoch", "orcid": "0000-0001-7630-7429", "clpid": "Yeung-Enoch" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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. We first demonstrated the utility of the RNA aptamer in combination with programmable synthetic transcription networks in vitro. As a step to quickly assess the feasibility of aptamer functions in vivo, we tested the aptamer and its sequence variants in the cell-free expression system, verifying the aptamer functionality in the cell-free testbed. The expression of aptamer in E. coli demonstrated control over GFP expression driven by T7 RNA polymerase, indicating its ability to serve as building blocks for logic circuits and transcriptional cascades. This work elucidates the potential of T7 RNA polymerase aptamer as regulators for synthetic biological circuits and metabolic engineering.", "doi": "10.1002/biot.202000449", "issn": "1860-7314", "publisher": "Wiley", "publication": "Biotechnology Journal", "publication_date": "2022-03", "series_number": "3", "volume": "17", "issue": "3", "pages": "Art. No. 2000449" }, { "id": "authors:8eqsz-zc081", "collection": "authors", "collection_id": "8eqsz-zc081", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220124-747977500", "type": "article", "title": "Robustness guarantees for structured model reduction of\u00a0dynamical systems with applications to biomolecular models", "author": [ { "family_name": "Pandey", "given_name": "Ayush", "orcid": "0000-0003-3590-4459", "clpid": "Pandey-Ayush" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Model reduction methods usually focus on the error performance analysis; however, in presence of uncertainties, it is important to analyze the robustness properties of the error in model reduction as well. This problem is particularly relevant for engineered biological systems that need to function in a largely unknown and uncertain environment. We give robustness guarantees for structured model reduction of linear and nonlinear dynamical systems under parametric uncertainties. We consider a model reduction problem where the states in the reduced model are a strict subset of the states of the full model, and the dynamics for all of the other states are collapsed to zero (similar to quasi-steady-state approximation). We show two approaches to compute a robustness guarantee metric for any such model reduction\u2014a direct linear analysis method for linear dynamics and a sensitivity analysis based approach that also works for nonlinear dynamics. Using the robustness guarantees with an error metric and an input-output mapping metric, we propose an automated model reduction method to determine the best possible reduced model for a given detailed system model. We apply our method for the (1) design space exploration of a gene expression system that leads to a new mathematical model that accounts for the limited resources in the system and (2) model reduction of a population control circuit in bacterial cells.", "doi": "10.1002/rnc.6013", "issn": "1049-8923", "publisher": "Wiley", "publication": "International Journal of Robust and Nonlinear Control", "publication_date": "2022-01-24" }, { "id": "authors:x7d2y-k8b85", "collection": "authors", "collection_id": "x7d2y-k8b85", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210311-095327802", "type": "article", "title": "Data-driven network models for genetic circuits from time-series data with incomplete measurements", "author": [ { "family_name": "Yeung", "given_name": "Enoch", "orcid": "0000-0001-7630-7429", "clpid": "Yeung-Enoch" }, { "family_name": "Kim", "given_name": "Jongmin", "orcid": "0000-0002-2713-1006", "clpid": "Kim-Jongmin" }, { "family_name": "Yuan", "given_name": "Ye", "orcid": "0000-0001-8669-7950", "clpid": "Yuan-Ye" }, { "family_name": "Gon\u00e7alves", "given_name": "Jorge", "orcid": "0000-0002-5228-6165", "clpid": "Gon\u00e7alves-Jorge-M" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Synthetic gene networks are frequently conceptualized and visualized as static graphs. This view of biological programming stands in stark contrast to the transient nature of biomolecular interaction, which is frequently enacted by labile molecules that are often unmeasured. Thus, the network topology and dynamics of synthetic gene networks can be difficult to verify in vivo or in vitro, due to the presence of unmeasured biological states. Here we introduce the dynamical structure function as a new mesoscopic, data-driven class of models to describe gene networks with incomplete measurements of state dynamics. We develop a network reconstruction algorithm and a code base for reconstructing the dynamical structure function from data, to enable discovery and visualization of graphical relationships in a genetic circuit diagram as time-dependent functions rather than static, unknown weights. We prove a theorem, showing that dynamical structure functions can provide a data-driven estimate of the size of crosstalk fluctuations from an idealized model. We illustrate this idea with numerical examples. Finally, we show how data-driven estimation of dynamical structure functions can explain failure modes in two experimentally implemented genetic circuits, a previously reported in vitro genetic circuit and a new E. coli-based transcriptional event detector.", "doi": "10.1098/rsif.2021.0413", "issn": "1742-5689", "publisher": "Royal Society", "publication": "Journal of the Royal Society Interface", "publication_date": "2021-09", "series_number": "182", "volume": "18", "issue": "182", "pages": "Art. No. 20210413" }, { "id": "authors:jdq62-d5n95", "collection": "authors", "collection_id": "jdq62-d5n95", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211122-221808622", "type": "article", "title": "Rapid Characterization of Genetic Parts with Cell-free Systems", "author": [ { "family_name": "McManus", "given_name": "John B.", "clpid": "McManus-John-B" }, { "family_name": "Bernhards", "given_name": "Casey B.", "clpid": "Bernhards-Casey-B" }, { "family_name": "Sharpes", "given_name": "Caitlin E.", "clpid": "Sharpes-Caitlin-E" }, { "family_name": "Garcia", "given_name": "David C.", "orcid": "0000-0002-6029-7964", "clpid": "Garcia-David-C" }, { "family_name": "Cole", "given_name": "Stephanie D.", "clpid": "Cole-Stephanie-D" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Emanuel", "given_name": "Peter A.", "orcid": "0000-0001-5475-7349", "clpid": "Emanuel-Peter-A" }, { "family_name": "Lux", "given_name": "Matthew W.", "orcid": "0000-0002-2773-742X", "clpid": "Lux-Matthew-W" } ], "abstract": "Characterizing and cataloging genetic parts are critical to the design of useful genetic circuits. Having well-characterized parts allows for the fine-tuning of genetic circuits, such that their function results in predictable outcomes. With the growth of synthetic biology as a field, there has been an explosion of genetic circuits that have been implemented in microbes to execute functions pertaining to sensing, metabolic alteration, and cellular computing. Here, we show a rapid and cost-effective method for characterizing genetic parts. Our method utilizes cell-free lysate, prepared in-house as a medium to evaluate parts via the expression of a reporter protein. Template DNA is prepared by PCR amplification using inexpensive primers to add variant parts to the reporter gene, and the template is added to the reaction as linear DNA without cloning. Parts that can be added in this way include promoters, operators, ribosome binding sites, insulators, and terminators. This approach, combined with the incorporation of an acoustic liquid handler and 384-well plates, allows the user to carry out high-throughput evaluations of genetic parts in a single day. By comparison, cell-based screening approaches require time-consuming cloning and have longer testing times due to overnight culture and culture density normalization steps. Further, working in cell-free lysate allows the user to exact tighter control over the expression conditions through the addition of exogenous components and DNA at precise concentrations. Results obtained from cell-free screening can be used directly in applications of cell-free systems or, in some cases, as a way to predict function in whole cells.", "doi": "10.3791/62816", "issn": "1940-087X", "publisher": "JoVE", "publication": "Journal of Visualized Experiments", "publication_date": "2021-08-31", "volume": "174", "pages": "Art. No. e62816" }, { "id": "authors:4t67z-nxz42", "collection": "authors", "collection_id": "4t67z-nxz42", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210513-144618998", "type": "article", "title": "Guiding Ethical Principles in Engineering Biology Research", "author": [ { "family_name": "Mackelprang", "given_name": "Rebecca", "clpid": "Mackelprang-Rebecca" }, { "family_name": "Aurand", "given_name": "Emily R.", "orcid": "0000-0003-4092-8551", "clpid": "Aurand-Emliy-R" }, { "family_name": "Bovenberg", "given_name": "Roel A. L.", "clpid": "Bovenberg-Roel-A-L" }, { "family_name": "Brink", "given_name": "Kathryn R.", "clpid": "Brink-Kathryn-R" }, { "family_name": "Charo", "given_name": "R. Alta", "clpid": "Charo-R-Alta" }, { "family_name": "Delborne", "given_name": "Jason A.", "clpid": "Delborne-James-A" }, { "family_name": "Diggans", "given_name": "James", "clpid": "Diggans-James" }, { "family_name": "Ellington", "given_name": "Andrew D.", "orcid": "0000-0001-6246-5338", "clpid": "Ellington-Andrew-D" }, { "family_name": "Fortman", "given_name": "Jeffrey L. \"Clem\"", "clpid": "Fortman-Jeffrey-L-Clem" }, { "family_name": "Isaacs", "given_name": "Farren J.", "orcid": "0000-0001-8615-8236", "clpid": "Isaacs-Farren-J" }, { "family_name": "Medford", "given_name": "June I.", "orcid": "0000-0002-0599-4863", "clpid": "Medford-June-I" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Noireaux", "given_name": "Vincent", "orcid": "0000-0002-5213-273X", "clpid": "Noireaux-Vincent" }, { "family_name": "Palmer", "given_name": "Megan J.", "clpid": "Palmer-Megan-J" }, { "family_name": "Zoloth", "given_name": "Laurie", "clpid": "Zoloth-Laurie" }, { "family_name": "Friedman", "given_name": "Douglas C.", "orcid": "0000-0001-7234-4943", "clpid": "Friedman-Douglas-C" } ], "abstract": "Engineering biology is being applied toward solving or mitigating some of the greatest challenges facing society. As with many other rapidly advancing technologies, the development of these powerful tools must be considered in the context of ethical uses for personal, societal, and/or environmental advancement. Researchers have a responsibility to consider the diverse outcomes that may result from the knowledge and innovation they contribute to the field. Together, we developed a Statement of Ethics in Engineering Biology Research to guide researchers as they incorporate the consideration of long-term ethical implications of their work into every phase of the research lifecycle. Herein, we present and contextualize this Statement of Ethics and its six guiding principles. Our goal is to facilitate ongoing reflection and collaboration among technical researchers, social scientists, policy makers, and other stakeholders to support best outcomes in engineering biology innovation and development.", "doi": "10.1021/acssynbio.1c00129", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2021-05-21", "series_number": "5", "volume": "10", "issue": "5", "pages": "907-910" }, { "id": "authors:bygwm-0wk74", "collection": "authors", "collection_id": "bygwm-0wk74", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200806-153554109", "type": "article", "title": "A MATLAB toolbox for modeling genetic circuits in cell-free systems", "author": [ { "family_name": "Singhal", "given_name": "Vipul", "orcid": "0000-0003-1670-1824", "clpid": "Singhal-Vipul" }, { "family_name": "Tuza", "given_name": "Zoltan A.", "orcid": "0000-0003-2896-1527", "clpid": "Tuza-Zoltan-A" }, { "family_name": "Sun", "given_name": "Zachary Z.", "orcid": "0000-0002-9425-2924", "clpid": "Sun-Zachary-Z" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We introduce a MATLAB-based simulation toolbox, called txtlsim, for an Escherichia coli-based Transcription\u2013Translation (TX\u2013TL) system. This toolbox accounts for several cell-free-related phenomena, such as resource loading, consumption and degradation, and in doing so, models the dynamics of TX\u2013TL reactions for the entire duration of solution phase batch-mode experiments. We use a Bayesian parameter inference approach to characterize the reaction rate parameters associated with the core transcription, translation and mRNA degradation mechanics of the toolbox, allowing it to reproduce constitutive mRNA and protein-expression trajectories. We demonstrate the use of this characterized toolbox in a circuit behavior prediction case study for an incoherent feed-forward loop.", "doi": "10.1093/synbio/ysab007", "pmcid": "PMC8102020", "issn": "2397-7000", "publisher": "Oxford University Press", "publication": "Synthetic Biology", "publication_date": "2021-02-05", "series_number": "1", "volume": "6", "issue": "1", "pages": "Art. No. ysab007" }, { "id": "authors:e3dmx-5p177", "collection": "authors", "collection_id": "e3dmx-5p177", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200401-104547968", "type": "article", "title": "Guidelines for designing the antithetic feedback motif", "author": [ { "family_name": "Baetica", "given_name": "Ania-Ariadna", "orcid": "0000-0003-0421-8181", "clpid": "Baetica-A-A" }, { "family_name": "Leong", "given_name": "Yoke Peng", "orcid": "0000-0001-8560-8856", "clpid": "Leong-Yoke-Peng" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Integral feedback control is commonly used in mechanical and electrical systems to achieve zero steady-state error following an external disturbance. Equivalently, in biological systems, a property known as robust perfect adaptation guarantees robustness to environmental perturbations and return to the pre-disturbance state. Previously, Briat et al. proposed a biomolecular design for integral feedback control (robust perfect adaptation) called the antithetic feedback motif. The antithetic feedback controller uses the sequestration binding reaction of two biochemical species to record the integral of the error between the current and the desired output of the network it controls. The antithetic feedback motif has been successfully built using synthetic components in vivo in Escherichia coli and Saccharomyces cerevisiae cells. However, these previous synthetic implementations of antithetic feedback have not produced perfect integral feedback control due to the degradation and dilution of the two controller species. Furthermore, previous theoretical results have cautioned that integral control can only be achieved under stability conditions that not all antithetic feedback motifs necessarily fulfill. In this paper, we study how to design antithetic feedback motifs that simultaneously achieve good stability and small steady-state error properties, even as the controller species are degraded and diluted. We provide simple tuning guidelines to achieve flexible and practical synthetic biological implementations of antithetic feedback control. We use several tools and metrics from control theory to design antithetic feedback networks, paving the path for the systematic design of synthetic biological controllers.", "doi": "10.1088/1478-3975/ab8454", "issn": "1478-3967", "publisher": "IOP", "publication": "Physical Biology", "publication_date": "2020-09", "series_number": "5", "volume": "17", "issue": "5", "pages": "Art. No. 055002" }, { "id": "authors:3vtb4-p9h09", "collection": "authors", "collection_id": "3vtb4-p9h09", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190918-100800913", "type": "article", "title": "Assessment of Robustness to Temperature in a Negative Feedback Loop and a Feedforward Loop", "author": [ { "family_name": "Patel", "given_name": "Abhilash", "orcid": "0000-0001-6319-658X", "clpid": "Patel-Abhilash" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Sen", "given_name": "Shaunak", "orcid": "0000-0002-1412-8633", "clpid": "Sen-Shaunak" } ], "abstract": "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\u2014a 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.", "doi": "10.1021/acssynbio.0c00023", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2020-07-17", "series_number": "7", "volume": "9", "issue": "7", "pages": "1581-1590" }, { "id": "authors:2x9e7-s7y33", "collection": "authors", "collection_id": "2x9e7-s7y33", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190422-091140360", "type": "article", "title": "A Method for Cost-Effective and Rapid Characterization of Engineered T7-based Transcription Factors by Cell-Free Protein Synthesis Reveals Insights into the Regulation of T7 RNA Polymerase-Driven Expression", "author": [ { "family_name": "McManus", "given_name": "John B.", "clpid": "McManus-John-B" }, { "family_name": "Lux", "given_name": "Matthew W.", "clpid": "Lux-Matthew-W" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Emanuel", "given_name": "Peter A.", "orcid": "0000-0001-5475-7349", "clpid": "Emanuel-Peter-A" } ], "abstract": "The T7 bacteriophage RNA polymerase (T7 RNAP) serves as a model for understanding RNA synthesis, as a tool for protein expression, and as an actuator for synthetic gene circuit design in bacterial cells and cell-free extract. T7 RNAP is an attractive tool for orthogonal protein expression in bacteria owing to its compact single subunit structure and orthogonal promoter specificity. Understanding the mechanisms underlying T7 RNAP regulation is important to the design of engineered T7-based transcription factors, which can be used in gene circuit design. To explore regulatory mechanisms for T7 RNAP-driven expression, we developed a rapid and cost-effective method to characterize engineered T7-based transcription factors using cell-free protein synthesis and an acoustic liquid handler. Using this method, we investigated the effects of the tetracycline operator's proximity to the T7 promoter on the regulation of T7 RNAP-driven expression. Our results reveal a mechanism for regulation that functions by interfering with the transition of T7 RNAP from initiation to elongation and validates the use of the method described here to engineer future T7-based transcription factors.", "doi": "10.1016/j.abb.2019.07.010", "issn": "0003-9861", "publisher": "Elsevier", "publication": "Archives of Biochemistry and Biophysics", "publication_date": "2019-10-15", "volume": "674", "pages": "Art. No. 108045" }, { "id": "authors:ky3xs-87k68", "collection": "authors", "collection_id": "ky3xs-87k68", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190708-153642582", "type": "article", "title": "Hard Limits and Performance Tradeoffs in a Class of Antithetic Integral Feedback Networks", "author": [ { "family_name": "Olsman", "given_name": "Noah", "orcid": "0000-0002-4351-3880", "clpid": "Olsman-N" }, { "family_name": "Baetica", "given_name": "Ania-Ariadna", "orcid": "0000-0003-0421-8181", "clpid": "Baetica-A-A" }, { "family_name": "Xiao", "given_name": "Fangzhou", "orcid": "0000-0002-5001-5644", "clpid": "Xiao-Fangzhou" }, { "family_name": "Leong", "given_name": "Yoke Peng", "orcid": "0000-0001-8560-8856", "clpid": "Leong-Yoke-Peng" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Doyle", "given_name": "John C.", "orcid": "0000-0002-1828-2486", "clpid": "Doyle-J-C" } ], "abstract": "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 called antithetic integral feedback, which can be implemented using the 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 antithetic integral feedback and contribute to a more general theory of biological control systems.", "doi": "10.1016/j.cels.2019.06.001", "issn": "2405-4712", "publisher": "Elsevier", "publication": "Cell Systems", "publication_date": "2019-07-24", "series_number": "1", "volume": "9", "issue": "1", "pages": "49-63" }, { "id": "authors:st9ft-4kk15", "collection": "authors", "collection_id": "st9ft-4kk15", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200131-125317403", "type": "article", "title": "Analysis of primitive genetic interactions for the design of a genetic signal differentiator", "author": [ { "family_name": "Halter", "given_name": "Wolfgang", "orcid": "0000-0001-9902-5782", "clpid": "Halter-W" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Allg\u00f6wer", "given_name": "Frank", "clpid": "Allg\u00f6wer-F" } ], "abstract": "We study the dynamic and static input\u2013output behavior of several primitive genetic interactions and their effect on the performance of a genetic signal differentiator. In a simplified design, several requirements for the linearity and time-scales of processes like transcription, translation and competitive promoter binding were introduced. By experimentally probing simple genetic constructs in a cell-free experimental environment and fitting semi-mechanistic models to these data, we show that some of these requirements can be verified, while others are only met with reservations in certain operational regimes. Analyzing the linearized model of the resulting genetic network, we conclude that it approximates a differentiator with relative degree one. Taking also the discovered nonlinearities into account and using a describing function approach, we further determine the particular frequency and amplitude ranges where the genetic differentiator can be expected to behave as such.", "doi": "10.1093/synbio/ysz015", "issn": "2397-7000", "publisher": "Oxford University Press", "publication": "Synthetic Biology", "publication_date": "2019-06-27", "series_number": "1", "volume": "4", "issue": "1", "pages": "Art. No. ysz015" }, { "id": "authors:x3d00-g0f42", "collection": "authors", "collection_id": "x3d00-g0f42", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190312-134813069", "type": "article", "title": "Construction of Incoherent Feedforward Loop Circuits in a Cell-Free System and in Cells", "author": [ { "family_name": "Guo", "given_name": "Shaobin", "orcid": "0000-0001-9736-4078", "clpid": "Guo-Shaobin" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Cells utilize transcriptional regulation networks to respond to environmental signals. Network motifs, such as feedforward loops, play essential roles in these regulatory networks. In this work, we construct two different functional and modular incoherent type 1 feedforward loop circuits in a cell-free transcription\u2013translation system and in cells. With the help of mathematical modeling and the cell-free system, we can streamline the design\u2013build\u2013test cycles of the circuits, in which we characterize and optimize these circuits in vitro to confirm that they function as expected before implementing them in vivo. We show that the performance of these circuits from in vitro studies closely recapitulates those from in vivo experiments. We demonstrate that these feedforward loops show dynamic response and pulse-like behavior both in vitro and in vivo. These novel feedforward loop network motifs can be incorporated in more complicated biological circuits as detectors or responders.", "doi": "10.1021/acssynbio.8b00493", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2019-03-15", "series_number": "3", "volume": "8", "issue": "3", "pages": "606-610" }, { "id": "authors:71fsr-jjb78", "collection": "authors", "collection_id": "71fsr-jjb78", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190228-112317657", "type": "article", "title": "Synthesizing voluntary lane-change policy using control improvisation", "author": [ { "family_name": "Ge", "given_name": "Jin I.", "orcid": "0000-0001-6429-9337", "clpid": "Ge-Jin-I" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "In this work, we propose control improvisation to synthesize voluntary lane-change policy that meets human preferences under given traffic environments. We first train Markov models to describe the lane-change environment for an automated vehicle under assumed traffic patterns. Parameters in the environment model are trained using traffic data and calibrated using control improvisation. Then, based on human lane-change behavior, we train a voluntary lane-change policy using explicit-duration Markov decision process. Parameters in the lane-change policy are calibrated through control improvisation to allow an automated car to voluntarily change lanes while avoiding overly frequent lane-change maneuvers under various traffic environments.", "doi": "10.1016/j.ifacol.2019.01.007", "issn": "2405-8963", "publisher": "Elsevier", "publication": "IFAC-PapersOnLine", "publication_date": "2019-02-08", "series_number": "34", "volume": "51", "issue": "34", "pages": "396-399" }, { "id": "authors:cy5e7-6dq47", "collection": "authors", "collection_id": "cy5e7-6dq47", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180622-104112749", "type": "article", "title": "On-chip membrane protein cell-free expression enables development of a direct binding assay: A curious case of potassium channel KcsA-Kv1.3", "author": [ { "family_name": "Vaish", "given_name": "Amit", "clpid": "Vaish-A" }, { "family_name": "Guo", "given_name": "Shaobin", "orcid": "0000-0001-9736-4078", "clpid": "Guo-Shaobin" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Grandsard", "given_name": "Peter J.", "clpid": "Grandsard-P-J" }, { "family_name": "Chen", "given_name": "Qing", "clpid": "Chen-Qing" } ], "abstract": "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.", "doi": "10.1016/j.ab.2018.06.018", "issn": "0003-2697", "publisher": "Elsevier", "publication": "Analytical Biochemistry", "publication_date": "2018-09-01", "volume": "556", "pages": "70-77" }, { "id": "authors:r6eba-5m902", "collection": "authors", "collection_id": "r6eba-5m902", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180920-104049492", "type": "article", "title": "Layering Assume-Guarantee Contracts for Hierarchical System Design", "author": [ { "family_name": "Filippidis", "given_name": "Ioannis", "orcid": "0000-0003-4704-3334", "clpid": "Filippidis-I" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Specifications for complex engineering systems are typically decomposed into specifications for individual subsystems in a manner that ensures they are implementable and simpler to develop further. We describe a method to algorithmically construct component specifications that implement a given specification when assembled. By eliminating variables that are irrelevant to realizability of each component, we simplify the specifications and reduce the amount of information necessary for operation. We parametrize the information flow between components by introducing parameters that select whether each variable is visible to a component. The decomposition algorithm identifies which variables can be hidden while preserving realizability and ensuring correct composition, and these are eliminated from component specifications by quantification and conversion of binary decision diagrams to formulas. The resulting specifications describe component viewpoints with full information with respect to the remaining variables, which is essential for tractable algorithmic synthesis of implementations. The specifications are written in TLA + , with liveness properties restricted to an implication of conjoined recurrence properties, known as GR(1). We define an operator for forming open systems from closed systems, based on a variant of the \"while-plus\" operator. This operator simplifies the writing of specifications that are realizable without being vacuous. To convert the generated specifications from binary decision diagrams to readable formulas over integer variables, we symbolically solve a minimal covering problem. We show with examples how the method can be applied to obtain contracts that formalize the hierarchical structure of system design.", "doi": "10.1109/JPROC.2018.2834926", "issn": "0018-9219", "publisher": "IEEE", "publication": "Proceedings of the IEEE", "publication_date": "2018-09", "series_number": "9", "volume": "106", "issue": "9", "pages": "1616-1654" }, { "id": "authors:wec2t-gmq84", "collection": "authors", "collection_id": "wec2t-gmq84", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171103-115106585", "type": "article", "title": "Simulations and bisimulations for analysis of stability with respect to inputs of hybrid systems", "author": [ { "family_name": "Prabhakar", "given_name": "Pavithra", "clpid": "Prabhakar-Pavithra" }, { "family_name": "Liu", "given_name": "Jun", "clpid": "Liu-Jun" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Simulation and bisimulation relations define pre-orders on processes which serve as the basis for approximation based verification techniques, and have been extended towards the design of continuous and hybrid systems with complex logic specifications. We study pre-orders between hybrid systems which preserve stability properties with respect to input. We show that these properties are not bisimulation invariant, and hence propose stronger notions which strengthen simulation and bisimulation relations with uniform continuity constraints. We show that uniform continuity is necessary on the relations corresponding to both the state-space and the input-space, and continuity itself does not suffice. Finally, we demonstrate the satisfiability of our definitions by casting the well-known Lyapunov function based techniques for stability analysis as constructing a simple one-dimensional system which is stable and uniformly continuously simulates the original system.", "doi": "10.1007/s10626-017-0262-9", "issn": "0924-6703", "publisher": "Springer", "publication": "Discrete Event Dynamic Systems", "publication_date": "2018-09", "series_number": "3", "volume": "28", "issue": "3", "pages": "349-374" }, { "id": "authors:8652e-1ns11", "collection": "authors", "collection_id": "8652e-1ns11", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180912-130453647", "type": "article", "title": "Temporal Logic Control of POMDPs via Label-based Stochastic Simulation Relations", "author": [ { "family_name": "Haesaert", "given_name": "S.", "clpid": "Haesaert-Sofie" }, { "family_name": "Nilsson", "given_name": "P.", "orcid": "0000-0001-8748-6936", "clpid": "Nilsson-Petter" }, { "family_name": "Vasile", "given_name": "C. I.", "clpid": "Vasile-C-I" }, { "family_name": "Thakker", "given_name": "R.", "clpid": "Thakker-Rohan-A" }, { "family_name": "Agha-Mohammadi", "given_name": "A.", "orcid": "0000-0001-5509-1841", "clpid": "Agha-Mohammadi-A-A" }, { "family_name": "Ames", "given_name": "A. D.", "orcid": "0000-0003-0848-3177", "clpid": "Ames-A-D" }, { "family_name": "Murray", "given_name": "R. M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The synthesis of controllers guaranteeing linear temporal logic specifications on partially observable Markov decision processes (POMDP) via their belief models causes computational issues due to the continuous spaces. In this work, we construct a finite-state abstraction on which a control policy is synthesized and refined back to the original belief model. We introduce a new notion of label-based approximate stochastic simulation to quantify the deviation between belief models. We develop a robust synthesis methodology that yields a lower bound on the satisfaction probability, by compensating for deviations a priori, and that utilizes a less conservative control refinement.", "doi": "10.1016/j.ifacol.2018.08.046", "issn": "2405-8963", "publisher": "Elsevier", "publication": "IFAC-PapersOnLine", "publication_date": "2018-08-31", "series_number": "16", "volume": "51", "issue": "16", "pages": "271-276" }, { "id": "authors:rqwpc-d9137", "collection": "authors", "collection_id": "rqwpc-d9137", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180524-091716800", "type": "article", "title": "Control Theory for Synthetic Biology: Recent Advances in System Characterization, Control Design, and Controller Implementation for Synthetic Biology", "author": [ { "family_name": "Hsiao", "given_name": "Victoria", "orcid": "0000-0001-9297-1522", "clpid": "Hsiao-Victoria" }, { "family_name": "Swaminathan", "given_name": "Anandh", "orcid": "0000-0001-9935-6530", "clpid": "Swaminathan-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Living organisms are differentiated by their genetic material-millions to billions of DNA bases encoding thousands of genes. These genes are translated into a vast array of proteins, many of which have functions that are still unknown. Previously, it was believed that simply knowing the genetic sequence of an organism would be the key to unlocking all understanding. However, as DNA sequencing technology has become affordable, it has become clear that living cells are governed by complex, multilayered networks of gene regulation that cannot be deduced from sequence alone. Synthetic biology as a field might best be characterized as a learn-by-building approach, in which scientists attempt to engineer molecular pathways that do not exist in nature. In doing so, they test the limits of both natural and engineered organisms.", "doi": "10.1109/MCS.2018.2810459", "issn": "0272-1708", "publisher": "IEEE", "publication": "IEEE Control Systems Magazine", "publication_date": "2018-06", "series_number": "3", "volume": "38", "issue": "3", "pages": "32-62" }, { "id": "authors:734vp-ew070", "collection": "authors", "collection_id": "734vp-ew070", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180525-123941302", "type": "article", "title": "Future systems and control research in synthetic biology", "author": [ { "family_name": "Del Vecchio", "given_name": "Domitilla", "clpid": "Del-Vecchio-D" }, { "family_name": "Qian", "given_name": "Yili", "clpid": "Qian-Yili" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Sontag", "given_name": "Eduardo D.", "clpid": "Sontag-E-D" } ], "abstract": "Synthetic biology is the application of engineering principles to the fundamental components of biology, with the aim of creating systems with novel functionalities that can be used for energy, environment, and medical applications. While the potential impact of this new technology is enormous, there are challenges that we need to overcome before the impact of synthetic biology can be fully realized. Many of these challenges fall beyond the scope of molecular biology and are indeed \"system-level\" problems, where very little research is being performed. This paper identifies pressing challenges in synthetic biology that can be formulated as systems and control theoretic problems and outlines potentially new systems and control theories/tools that are required to tackle such problems. The aim is to attract more systems and control theorists to collaborate with molecular biologists and biophysicists and help synthetic biology reach its promise. At the same time, engaging the systems and control community more broadly into the rich research opportunities and life-changing applications of synthetic biology may provide added visibility to the field of systems and controls.", "doi": "10.1016/j.arcontrol.2018.04.007", "issn": "1367-5788", "publisher": "Elsevier", "publication": "Annual Reviews in Control", "publication_date": "2018-05-24", "volume": "45", "pages": "5-17" }, { "id": "authors:p4e4h-pkg93", "collection": "authors", "collection_id": "p4e4h-pkg93", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180409-133942183", "type": "article", "title": "Single Day Construction of Multigene Circuits with 3G Assembly", "author": [ { "family_name": "Halleran", "given_name": "Andrew D.", "orcid": "0000-0001-8720-1451", "clpid": "Halleran-A-D" }, { "family_name": "Swaminathan", "given_name": "Anandh", "orcid": "0000-0001-9935-6530", "clpid": "Swaminathan-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The ability to rapidly design, build, and test prototypes is of key importance to every engineering discipline. DNA assembly often serves as a rate limiting step of the prototyping cycle for synthetic biology. Recently developed DNA assembly methods such as isothermal assembly and type IIS restriction enzyme systems take different approaches to accelerate DNA construction. We introduce a hybrid method, Golden Gate-Gibson (3G), that takes advantage of modular part libraries introduced by type IIS restriction enzyme systems and isothermal assembly's ability to build large DNA constructs in single pot reactions. Our method is highly efficient and rapid, facilitating construction of entire multigene circuits in a single day. Additionally, 3G allows generation of variant libraries enabling efficient screening of different possible circuit constructions. We characterize the efficiency and accuracy of 3G assembly for various construct sizes, and demonstrate 3G by characterizing variants of an inducible cell-lysis circuit.", "doi": "10.1021/acssynbio.8b00060", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2018-05-18", "series_number": "5", "volume": "7", "issue": "5", "pages": "1477-1480" }, { "id": "authors:nynqd-29b21", "collection": "authors", "collection_id": "nynqd-29b21", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180626-144153512", "type": "article", "title": "Richard M. Murray [People in Control]", "author": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This issue of IEEE Control Systems Magazine speaks with Richard Murray, the recipient of the 2017 IEEE Control Systems Award; Yongxin Chen, the lead author of the paper that received the 2017 George S. Axelby Outstanding Paper Award; and Joseph Bentsman, the chair of the IEEE Control Systems Society (CSS) Technical Committee on Power Generation.", "doi": "10.1109/MCS.2017.2786445", "issn": "1066-033X", "publisher": "IEEE", "publication": "IEEE Control Systems Magazine", "publication_date": "2018-04", "series_number": "2", "volume": "38", "issue": "2", "pages": "38-40" }, { "id": "authors:rjf0e-4e484", "collection": "authors", "collection_id": "rjf0e-4e484", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171204-081929055", "type": "article", "title": "Cell-Free and In Vivo Characterization of Lux, Las, and Rpa Quorum Activation Systems in E. coli", "author": [ { "family_name": "Halleran", "given_name": "Andrew D.", "orcid": "0000-0001-8720-1451", "clpid": "Halleran-A-D" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Synthetic biologists have turned toward quorum systems as a path for building sophisticated microbial consortia that exhibit group decision making. Currently, however, even the most complex consortium circuits rely on only one or two quorum sensing systems, greatly restricting the available design space. High-throughput characterization of available quorum sensing systems is useful for finding compatible sets of systems that are suitable for a defined circuit architecture. Recently, cell-free systems have gained popularity as a test-bed for rapid prototyping of genetic circuitry. We take advantage of the transcription\u2013translation cell-free system to characterize three commonly used Lux-type quorum activators, Lux, Las, and Rpa. We then compare the cell-free characterization to results obtained in vivo. We find significant genetic crosstalk in both the Las and Rpa systems and substantial signal crosstalk in Lux activation. We show that cell-free characterization predicts crosstalk observed in vivo.", "doi": "10.1021/acssynbio.7b00376", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2018-02-16", "series_number": "2", "volume": "7", "issue": "2", "pages": "752-755" }, { "id": "authors:hvx8c-p7054", "collection": "authors", "collection_id": "hvx8c-p7054", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170807-111733897", "type": "article", "title": "Cell-free extract based optimization of biomolecular circuits with droplet microfluidics", "author": [ { "family_name": "Hori", "given_name": "Yutaka", "orcid": "0000-0002-3253-4985", "clpid": "Hori-Yutaka" }, { "family_name": "Kantak", "given_name": "Chaitanya", "orcid": "0000-0003-1620-7084", "clpid": "Kantak-Chaitanya" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Abate", "given_name": "Adam R.", "orcid": "0000-0001-9614-4831", "clpid": "Abate-Adam-R" } ], "abstract": "Engineering an efficient biomolecular circuit often requires time-consuming iterations of optimization. Cell-free protein expression systems allow rapid testing of biocircuits in vitro, speeding the design\u2013build\u2013test cycle of synthetic biology. In this paper, we combine this with droplet microfluidics to densely scan a transcription\u2013translation biocircuit space. Our system assays millions of parameter combinations per hour, providing a detailed map of function. The ability to comprehensively map biocircuit parameter spaces allows accurate modeling to predict circuit function and identify optimal circuits and conditions.", "doi": "10.1039/C7LC00552K", "issn": "1473-0197", "publisher": "Royal Society of Chemistry", "publication": "Lab on a Chip", "publication_date": "2017-09-21", "series_number": "18", "volume": "17", "issue": "18", "pages": "3037-3042" }, { "id": "authors:qj7zc-1bp57", "collection": "authors", "collection_id": "qj7zc-1bp57", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160516-100511848", "type": "article", "title": "Design of a Toolbox of RNA Thermometers", "author": [ { "family_name": "Sen", "given_name": "Shaunak", "orcid": "0000-0002-1412-8633", "clpid": "Sen-Shaunak" }, { "family_name": "Apurva", "given_name": "Divyansh", "clpid": "Apurva-D" }, { "family_name": "Satija", "given_name": "Rohit", "clpid": "Satija-R" }, { "family_name": "Siegal", "given_name": "Dan", "orcid": "0000-0002-6821-2769", "clpid": "Siegal-D" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Biomolecular temperature sensors can be used for efficient control of large-volume bioreactors, for spatiotemporal imaging and control of gene expression, and to engineer robustness to temperature in biomolecular circuit design. While RNA-based sensors, called 'thermometers', have been investigated in both natural and synthetic contexts, an important challenge is to design diverse responses to temperature, differing in sensitivities and thresholds. We address this issue by constructing a library of RNA thermometers, based on thermodynamic computations, and experimentally measuring their activities in cell-free biomolecular 'breadboards'. Using free energies of the minimum free energy structures as well as melt profile computations, we estimated thata diverse set of temperature responses were possible. We experimentally found a wide range of responses to temperature in the temperature range 29 \u25e6C\u201337 \u25e6C, with fold-changes varying over 3-fold around the starting thermometer. The sensitivities of these responses ranged over 10-fold around the starting thermometer. We correlated these measurements with computational expectations, finding that while there was no strong correlation for the individual thermometers, overall trends of diversity, fold-changes, and sensitivities were similar. These results present a toolbox of RNA-based circuit elements with diverse temperature responses.", "doi": "10.1021/acssynbio.6b00301", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2017-08-18", "series_number": "8", "volume": "6", "issue": "8", "pages": "1461-1470" }, { "id": "authors:jx7y1-57e24", "collection": "authors", "collection_id": "jx7y1-57e24", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170731-080503943", "type": "article", "title": "Biophysical Constraints Arising from Compositional Context in Synthetic Gene Networks", "author": [ { "family_name": "Yeung", "given_name": "Enoch", "orcid": "0000-0001-7630-7429", "clpid": "Yeung-Enoch" }, { "family_name": "Dy", "given_name": "Aaron J.", "orcid": "0000-0003-0535-517X", "clpid": "Dy-Aaron-J" }, { "family_name": "Martin", "given_name": "Kyle B.", "clpid": "Martin-K-B" }, { "family_name": "Ng", "given_name": "Andrew H.", "clpid": "Ng-Andrew-H" }, { "family_name": "Del Vecchio", "given_name": "Domitilla", "orcid": "0000-0001-6472-8576", "clpid": "Del-Vecchio-D" }, { "family_name": "Beck", "given_name": "James L.", "clpid": "Beck-J-L" }, { "family_name": "Collins", "given_name": "James J.", "clpid": "Collins-J-J" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Synthetic gene expression is highly sensitive to intragenic compositional context (promoter structure, spacing regions between promoter and coding sequences, and ribosome binding sites). However, much less is known about the effects of intergenic compositional context (spatial arrangement and orientation of entire genes on DNA) on expression levels in synthetic gene networks. We compare expression of induced genes arranged in convergent, divergent, or tandem orientations. Induction of convergent genes yielded up to 400% higher expression, greater ultrasensitivity, and dynamic range than divergent- or tandem-oriented genes. Orientation affects gene expression whether one or both genes are induced. We postulate that transcriptional interference in divergent and tandem genes, mediated by supercoiling, can explain differences in expression and validate this hypothesis through modeling and in vitro supercoiling relaxation experiments. Treatment with gyrase abrogated intergenic context effects, bringing expression levels within 30% of each other. We rebuilt the toggle switch with convergent genes, taking advantage of supercoiling effects to improve threshold detection and switch stability.", "doi": "10.1016/j.cels.2017.06.001", "issn": "2405-4712", "publisher": "Cell Press", "publication": "Cell Systems", "publication_date": "2017-07-26", "series_number": "1", "volume": "5", "issue": "1", "pages": "11-24" }, { "id": "authors:zjdnn-bxw82", "collection": "authors", "collection_id": "zjdnn-bxw82", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170614-142315589", "type": "article", "title": "Recursively constructing analytic expressions for equilibrium distributions of stochastic biochemical reaction networks", "author": [ { "family_name": "Meng", "given_name": "X. Flora", "clpid": "Meng-X-Flora" }, { "family_name": "Baetica", "given_name": "Ania-Ariadna", "orcid": "0000-0003-0421-8181", "clpid": "Baetica-Ania-Ariadna" }, { "family_name": "Singhal", "given_name": "Vipul", "orcid": "0000-0003-1670-1824", "clpid": "Singhal-Vipul" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Noise is often indispensable to key cellular activities, such as gene expression, necessitating the use of stochastic models to capture its dynamics. The chemical master equation (CME) is a commonly used stochastic model of Kolmogorov forward equations that describe how the probability distribution of a chemically reacting system varies with time. Finding analytic solutions to the CME can have benefits, such as expediting simulations of multiscale biochemical reaction networks and aiding the design of distributional responses. However, analytic solutions are rarely known. A recent method of computing analytic stationary solutions relies on gluing simple state spaces together recursively at one or two states. We explore the capabilities of this method and introduce algorithms to derive analytic stationary solutions to the CME. \nWe first formally characterize state spaces that can be constructed by performing single-state gluing of paths, cycles or both sequentially. We then study stochastic biochemical reaction networks that consist of reversible, elementary reactions with two-dimensional state spaces. We also discuss extending the method to infinite state spaces and designing the stationary behaviour of stochastic biochemical reaction networks. Finally, we illustrate the aforementioned ideas using examples that include two interconnected transcriptional components and biochemical reactions with two-dimensional state spaces.", "doi": "10.1098/rsif.2017.0157", "pmcid": "PMC5454304", "issn": "1742-5689", "publisher": "The Royal Society", "publication": "Journal of the Royal Society Interface", "publication_date": "2017-05", "series_number": "130", "volume": "14", "issue": "130", "pages": "Art. No. 20170157" }, { "id": "authors:myf9p-n3161", "collection": "authors", "collection_id": "myf9p-n3161", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170629-080527577", "type": "article", "title": "Systems & Control for the future of humanity, research agenda: Current and future roles, impact and grand challenges", "author": [ { "family_name": "Lamnabhi-Lagarrigue", "given_name": "Francoise", "clpid": "Lamnabhi-Lagarrigue-F" }, { "family_name": "Annaswamy", "given_name": "Anuradha", "clpid": "Annaswamy-A" }, { "family_name": "Engell", "given_name": "Sebastian", "clpid": "Engell-S" }, { "family_name": "Isaksson", "given_name": "Alf", "clpid": "Isaksson-A" }, { "family_name": "Khargonekar", "given_name": "Pramod", "clpid": "Khargonekar-P" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Nijmeijer", "given_name": "Henk", "clpid": "Nijmeijer-H" }, { "family_name": "Samad", "given_name": "Tariq", "clpid": "Samad-T" }, { "family_name": "Tilbury", "given_name": "Dawn", "clpid": "Tilbury-D" }, { "family_name": "Van den Hof", "given_name": "Paul", "clpid": "Van-den-Hof-P" } ], "abstract": "Following in the footsteps of the renowned report \"Control in an Information Rich World,\" Report of the Panel on \"Future Directions in Control, Dynamics, and Systems\" chaired by Richard Murray (2002), this paper aims to demonstrate that Systems & Control is at the heart of the Information and Communication Technologies to most application domains. As such, Systems & Control should be acknowledged as a priority by funding agencies and supported at the levels necessary to enable technologies addressing critical societal challenges. A second intention of this paper is to present to the industrials and the young research generation, a global picture of the societal and research challenges where the discipline of Systems & Control will play a key role. Throughout, this paper demonstrates the extremely rich, current and future, cross-fertilization between five critical societal challenges and seven key research and innovation Systems & Control scientific challenges. This paper is authored by members of the IFAC Task Road Map Committee, established following the 19th IFAC World Congress in Cape Town. Other experts who authored specific parts are listed below.", "doi": "10.1016/j.arcontrol.2017.04.001", "issn": "1367-5788", "publisher": "Elsevier", "publication": "Annual Reviews in Control", "publication_date": "2017-04-26", "volume": "43", "pages": "1-64" }, { "id": "authors:902cn-7xz30", "collection": "authors", "collection_id": "902cn-7xz30", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170202-080959480", "type": "article", "title": "Privacy Preserving Average Consensus", "author": [ { "family_name": "Mo", "given_name": "Yilin", "orcid": "0000-0001-7937-6737", "clpid": "Mo-Yilin" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Average consensus is a widely used algorithm for distributed computing and control, 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 an agent to the other agents. In this paper, we propose a privacy preserving average consensus algorithm to guarantee the privacy of the initial state and asymptotic consensus on the exact average of the initial values, by adding and subtracting random noises to the consensus process. We characterize the mean square convergence rate of our consensus algorithm and derive the covariance matrix of the maximum likelihood estimate on the initial state. Moreover, we prove that our proposed algorithm is optimal in the sense that it does not disclose any information more than necessary to achieve the average consensus. A numerical example is provided to illustrate the effectiveness of the proposed design.", "doi": "10.1109/TAC.2016.2564339", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "2017-02", "series_number": "2", "volume": "62", "issue": "2", "pages": "753-765" }, { "id": "authors:qancn-eky27", "collection": "authors", "collection_id": "qancn-eky27", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170202-073327562", "type": "article", "title": "Stability of Systems with Stochastic Delays and Applications to Genetic Regulatory Networks", "author": [ { "family_name": "Gomez", "given_name": "Marcella M.", "clpid": "Gomez-Marcella-M" }, { "family_name": "Sadeghpour", "given_name": "Mehdi", "orcid": "0000-0003-3946-960X", "clpid": "Sadeghpour-Mehdi" }, { "family_name": "Bennett", "given_name": "Matthew R.", "orcid": "0000-0002-4975-8854", "clpid": "Bennett-Mathew-R" }, { "family_name": "Orosz", "given_name": "G\u00e1bor", "orcid": "0000-0002-9000-3736", "clpid": "Orosz-G\u00e1bor" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The dynamics of systems with stochastically varying time delays are investigated in this paper. It is shown that the mean dynamics can be used to derive necessary conditions for the stability of equilibria of the stochastic system. Moreover, the second moment dynamics can be used to derive sufficient conditions for almost sure stability of equilibria. The results are summarized using stability charts that are obtained via semidiscretization. The theoretical methods are applied to simple gene regulatory networks where it is demonstrated that stochasticity in the delay can improve the stability of steady protein production.", "doi": "10.1137/15M1031965", "pmcid": "PMC5603244", "issn": "1536-0040", "publisher": "Society for Industrial and Applied Mathematics", "publication": "SIAM Journal on Applied Dynamical Systems", "publication_date": "2016-10-13", "series_number": "4", "volume": "15", "issue": "4", "pages": "1844-1873" }, { "id": "authors:96j27-syv30", "collection": "authors", "collection_id": "96j27-syv30", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160513-150803580", "type": "article", "title": "The effects of time-varying temperature on delays in genetic networks", "author": [ { "family_name": "Gomez", "given_name": "Marcella M.", "clpid": "Gomez-Marcella-M" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Bennett", "given_name": "Matthew R.", "orcid": "0000-0002-4975-8854", "clpid": "Bennett-Mathew-R" } ], "abstract": "Delays in gene networks result from the sequential nature of protein assembly. However, it is unclear how models of gene networks that use delays should be modified when considering time-dependent changes in temperature. This is important, as delay is often used in models of genetic oscillators that can be entrained by periodic fluctuations in temperature. Here, we analytically derive the time dependence of delay distributions in response to time-varying temperature changes. We find that the resulting time-varying delay is nonlinearly dependent on parameters of the time-varying temperature such as amplitude and frequency; therefore, applying an Arrhenius scaling may result in erroneous conclusions. We use these results to examine a model of a synthetic gene oscillator with temperature compensation. We show that temperature entrainment follows from the same mechanism that results in temperature compensation. Under a common Arrhenius scaling alone, the frequency of the oscillator is sensitive to changes in the mean temperature but robust to changes in the frequency of a periodically time-varying temperature. When a mechanism for temperature compensation is included in the model, however, we show that the oscillator is entrained by periodically varying temperature even when maintaining insensitivity to the mean temperature.", "doi": "10.1137/15M1040979", "pmcid": "PMC5656297", "issn": "1536-0040", "publisher": "Society for Industrial and Applied Mathematics", "publication": "SIAM Journal on Applied Dynamical Systems", "publication_date": "2016-09-15", "series_number": "3", "volume": "15", "issue": "3", "pages": "1734-1752" }, { "id": "authors:hxd5m-m8p20", "collection": "authors", "collection_id": "hxd5m-m8p20", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151116-095719395", "type": "article", "title": "A population-based temporal logic gate for timing and recording chemical events", "author": [ { "family_name": "Hsiao", "given_name": "Victoria", "orcid": "0000-0001-9297-1522", "clpid": "Hsiao-Victoria" }, { "family_name": "Hori", "given_name": "Yutaka", "orcid": "0000-0002-3253-4985", "clpid": "Hori-Yutaka" }, { "family_name": "Rothemund", "given_name": "Paul W. K.", "orcid": "0000-0002-1653-3202", "clpid": "Rothemund-P-W-K" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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\u2010input 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\u2010cell responses that translated into analog population responses. Furthermore, when single\u2010cell genetic states were aggregated into population\u2010level distributions, these distributions contained unique information not encoded in individual cells. Thus, final differentiated sub\u2010populations could be used to deduce order, timing, and duration of transient chemical events.", "doi": "10.15252/msb.20156663", "pmcid": "PMC5289221", "issn": "1744-4292", "publisher": "Nature Publishing Group", "publication": "Molecular Systems Biology", "publication_date": "2016-05", "series_number": "5", "volume": "12", "issue": "5", "pages": "Art. No. 869" }, { "id": "authors:rs15w-xt215", "collection": "authors", "collection_id": "rs15w-xt215", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150303-123633257", "type": "article", "title": "Engineering Transcriptional Regulator Effector Specificity using Computational Design and In Vitro Rapid Prototyping: Developing a Vanillin Sensor", "author": [ { "family_name": "de los Santos", "given_name": "Emmanuel L. C.", "clpid": "de-los-Santos-E-L-C" }, { "family_name": "Meyerowitz", "given_name": "Joseph T.", "clpid": "Meyerowitz-J-T" }, { "family_name": "Mayo", "given_name": "Stephen L.", "orcid": "0000-0002-9785-5018", "clpid": "Mayo-S-L" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The pursuit of circuits and metabolic pathways of increasing complexity and robustness in synthetic biology will require engineering new regulatory tools. Feedback control based on relevant molecules, including toxic intermediates and environmental signals, would enable genetic circuits to react appropriately to changing conditions. In this work, variants of qacR, a tetR family repressor, were generated by computational protein design and screened in a cell-free transcription\u2013translation (TX-TL) system for responsiveness to a new targeted effector. The modified repressors target vanillin, a growth-inhibiting small molecule found in lignocellulosic hydrolysates and other industrial processes. Promising candidates from the in vitro screen were further characterized in vitro and in vivo in a gene circuit. The screen yielded two qacR mutants that respond to vanillin both in vitro and in vivo. While the mutants exhibit some toxicity to cells, presumably due to off-target effects, they are prime starting points for directed evolution toward vanillin sensors with the specifications required for use in a dynamic control loop. We believe this process, a combination of the generation of variants coupled with in vitro screening, can serve as a framework for designing new sensors for other target compounds.", "doi": "10.1021/acssynbio.5b00090", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2016-04-15", "series_number": "4", "volume": "5", "issue": "4", "pages": "287-295" }, { "id": "authors:q8cvf-zyk68", "collection": "authors", "collection_id": "q8cvf-zyk68", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190410-120619515", "type": "article", "title": "A multi-paradigm language for reactive synthesis", "author": [ { "family_name": "Filippidis", "given_name": "Ioannis", "orcid": "0000-0003-4704-3334", "clpid": "Filippidis-I" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Holzmann", "given_name": "Gerard J.", "clpid": "Holzmann-G-J" } ], "abstract": "This paper proposes a language for describing reactive synthesis problems that integrates imperative and declarative elements. The semantics is defined in terms of two-player turn-based infinite games with full information. Currently, synthesis tools accept linear temporal logic (LTL) as input, but this description is less structured and does not facilitate the expression of sequential constraints. This motivates the use of a structured programming language to specify synthesis problems. Transition systems and guarded commands serve as imperative constructs, expressed in a syntax based on that of the modeling language Promela. The syntax allows defining which player controls data and control flow, and separating a program into assumptions and guarantees. These notions are necessary for input to game solvers. The integration of imperative and declarative paradigms allows using the paradigm that is most appropriate for expressing each requirement. The declarative part is expressed in the LTL fragment of generalized reactivity(1), which admits efficient synthesis algorithms, extended with past LTL. The implementation translates Promela to input for the Slugs synthesizer and is written in Python. The AMBA AHB bus case study is revisited and synthesized efficiently, identifying the need to reorder binary decision diagrams during strategy construction, in order to prevent the exponential blowup observed in previous work.", "doi": "10.4204/EPTCS.202.6", "issn": "2075-2180", "publisher": "Open Publishing Association", "publication": "Electronic Proceedings in Theoretical Computer Science (EPTCS)", "publication_date": "2016-02-02", "volume": "202", "pages": "73-97" }, { "id": "authors:9nr6z-ggz73", "collection": "authors", "collection_id": "9nr6z-ggz73", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151013-090251954", "type": "article", "title": "Rapid cell-free forward engineering of novel genetic ring oscillators", "author": [ { "family_name": "Niederholtmeyer", "given_name": "Henrike", "orcid": "0000-0002-1375-0287", "clpid": "Niederholtmeyer-H" }, { "family_name": "Sun", "given_name": "Zachary Z.", "orcid": "0000-0002-9425-2924", "clpid": "Sun-Zachary-Z" }, { "family_name": "Hori", "given_name": "Yutaka", "orcid": "0000-0002-3253-4985", "clpid": "Hori-Yutaka" }, { "family_name": "Yeung", "given_name": "Enoch", "orcid": "0000-0001-7630-7429", "clpid": "Yeung-Enoch" }, { "family_name": "Verpoorte", "given_name": "Amanda", "clpid": "Verpoorte-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Maerkl", "given_name": "Sebastian J.", "orcid": "0000-0003-1917-5268", "clpid": "Maerkl-S-J" } ], "abstract": "While complex dynamic biological networks control gene expression in all living organisms, the forward engineering of comparable synthetic networks remains challenging. The current paradigm of characterizing synthetic networks in cells results in lengthy design-build-test cycles, minimal data collection, and poor quantitative characterization. Cell-free systems are appealing alternative environments, but it remains questionable whether biological networks behave similarly in cell-free systems and in cells. We characterized in a cell-free system the 'repressilator,' a three-node synthetic oscillator. We then engineered novel three, four, and five-gene ring architectures, from characterization of circuit components to rapid analysis of complete networks. When implemented in cells, our novel 3-node networks produced population-wide oscillations and 95% of 5-node oscillator cells oscillated for up to 72 hours. Oscillation periods in cells matched the cell-free system results for all networks tested. An alternate forward engineering paradigm using cell-free systems can thus accurately capture cellular behavior.", "doi": "10.7554/eLife.09771", "pmcid": "PMC4714972", "issn": "2050-084X", "publisher": "eLife Sciences Publications", "publication": "eLife", "publication_date": "2015-10-02", "volume": "4", "pages": "Art. No. e09771" }, { "id": "authors:55fn6-eyd49", "collection": "authors", "collection_id": "55fn6-eyd49", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170404-101550871", "type": "article", "title": "Methodology and Tools for Next Generation Cyber-Physical Systems: The iCyPhy Approach", "author": [ { "family_name": "Nuzzo", "given_name": "Pierluigi", "clpid": "Nuzzo-P" }, { "family_name": "Sangiovanni-Vincentelli", "given_name": "Alberto L.", "orcid": "0000-0003-1298-8389", "clpid": "Sangiovanni-Vincentelli-A-L" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The realization of complex, cyber-physical \"systems of systems\" can substantially benefit from model-based hierarchical and compositional methodologies to make their design possible let alone optimal. In this paper, we introduce the methodology being developed within the industrial Cyber-Physical (iCyPhy) research consortium, which addresses the complexity and heterogeneity of cyber-physical systems by formalizing the design process in a hierarchical and compositional way, and provides a unifying framework where different modeling, analysis and synthesis tools can seamlessly interconnect. We use assume-guarantee contracts and their algebra (e.g. composition, conjunction, refinement) to provide formal support to the entire design flow. The design is carried out as a sequence of refinement steps from a high-level specification (top-down phase) to an implementation built out of a library of components at the lower level (bottom-up phase). At each step, the design is refined by combining synthesis from requirements, optimization and simulation-based design space exploration methods. We illustrate our approach on design examples of embedded controllers for aircraft power distribution and air management systems.", "doi": "10.1002/j.2334-5837.2015.00060.x", "issn": "2334-5837", "publisher": "Wiley", "publication": "INCOSE International Symposium", "publication_date": "2015-10", "series_number": "1", "volume": "25", "issue": "1", "pages": "235-249" }, { "id": "authors:paryp-fqz66", "collection": "authors", "collection_id": "paryp-fqz66", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150608-135213453", "type": "article", "title": "Characterizing and prototyping genetic networks with cell-free transcription\u2013translation reactions", "author": [ { "family_name": "Takahashi", "given_name": "Melissa K.", "orcid": "0000-0003-4937-2924", "clpid": "Takahashi-Melissa-K" }, { "family_name": "Hayes", "given_name": "Clarmyra A.", "clpid": "Hayes-C-A" }, { "family_name": "Chappell", "given_name": "James", "clpid": "Chappell-J" }, { "family_name": "Sun", "given_name": "Zachary Z.", "orcid": "0000-0002-9425-2924", "clpid": "Sun-Zachary-Z" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Noireaux", "given_name": "Vincent", "orcid": "0000-0002-5213-273X", "clpid": "Noireaux-V" }, { "family_name": "Lucks", "given_name": "Julius B.", "clpid": "Lucks-J-B" } ], "abstract": "A central goal of synthetic biology is to engineer cellular behavior by engineering synthetic gene networks for a variety of biotechnology and medical applications. The process of engineering gene networks often involves an iterative 'design\u2013build\u2013test' cycle, whereby the parts and connections that make up the network are built, characterized and varied until the desired network function is reached. Many advances have been made in the design and build portions of this cycle. However, the slow process of in vivo characterization of network function often limits the timescale of the testing step. Cell-free transcription\u2013translation (TX\u2013TL) systems offer a simple and fast alternative to performing these characterizations in cells. Here we provide an overview of a cell-free TX\u2013TL system that utilizes the native Escherichia coli TX\u2013TL machinery, thereby allowing a large repertoire of parts and networks to be characterized. As a way to demonstrate the utility of cell-free TX\u2013TL, we illustrate the characterization of two genetic networks: an RNA transcriptional cascade and a protein regulated incoherent feed-forward loop. We also provide guidelines for designing TX\u2013TL experiments to characterize new genetic networks. We end with a discussion of current and emerging applications of cell free systems.", "doi": "10.1016/j.ymeth.2015.05.020", "issn": "1046-2023", "publisher": "Elsevier", "publication": "Methods", "publication_date": "2015-09-15", "volume": "86", "pages": "60-72" }, { "id": "authors:bj557-86f87", "collection": "authors", "collection_id": "bj557-86f87", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151030-084615377", "type": "article", "title": "Convex Optimal Uncertainty Quantification", "author": [ { "family_name": "Han", "given_name": "Shuo", "clpid": "Han-Shuo" }, { "family_name": "Tao", "given_name": "Molei", "clpid": "Tao-Molei" }, { "family_name": "Topcu", "given_name": "Ufuk", "clpid": "Topcu-U" }, { "family_name": "Owhadi", "given_name": "Houman", "orcid": "0000-0002-5677-1600", "clpid": "Owhadi-H" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Optimal uncertainty quantification (OUQ) is a framework for numerical extreme-case analysis of stochastic systems with imperfect knowledge of the underlying probability distribution. This paper presents sufficient conditions under which an OUQ problem can be reformulated as a finite-dimensional convex optimization problem, for which efficient numerical solutions can be obtained. The sufficient conditions include that the objective function is piecewise concave and the constraints are piecewise convex. In particular, we show that piecewise concave objective functions may appear in applications where the objective is defined by the optimal value of a parameterized linear program.", "doi": "10.1137/13094712X", "issn": "1052-6234", "publisher": "Society for Industrial and Applied Mathematics", "publication": "SIAM Journal of Optimization", "publication_date": "2015-07-14", "series_number": "3", "volume": "25", "issue": "3", "pages": "1368-1387" }, { "id": "authors:pdgxh-9gh88", "collection": "authors", "collection_id": "pdgxh-9gh88", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150903-084342383", "type": "article", "title": "An analytical approach to bistable biological circuit discrimination using real algebraic geometry", "author": [ { "family_name": "Siegal-Gaskins", "given_name": "Dan", "clpid": "Siegal-Gaskins-D" }, { "family_name": "Franco", "given_name": "Elisa", "orcid": "0000-0003-1103-2668", "clpid": "Franco-E" }, { "family_name": "Zhou", "given_name": "Tiffany", "clpid": "Zhou-Tiffany" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Biomolecular circuits with two distinct and stable steady states have been identified as essential components in a wide range of biological networks, with a variety of mechanisms and topologies giving rise to their important bistable property. Understanding the differences between circuit implementations is an important question, particularly for the synthetic biologist faced with determining which bistable circuit design out of many is best for their specific application. In this work we explore the applicability of Sturm's theorem\u2014a tool from nineteenth-century real algebraic geometry\u2014to comparing 'functionally equivalent' bistable circuits without the need for numerical simulation. We first consider two genetic toggle variants and two different positive feedback circuits, and show how specific topological properties present in each type of circuit can serve to increase the size of the regions of parameter space in which they function as switches. We then demonstrate that a single competitive monomeric activator added to a purely monomeric (and otherwise monostable) mutual repressor circuit is sufficient for bistability. Finally, we compare our approach with the Routh\u2013Hurwitz method and derive consistent, yet more powerful, parametric conditions. The predictive power and ease of use of Sturm's theorem demonstrated in this work suggest that algebraic geometric techniques may be underused in biomolecular circuit analysis.", "doi": "10.1098/rsif.2015.0288", "issn": "1742-5689", "publisher": "The Royal Society", "publication": "Journal of the Royal Society Interface", "publication_date": "2015-07-06", "series_number": "108", "volume": "12", "issue": "108", "pages": "Art. No. 20150288" }, { "id": "authors:vhjq4-x1k88", "collection": "authors", "collection_id": "vhjq4-x1k88", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150813-145738981", "type": "article", "title": "Bootstrapping bilinear models of Simple Vehicles", "author": [ { "family_name": "Censi", "given_name": "Andrea", "orcid": "0000-0001-5162-0398", "clpid": "Censi-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Learning and adaptivity will play a large role in robotics in the future. Two questions are open: (1) in principle, how much it is possible to learn; and (2) in practice, how much should an agent be able to learn. The bootstrapping scenario describes the extreme case in which agents need to learn \"everything\" from scratch, including a torque-to-pixels model for its robotic body. This paper considers the bootstrapping problem for a subset of the set of all robots. The Simple Vehicles are an idealization of mobile robots equipped with a set of \"canonical\" exteroceptive sensors: the camera, the range finder and the field sampler. The sensorimotor dynamics of these sensors are derived and shown to be surprising similar. These sensorimotor dynamics are well approximated by a class of nonlinear systems that assume an instantaneous bilinear relation among observations, commands, and changes in the observations. The bilinear approximation is sufficient to guarantee success in the task of generalized \"servoing\": driving the observations to a given goal snapshot. Simulations and experiments substantiate the theoretical results. This is the first instance of a bootstrapping agent that can learn the model of the dynamics of a relatively large universe of systems and use the models to solve well-defined tasks, with no parameter tuning or hand-designed features.", "doi": "10.1177/0278364914557708", "issn": "0278-3649", "publisher": "Sage", "publication": "International Journal of Robotics Research", "publication_date": "2015-07", "series_number": "8", "volume": "34", "issue": "8", "pages": "1087-1113" }, { "id": "authors:03zew-2r462", "collection": "authors", "collection_id": "03zew-2r462", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190327-154909216", "type": "article", "title": "Specification and Synthesis of Reactive Protocols for Aircraft Electric Power Distribution", "author": [ { "family_name": "Xu", "given_name": "Huan", "clpid": "Xu-Huan" }, { "family_name": "Topcu", "given_name": "Ufuk", "clpid": "Topcu-U" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The increasing complexity of electric power systems leads to challenges in integration and verification. We consider the problem of designing a control protocol for an aircraft electric power system that meets a set of requirements describing the correct behaviors of the system and reacts dynamically to changes in internal system states. We formalize the requirements by translating them into a temporal logic specification language and apply game-based, temporal logic formal methods to automatically synthesize a controller protocol that satisfies these overall properties and requirements. Through a case study, we perform a design exploration to show the benefits and tradeoffs between centralized and distributed control architectures.", "doi": "10.1109/TCNS.2015.2401174", "issn": "2325-5870", "publisher": "IEEE", "publication": "IEEE Transactions on Control of Network Systems", "publication_date": "2015-06", "series_number": "2", "volume": "2", "issue": "2", "pages": "193-203" }, { "id": "authors:tds42-yk640", "collection": "authors", "collection_id": "tds42-yk640", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150612-140758750", "type": "article", "title": "Rapidly Characterizing the Fast Dynamics of RNA Genetic Circuitry with Cell-Free Transcription Translation (TX-TL) Systems", "author": [ { "family_name": "Takahashi", "given_name": "Melissa K.", "orcid": "0000-0003-4937-2924", "clpid": "Takahashi-Melissa-K" }, { "family_name": "Chappell", "given_name": "James", "clpid": "Chappell-J" }, { "family_name": "Hayes", "given_name": "Clarmyra A.", "clpid": "Hayes-C-A" }, { "family_name": "Sun", "given_name": "Zachary Z.", "orcid": "0000-0002-9425-2924", "clpid": "Sun-Zachary-Z" }, { "family_name": "Kim", "given_name": "Jongmin", "orcid": "0000-0002-2713-1006", "clpid": "Kim-Jongmin" }, { "family_name": "Singhal", "given_name": "Vipul", "orcid": "0000-0003-1670-1824", "clpid": "Singhal-V" }, { "family_name": "Spring", "given_name": "Kevin J.", "clpid": "Spring-K-J" }, { "family_name": "Al-Khabouri", "given_name": "Shaima", "orcid": "0000-0002-5147-9627", "clpid": "Al-Khabouri-S" }, { "family_name": "Fall", "given_name": "Christopher P.", "clpid": "Fall-C-P" }, { "family_name": "Noireaux", "given_name": "Vincent", "orcid": "0000-0002-5213-273X", "clpid": "Noireaux-V" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Lucks", "given_name": "Julius B.", "clpid": "Lucks-J-B" } ], "abstract": "RNA regulators are emerging as powerful tools to engineer synthetic genetic networks or rewire existing ones. A potential strength of RNA networks is that they may be able to propagate signals on time scales that are set by the fast degradation rates of RNAs. However, a current bottleneck to verifying this potential is the slow design-build-test cycle of evaluating these networks in vivo. Here, we adapt an Escherichia coli-based cell-free transcription-translation (TX-TL) system for rapidly prototyping RNA networks. We used this system to measure the response time of an RNA transcription cascade to be approximately five minutes per step of the cascade. We also show that this response time can be adjusted with temperature and regulator threshold tuning. Finally, we use TX-TL to prototype a new RNA network, an RNA single input module, and show that this network temporally stages the expression of two genes in vivo.", "doi": "10.1021/sb400206c", "pmcid": "PMC4487224", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2015-05", "series_number": "5", "volume": "4", "issue": "5", "pages": "503-515" }, { "id": "authors:64682-sx438", "collection": "authors", "collection_id": "64682-sx438", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150316-104657793", "type": "article", "title": "Robot navigation in dense human crowds: Statistical models and experimental studies of human\u2013robot cooperation", "author": [ { "family_name": "Trautman", "given_name": "Pete", "clpid": "Trautman-P" }, { "family_name": "Ma", "given_name": "Jeremy", "clpid": "Ma-J" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Krause", "given_name": "Andreas", "orcid": "0000-0001-7260-9673", "clpid": "Krause-A" } ], "abstract": "We consider the problem of navigating a mobile robot through dense human crowds. We begin by exploring a fundamental impediment to classical motion planning algorithms called the \"freezing robot problem\": once the environment surpasses a certain level of dynamic complexity, the planner decides that all forward paths are unsafe, and the robot freezes in place (or performs unnecessary maneuvers) to avoid collisions. We argue that this problem can be avoided if the robot anticipates human cooperation, and accordingly we develop interacting Gaussian processes, a prediction density that captures cooperative collision avoidance, and a \"multiple goal\" extension that models the goal-driven nature of human decision making. We validate this model with an empirical study of robot navigation in dense human crowds (488 runs), specifically testing how cooperation models effect navigation performance. The multiple goal interacting Gaussian processes algorithm performs comparably with human teleoperators in crowd densities nearing 0.8 humans/m^2, while a state-of-the-art non-cooperative planner exhibits unsafe behavior more than three times as often as the multiple goal extension, and twice as often as the basic interacting Gaussian process approach. Furthermore, a reactive planner based on the widely used dynamic window approach proves insufficient for crowd densities above 0.55 people/m^2. We also show that our non-cooperative planner or our reactive planner capture the salient characteristics of nearly any dynamic navigation algorithm. Based on these experimental results and theoretical observations, we conclude that a cooperation model is critical for safe and efficient robot navigation in dense human crowds.", "doi": "10.1177/0278364914557874", "issn": "0278-3649", "publisher": "Sage", "publication": "International Journal of Robotics Research", "publication_date": "2015-03", "series_number": "3", "volume": "34", "issue": "3", "pages": "335-356" }, { "id": "authors:18ykk-gy939", "collection": "authors", "collection_id": "18ykk-gy939", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140424-150617268", "type": "article", "title": "Design and implementation of a synthetic biomolecular concentration tracker", "author": [ { "family_name": "Hsiao", "given_name": "Victoria", "orcid": "0000-0001-9297-1522", "clpid": "Hsiao-Victoria" }, { "family_name": "de los Santos", "given_name": "Emmanuel L. C.", "clpid": "de-los-Santos-E-L-C" }, { "family_name": "Whitaker", "given_name": "Weston R.", "clpid": "Whitaker-W-R" }, { "family_name": "Dueber", "given_name": "John E.", "clpid": "Dueber-J-E" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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.", "doi": "10.1021/sb500024b", "pmcid": "PMC4384833", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2015-02", "series_number": "2", "volume": "4", "issue": "2", "pages": "150-161" }, { "id": "authors:qd0w7-9ss70", "collection": "authors", "collection_id": "qd0w7-9ss70", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150313-113120630", "type": "article", "title": "Population Diversification in a Yeast Metabolic Program Promotes Anticipation of Environmental Shifts", "author": [ { "family_name": "Venturelli", "given_name": "Ophelia S.", "clpid": "Venturelli-O-S" }, { "family_name": "Zuleta", "given_name": "Ignacio", "clpid": "Zuleta-I" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "El-Samad", "given_name": "Hana", "orcid": "0000-0001-6239-9916", "clpid": "El-Samad-H" } ], "abstract": "Delineating the strategies by which cells contend with combinatorial changing environments is crucial for understanding cellular regulatory organization. When presented with two carbon sources, microorganisms first consume the carbon substrate that supports the highest growth rate (e.g., glucose) and then switch to the secondary carbon source (e.g., galactose), a paradigm known as the Monod model. Sequential sugar utilization has been attributed to transcriptional repression of the secondary metabolic pathway, followed by activation of this pathway upon depletion of the preferred carbon source. In this work, we demonstrate that although Saccharomyces cerevisiae cells consume glucose before galactose, the galactose regulatory pathway is activated in a fraction of the cell population hours before glucose is fully consumed. This early activation reduces the time required for the population to transition between the two metabolic programs and provides a fitness advantage that might be crucial in competitive environments.", "doi": "10.1101/002907", "pmcid": "PMC4307983", "issn": "1544-9173", "publisher": "Public Library of Science", "publication": "PLoS Biology", "publication_date": "2015-01", "series_number": "1", "volume": "13", "issue": "1", "pages": "Art. No. e1002042" }, { "id": "authors:86hnb-3n106", "collection": "authors", "collection_id": "86hnb-3n106", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150302-124651398", "type": "article", "title": "Editorial for SEED 2014 Special Issue", "author": [ { "family_name": "Jackson", "given_name": "Alicia", "clpid": "Jackson-A" }, { "family_name": "Voigt", "given_name": "Chris", "clpid": "Voigt-C" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This issue of ACS Synthetic Biology contains articles that\nwere originally submitted as part of the inaugural\nSynthetic Biology: Engineering, Evolution, and Design\n(SEED) conference, held July, 2014, in Manhattan Beach,\nCA. SEED is an annual technical conference dedicated to the\nbroad set of technologies that make up the discipline of\nSynthetic Biology. SEED will be a regularly held meeting, the\nnext iteration of which will be held in Boston in the summer of\n2015.", "doi": "10.1021/acssynbio.5b00001", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2015-01", "series_number": "1", "volume": "4", "issue": "1", "pages": "1" }, { "id": "authors:d57b5-jw847", "collection": "authors", "collection_id": "d57b5-jw847", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150202-112319257", "type": "article", "title": "Control Software Synthesis and Validation for a Vehicular\n Electric Power Distribution Testbed", "author": [ { "family_name": "Rogersten", "given_name": "Robert", "clpid": "Rogersten-R" }, { "family_name": "Xu", "given_name": "Huan", "clpid": "Xu-Huan" }, { "family_name": "Ozay", "given_name": "Necmiye", "clpid": "Ozay-N" }, { "family_name": "Topcu", "given_name": "Ufuk", "clpid": "Topcu-U" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Modern aircraft increasingly rely on electric power, resulting in high safety criticality and complexity in their electric power generation and distribution systems. Motivated by the resulting rapid increase in the costs and duration of the design cycles for such systems, the use of formal specification and automated correct-by-construction control protocols synthesis for primary distribution in vehicular electric power networks is investigated. A design workflow is discussed that aims to transition from the traditional \"design and verify\" approach to a \"specify and synthesize\" approach. An overview is given of a subset of the recent advances in the synthesis of reactive control protocols. These techniques are applied in the context of reconfiguration of the networks in reaction to the changes in their operating environment. These automatically synthesized control protocols are also validated on high-fidelity simulation models and on an academic-scale hardware testbed.", "doi": "10.2514/1.I010167", "issn": "1940-3151", "publisher": "American Institute of Aeronautics and Astronautics", "publication": "Journal of Aerospace Information Systems", "publication_date": "2014-10", "series_number": "10", "volume": "11", "issue": "10", "pages": "665-678" }, { "id": "authors:jy3xk-15609", "collection": "authors", "collection_id": "jy3xk-15609", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140424-151429285", "type": "article", "title": "Negative autoregulation matches production and demand in synthetic transcriptional networks", "author": [ { "family_name": "Franco", "given_name": "Elisa", "orcid": "0000-0003-1103-2668", "clpid": "Franco-E" }, { "family_name": "Giordano", "given_name": "Giulia", "clpid": "Giordano-G" }, { "family_name": "Forsberg", "given_name": "Per-Ola", "clpid": "Forsberg-O-O" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We propose a negative feedback architecture that regulates activity of artificial genes, or \"genelets\", to meet their output downstream demand, achieving robustness with respect to uncertain open-loop output production rates. In particular, we consider the case where the outputs of two genelets interact to form a single assembled product. We show with analysis and experiments that negative autoregulation matches the production and demand of the outputs: the magnitude of the regulatory signal is proportional to the \"error\" between the circuit output concentration and its actual demand. This two-device system is experimentally implemented using in vitro transcriptional networks, where reactions are systematically designed by optimizing nucleic acid sequences with publicly available software packages. We build a predictive ordinary differential equation (ODE) model that captures the dynamics of the system and can be used to numerically assess the scalability of this architecture to larger sets of interconnected genes. Finally, with numerical simulations we contrast our negative autoregulation scheme with a cross-activation architecture, which is less scalable and results in slower response times.", "doi": "10.1101/000430", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2014-08", "series_number": "8", "volume": "3", "issue": "8", "pages": "589-599" }, { "id": "authors:vnbt3-mh588", "collection": "authors", "collection_id": "vnbt3-mh588", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141113-140158076", "type": "article", "title": "The Swarm at the Edge of the Cloud", "author": [ { "family_name": "Lee", "given_name": "Edward A.", "clpid": "Lee-E-A" }, { "family_name": "Rabaey", "given_name": "Jan", "clpid": "Rabaey-J" }, { "family_name": "Hartmann", "given_name": "Bj\u00f6rn", "clpid": "Hartmann-B" }, { "family_name": "Kubiatowics", "given_name": "John", "clpid": "Kubiatowics-J" }, { "family_name": "Pister", "given_name": "Kris", "clpid": "Pister-K" }, { "family_name": "Sangiovanni-Vincentelli", "given_name": "Alberto", "orcid": "0000-0003-1298-8389", "clpid": "Sangiovanni-Vincentelli-A-L" }, { "family_name": "Seshia", "given_name": "Sanjit A.", "clpid": "Seshia-S-A" }, { "family_name": "Wawrzynek", "given_name": "John", "clpid": "Wawrzynek-J" }, { "family_name": "Wessel", "given_name": "David", "clpid": "Wessel-D" }, { "family_name": "Rosing", "given_name": "Tajana Simunic", "clpid": "Rosing-T-S" }, { "family_name": "Blaauw", "given_name": "David", "clpid": "Blaauw-D" }, { "family_name": "Dutta", "given_name": "Prabal", "clpid": "Dutta-P" }, { "family_name": "Fu", "given_name": "Kevin", "clpid": "Fu-K" }, { "family_name": "Guestrin", "given_name": "Carlos", "clpid": "Guestrin-C" }, { "family_name": "Taskar", "given_name": "Ben", "clpid": "Taskar-B" }, { "family_name": "Jafari", "given_name": "Roozbeh", "clpid": "Jafari-R" }, { "family_name": "Jones", "given_name": "Douglas", "clpid": "Jones-D" }, { "family_name": "Kumar", "given_name": "Vijay", "orcid": "0000-0002-3902-9391", "clpid": "Kumar-Vijay" }, { "family_name": "Mangharam", "given_name": "Raul", "clpid": "Mangharam-R" }, { "family_name": "Pappas", "given_name": "George J.", "clpid": "Pappas-G-J" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Rowe", "given_name": "Anthony", "clpid": "Rowe-A" } ], "abstract": "The paper explains how to use sensors as the eyes, ears, hands, and feet for the cloud. This paper describes the opportunities and challenges when integrating sensors and cloud computing.", "doi": "10.1109/MDAT.2014.2314600", "issn": "2168-2356", "publisher": "IEEE", "publication": "IEEE Design & Test", "publication_date": "2014-07-23", "series_number": "3", "volume": "31", "issue": "3", "pages": "8-20" }, { "id": "authors:gryp7-0z868", "collection": "authors", "collection_id": "gryp7-0z868", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140724-160305011", "type": "article", "title": "Linear DNA for Rapid Prototyping of Synthetic Biological Circuits in an Escherichia coli Based TX-TL Cell-Free System", "author": [ { "family_name": "Sun", "given_name": "Zachary Z.", "orcid": "0000-0002-9425-2924", "clpid": "Sun-Zachary-Z" }, { "family_name": "Yeung", "given_name": "Enoch", "orcid": "0000-0001-7630-7429", "clpid": "Yeung-Enoch" }, { "family_name": "Hayes", "given_name": "Clarmyra A.", "clpid": "Hayes-C-A" }, { "family_name": "Noireaux", "given_name": "Vincent", "orcid": "0000-0002-5213-273X", "clpid": "Noireaux-V" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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 enabled the use of linear DNA PCR products in TX-TL. We then compared expression levels and binding dynamics of different promoters on linear DNA and plasmid DNA. We also demonstrated assembly technology to rapidly build circuits entirely in vitro from separate parts. Using this strategy, we prototyped a four component genetic switch in under 8 h entirely in vitro. Rapid in vitro assembly has future applications for prototyping multiple component circuits if combined with predictive computational models.", "doi": "10.1021/sb400131a", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2014-06-20", "series_number": "6", "volume": "3", "issue": "6", "pages": "387-397" }, { "id": "authors:aag12-q0f24", "collection": "authors", "collection_id": "aag12-q0f24", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140414-094313495", "type": "article", "title": "Gene Circuit Performance Characterization and Resource Usage in a Cell-Free \"Breadboard\"", "author": [ { "family_name": "Siegal-Gaskins", "given_name": "Dan", "clpid": "Siegal-Gaskins-D" }, { "family_name": "Tuza", "given_name": "Zoltan A.", "orcid": "0000-0003-2896-1527", "clpid": "Tuza-Zoltan-A" }, { "family_name": "Kim", "given_name": "Jongmin", "orcid": "0000-0002-2713-1006", "clpid": "Kim-Jongmin" }, { "family_name": "Noireaux", "given_name": "Vincent", "orcid": "0000-0002-5213-273X", "clpid": "Noireaux-V" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The many successes of synthetic biology have come in a manner largely different from those in other engineering disciplines; in particular, without well-characterized and simplified prototyping environments to play a role analogous to wind-tunnels in aerodynamics and breadboards in electrical engineering. However, as the complexity of synthetic circuits increases, the benefits\u2014in cost savings and design cycle time\u2014of a more traditional engineering approach can be significant. We have recently developed an in vitro \"breadboard\" prototyping platform based on E. coli cell extract that allows biocircuits to operate in an environment considerably simpler than, but functionally similar to, in vivo. The simplicity of this system makes it a promising tool for rapid biocircuit design and testing, as well as for probing fundamental aspects of gene circuit operation normally masked by cellular complexity. In this work, we characterize the cell-free breadboard using real-time and simultaneous measurements of transcriptional and translational activities of a small set of reporter genes and a transcriptional activation cascade. We determine the effects of promoter strength, gene concentration, and nucleoside triphosphate concentration on biocircuit properties, and we isolate the specific contributions of essential biomolecular resources\u2014core RNA polymerase and ribosomes\u2014to overall performance. Importantly, we show how limits on resources, particularly those involved in translation, are manifested as reduced expression in the presence of orthogonal genes that serve as additional loads on the system.", "doi": "10.1021/sb400203p", "issn": "2161-5063", "publisher": "American Chemical Society", "publication": "ACS Synthetic Biology", "publication_date": "2014-06", "series_number": "6", "volume": "3", "issue": "6", "pages": "416-425" }, { "id": "authors:pv91t-rnn26", "collection": "authors", "collection_id": "pv91t-rnn26", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140421-101928940", "type": "article", "title": "Synthetic circuit for exact adaptation and fold-change detection", "author": [ { "family_name": "Kim", "given_name": "Jongmin", "orcid": "0000-0002-2713-1006", "clpid": "Kim-Jongmin" }, { "family_name": "Khetarpal", "given_name": "Ishan", "clpid": "Khetarpal-I" }, { "family_name": "Sen", "given_name": "Shaunak", "orcid": "0000-0002-1412-8633", "clpid": "Sen-Shaunak" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Biological organisms use their sensory systems to\ndetect changes in their environment. The ability of\nsensory systems to adapt to static inputs allows wide\ndynamic range as well as sensitivity to input changes\nincluding fold-change detection, a response that depends\nonly on fold changes in input, and not on absolute\nchanges. This input scale invariance underlies\nan important strategy for search that depends solely\non the spatial profile of the input. Synthetic efforts\nto reproduce the architecture and response of cellular\ncircuits provide an important step to foster understanding\nat themolecular level. We report the bottom-up\nassembly of biochemical systems that show exact\nadaptation and fold-change detection. Using a malachite\ngreen aptamer as the output, a synthetic transcriptional\ncircuit with the connectivity of an incoherent\nfeed-forward loop motif exhibits pulse generation\nand exact adaptation. A simple mathematical model\nwas used to assess the amplitude and duration of\npulse response as well as the parameter regimes\nrequired for fold-change detection. Upon parameter\ntuning, this synthetic circuit exhibits fold-change detection\nfor four successive rounds of two-fold input\nchanges. The experimental realization of fold-change\ndetection circuit highlights the programmability of\ntranscriptional switches and the ability to obtain predictive\ndynamical systems in a cell-free environment\nfor technological applications.", "doi": "10.1093/nar/gku233", "pmcid": "PMC4027175", "issn": "0305-1048", "publisher": "Oxford University Press", "publication": "Nucleic Acids Research", "publication_date": "2014-04-11", "series_number": "9", "volume": "42", "issue": "9", "pages": "6078-6089" }, { "id": "authors:1hbxc-n8d57", "collection": "authors", "collection_id": "1hbxc-n8d57", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140502-103349067", "type": "article", "title": "Flying Drosophila stabilize their vision-based velocity controller by sensing wind with their antennae", "author": [ { "family_name": "Fuller", "given_name": "Sawyer Buckminster", "clpid": "Fuller-S-B" }, { "family_name": "Straw", "given_name": "Andrew D.", "orcid": "0000-0001-8381-0858", "clpid": "Straw-A-D" }, { "family_name": "Peek", "given_name": "Martin Y.", "clpid": "Peek-M-Y" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" } ], "abstract": "Flies and other insects use vision to regulate their groundspeed in flight, enabling them to fly in varying wind conditions. Compared with mechanosensory modalities, however, vision requires a long processing delay (~100 ms) that might introduce instability if operated at high gain. Flies also sense air motion with their antennae, but how this is used in flight control is unknown. We manipulated the antennal function of fruit flies by ablating their aristae, forcing them to rely on vision alone to regulate groundspeed. Arista-ablated flies in flight exhibited significantly greater groundspeed variability than intact flies. We then subjected them to a series of controlled impulsive wind gusts delivered by an air piston and experimentally manipulated antennae and visual feedback. The results show that an antenna-mediated response alters wing motion to cause flies to accelerate in the same direction as the gust. This response opposes flying into a headwind, but flies regularly fly upwind. To resolve this discrepancy, we obtained a dynamic model of the fly's velocity regulator by fitting parameters of candidate models to our experimental data. The model suggests that the groundspeed variability of arista-ablated flies is the result of unstable feedback oscillations caused by the delay and high gain of visual feedback. The antenna response drives active damping with a shorter delay (~20 ms) to stabilize this regulator, in exchange for increasing the effect of rapid wind disturbances. This provides insight into flies' multimodal sensory feedback architecture and constitutes a previously unknown role for the antennae.", "doi": "10.1073/pnas.1323529111", "pmcid": "PMC3977237", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2014-04-01", "series_number": "13", "volume": "111", "issue": "13", "pages": "E1182-E1191" }, { "id": "authors:v1qcn-rhw28", "collection": "authors", "collection_id": "v1qcn-rhw28", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170524-161850962", "type": "article", "title": "A Contract-Based Methodology for Aircraft Electric Power System Design", "author": [ { "family_name": "Nuzzo", "given_name": "Pierluigi", "clpid": "Nuzzo-P" }, { "family_name": "Xu", "given_name": "Huan", "clpid": "Xu-Huan" }, { "family_name": "Ozay", "given_name": "Necmiye", "clpid": "Ozay-N" }, { "family_name": "Finn", "given_name": "John B.", "clpid": "Finn-J-B" }, { "family_name": "Sangiovanni-Vincentelli", "given_name": "Alberto L.", "orcid": "0000-0003-1298-8389", "clpid": "Sangiovanni-Vincentelli-A-L" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Donz\u00e9", "given_name": "Alexandre", "clpid": "Donz\u00e9-A" }, { "family_name": "Seshia", "given_name": "Sanjit A.", "clpid": "Seshia-S-A" } ], "abstract": "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.", "doi": "10.1109/ACCESS.2013.2295764", "issn": "2169-3536", "publisher": "IEEE", "publication": "IEEE Access", "publication_date": "2014-01-07", "volume": "2", "pages": "1-25" }, { "id": "authors:030yt-mda27", "collection": "authors", "collection_id": "030yt-mda27", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131031-134823487", "type": "article", "title": "Protocols for Implementing an Escherichia coli Based TX-TL Cell-Free Expression System for Synthetic Biology", "author": [ { "family_name": "Sun", "given_name": "Zachary Z.", "orcid": "0000-0002-9425-2924", "clpid": "Sun-Zachary-Z" }, { "family_name": "Hayes", "given_name": "Clarmyra A.", "clpid": "Hayes-C-A" }, { "family_name": "Shin", "given_name": "Jonghyeon", "clpid": "Shin-Jonghyeon" }, { "family_name": "Caschera", "given_name": "Filippo", "clpid": "Caschera-F" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Noireaux", "given_name": "Vincent", "orcid": "0000-0002-5213-273X", "clpid": "Noireaux-V" } ], "abstract": "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. 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.\"", "doi": "10.3791/50762", "issn": "1940-087X", "publisher": "JoVE", "publication": "Journal of Visualized Experiments", "publication_date": "2013-09", "volume": "79", "pages": "Art. No. e50762" }, { "id": "authors:yvrq3-5bn64", "collection": "authors", "collection_id": "yvrq3-5bn64", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130916-113727132", "type": "article", "title": "Verifying Cyber-Physical Interactions in Safety-Critical Systems", "author": [ { "family_name": "Mitra", "given_name": "Sayan", "clpid": "Mitra-Sayan" }, { "family_name": "Wongpiromsarn", "given_name": "Tichakorn", "clpid": "Wongpiromsarn-Tichakorn" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Safety-compromising bugs in software-controlled systems are often hard to detect. In a 2007 DARPA Urban Challenge vehicle, such a defect remained hidden during more than 300 miles of test-driving, manifesting for the first time during the competition. With this incident as an example, the authors discuss formalisms and techniques available for safety analysis of cyber-physical systems.", "doi": "10.1109/MSP.2013.77", "issn": "1540-7993", "publisher": "IEEE", "publication": "IEEE Security and Privacy", "publication_date": "2013-07", "series_number": "4", "volume": "11", "issue": "4", "pages": "28-37" }, { "id": "authors:c2n5c-etp30", "collection": "authors", "collection_id": "c2n5c-etp30", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130812-094851124", "type": "article", "title": "Optimization of convergence rate and stability margin of information flow in cooperative systems", "author": [ { "family_name": "Zabarankin", "given_name": "Michael", "clpid": "Zabarankin-M" }, { "family_name": "Murphey", "given_name": "Robert", "clpid": "Murphey-R" }, { "family_name": "Murray", "given_name": "Richard", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The interplay between the convergence rate and stability margin (e.g. ability to reject disturbances) for a discrete-time information flow filter in cooperative systems is analyzed. For a given communication graph, the convergence rate is defined as the absolute value of the largest nonunit characteristic root of a matrix associated with the filter. The maximal convergence rate, obtained by \"tuning\" the control gains, is highly correlated to the number of distinct eigenvalues of the graph Laplacian (it is 1 for the complete graph). A stability margin is introduced for multiple-input\u2013multiple-output (MIMO) systems and is then maximized with respect to the control gains subject to a constraint on the convergence rate. The optimal stability margin as a function of the convergence rate is bounded above for any order of the filter, and the bound is attained for the complete graph. For the zero-order filter and all strongly connected communication graphs, the optimal stability margin is found analytically, whereas for the first-order filter and undirected communication graphs, it is evaluated numerically. The results demonstrate the ability to distinguish graph topologies that dominate others in their ability to reject disturbances and converge rapidly to a consensus.", "doi": "10.1016/j.automatica.2013.03.018", "issn": "0005-1098", "publisher": "Elsevier", "publication": "Automatica", "publication_date": "2013-07", "series_number": "7", "volume": "49", "issue": "7", "pages": "2030-2038" }, { "id": "authors:bphqk-1yj72", "collection": "authors", "collection_id": "bphqk-1yj72", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130802-112333498", "type": "article", "title": "Synthesis of Reactive Switching Protocols From Temporal Logic Specifications", "author": [ { "family_name": "Liu", "given_name": "Jun", "clpid": "Liu-Jun" }, { "family_name": "Ozay", "given_name": "Necmiye", "clpid": "Ozay-N" }, { "family_name": "Topcu", "given_name": "Ufuk", "clpid": "Topcu-U" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We propose formal means for synthesizing switching protocols that determine the sequence in which the modes of a switched system are activated to satisfy certain high-level specifications in linear temporal logic (LTL). The synthesized protocols are robust against exogenous disturbances on the continuous dynamics and can react to possibly adversarial events (both external and internal). Finite-state approximations that abstract the behavior of the underlying continuous dynamics are defined using finite transition systems. Such approximations allow us to transform the continuous switching synthesis problem into a discrete synthesis problem in the form of a two-player game between the system and the environment, where the winning conditions represent the high-level temporal logic specifications. Restricting to an expressive subclass of LTL formulas, these temporal logic games are amenable to solutions with polynomial-time complexity. By construction, existence of a discrete switching strategy for the discrete synthesis problem guarantees the existence of a switching protocol that can be implemented at the continuous level to ensure the correctness of the nonlinear switched system and to react to the environment at run time.", "doi": "10.1109/TAC.2013.2246095", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "2013-07", "series_number": "7", "volume": "58", "issue": "7", "pages": "1771-1785" }, { "id": "authors:e9n8z-nmk20", "collection": "authors", "collection_id": "e9n8z-nmk20", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130709-103021335", "type": "article", "title": "A robust model predictive control algorithm augmented with a reactive safety mode", "author": [ { "family_name": "Carson", "given_name": "John M., III", "clpid": "Carson-J-M-III" }, { "family_name": "A\u00e7\u0131kme\u015fe", "given_name": "Beh\u00e7et", "clpid": "A\u00e7\u0131kme\u015fe-B" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "MacMartin", "given_name": "Douglas G.", "orcid": "0000-0003-1987-9417", "clpid": "MacMartin-D-G" } ], "abstract": "A reactive safety mode is built into a robust model predictive control algorithm for uncertain nonlinear systems with bounded disturbances. The algorithm enforces state and control constraints and blends two modes: (I) standard, guarantees re-solvability and asymptotic convergence in a robust receding-horizon manner; (II) safety, if activated, guarantees containment within an invariant set about a reference. The reactive safety mode provides robustness to unexpected, but real-time anticipated, state-constraint changes during standard mode operation. The safety-mode control policy is designed offline and can be activated at any arbitrary time. The standard-mode control has feedforward and feedback components: feedforward is from online solution of a finite-horizon optimal control problem; feedback is designed offline to provide robustness to system uncertainty and disturbances and to establish an invariant \"state tube\" that guarantees standard-mode re-solvability at any time. The algorithm design is shown for a class of systems with incrementally-conic uncertain/nonlinear terms and bounded disturbances.", "doi": "10.1016/j.automatica.2013.02.025", "issn": "0005-1098", "publisher": "Elsevier", "publication": "Automatica", "publication_date": "2013-05", "series_number": "5", "volume": "49", "issue": "5", "pages": "1251-1260" }, { "id": "authors:f5rz8-ts294", "collection": "authors", "collection_id": "f5rz8-ts294", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151124-141949989", "type": "article", "title": "Discriminating External and Internal Causes for Heading Changes in Freely Flying Drosophila", "author": [ { "family_name": "Censi", "given_name": "Andrea", "orcid": "0000-0001-5162-0398", "clpid": "Censi-A" }, { "family_name": "Straw", "given_name": "Andrew D.", "orcid": "0000-0001-8381-0858", "clpid": "Straw-A-D" }, { "family_name": "Sayaman", "given_name": "Rosalyn W.", "clpid": "Sayaman-R-W" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" } ], "abstract": "As animals move through the world in search of resources, they change course in reaction to both external sensory cues and internally-generated programs. Elucidating the functional logic of complex search algorithms is challenging because the observable actions of the animal cannot be unambiguously assigned to externally- or internally-triggered events. We present a technique that addresses this challenge by assessing quantitatively the contribution of external stimuli and internal processes. We apply this technique to the analysis of rapid turns (\"saccades\") of freely flying Drosophila melanogaster. We show that a single scalar feature computed from the visual stimulus experienced by the animal is sufficient to explain a majority (93%) of the turning decisions. We automatically estimate this scalar value from the observable trajectory, without any assumption regarding the sensory processing. A posteriori, we show that the estimated feature field is consistent with previous results measured in other experimental conditions. The remaining turning decisions, not explained by this feature of the visual input, may be attributed to a combination of deterministic processes based on unobservable internal states and purely stochastic behavior. We cannot distinguish these contributions using external observations alone, but we are able to provide a quantitative bound of their relative importance with respect to stimulus-triggered decisions. Our results suggest that comparatively few saccades in free-flying conditions are a result of an intrinsic spontaneous process, contrary to previous suggestions. We discuss how this technique could be generalized for use in other systems and employed as a tool for classifying effects into sensory, decision, and motor categories when used to analyze data from genetic behavioral screens.", "doi": "10.1371/journal.pcbi.1002891", "pmcid": "PMC3585425", "issn": "1553-7358", "publisher": "Public Library of Science", "publication": "PLOS Computational Biology", "publication_date": "2013-02", "series_number": "2", "volume": "9", "issue": "2", "pages": "Art. No. e1002891" }, { "id": "authors:we9eb-z1346", "collection": "authors", "collection_id": "we9eb-z1346", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130110-104823261", "type": "article", "title": "Synergistic dual positive feedback loops established by molecular sequestration generate robust bimodal response", "author": [ { "family_name": "Venturelli", "given_name": "Ophelia S.", "clpid": "Venturelli-O-S" }, { "family_name": "El-Samad", "given_name": "Hana", "orcid": "0000-0001-6239-9916", "clpid": "El-Samad-H" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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 system's 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 system's 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.", "doi": "10.1073/pnas.1211902109", "pmcid": "PMC3511703", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2012-11-27", "series_number": "48", "volume": "109", "issue": "48", "pages": "E3324-E3333" }, { "id": "authors:t8589-smq26", "collection": "authors", "collection_id": "t8589-smq26", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20121220-142113975", "type": "article", "title": "Receding Horizon Temporal Logic Planning", "author": [ { "family_name": "Wongpiromsarn", "given_name": "Tichakorn", "clpid": "Wongpiromsarn-T" }, { "family_name": "Topcu", "given_name": "Ufuk", "clpid": "Topcu-U" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We present a methodology for automatic synthesis of embedded control software that incorporates a class of linear temporal logic (LTL) specifications sufficient to describe a wide range of properties including safety, stability, progress, obligation, response and guarantee. To alleviate the associated computational complexity of LTL synthesis, we propose a receding horizon framework that effectively reduces the synthesis problem into a set of smaller problems. The proposed control structure consists of a goal generator, a trajectory planner, and a continuous controller. The goal generator reduces the trajectory generation problem into a sequence of smaller problems of short horizon while preserving the desired system-level temporal properties. Subsequently, in each iteration, the trajectory planner solves the corresponding short-horizon problem with the currently observed state as the initial state and generates a feasible trajectory to be implemented by the continuous controller. Based on the simulation property, we show that the composition of the goal generator, trajectory planner and continuous controller and the corresponding receding horizon framework guarantee the correctness of the system with respect to its specification regardless of the environment in which the system operates. In addition, we present a response mechanism to handle failures that may occur due to a mismatch between the actual system and its model. The effectiveness of the proposed technique is demonstrated through an example of an autonomous vehicle navigating an urban environment. This example also illustrates that the system is not only robust with respect to exogenous disturbances but is also capable of properly handling violation of the environment assumption that is explicitly stated as part of the system specification.", "doi": "10.1109/TAC.2012.2195811", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "2012-11", "series_number": "11", "volume": "57", "issue": "11", "pages": "2817-2830" }, { "id": "authors:7ecg9-nwz14", "collection": "authors", "collection_id": "7ecg9-nwz14", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20121026-084418812", "type": "article", "title": "Verification of Periodically Controlled Hybrid Systems: Application to an Autonomous Vehicle", "author": [ { "family_name": "Wongpiromsarn", "given_name": "Tichakorn", "clpid": "Wongpiromsarn-T" }, { "family_name": "Mitra", "given_name": "Sayan", "clpid": "Mitra-S" }, { "family_name": "Lamperski", "given_name": "Andrew", "clpid": "Lamperski-A-G" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This article introduces Periodically Controlled Hybrid Automata (PCHA) for modular specification of embedded\ncontrol systems. In a PCHA, control actions that change the control input to the plant occur roughly\nperiodically, while other actions that update the state of the controller may occur in the interim. Such actions\ncould model, for example, sensor updates and information received from higher-level planning modules that\nchange the set point of the controller. Based on periodicity and subtangential conditions, a new sufficient\ncondition for verifying invariant properties of PCHAs is presented. For PCHAs with polynomial continuous\nvector fields, it is possible to check these conditions automatically using, for example, quantifier elimination\nor sum of squares decomposition. We examine the feasibility of this automatic approach on a small example.\nThe proposed technique is also used to manually verify safety and progress properties of a fairly complex\nplanner-controller subsystem of an autonomous ground vehicle. Geometric properties of planner-generated\npaths are derived which guarantee that such paths can be safely followed by the controller.", "doi": "10.1145/2331147.2331163", "issn": "1539-9087", "publisher": "Association for Computing Machinery", "publication": "ACM Transactions in Embedded Computing Systems", "publication_date": "2012-08", "series_number": "S2", "volume": "11", "issue": "S2", "pages": "Art. No. 53" }, { "id": "authors:sc7fe-hs832", "collection": "authors", "collection_id": "sc7fe-hs832", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120207-074159029", "type": "article", "title": "Quantized Consensus by Means of Gossip Algorithm", "author": [ { "family_name": "Lavaei", "given_name": "Javad", "clpid": "Lavaei-J" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This paper deals with the distributed averaging problem over a connected network of agents, subject to a quantization constraint. It is assumed that at each time update, only a pair of agents can update their own states in terms of the quantized data being exchanged. The agents are also required to communicate with one another in a stochastic fashion. It is shown that a quantized consensus is reached for an arbitrary quantizer by means of the stochastic gossip algorithm proposed in a recent paper. The expected value of the time at which a quantized consensus is reached is lower and upper bounded in terms of the topology of the graph for a uniform quantizer. In particular, it is shown that these bounds are related to the principal submatrices of the weighted Laplacian matrix. A convex optimization is also proposed to determine a set of probabilities used to pick a pair of agents that leads to a fast convergence of the gossip algorithm.", "doi": "10.1109/TAC.2011.2160593", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "2012-01", "series_number": "1", "volume": "57", "issue": "1", "pages": "19-32" }, { "id": "authors:3xw46-ycg28", "collection": "authors", "collection_id": "3xw46-ycg28", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111020-091851903", "type": "article", "title": "Timing molecular motion and production with a synthetic transcriptional clock", "author": [ { "family_name": "Franco", "given_name": "Elisa", "orcid": "0000-0003-1103-2668", "clpid": "Franco-E" }, { "family_name": "Friedrichs", "given_name": "Eike", "clpid": "Friedrichs-Eike" }, { "family_name": "Kim", "given_name": "Jongmin", "orcid": "0000-0002-2713-1006", "clpid": "Kim-Jongmin" }, { "family_name": "Jungmann", "given_name": "Ralf", "clpid": "Jungmann-R" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Winfree", "given_name": "Erik", "orcid": "0000-0002-5899-7523", "clpid": "Winfree-E" }, { "family_name": "Simmel", "given_name": "Friedrich C.", "orcid": "0000-0003-3829-3446", "clpid": "Simmel-F-C" } ], "abstract": "The realization of artificial biochemical reaction networks with unique functionality is one of the main challenges for the development of synthetic biology. Due to the reduced number of components, biochemical circuits constructed in vitro promise to be more amenable to systematic design and quantitative assessment than circuits embedded within living organisms. To make good on that promise, effective methods for composing subsystems into larger systems are needed. Here we used an artificial biochemical oscillator based on in vitro transcription and RNA degradation reactions to drive a variety of \"load\" processes such as the operation of a DNA-based nanomechanical device (\"DNA tweezers\") or the production of a functional RNA molecule (an aptamer for malachite green). We implemented several mechanisms for coupling the load processes to the oscillator circuit and compared them based on how much the load affected the frequency and amplitude of the core oscillator, and how much of the load was effectively driven. Based on heuristic insights and computational modeling, an \"insulator circuit\" was developed, which strongly reduced the detrimental influence of the load on the oscillator circuit. Understanding how to design effective insulation between biochemical subsystems will be critical for the synthesis of larger and more complex systems.", "doi": "10.1073/pnas.1100060108", "pmcid": "PMC3189071", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2011-10-04", "series_number": "40", "volume": "108", "issue": "40", "pages": "E784-E793" }, { "id": "authors:cawcc-d0n69", "collection": "authors", "collection_id": "cawcc-d0n69", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110308-123056956", "type": "article", "title": "Bisimulation conversion and verification procedure for goal-based control systems", "author": [ { "family_name": "Braman", "given_name": "Julia M. B.", "clpid": "Braman-J-M-B" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Fault tolerance and safety verification of control systems are essential for the success of autonomous robotic systems. A control architecture called Mission Data System\n(MDS), developed at the Jet Propulsion Laboratory, addresses these needs with a goal-based control approach. In this paper, a software algorithm for converting goal network control systems into linear hybrid systems is described. The conversion process is a bisimulation; the\nresulting 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 example goal network control system is converted to a linear hybrid system using the automatic conversion software that is based on the bisimulation and then is verified.", "doi": "10.1007/s10703-010-0109-6", "issn": "0925-9856", "publisher": "Springer", "publication": "Formal Methods in System Design", "publication_date": "2011-02", "series_number": "1", "volume": "38", "issue": "1", "pages": "62-95" }, { "id": "authors:b0vry-krq46", "collection": "authors", "collection_id": "b0vry-krq46", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20111031-100248775", "type": "article", "title": "Dynamics and Stability of Low-Reynolds-Number Swimming Near a Wall", "author": [ { "family_name": "Or", "given_name": "Yizhar", "orcid": "0000-0002-9091-9357", "clpid": "Or-Y" }, { "family_name": "Zhang", "given_name": "Sebastian", "clpid": "Zhang-S" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The locomotion of microorganisms and tiny artificial swimmers is governed by low-Reynolds-number\nhydrodynamics, where viscous effects dominate and inertial effects are negligible. While the theory\nof low-Reynolds-number locomotion is well studied for unbounded fluid domains, the presence of a\nboundary has a significant influence on the swimmer's trajectories and poses problems of dynamic\nstability of its motion. In this paper we consider a simple theoretical model of a microswimmer near\na wall, study its dynamics, and analyze the stability of its motion. We highlight the underlying\ngeometric structure of the dynamics, and establish a relation between the reversing symmetry of\nthe system and existence and stability of periodic and steady solutions of motion near the wall.\nThe results are demonstrated by numerical simulations and validated by motion experiments with\nmacroscale robotic swimmer prototypes.", "doi": "10.1137/100808745", "issn": "1536-0040", "publisher": "Society for Industrial and Applied Mathematics", "publication": "SIAM Journal on Applied Dynamical Systems", "publication_date": "2011", "series_number": "3", "volume": "10", "issue": "3", "pages": "1013-1041" }, { "id": "authors:2zzeq-nvb04", "collection": "authors", "collection_id": "2zzeq-nvb04", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101029-082222753", "type": "article", "title": "Autonomous driving in urban environments: approaches, lessons and challenges", "author": [ { "family_name": "Campbell", "given_name": "Mark", "clpid": "Campbell-M" }, { "family_name": "Egerstedt", "given_name": "Magnus", "clpid": "Egerstedt-M" }, { "family_name": "How", "given_name": "Jonathan P.", "clpid": "How-J-P" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The development of autonomous vehicles for urban driving has seen rapid progress in the past 30 years. This paper provides a summary of the current state of the art in autonomous driving in urban environments, based primarily on the experiences of the authors in the 2007 DARPA Urban Challenge (DUC). The paper briefly summarizes the approaches that different teams used in the DUC, with the goal of describing some of the challenges that the teams faced in driving in urban environments. The paper also highlights the long-term research challenges that must be overcome in order to enable autonomous driving and points to opportunities for new technologies to be applied in improving vehicle safety, exploiting intelligent road infrastructure and enabling robotic vehicles operating in human environments.", "doi": "10.1098/rsta.2010.0110", "issn": "1364-503X", "publisher": "Royal Society of London", "publication": "Philosophical Transactions A: Mathematical, Physical and Engineering Sciences", "publication_date": "2010-10-13", "series_number": "1928", "volume": "368", "issue": "1928", "pages": "4649-4672" }, { "id": "authors:y7zqq-asy15", "collection": "authors", "collection_id": "y7zqq-asy15", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100709-164812328", "type": "article", "title": "Reply to \"Comments on \"Consensus and Cooperation in Networked Multi-Agent Systems\"\"", "author": [ { "family_name": "Olfati-Saber", "given_name": "R.", "clpid": "Olfati-Saber-R" }, { "family_name": "Fax", "given_name": "J. A.", "clpid": "Fax-J-A" }, { "family_name": "Murray", "given_name": "R. M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "[No abstract]", "doi": "10.1109/JPROC.2010.2049912", "issn": "0018-9219", "publisher": "IEEE", "publication": "Proceedings of the IEEE", "publication_date": "2010-07", "series_number": "7", "volume": "98", "issue": "7", "pages": "1354-1355" }, { "id": "authors:ph80z-k8g73", "collection": "authors", "collection_id": "ph80z-k8g73", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100712-154830591", "type": "article", "title": "Resource optimisation in a wireless sensor network with guaranteed estimator performance", "author": [ { "family_name": "Shi", "given_name": "L.", "clpid": "Shi-Ling" }, { "family_name": "Capponi", "given_name": "A.", "clpid": "Capponi-A" }, { "family_name": "Johansson", "given_name": "K. H.", "clpid": "Johansson-K-H" }, { "family_name": "Murray", "given_name": "R. M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "New control paradigms are needed for large networks of wireless sensors and actuators in order to\nefficiently utilise system resources. In this study, the authors consider the problem of discrete-time state\nestimation over a wireless sensor network. Given a tree that represents the sensor communications with the\nfusion centre, the authors derive the optimal estimation algorithm at the fusion centre, and provide a closedform\nexpression for the steady-state error covariance matrix. They then present a tree reconfiguration\nalgorithm that produces a sensor tree that has low overall energy consumption and guarantees a desired\nlevel of estimation quality at the fusion centre. The authors further propose a sensor tree construction and\nscheduling algorithm that leads to a longer network lifetime than the tree reconfiguration algorithm.\nExamples are provided throughout the paper to demonstrate the algorithms and theory developed.", "doi": "10.1049/iet-cta.2009.0104", "issn": "1751-8644", "publisher": "Institution of Engineering and Technology", "publication": "IET Control Theory and Applications", "publication_date": "2010-05", "series_number": "5", "volume": "4", "issue": "5", "pages": "710-723" }, { "id": "authors:q8212-xtv70", "collection": "authors", "collection_id": "q8212-xtv70", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100407-095207612", "type": "article", "title": "Kalman Filtering Over a Packet-Dropping Network: A Probabilistic Perspective", "author": [ { "family_name": "Shi", "given_name": "Ling", "clpid": "Shi-Ling" }, { "family_name": "Epstein", "given_name": "Michael", "clpid": "Epstein-M" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We consider the problem of state estimation of a discrete time process over a packet-dropping network. Previous work on Kalman filtering with intermittent observations is concerned with the asymptotic behavior of E[P_k], i.e., the expected value of the error covariance, for a given packet arrival rate. We consider a different performance metric, Pr[P_k \u2264 M], i.e., the probability that P_k is bounded by a given M. We consider two scenarios in the paper. In the first scenario, when the sensor sends its measurement data to the remote estimator via a packet-dropping network, we derive lower and upper bounds on Pr[P_k \u2264 M]. In the second scenario, when the sensor preprocesses the measurement data and sends its local state estimate to the estimator, we show that the previously derived lower and upper bounds are equal to each other, hence we are able to provide a closed form expression for Pr[P_k \u2264 M]. We also recover the results in the literature when using Pr[P_k \u2264 M] as a metric for scalar systems. Examples are provided to illustrate the theory developed in the paper.", "doi": "10.1109/TAC.2009.2039236", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "2010-03", "series_number": "3", "volume": "55", "issue": "3", "pages": "594-604" }, { "id": "authors:9dhrr-zwq55", "collection": "authors", "collection_id": "9dhrr-zwq55", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100120-105437457", "type": "article", "title": "Controlling biological networks by time-delayed signals", "author": [ { "family_name": "Orosz", "given_name": "G\u00e1bor", "orcid": "0000-0002-9000-3736", "clpid": "Orosz-G" }, { "family_name": "Moehlis", "given_name": "Jeff", "clpid": "Moehlis-J" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This paper describes the use of time-delayed feedback to regulate the behaviour of biological networks. The general ideas on specific transcriptional regulatory and neural networks are demonstrated. It is shown that robust yet tunable controllers can be constructed that provide the biological systems with model-engineered inputs. The results indicate that time delay modulation may serve as an efficient biocompatible control tool.", "doi": "10.1098/rsta.2009.0242", "issn": "1364-503X", "publisher": "Royal Society of London", "publication": "Philosophical Transactions A: Mathematical, Physical and Engineering Sciences", "publication_date": "2010-01-28", "series_number": "1911", "volume": "368", "issue": "1911", "pages": "439-454" }, { "id": "authors:wt3pj-rbq43", "collection": "authors", "collection_id": "wt3pj-rbq43", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100121-153456533", "type": "article", "title": "Kalman filtering over wireless fading channels\u2014How to handle\n packet drop", "author": [ { "family_name": "Mostofi", "given_name": "Yasamin", "clpid": "Mostofi-Y" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "In this paper we consider estimation of dynamical systems over wireless fading communication channels using a Kalman filter. We show the impact of the stochastic communication noise on the estimation process. We furthermore show how noisy packets should be handled in the receiver. More specifically, we illustrate the impact of the availability of a cross-layer information path on the optimum receiver design. In the absence of a cross-layer information path, it was shown that packet drop should be designed to balance information loss and communication noise in order to optimize the performance. In the presence of a cross-layer path, we show that keeping all the packets will minimize the average estimation error covariance. We also derive the stability condition in the presence of noisy packets and show that it is independent of the shape of the communication noise variance or availability of a cross-layer information path.", "doi": "10.1002/rnc.1398", "issn": "1049-8923", "publisher": "Wiley", "publication": "International Journal of Robust and Nonlinear Control", "publication_date": "2009-12", "series_number": "18", "volume": "19", "issue": "18", "pages": "1993-2015" }, { "id": "authors:cmvck-g9104", "collection": "authors", "collection_id": "cmvck-g9104", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090930-152710419", "type": "article", "title": "Kalman filtering over a packet-delaying network: A probabilistic approach", "author": [ { "family_name": "Shi", "given_name": "Ling", "clpid": "Shi-L" }, { "family_name": "Xie", "given_name": "Linhua", "clpid": "Xie-L" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "In this paper, we consider Kalman filtering over a packet-delaying network. Given the probability distribution of the delay, we can characterize the filter performance via a probabilistic approach. We assume that the estimator maintains a buffer of length D so that at each time k, the estimator is able to retrieve all available data packets up to time k\u2212D+1. Both the cases of sensor with and without necessary computation capability for filter updates are considered. When the sensor has no computation capability, for a given D, we give lower and upper bounds on the probability for which the estimation error covariance is within a prescribed bound. When the sensor has computation capability, we show that the previously derived lower and upper bounds are equal to each other. An approach for determining the minimum buffer length for a required performance in probability is given and an evaluation on the number of expected filter updates is provided. Examples are provided to demonstrate the theory developed in the paper.", "doi": "10.1016/j.automatica.2009.05.018", "issn": "0005-1098", "publisher": "Elsevier", "publication": "Automatica", "publication_date": "2009-09", "series_number": "9", "volume": "45", "issue": "9", "pages": "2134-2140" }, { "id": "authors:fpk3r-2n729", "collection": "authors", "collection_id": "fpk3r-2n729", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20091106-154852106", "type": "article", "title": "Cone invariance and rendezvous of multiple agents", "author": [ { "family_name": "Bhattacharya", "given_name": "R.", "clpid": "Bhattacharya-R" }, { "family_name": "Tiwari", "given_name": "A.", "clpid": "Tiwari-A" }, { "family_name": "Fung", "given_name": "J.", "clpid": "Fung-J" }, { "family_name": "Murray", "given_name": "R. M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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.\n\nThe 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\u2013Kamke 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.", "doi": "10.1243/09544100JAERO443", "issn": "0954-4100", "publisher": "Professional Engineering Publishing", "publication": "Proceedings of the Institution of Mechanical Engineers, Part G: Journal of Aerospace Engineering", "publication_date": "2009-09", "series_number": "6", "volume": "223", "issue": "6", "pages": "779-789" }, { "id": "authors:rxhzq-sat22", "collection": "authors", "collection_id": "rxhzq-sat22", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090828-100125867", "type": "article", "title": "Flight Dynamics and Control of Evasive Maneuvers: The Fruit Fly's Takeoff", "author": [ { "family_name": "Zabala", "given_name": "Francisco A.", "clpid": "Zabala-F-A" }, { "family_name": "Card", "given_name": "Gwyneth M.", "orcid": "0000-0002-7679-3639", "clpid": "Card-G-M" }, { "family_name": "Fontaine", "given_name": "Ebraheem I.", "clpid": "Fontaine-E-I" }, { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We have approached the problem of reverse-engineering the flight control mechanism of the fruit fly by studying the dynamics of the responses to a visual stimulus during takeoff. Building upon a prior framework [G. Card and M. Dickinson, J. Exp. Biol., vol. 211, pp. 341\u2013353, 2008], we seek to understand the strategies employed by the animal to stabilize attitude and orientation during these evasive, highly dynamical maneuvers. As a first step, we consider the dynamics from a gray-box perspective: examining lumped forces produced by the insect's legs and wings. The reconstruction of the flight initiation dynamics, based on the unconstrained motion formulation for a rigid body, allows us to assess the fly's responses to a variety of initial conditions induced by its jump. Such assessment permits refinement by using a visual tracking algorithm to extract the kinematic envelope of the wings [E. I. Fontaine, F. Zabala, M. Dickinson, and J. Burdick, \"Wing and body motion during flight initiation in Drosophila revealed by automated visual tracking,\" submitted for publication] in order to estimate lift and drag forces [F. Zabala, M. Dickinson, and R. Murray, \"Control and stability of insect flight during highly dynamical maneuvers,\" submitted for publication], and recording actual leg-joint kinematics and using them to estimate jump forces [F. Zabala, \"A bio-inspired model for directionality control of flight initiation,\" to be published.]. In this paper, we present the details of our approach in a comprehensive manner, including the salient results.", "doi": "10.1109/TBME.2009.2027606", "issn": "0018-9294", "publisher": "IEEE", "publication": "IEEE Transactions on Biomedical Engineering", "publication_date": "2009-09", "series_number": "9, par", "volume": "56", "issue": "9, par", "pages": "2295-2298" }, { "id": "authors:1gnam-v4926", "collection": "authors", "collection_id": "1gnam-v4926", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090826-112853239", "type": "article", "title": "Data Transmission Over Networks for Estimation and Control", "author": [ { "family_name": "Gupta", "given_name": "Vijay", "clpid": "Gupta-V" }, { "family_name": "Dana", "given_name": "Amir F.", "clpid": "Dana-A-F" }, { "family_name": "Hespanha", "given_name": "Joao P.", "clpid": "Hespanha-J-P" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Hassibi", "given_name": "Babak", "orcid": "0000-0002-1375-5838", "clpid": "Hassibi-B" } ], "abstract": "We consider the problem of controlling a linear time invariant process when the controller is located at a location remote from where the sensor measurements are being generated. The communication from the sensor to the controller is supported by a communication network with arbitrary topology composed of analog erasure channels. Using a separation principle, we prove that the optimal linear-quadratic-Gaussian (LQG) controller consists of an LQ optimal regulator along with an estimator that estimates the state of the process across the communication network. We then determine the optimal information processing strategy that should be followed by each node in the network so that the estimator is able to compute the best possible estimate in the minimum mean squared error sense. The algorithm is optimal for any packet-dropping process and at every time step, even though it is recursive and hence requires a constant amount of memory, processing and transmission at every node in the network per time step. For the case when the packet drop processes are memoryless and independent across links, we analyze the stability properties and the performance of the closed loop system. The algorithm is an attempt to escape the viewpoint of treating a network of communication links as a single end-to-end link with the probability of successful transmission determined by some measure of the reliability of the network.", "doi": "10.1109/TAC.2009.2024567", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "2009-08", "series_number": "8", "volume": "54", "issue": "8", "pages": "1807-1819" }, { "id": "authors:mda6j-hbv93", "collection": "authors", "collection_id": "mda6j-hbv93", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20091006-094144123", "type": "article", "title": "Model reduction of interconnected linear systems", "author": [ { "family_name": "Sandberg", "given_name": "H.", "clpid": "Sandberg-H" }, { "family_name": "Murray", "given_name": "R. M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "The problem of model reduction of linear systems with certain interconnection structure is considered in this paper. To preserve the interconnection structure between subsystems in the reduction, special care needs to be taken. This problem is important and timely because of the recent focus on complex networked systems in control engineering. Two different model reduction methods are introduced and compared in this paper. Both methods are extensions to the well-known balanced truncation method. Compared with earlier work in the area these methods use a more general linear fractional transformation framework, and utilize linear matrix inequalities. Furthermore, new approximation error bounds that reduce to classical bounds in special cases are derived. The so-called structured Hankel singular values are used in the methods, and indicate how important states in the subsystems are with respect to a chosen input-output map for the entire interconnected system. It is shown how these structured Hankel singular values can be used to select an approximation order. Finally, the two methods are applied to a model of a mechanical device.", "doi": "10.1002/oca.854", "issn": "0143-2087", "publisher": "Wiley Interscience", "publication": "Optimal Control Applications and Methods", "publication_date": "2009-05", "series_number": "3", "volume": "30", "issue": "3", "pages": "225-245" }, { "id": "authors:v69bs-h3b78", "collection": "authors", "collection_id": "v69bs-h3b78", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090708-083134251", "type": "article", "title": "Dynamics and stability of a class of low Reynolds number swimmers near a wall", "author": [ { "family_name": "Or", "given_name": "Yizhar", "orcid": "0000-0002-9091-9357", "clpid": "Or-Y" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We study the dynamic stability of low Reynolds number swimming near a plane wall from a control-theoretic viewpoint. We consider a special class of swimmers having a constant shape, focus on steady motion parallel to the wall, and derive conditions under which it is passively stable without sensing or feedback. We study the geometric structure of the swimming equation and highlight the relation between stability and reversing symmetry of the dynamical system. Finally, our numerical simulations reveal the existence of stable periodic motion. The results have implications for design of miniature robotic swimmers, as well as for explaining the attraction of micro-organisms to surfaces.", "doi": "10.1103/PhysRevE.79.045302", "issn": "1539-3755", "publisher": "American Physical Society", "publication": "Physical Review E", "publication_date": "2009-04", "series_number": "4", "volume": "79", "issue": "4", "pages": "045302" }, { "id": "authors:0qa9f-gx913", "collection": "authors", "collection_id": "0qa9f-gx913", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090416-092107354", "type": "article", "title": "To Drop or Not to Drop: Design Principles for Kalman Filtering Over Wireless Fading Channels", "author": [ { "family_name": "Mostofi", "given_name": "Yasamin", "clpid": "Mostofi-Y" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "It is the general assumption that in estimation and control over wireless links, the receiver should drop any erroneous packets. While this approach is appropriate for non real-time data-network applications, it can result in instability and loss of performance in networked control systems. In this technical note we consider estimation of a multiple-input multiple-output dynamical system over a mobile fading communication channel using a Kalman filter. We show that the communication protocols suitable for other already-existing applications like data networks may not be entirely applicable for estimation and control of a rapidly changing dynamical system. We then develop new design paradigms in terms of handling noisy packets for such delay-sensitive applications. We reformulate the estimation problem to include the impact of stochastic communication noise in the erroneous packets. We prove that, in the absence of a permanent cross-layer information path, packet drop should be designed to balance information loss and communication noise in order to optimize the performance.", "doi": "10.1109/TAC.2008.2008331", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "2009-02", "series_number": "2", "volume": "54", "issue": "2", "pages": "376-381" }, { "id": "authors:rrnt4-76r98", "collection": "authors", "collection_id": "rrnt4-76r98", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:EPSa08", "type": "article", "title": "Probabilistic performance of state estimation across a lossy network", "author": [ { "family_name": "Epstein", "given_name": "Michael", "clpid": "Epstein-M" }, { "family_name": "Shi", "given_name": "Ling", "clpid": "Shi-L" }, { "family_name": "Tiwari", "given_name": "Abhishek", "clpid": "Tiwari-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We consider a discrete time state estimation problem over a packet-based network. In each discrete time step, a measurement packet is sent across a lossy network to an estimator unit consisting of a modified Kalman filter. Using the designed estimator algorithm, the importance of placing a measurement buffer at the sensor that allows transmission of the current and several previous measurements is shown. Previous pioneering work on Kalman filtering with intermittent observation losses is concerned with the asymptotic behavior of the expected value of the error covariance, i.e. E [P-k] < \u221e as k \u2192 \u221e. We consider a different performance metric, namely a probabilistic statement of the error covariance Pr[P-k \u2264 M] \u2265 1 - \u03b5, meaning that with high probability the error covariance is bounded above at any instant in time. Provided the estimator error covariance has an upper bound whenever a measurement packet arrives, we show that for any finite M this statement will hold so long as the probability of receiving a measurement packet is nonzero. We also give an explicit relationship between M and E and provide examples to illustrate the theory.", "doi": "10.1016/j.automatica.2008.05.026", "issn": "0005-1098", "publisher": "Elsevier", "publication": "Automatica", "publication_date": "2008-12", "series_number": "12", "volume": "44", "issue": "12", "pages": "3046-3053" }, { "id": "authors:xe98t-9dg72", "collection": "authors", "collection_id": "xe98t-9dg72", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:DUNng08", "type": "article", "title": "Regulatory activity revealed by dynamic correlations in gene expression noise", "author": [ { "family_name": "Dunlop", "given_name": "Mary J.", "clpid": "Dunlop-M-J" }, { "family_name": "Cox", "given_name": "Robert Sidney, III", "clpid": "Cox-R-S-III" }, { "family_name": "Levine", "given_name": "Joseph H.", "clpid": "Levine-J-H" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Elowitz", "given_name": "Michael B.", "orcid": "0000-0002-1221-0967", "clpid": "Elowitz-M-B" } ], "abstract": "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^(1,2). 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.", "doi": "10.1038/ng.281", "pmcid": "PMC2829635", "issn": "1061-4036", "publisher": "Nature Publishing Group", "publication": "Nature Genetics", "publication_date": "2008-12", "series_number": "12", "volume": "40", "issue": "12", "pages": "1493-1498" }, { "id": "authors:s5v92-9f839", "collection": "authors", "collection_id": "s5v92-9f839", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:INAjgcd08", "type": "article", "title": "Framework for low-observable trajectory generation in presence of multiple radars", "author": [ { "family_name": "Inanc", "given_name": "Tamer", "clpid": "Inanc -T" }, { "family_name": "Muezzinoglu", "given_name": "Mehmet K.", "clpid": "Muezzinoglu-M-K" }, { "family_name": "Misovec", "given_name": "Kathleen", "clpid": "Misovec-K" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This paper explores the problem of finding a real-time optimal trajectory for unmanned aerial vehicles to minimize their probability of detection by opponent multiple radar detection systems. The problem is handled using the nonlinear trajectory generation method developed by Milam et al. (Milam, M., Mushambi, K., and Murray, R., \"New Computational Approach to Real-Time Trajectory Generation for Constrained Mechanical Systems,\" Proceedings of the 39th IEEE Conference on Decision and Control, Vol. 1, Institute of Electrical and Electronics Engineers, New York, Dec. 2000, pp. 845-851.) The paper presents a formulation of the trajectory generation task as an optimal control problem, where temporal constraints allow periods of high observability interspersed with periods of low observability. This feature can be used strategically to aid in avoiding detection by an opponent radar. The guidance is provided in the form of sampled tabular data. It is then shown that the success of nonlinear trajectory generation on the proposed low-observable trajectory generation problem depends upon an accurate parameterization of the guidance data. In particular, such an approximator is desired to have a compact architecture, a minimum number of design parameters, and a smooth continuously differentiable input-output mapping. Artificial neural networks as universal approximators are known to possess these features, and thus are considered here as appropriate candidates for this task. Comparison of artificial neural networks against B-spline approximators is provided, as well. Numerical simulations on multiple radar scenarios illustrate unmanned air vehicle trajectories optimized for both detectability and time.", "doi": "10.2514/1.35287", "issn": "0731-5090", "publisher": "AIAA", "publication": "Journal of Guidance, Control, and Dynamics", "publication_date": "2008-11", "series_number": "6", "volume": "31", "issue": "6", "pages": "1740-1749" }, { "id": "authors:7w8h6-7pb67", "collection": "authors", "collection_id": "7w8h6-7pb67", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180815-095447771", "type": "article", "title": "Communication and sensing trade\u2010offs in cooperative mobile networks", "author": [ { "family_name": "Mostofi", "given_name": "Yasamin", "clpid": "Mostofi-Y" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "In this paper we consider the impact of communication noise on distributed sensing and estimation in mobile networks. We characterize when a node should rely on getting information from others and when it should rely on self exploration. In doing so, we explore the trade\u2010offs between sensing and communication by finding the optimum network configuration under communication constraints. We also show how to achieve the optimum configuration in a distributed manner. While our main results are presented in one dimension (1D), we provide insight into the two dimension (2D) setup and extend a number of key results to 2D.", "doi": "10.1002/asjc.16", "issn": "1561-8625", "publisher": "Wiley", "publication": "Asian Journal of Control", "publication_date": "2008-03", "series_number": "2", "volume": "10", "issue": "2", "pages": "156-170" }, { "id": "authors:qsj9z-k9q65", "collection": "authors", "collection_id": "qsj9z-k9q65", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20101019-100253770", "type": "article", "title": "Recent Research in Cooperative Control of Multivehicle Systems", "author": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This paper presents a survey of recent research in cooperative control of multivehicle systems, using a common mathematical framework to allow different methods to be described in a unified way. The survey has three primary parts: an overview of current applications of cooperative control, a summary of some of the key technical approaches that have been explored, and a description of some possible future directions for research. Specific technical areas that are discussed include formation control, cooperative tasking, spatiotemporal planning, and consensus.", "doi": "10.1115/1.2766721", "issn": "0022-0434", "publisher": "American Society of Mechanical Engineers", "publication": "Journal of Dynamic Systems, Measurement, and Control", "publication_date": "2007-09", "series_number": "5", "volume": "129", "issue": "5", "pages": "571-583" }, { "id": "authors:0x9gc-13w17", "collection": "authors", "collection_id": "0x9gc-13w17", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:WAYieeetcst07", "type": "article", "title": "UAV as a Reliable Wingman: A Flight Demonstration", "author": [ { "family_name": "Waydo", "given_name": "S.", "clpid": "Waydo-S" }, { "family_name": "Hauser", "given_name": "J.", "clpid": "Hauser-J" }, { "family_name": "Bailey", "given_name": "R.", "clpid": "Bailey-R" }, { "family_name": "Klavins", "given_name": "E.", "clpid": "Klavins-E" }, { "family_name": "Murray", "given_name": "R. M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "In this brief, we present the results from a flight experiment demonstrating two significant advances in software enabled control: optimization-based control using real-time trajectory generation and logical programming environments for formal analysis of control software. Our demonstration platform consisted of a human-piloted F-15 jet flying together with an autonomous T-33 jet. We describe the behavior of the system in two scenarios. In the first, nominal state communications were present and the autonomous aircraft maintained formation as the human pilot flew maneuvers. In the second, we imposed the loss of high-rate communications and demonstrated an autonomous safe \"lost wingman\" procedure to increase separation and reacquire contact. The flight demonstration included both a nominal formation flight component and an execution of the lost wingman scenario.", "doi": "10.1109/TCST.2007.899172", "issn": "1063-6536", "publisher": "IEEE Transactions on Control Systems Technology", "publication": "IEEE Transactions on Control Systems Technology", "publication_date": "2007-07", "series_number": "4", "volume": "15", "issue": "4", "pages": "680-688" }, { "id": "authors:90y8e-k4732", "collection": "authors", "collection_id": "90y8e-k4732", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:MEHieeeacmtn07", "type": "article", "title": "Asynchronous Distributed Averaging on Communication Networks", "author": [ { "family_name": "Mehyar", "given_name": "Mortada", "clpid": "Mehyar-M" }, { "family_name": "Spanos", "given_name": "Demetri", "clpid": "Spanos-D-P" }, { "family_name": "Pongsajapan", "given_name": "John", "clpid": "Pongsajapan-J" }, { "family_name": "Low", "given_name": "Steven H.", "orcid": "0000-0001-6476-3048", "clpid": "Low-S-H" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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 such as the Internet. In this paper, we present several implementable algorithms that are robust to asynchronism and dynamic topology changes. The algorithms are completely distributed and do not require any global coordination. In addition, they can be proven to converge under very general asynchronous timing assumptions. Our results are verified by both simulation and experiments on Planetlab, a real-world TCP/IP network. We also present some extensions that are likely to be useful in applications.", "doi": "10.1109/TNET.2007.893226", "issn": "1063-6692", "publisher": "IEEE/ACM Transactions on Networking", "publication": "IEEE/ACM Transactions on Networking", "publication_date": "2007-06", "series_number": "3", "volume": "15", "issue": "3", "pages": "512-520" }, { "id": "authors:dyha8-v6k82", "collection": "authors", "collection_id": "dyha8-v6k82", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-075834386", "type": "article", "title": "Optimal LQG control across packet-dropping links", "author": [ { "family_name": "Gupta", "given_name": "Vijay", "clpid": "Gupta-V" }, { "family_name": "Hassibi", "given_name": "Babak", "orcid": "0000-0002-1375-5838", "clpid": "Hassibi-B" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We examine two special cases of the problem of optimal linear quadratic Gaussian control of a system whose state is being measured by sensors that communicate with the controller over packet-dropping links. We pose the problem as an information transmission problem. Using a separation principle, we decompose the problem into a standard LQR state-feedback controller design, along with an optimal encoder\u2013decoder design for propagating and using the information across the unreliable links. Our design is optimal among all causal algorithms for any arbitrary packet-drop pattern. Further, the solution is appealing from a practical point of view because it can be implemented as a small modification of an existing LQG control design.", "doi": "10.1016/j.sysconle.2006.11.003", "issn": "0167-6911", "publisher": "Elsevier", "publication": "Systems & Control Letters", "publication_date": "2007-06", "series_number": "6", "volume": "56", "issue": "6", "pages": "439-446" }, { "id": "authors:5j7kx-bdm52", "collection": "authors", "collection_id": "5j7kx-bdm52", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110426-130530739", "type": "article", "title": "On a stochastic sensor selection algorithm with applications in sensor scheduling and sensor coverage", "author": [ { "family_name": "Gupta", "given_name": "Vijay", "clpid": "Gupta-V" }, { "family_name": "Chung", "given_name": "Timothy H.", "clpid": "Chung-Timothy-H" }, { "family_name": "Hassibi", "given_name": "Babak", "orcid": "0000-0002-1375-5838", "clpid": "Hassibi-B" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "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 minimum error covariance? We describe a stochastic 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 (e.g., 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 view-point of the area and the sensors need to optimize their trajectories. The algorithm is applied to these problems and illustrated through simple examples.", "doi": "10.1016/j.automatica.2005.09.016", "issn": "0005-1098", "publisher": "Elsevier", "publication": "Automatica", "publication_date": "2006-02", "series_number": "2", "volume": "42", "issue": "2", "pages": "251-260" }, { "id": "authors:cs1cy-78146", "collection": "authors", "collection_id": "cs1cy-78146", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:ROWjfm06", "type": "article", "title": "Linear models for control of cavity flow oscillations", "author": [ { "family_name": "Rowley", "given_name": "Clarence W.", "orcid": "0000-0002-9099-5739", "clpid": "Rowley-C-W" }, { "family_name": "Williams", "given_name": "David R.", "clpid": "Williams-D-R" }, { "family_name": "Colonius", "given_name": "Tim", "orcid": "0000-0003-0326-3909", "clpid": "Colonius-T" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "MacMynowski", "given_name": "Douglas G.", "orcid": "0000-0003-1987-9417", "clpid": "MacMartin-D-G" } ], "abstract": "Models for understanding and controlling oscillations in the flow past a rectangular cavity are developed. These models may be used to guide control designs, to understand performance limits of feedback, and to interpret experimental results. Traditionally, cavity oscillations are assumed to be self-sustained: no external disturbances are necessary to maintain the oscillations, and amplitudes are limited by nonlinearities. We present experimental data which suggests that in some regimes, the oscillations may not be self-sustained, but lightly damped: oscillations are sustained by external forcing, such as boundary-layer turbulence. In these regimes, linear models suffice to describe the behaviour, and the final amplitude of oscillations depends on the characteristics of the external disturbances. These linear models are particularly appropriate for describing cavities in which feedback has been used for noise suppression, as the oscillations are small and nonlinearities are less likely to be important. It is shown that increasing the gain too much in such feedback control experiments can lead to a peak-splitting phenomenon, which is explained by the linear models. Fundamental performance limits indicate that peak splitting is likely to occur for narrow-bandwidth actuators and controllers.", "doi": "10.1017/S0022112005007299", "issn": "0022-1120", "publisher": "Cambridge University Press", "publication": "Journal of Fluid Mechanics", "publication_date": "2006-01-25", "volume": "547", "pages": "317-330" }, { "id": "authors:bg776-6h587", "collection": "authors", "collection_id": "bg776-6h587", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170725-151737146", "type": "article", "title": "Sensorimotor convergence in visual navigation and flight control systems", "author": [ { "family_name": "Humbert", "given_name": "J. Sean", "clpid": "Humbert-J-S" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Dickinson", "given_name": "Michael H.", "orcid": "0000-0002-8587-9936", "clpid": "Dickinson-M-H" } ], "abstract": "Insects exhibit unparalleled and incredibly robust flight dynamics in the face of uncertainties. A fundamental principle contributing to this amazing behavior is rapid processing and convergence of visual sensory information to flight motor commands via spatial wide-field integration, accomplished by motion pattern sensitive interneurons in the lobula plate portion of the visual ganglia. Within a control-theoretic framework, a model for wide-field integration of retinal image flow is developed, establishing the connection between image flow kernels (retinal motion pattern sensitivities) and the feedback terms they represent. It is demonstrated that the proposed output feedback methodology is sufficient to give rise to experimentally observed navigational heuristics as the centering and forward speed regulation responses exhibited by honeybees.", "doi": "10.3182/20050703-6-CZ-1902.02003", "issn": "1474-6670", "publisher": "Elsevier", "publication": "IFAC Proceedings Volumes", "publication_date": "2005-07", "series_number": "1", "volume": "38", "issue": "1", "pages": "253-258" }, { "id": "authors:dd0ap-kct14", "collection": "authors", "collection_id": "dd0ap-kct14", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170725-103031239", "type": "article", "title": "Cascade Discrete-Continuous State Estimators for a Class of Monotone Systems", "author": [ { "family_name": "Del Vecchio", "given_name": "D.", "clpid": "Del-Vecchio-D" }, { "family_name": "Murray", "given_name": "R. M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "A cascade discrete-continuous state estimator is proposed for a class of monotone systems with both continuous and discrete state. The proposed estimator exploits the partial order preserved by the system dynamics in order to satisfy two properties. First, its computation complexity scales with the number of variables to be estimated instead of scaling with the size of the discrete state space. Second, a separation principle holds: the continuous state estimation error is bounded by a monotonically decreasing function of the discrete state estimation error, the latter one converging to zero. A multi-robot example is proposed.", "doi": "10.3182/20050703-6-CZ-1902.00335", "issn": "1474-6670", "publisher": "Elsevier", "publication": "IFAC Proceedings Volumes", "publication_date": "2005-07", "series_number": "1", "volume": "38", "issue": "1", "pages": "307-312" }, { "id": "authors:ggncp-vex58", "collection": "authors", "collection_id": "ggncp-vex58", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170408-172516757", "type": "article", "title": "Receding horizon control of vectored thrust flight experiment", "author": [ { "family_name": "Milam", "given_name": "M. B.", "clpid": "Milam-M-B" }, { "family_name": "Franz", "given_name": "R.", "clpid": "Franz-R" }, { "family_name": "Hauser", "given_name": "J. E.", "clpid": "Hauser-J-E" }, { "family_name": "Murray", "given_name": "R. M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Abstract:\nThe application of a constrained receding horizon control technique to stabilise an indoor vectored-thrust flight experiment, known as the Caltech ducted fan, is given. The receding horizon control problem is formulated as a constrained optimal control problem and solved in real time with an efficient, computational method that combines nonlinear control theory, B-spline basis functions, and nonlinear programming. Characteristic issues, including non-zero computational times, convergence properties, choice of horizon length and terminal cost are discussed. The study validates the applicability of real-time receding horizon control for constrained systems with fast dynamics.", "doi": "10.1049/ip-cta:20059031", "issn": "1350-2379", "publisher": "IEE", "publication": "IEE Proceedings - Control Theory and Applications", "publication_date": "2005-05", "series_number": "3", "volume": "152", "issue": "3", "pages": "340-348" }, { "id": "authors:rf9tb-den49", "collection": "authors", "collection_id": "rf9tb-den49", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:MURieeecsm04", "type": "article", "title": "A new approach to teaching feedback", "author": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Waydo", "given_name": "Stephen", "clpid": "Waydo-S" }, { "family_name": "Cremean", "given_name": "Lars B.", "clpid": "Cremean-L-B" }, { "family_name": "Mabuchi", "given_name": "Hideo", "clpid": "Mabuchi-H" } ], "abstract": "The Control and Dynamical Systems (CDS) Department at the California Institute of Technology (Caltech) has revised its entry-level curriculum in dynamics, feedback, and control with the goals of updating the subject matter to include modern tools and making control tools accessible to a nontraditional audience. One of the approaches made was to divide the introductory control theory class into two tracks, with a conceptual track geared toward students who need only a conceptual overview of control tools and an analytical track providing a more detailed mathematical treatment of feedback. The conceptual track, CDS 101, which is mainly discussed in the paper, is intended for advanced students in science and engineering who can benefit from an overview of control techniques but who might not have the need for the mathematical depth underlying the material. Special attention is paid to ensuring that the course is accessible to students from biological, physical, and information sciences, using examples from these domains to illustrate concepts. The goal of the course is to enable students to use the principles and tools of feedback in their research activities.", "doi": "10.1109/MCS.2004.1337856", "issn": "0272-1708", "publisher": "IEEE", "publication": "IEEE Control Systems Magazine", "publication_date": "2004-10", "series_number": "5", "volume": "24", "issue": "5", "pages": "38-42" }, { "id": "authors:kh9pq-wj662", "collection": "authors", "collection_id": "kh9pq-wj662", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:FAXieeetac04", "type": "article", "title": "Information flow and cooperative control of vehicle formations", "author": [ { "family_name": "Fax", "given_name": "J. Alexander", "clpid": "Fax-J-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We consider the problem of cooperation among a collection of vehicles performing a shared task using intervehicle communication to coordinate their actions. Tools from algebraic graph theory prove useful in modeling the communication network and relating its topology to formation stability. We prove a Nyquist criterion that uses the eigenvalues of the graph Laplacian matrix to determine the effect of the communication topology on formation stability. We also propose a method for decentralized information exchange between vehicles. This approach realizes a dynamical system that supplies each vehicle with a common reference to be used for cooperative motion. We prove a separation principle that decomposes formation stability into two components: Stability of this is achieved information flow for the given graph and stability of an individual vehicle for the given controller. The information flow can thus be rendered highly robust to changes in the graph, enabling tight formation control despite limitations in intervehicle communication capability.", "doi": "10.1109/TAC.2004.834433", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "2004-09", "series_number": "9", "volume": "49", "issue": "9", "pages": "1465-1476" }, { "id": "authors:t2gnt-vd720", "collection": "authors", "collection_id": "t2gnt-vd720", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:OLFieeetac04", "type": "article", "title": "Consensus problems in networks of agents with switching topology and time-delays", "author": [ { "family_name": "Olfati-Saber", "given_name": "Reza", "clpid": "Olfati-Saber-R" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "In this paper, we discuss consensus problems for networks of dynamic agents with fixed and switching topologies. We analyze three cases: 1) directed networks with fixed topology; 2) directed networks with switching topology; and 3) undirected networks with communication time-delays and fixed topology. We introduce two consensus protocols for networks with and without time-delays and provide a convergence analysis in all three cases. We establish a direct connection between the algebraic connectivity (or Fiedler eigenvalue) of the network and the performance (or negotiation speed) of a linear consensus protocol. This required the generalization of the notion of algebraic connectivity of undirected graphs to digraphs. It turns out that balanced digraphs play a key role in addressing average-consensus problems. We introduce disagreement functions for convergence analysis of consensus protocols. A disagreement function is a Lyapunov function for the disagreement network dynamics. We proposed a simple disagreement function that is a common Lyapunov function for the disagreement dynamics of a directed network with switching topology. A distinctive feature of this work is to address consensus problems for networks with directed information flow. We provide analytical tools that rely on algebraic graph theory, matrix theory, and control theory. Simulations are provided that demonstrate the effectiveness of our theoretical results.", "doi": "10.1109/TAC.2004.834113", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "2004-09", "series_number": "9", "volume": "49", "issue": "9", "pages": "1520-1533" }, { "id": "authors:ce0j2-w8k30", "collection": "authors", "collection_id": "ce0j2-w8k30", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:GALprb04", "type": "article", "title": "Effective transition rates for epitaxial growth using fast modulation", "author": [ { "family_name": "Gallivan", "given_name": "Martha A.", "clpid": "Gallivan-M-A" }, { "family_name": "Goodwin", "given_name": "David G.", "clpid": "Goodwin-D-G" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Thin-film deposition is an industrially important process that is highly dependent on the processing conditions. Most films are grown under constant conditions, but a few studies show that modified properties may be obtained with periodic inputs. However, assessing the effects of modulation experimentally becomes impractical with increasing material complexity. Here we consider periodic conditions in which the period is short relative to the time scales of growth. We analyze a stochastic model of thin-film growth, computing effective transition rates associated with rapid periodic process parameters. Combinations of effective rates may exist that are not attainable under steady conditions, potentially enabling new film properties. An algorithm is presented to construct the periodic input for a desired set of effective transition rates. These ideas are demonstrated in three simple examples using kinetic Monte Carlo simulations of epitaxial growth.", "doi": "10.1103/PhysRevB.70.045409", "issn": "1098-0121", "publisher": "Physical Review B", "publication": "Physical Review B", "publication_date": "2004-07-15", "series_number": "4", "volume": "70", "issue": "4", "pages": "Art. No. 045409" }, { "id": "authors:2fex1-0xr95", "collection": "authors", "collection_id": "2fex1-0xr95", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190214-075224908", "type": "article", "title": "Model reduction for compressible flows using POD and Galerkin projection", "author": [ { "family_name": "Rowley", "given_name": "Clarence W.", "orcid": "0000-0002-9099-5739", "clpid": "Rowley-C-W" }, { "family_name": "Colonius", "given_name": "Tim", "orcid": "0000-0003-0326-3909", "clpid": "Colonius-T" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "We present a framework for applying the method of proper orthogonal decomposition (POD) and Galerkin projection to compressible fluids. For incompressible flows, only the kinematic variables are important, and the techniques are well known. In a compressible flow, both the kinematic and thermodynamic variables are dynamically important, and must be included in the configuration space. We introduce an energy-based inner product which may be used to obtain POD modes for this configuration space. We then obtain an approximate version of the Navier\u2013Stokes equations, valid for cold flows at moderate Mach number, and project these equations onto a POD basis. The resulting equations of motion are quadratic, and are much simpler than projections of the full compressible Navier\u2013Stokes equations.", "doi": "10.1016/j.physd.2003.03.001", "issn": "0167-2789", "publisher": "Elsevier", "publication": "Physica D", "publication_date": "2004-02-15", "series_number": "1-2", "volume": "189", "issue": "1-2", "pages": "115-129" }, { "id": "authors:kff11-yt740", "collection": "authors", "collection_id": "kff11-yt740", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140730-101719175", "type": "article", "title": "Decomposition of human motion into dynamics-based primitives with application to drawing tasks", "author": [ { "family_name": "Del Vecchio", "given_name": "Domitilla", "clpid": "Del-Vecchio-D" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Perona", "given_name": "Pietro", "orcid": "0000-0002-7583-5809", "clpid": "Perona-P" } ], "abstract": "Using tools from dynamical systems and systems identification, we develop a framework for the study of primitives for human motion, which we refer to as movemes. The objective is understanding human motion by decomposing it into a sequence of elementary building blocks that belong to a known alphabet of dynamical systems. We develop a segmentation and classification algorithm in order to reduce a complex activity into the sequence of movemes that have generated it. We test our ideas on data sampled from five human subjects who were drawing figures using a computer mouse. Our experiments show that we are able to distinguish between movemes and recognize them even when they take place in activities containing an unspecified number of movemes.", "doi": "10.1016/S0005-1098(03)00250-4", "issn": "0005-1098", "publisher": "Elsevier", "publication": "Automatica", "publication_date": "2003-12", "series_number": "12", "volume": "39", "issue": "12", "pages": "2085-2098" }, { "id": "authors:bs4d5-7z144", "collection": "authors", "collection_id": "bs4d5-7z144", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170824-092713962", "type": "article", "title": "Distributed cooperative control of multiple vehicle formations using structural potential functions", "author": [ { "family_name": "Olfati-Saber", "given_name": "Reza", "clpid": "Olfati-Saber-R" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "In this paper, we propose a framework for formation stabilization of multiple autonomous vehicles in a distributed fashion. Each vehicle is assumed to have simple dynamics, i.e. a double-integrator, with a directed (or an undirected) information flow over the formation graph of the vehicles. Our goal is to find a distributed control law (with an efficient computational cost) for each vehicle that makes use of limited information regarding the state of other vehicles. Here, the key idea in formation stabilization is the use of natural potential functions obtained from structural constraints of a desired formation in a way that leads to a collision-free, distributed, and bounded state feedback law for each vehicle.", "doi": "10.3182/20020721-6-ES-1901.00244", "issn": "1474-6670", "publisher": "Elsevier", "publication": "IFAC Proceedings Volumes", "publication_date": "2002", "series_number": "1", "volume": "35", "issue": "1", "pages": "495-500" }, { "id": "authors:0tsab-w9b27", "collection": "authors", "collection_id": "0tsab-w9b27", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170814-124254157", "type": "article", "title": "Information flow and cooperative control of vehicle formations", "author": [ { "family_name": "Fax", "given_name": "J. Alexander", "clpid": "Fax-J-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "Vehicles in formation often lack global information regarding the state of all the vehicles, a deficiency which can lead to instability and poor performance. In this paper, we demonstrate how exchange of minimal amounts of information between vehicles can be designed to realize a dynamical system which supplies each vehicle with a shared reference trajectory. When the information flow law is placed in the control loop, a separation principle is proven which guarantees stability of the formation and convergence of the information flow law regardless of the information flow topology.", "doi": "10.3182/20020721-6-ES-1901.00100", "issn": "1474-6670", "publisher": "Elsevier", "publication": "IFAC Proceedings Volumes", "publication_date": "2002", "series_number": "1", "volume": "35", "issue": "1", "pages": "115-120" }, { "id": "authors:m3j71-n6y18", "collection": "authors", "collection_id": "m3j71-n6y18", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:LEWsiamr99", "type": "article", "title": "Configuration Controllability of Simple Mechanical Control Systems", "author": [ { "family_name": "Lewis", "given_name": "Andrew D.", "clpid": "Lewis-A-D" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "In this paper we present a definition of 'configuration controllability' for mechanical systems whose Lagrangian is kinetic energy with respect to a Riemannian metric minus potential energy. A computable test for this new version of controllability is derived. This condition involves an object that we call the symmetric product. Of particular interest is a definition of 'equilibrium controllability' for which we are able to derive computable sufficient conditions. Examples illustrate the theory.", "doi": "10.1137/S0036144599351065", "issn": "0036-1445", "publisher": "SIAM Review", "publication": "SIAM Review", "publication_date": "1999", "series_number": "3", "volume": "41", "issue": "3", "pages": "555-574" }, { "id": "authors:xz0xc-bjh80", "collection": "authors", "collection_id": "xz0xc-bjh80", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:MCLieeetac97", "type": "article", "title": "Exponential stabilization of driftless nonlinear control systems using homogeneous feedback", "author": [ { "family_name": "M'Closkey", "given_name": "Robert T.", "clpid": "M'Closkey-R-T" }, { "family_name": "Murray", "given_name": "Ruchard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This paper focuses on the problem of exponential stabilization of controllable, driftless systems using time-varying, homogeneous feedback. The analysis is performed with respect to a homogeneous norm in a nonstandard dilation that is compatible with the algebraic structure of the control Lie algebra. It can be shown that any continuous, time-varying controller that achieves exponential stability relative to the Euclidean norm is necessarily non-Lipschitz. Despite these restrictions, we provide a set of constructive, sufficient conditions for extending smooth, asymptotic stabilizers to homogeneous, exponential stabilizers. The modified feedbacks are everywhere continuous, smooth away from the origin, and can be extended to a large class of systems with torque inputs. The feedback laws are applied to an experimental mobile robot and show significant improvement in convergence rate over smooth stabilizers.", "doi": "10.1109/9.580865", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "1997-05", "series_number": "5", "volume": "42", "issue": "5", "pages": "614-628" }, { "id": "authors:9c31n-drs27", "collection": "authors", "collection_id": "9c31n-drs27", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:LEWsiamjco97", "type": "article", "title": "Configuration Controllability of Simple Mechanical Control Systems", "author": [ { "family_name": "Lewis", "given_name": "Andrew D.", "clpid": "Lewis-A-D" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "In this paper we present a definition of \"configuration controllability\" for mechanical systems whose Lagrangian is kinetic energy with respect to a Riemannian metric minus potential energy. A computable test for this new version of controllability is derived. This condition involves an object which we call the symmetric product. Of particular interest is a definition of \"equilibrium controllability\" for which we are able to derive computable sufficient conditions. Examples illustrate the theory.", "doi": "10.1137/S0363012995287155", "issn": "0363-0129", "publisher": "SIAM Journal on Control and Optimization", "publication": "SIAM Journal on Control and Optimization", "publication_date": "1997-05", "series_number": "3", "volume": "35", "issue": "3", "pages": "766-790" }, { "id": "authors:r7d0r-2ws36", "collection": "authors", "collection_id": "r7d0r-2ws36", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100713-091226984", "type": "article", "title": "Nonholonomic Mechanical Systems with Symmetry", "author": [ { "family_name": "Bloch", "given_name": "Anthony M.", "clpid": "Bloch-A-M" }, { "family_name": "Krishnaprasad", "given_name": "P. S.", "clpid": "Krishnaprasad-P-S" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This work develops the geometry and dynamics of mechanical systems with nonholonomic constraints and symmetry from the perspective of Lagrangian mechanics and with a view to control-theoretical applications. The basic methodology is that of geometric mechanics applied to the Lagrange-d'Alembert formulation, generalizing the use of connections and momentum maps associated with a given symmetry group to this case. We begin by formulating the mechanics of nonholonomic systems using an Ehresmann connection to model the constraints, and show how the curvature of this connection enters into Lagrange's equations. Unlike the situation with standard configuration-space constraints, the presence of symmetries in the nonholonomic case may or may not lead to conservation laws. However, the momentum map determined by the symmetry group still satisfies a useful differential equation that decouples from the group variables. This momentum equation, which plays an important role in control problems, involves parallel transport operators and is computed explicitly in coordinates. An alternative description using a ldquobody reference framerdquo relates part of the momentum equation to the components of the Euler-Poincar\u00e9 equations along those symmetry directions consistent with the constraints. One of the purposes of this paper is to derive this evolution equation for the momentum and to distinguish geometrically and mechanically the cases where it is conserved and those where it is not. An example of the former is a ball or vertical disk rolling on a flat plane and an example of the latter is the snakeboard, a modified version of the skateboard which uses momentum coupling for locomotion generation. We construct a synthesis of the mechanical connection and the Ehresmann connection defining the constraints, obtaining an important new object we call the nonholonomic connection. When the nonholonomic connection is a principal connection for the given symmetry group, we show how to perform Lagrangian reduction in the presence of nonholonomic constraints, generalizing previous results which only held in special cases. Several detailed examples are given to illustrate the theory.", "doi": "10.1007/BF02199365", "issn": "0003-9527", "publisher": "Springer", "publication": "Archive for Rational Mechanics and Analysis", "publication_date": "1996-12", "series_number": "1", "volume": "136", "issue": "1", "pages": "21-99" }, { "id": "authors:mg3f9-08n32", "collection": "authors", "collection_id": "mg3f9-08n32", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200310-145803556", "type": "article", "title": "Robust Nonlinear Control Theory with Applications to Aerospace Vehicles", "author": [ { "family_name": "Doyle", "given_name": "John", "orcid": "0000-0002-1828-2486", "clpid": "Doyle-J-C" }, { "family_name": "Murray", "given_name": "Richard", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This paper is a very brief outline of an invited poster session giving a first-year progress report on a research program with the above title being carried out in the Control and Dynamical Systems (CDS) department at Caltech. This 5-year grant funded by the AFOSR Partnership for Research Excellence Transition (PRET) Program has a special emphasis on transitioning new methods to industrial practice and thus involves a high level of industrial participation. The focus of our program is fundamental research in general methods of analysis and design of complex uncertain nonlinear systems, from creating new mathematical theory to working to make that theory help engineers solve a variety of real industrial problems. Caltech's Control and Dynamical Systems department was created with precisely this goal, which is shared by our industrial collaborators, led by Honeywell. Further details will be available at the poster session.", "doi": "10.1016/s1474-6670(17)58916-8", "issn": "1474-6670", "publisher": "Pergamon", "publication": "IFAC Proceedings Volumes", "publication_date": "1996-06", "series_number": "1", "volume": "29", "issue": "1", "pages": "7624-7629" }, { "id": "authors:t154n-f4e63", "collection": "authors", "collection_id": "t154n-f4e63", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:TILieeetac95", "type": "article", "title": "Trajectory generation for the N-trailer problem using Goursat normal form", "author": [ { "family_name": "Tilbury", "given_name": "Dawn", "clpid": "Tilbury-D" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Sastry", "given_name": "S. Shankar", "clpid": "Sastry-S-Shankar" } ], "abstract": "Develops the machinery of exterior differential forms, more particularly the Goursat normal form for a Pfaffian system, for solving nonholonomic motion planning problems, i.e., motion planning for systems with nonintegrable velocity constraints. The authors use this technique to solve the problem of steering a mobile robot with n trailers. The authors present an algorithm for finding a family of transformations which will convert the system of rolling constraints on the wheels of the robot with n trailers into the Goursat canonical form. Two of these transformations are studied in detail. The Goursat normal form for exterior differential systems is dual to the so-called chained-form for vector fields that has been studied previously. Consequently, the authors are able to give the state feedback law and change of coordinates to convert the N-trailer system into chained-form. Three methods for planning trajectories for chained-form systems using sinusoids, piecewise constants, and polynomials as inputs are presented. The motion planning strategy is therefore to first convert the N-trailer system into Goursat form, use this to find the chained-form coordinates, plan a path for the corresponding chained-form system, and then transform the resulting trajectory back into the original coordinates. Simulations and frames of movie animations of the N-trailer system for parallel parking and backing into a loading dock using this strategy are included.", "doi": "10.1109/9.384215", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "1995-05", "series_number": "5", "volume": "40", "issue": "5", "pages": "802-819" }, { "id": "authors:606zf-tfc37", "collection": "authors", "collection_id": "606zf-tfc37", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190318-150352226", "type": "article", "title": "A motion planner for nonholonomic mobile robots", "author": [ { "family_name": "Laumond", "given_name": "Jean-Paul", "clpid": "Laumond-J-P" }, { "family_name": "Jacobs", "given_name": "Paul E.", "clpid": "Jacobs-P-E" }, { "family_name": "Ta\u00efx", "given_name": "Michel", "clpid": "Ta\u00efx-M" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "abstract": "This paper considers the problem of motion planning for a car-like robot (i.e., a mobile robot with a nonholonomic constraint whose turning radius is lower-bounded). We present a fast and exact planner for our mobile robot model, based upon recursive subdivision of a collision-free path generated by a lower-level geometric planner that ignores the motion constraints. The resultant trajectory is optimized to give a path that is of near-minimal length in its homotopy class. Our claims of high speed are supported by experimental results for implementations that assume a robot moving amid polygonal obstacles. The completeness and the complexity of the algorithm are proven using an appropriate metric in the configuration space R^2 x S^1 of the robot. This metric is defined by using the length of the shortest paths in the absence of obstacles as the distance between two configurations. We prove that the new induced topology and the classical one are the same. Although we concentrate upon the car-like robot, the generalization of these techniques leads to new theoretical issues involving sub-Riemannian geometry and to practical results for nonholonomic motion planning.", "doi": "10.1109/70.326564", "issn": "1042-296X", "publisher": "IEEE", "publication": "IEEE Transactions on Robotics and Automation", "publication_date": "1994-10", "series_number": "5", "volume": "10", "issue": "5", "pages": "577-593" }, { "id": "authors:ghgf3-cps38", "collection": "authors", "collection_id": "ghgf3-cps38", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:WALieeetac94", "type": "article", "title": "Stabilization of trajectories for systems with nonholonomic constraints", "author": [ { "family_name": "Walsh", "given_name": "G.", "clpid": "Walsh-G" }, { "family_name": "Tilbury", "given_name": "D.", "clpid": "Tilbury-D" }, { "family_name": "Sastry", "given_name": "S.", "clpid": "Sastry-S-Shankar" }, { "family_name": "Murray", "given_name": "R.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Laumond", "given_name": "J. P.", "clpid": "Laumond-J-P" } ], "abstract": "A new technique for stabilizing nonholonomic systems to trajectories is presented. It is well known that such systems cannot be stabilized to a point using smooth static-state feedback. In this note, we suggest the use of control laws for stabilizing a system about a trajectory, instead of a point. Given a nonlinear system and a desired (nominal) feasible trajectory, the note gives an explicit control law which will locally exponentially stabilize the system to the desired trajectory. The theory is applied to several examples, including a car-like robot.", "doi": "10.1109/9.273373", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "1994-01", "series_number": "1", "volume": "39", "issue": "1", "pages": "216-222" }, { "id": "authors:4g4pk-07277", "collection": "authors", "collection_id": "4g4pk-07277", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:MURieeetac93", "type": "article", "title": "Nonholonomic motion planning: steering using sinusoids", "author": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Sastry", "given_name": "S. Shankar", "clpid": "Sastry-S-Shankar" } ], "abstract": "Methods for steering systems with nonholonomic constraints between arbitrary configurations are investigated. Suboptimal trajectories are derived for systems that are not in canonical form. Systems in which it takes more than one level of bracketing to achieve controllability are considered. The trajectories use sinusoids at integrally related frequencies to achieve motion at a given bracketing level. A class of systems that can be steered using sinusoids (claimed systems) is defined. Conditions under which a class of two-input systems can be converted into this form are given.", "doi": "10.1109/9.277235", "issn": "0018-9286", "publisher": "IEEE", "publication": "IEEE Transactions on Automatic Control", "publication_date": "1993-05", "series_number": "5", "volume": "38", "issue": "5", "pages": "700-716" } ]