Contemporary deep-learning models for the life-sciences have outpaced the tooling that lets experimentalists compose them. Three contributions are presented in response, a software platform, exemplary tasks built on it, and a predicted structural proteome of a defined gut microbiome. The underlying argument is that for experimentalists who use rather than build deep-learning methods, difficulties with composition and usability now outpace availability.
\r\n\r\nTRILL, a platform for AI-based protein engineering and analysis, is open-source, runs locally, and wraps models/methods behind a uniform vocabulary of thirteen top-level commands. Furthermore, TRILL is scalable, ranging from parallel fine-tuning of large models on a supercomputer to democratized, parameter off-loading in compute-limited scenarios. Models can be swapped with a one-argument change rather than a pipeline rewrite, and fast predictions can be paired with physics-based validation where overconfidence costs most.
\r\n\r\nProtein language models were fine-tuned using a homology-aware strategy, decreasing data leakage when evaluating generated proteins. Classifiers for cellulase, antimicrobial, and toxin activity were trained and applied to a scan of over two hundred million proteins from the NCBI non-redundant catalogue. An end-to-end pipeline carried seventeen predicted toxins of unknown function through structure prediction, binder design, and molecular dynamics on nearly nine hundred designed complexes.
\r\n\r\nThe third contribution targets hCom2, a defined synthetic gut consortium. We present a structural resource, where roughly four hundred thousand structures of its proteome were predicted using TRILL, segmented into eight hundred thousand domains, and assigned CATH designations. A case study demonstrating the utility of this structural database identifies nineteen carriers of the Helicobacter pylori virulence-factor TIPalpha fold across fourteen strains where sequence-only annotation fails.
", "doi": "10.7907/b5ye-jy33", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:17747", "collection": "thesis", "collection_id": "17747", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11032025-192332480", "primary_object_url": { "basename": "phd_thesis_submission.pdf", "content": "final", "filesize": 32786900, "license": "other", "mime_type": "application/pdf", "url": "/17747/1/phd_thesis_submission.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Leveraging Aerial Transformation for Enhanced Air\u2013Ground Robotic Mobility", "author": [ { "family_name": "Mandralis", "given_name": "Ioannis M.", "orcid": "0000-0001-5270-0672", "clpid": "Mandralis-Ioannis-M" } ], "thesis_advisor": [ { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Ames", "given_name": "Aaron D.", "orcid": "0000-0003-0848-3177", "clpid": "Ames-A-D" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Dabiri", "given_name": "John O.", "orcid": "0000-0002-6722-9008", "clpid": "Dabiri-J-O" } ], "local_group": [ { "literal": "GALCIT" }, { "literal": "div_eng" } ], "abstract": "Ground-aerial robots can extend endurance, versatility, and robustness by combining wheeled motion with flight, yet many flying-rolling robot designs add actuators that increase weight and reduce efficiency. Morphobots mitigate this by using multi-purpose actuators and body shape change to switch modes on the ground, but unpredictable vehicle-ground interactions can be an obstacle to robust operation. This dissertation develops the Aerially Transforming Morphobot (ATMO), a quadcopter that reconfigures in flight to land on wheels, enabling reliable air-ground transitions, mode switching without the hindrances of ground-morphing, and improved agility. We present ATMO\u2019s design and performance characterization, analyze its dynamics\u2013revealing transformation-induced couplings incompatible with standard quadcopter control\u2013and introduce a model-predictive control framework that stabilizes ATMO through aerial transformation to execute dynamic transitions. We then compare this approach with a learning-based controller that uses deep reinforcement learning for end-to-end morpho-transition, validating both experimentally. Finally, we revisit ATMO\u2019s design using aerodynamic principles to expand morphing flight through wake vectoring, showing that passive structures in the rotor wake substantially increase available thrust authority. Overall, we demonstrate that aerial shape change improves agility and reliability, highlighting a new direction for research in ground-aerial robotics.", "doi": "10.7907/srg8-sx98", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:17647", "collection": "thesis", "collection_id": "17647", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08252025-232825764", "primary_object_url": { "basename": "Manisha_Kapasiawala_Caltech_PhD_Thesis.pdf", "content": "final", "filesize": 35470940, "license": "other", "mime_type": "application/pdf", "url": "/17647/1/Manisha_Kapasiawala_Caltech_PhD_Thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Design Considerations for Synthetic Cells", "author": [ { "family_name": "Kapasiawala", "given_name": "Manisha Kaushik", "orcid": "0000-0002-0302-2921", "clpid": "Kapasiawala-Manisha-Kaushik" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Thomson", "given_name": "Matthew", "orcid": "0000-0003-1021-1234", "clpid": "Thomson-M-W" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Voorhees", "given_name": "Rebecca M.", "orcid": "0000-0003-1640-2293", "clpid": "Voorhees-R-M" }, { "family_name": "Winfree", "given_name": "Erik", "orcid": "0000-0002-5899-7523", "clpid": "Winfree-E" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Efforts to understand life as we know it and life as it can be have culminated in the field of synthetic cell research, which aims to build life from the bottom up using individual biological components. Recent progress in the field has enabled the reconstitution of many functions of living cells in synthetic cells, from cell-cell communication to membrane protein expression and function. However, future progress in the field is limited by many challenges, including irreproducibility, lack of predictability, difficulties in integrating existing synthetic cell modules (or subsystems), and the need for autonomous functionalities.
\r\n\r\nIn this work, I describe my efforts towards addressing these challenges. In Chapter 2, I describe sources of variability in transcription-translation (TX-TL) systems, the biological machinery used to implement biomolecular programs in synthetic cells. In Chapter 3, I describe a novel methodology for readily building more predictive models of TX-TL performance. In Chapter 4, I present a design for a proof-of-concept for integrating an energy regeneration subsystem and a motility subsystem to achieve autonomous programmable motility and highlight some early successes towards achieving that goal. Throughout this work, I highlight many design principles for building synthetic cells reproducibly, more predictably, and with novel functionalities.
", "doi": "10.7907/zfhy-bk03", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:17643", "collection": "thesis", "collection_id": "17643", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08212025-191338101", "primary_object_url": { "basename": "olson_blade_2026_thesis.pdf", "content": "final", "filesize": 8714374, "license": "other", "mime_type": "application/pdf", "url": "/17643/6/olson_blade_2026_thesis.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Synthetic Antigen-Presenting Vesicles for Selective Immunomodulation", "author": [ { "family_name": "Olson", "given_name": "Blade A.", "orcid": "0000-0002-1526-1399", "clpid": "Olson-Blade-A" } ], "thesis_advisor": [ { "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" } ], "thesis_committee": [ { "family_name": "Thomson", "given_name": "Matthew", "orcid": "0000-0003-1021-1234", "clpid": "Thomson-M-W" }, { "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" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "orcid": "0000-0002-2277-3990", "clpid": "Bjorkman-P-J" }, { "family_name": "Gradinaru", "given_name": "Viviana", "orcid": "0000-0001-5868-348X", "clpid": "Gradinaru-V" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "The rapid advancement of generative artificial intelligence has enabled unprecedented progress for the field of computational protein design. A forthcoming challenge for generative protein design algorithms is the immunocompatibility of these de novo designed molecules with organism physiology, namely humans. A separate, but related, aspirational goal for synthetic biology is to perform cellular reprogramming in vivo so that cell-based therapies and biologics are generated endogenously by patients rather than being externally manufactured or expanded before delivery, as is the case with biologics, T cell therapies, and stem cell therapies; again, a major hurdle for the in vivo production of these therapies and in vivo cellular reprogramming is immunogenicity.
\r\n\r\nTo address these challenges, we first demonstrate a cell-like, cell-free approach for in vivo cellular reprogramming with the induced release of pMHCI and pMHCII-loaded synthetic antigen-presenting vesicles that are secreted from non-immune cells by DNA and mRNA transfection to facilitate the selective expansion or silencing of immune responses. Next, we show initial results for the use of human tonsil organoids as a quantitative assay for adenoviral vector immunogenicity, enabling future directed evolution approaches for immunogenicity reduction as well as generation of an immunogenicity dataset to tailor modern computational protein design algorithms for human immunocompatibility. Together, these projects represent complementary methods to control protein immunogenicity, either through rationally engineered or directedly evolved modifications identified by physiologically-relevant in vitro models, or with an administered mRNA therapeutic that selectively modifies the immune response to a protein that cannot be computationally redesigned.
", "doi": "10.7907/fxzx-yn04", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:17771", "collection": "thesis", "collection_id": "17771", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11242025-191228061", "type": "thesis", "title": "Naturally-Inspired Circuits for Microbial Composition Control and Biosensing", "author": [ { "family_name": "Kratz", "given_name": "Matthieu Francois", "clpid": "Kratz-Matthieu-Francois" } ], "thesis_advisor": [ { "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" } ], "thesis_committee": [ { "family_name": "Demirer", "given_name": "G\u00f6zde S.", "orcid": "0000-0002-3007-1489", "clpid": "Demirer-G\u00f6zde-S" }, { "family_name": "Hay", "given_name": "Bruce A.", "orcid": "0000-0002-5486-0482", "clpid": "Hay-B-A" }, { "family_name": "Bois", "given_name": "Justin S.", "orcid": "0000-0001-7137-8746", "clpid": "Bois-J-S" }, { "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" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "When considering the design of gene circuits, there are many possible sources of inspiration. Many early synthetic gene circuits used nature as an inspiration, seeking to recreate biological behaviors with non-native components. As the field grew, alternative approaches sourcing designs from adjacent engineering fields and computational approaches emerged and grew in prominence. Despite this shift, there remains a great deal of naturally-inspired circuits that provide useful functions for biotechnology. Indeed nature has often been uniquely capable of exploiting typically undesirable phenomena, e.g. noise to create biologically useful function. This thesis presents two projects directly inspired by natural systems. Each project aims to replicate a behavior or circuit topology found in nature, leveraging its unique dynamics to address key challenges in biotechnology. Chapters 2 and 3 will cover the development of a circuit emulating the microbial behavior of phase variation, whereby individual cells reversibly and stochastically transition between distinct phenotypes. We recreate this behavior using serine recombinases and demonstrate how it can enable stable, bulk control of phenotype composition\u2014a task of great relevance to biotechnology. Chapter 4 lays the groundwork for applying the biologically-relevant feed-forward loop topology to the problem of spurious biosensor activation. We realize this topology in a modular manner using small transcription activating RNAs (STARs) and provide a preliminary characterization of its dynamical properties. Finally, we discuss alternative implementations that may provide more directly applicable properties than the current STAR implementation", "doi": "10.7907/d42b-jh46", "publication_date": "2026", "thesis_type": "phd", "thesis_year": "2026" }, { "id": "thesis:17345", "collection": "thesis", "collection_id": "17345", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06012025-210705210", "type": "thesis", "title": "Domestication of Environmental Bacteria for Biosensing Applications", "author": [ { "family_name": "Larsson", "given_name": "Elin Maria", "orcid": "0000-0003-1341-5937", "clpid": "Larsson-Elin-Maria" } ], "thesis_advisor": [ { "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" } ], "thesis_committee": [ { "family_name": "Leadbetter", "given_name": "Jared R.", "orcid": "0000-0002-7033-0844", "clpid": "Leadbetter-J-R" }, { "family_name": "Hay", "given_name": "Bruce A.", "orcid": "0000-0002-5486-0482", "clpid": "Hay-B-A" }, { "family_name": "Cao", "given_name": "Mengyi", "orcid": "0000-0002-3117-3401", "clpid": "Cao-Mengyi" }, { "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" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "The field of synthetic biology has made impressive progress in the past 25 years, but is still lacking when it comes to our capability to predictably engineer organisms outside of a small group of lab model organisms. In this thesis, I present the efforts to domesticate two soil bacteria important in agriculture for biosensing. The first, Pseudomonas synxantha, a wheat-colonizing bacterium that helps fight off fungal disease, was engineered into a bioreporter for phosphorus limitation. We also made cell-free extract from this organism, to enable rapid characterization of genetic elements. For the second, Xenorhabdus griffiniae, we asked the question of whether this bacterium can sense the presence of its entomopathogenic nematode host Steinernema hermaphroditum. We learned that X. griffiniae is able to sense its host and we were able to build an early variant of a nematode reporter by first characterizing genetic elements in X. griffiniae.", "doi": "10.7907/m077-7633", "publication_date": "2025", "thesis_type": "phd", "thesis_year": "2025" }, { "id": "thesis:16465", "collection": "thesis", "collection_id": "16465", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06022024-014038700", "primary_object_url": { "basename": "ApurvaBadithela_June2024.pdf", "content": "final", "filesize": 96248118, "license": "other", "mime_type": "application/pdf", "url": "/16465/9/ApurvaBadithela_June2024.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Test and Evaluation of Autonomous Systems: Reactive Test Synthesis and Task-Relevant Evaluation of Perception", "author": [ { "family_name": "Badithela", "given_name": "Apurva Srinivas", "orcid": "0000-0002-9788-2702", "clpid": "Apurva-Apurva-Srinivas" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Ames", "given_name": "Aaron D.", "orcid": "0000-0003-0848-3177", "clpid": "Ames-A-D" }, { "family_name": "Chandy", "given_name": "K. Mani", "orcid": "0000-0001-9190-1290", "clpid": "Chandy-K-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" }, { "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" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Autonomous robotic systems have potential for profound impact on our society -- legged and wheeled robots for search and rescue missions, drones for wildfire management, self-driving cars for improving mobility, and robotic space missions for exploration and repair of spacecraft. The complexity of these systems implies that formal guarantees during the design phase alone is not sufficient; mainstream deployment of these systems requires principled frameworks for test and evaluation, and verification and validation. This thesis studies two such challenges to mainstream deployment of these systems.
\r\n\r\nFirst, we consider the problem of evaluating perception models in a manner relevant to the system-level specification and the downstream planner. Perception and planning modules are often designed under different computational and mathematical paradigms. This talk will focus on evaluating models for classification and detection tasks, and leverages confusion matrices which are popularly used in computer vision to evaluate object detection models to derive probabilistic guarantees at the system-level. However, not all perception errors are equally safety-critical, and traditional confusion matrices account for all objects equally. Thus, task-relevant metrics such as proposition labeled confusion matrices are introduced. These are constructed by identifying propositional formulas relevant to the downstream planning logic and the system-level specification, and result in less conservative system-level guarantees. Using this analysis, fundamental tradeoffs in perception models are reflected in the tradeoffs of probabilistic guarantees. This framework is illustrated on a car-pedestrian example in simulation, and the confusion matrices are constructed from state-of-the-art detection models evaluated on the nuScenes dataset.
\r\n\r\nSecond, we consider the problem of automatically synthesizing tests for autonomous robotic systems. These systems reason over both discrete (e.g., navigate left or right around an obstacle) and continuous variables (e.g., continuous trajectories). This talk presents a flow-based approach for test environment synthesis which handles discrete variables and is also reactive to the system under test. Reactivity is important to account for uncertainties in system modeling, and to adapt to system behavior without knowledge of the system controller. These tests are synthesized from high-level specifications of desired behavior. Though the problem is shown to be NP-hard, a flow-based mixed-integer linear program formulation is used that scales well to medium-sized examples (e.g., >10,000 integer variables). The test environment can consist of static and reactive obstacles as well as dynamic test agents, whose strategies are synthesized to match the solution of the flow-based optimization. The overview of the approach is as follows. First, principles of automata theory are used to translate the high-level system and test objectives, and the non-deterministic abstraction of the system into a network flow optimization. The solution of this optimization is then parsed into GR(1) formulas in linear temporal logic. This GR(1) formula is used to synthesize reactive strategies of a dynamic test agent in a counterexample-guided fashion. We provide guarantees that the synthesized test strategy will realize the desired test behavior under the assumption of a well-designed system, the test strategy is reactive and least-restrictive,. This framework is illustrated on several simulation and hardware experiments with quadrupeds, showing promise towards a layered approach to test and evaluation.
", "doi": "10.7907/e8qz-rd26", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16481", "collection": "thesis", "collection_id": "16481", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06032024-141219249", "primary_object_url": { "basename": "JuradoQuiroga_Zoila_2024_Submitted.pdf", "content": "final", "filesize": 79519830, "license": "other", "mime_type": "application/pdf", "url": "/16481/1/JuradoQuiroga_Zoila_2024_Submitted.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Towards a Synthetic Nucleus: Separating Transcription and Translation in Cell-Free Protein Expression Systems", "author": [ { "family_name": "Jurado Quiroga", "given_name": "Zoila Estefani", "orcid": "0000-0003-4160-5068", "clpid": "Jurado-Quiroga-Zoila-Estefani" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Minnich", "given_name": "Austin J.", "orcid": "0000-0002-9671-9540", "clpid": "Minnich-A-J" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Voorhees", "given_name": "Rebecca M.", "orcid": "0000-0003-1640-2293", "clpid": "Voorhees-R-M" }, { "family_name": "Pandey", "given_name": "Ayush", "orcid": "0000-0003-3590-4459", "clpid": "Pandey-Ayush" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Synthetic cells represent the culmination of decades of research aimed at deciphering the intricacies of life at its most basic level. The result of the fusion of biology, chemistry, physics, and engineering, synthetic cells promise to revolutionize biotechnology, medicine, and beyond. This thesis focuses on the ramifications of incorporating a synthetic nucleus within a synthetic cell.
\r\n\r\nTo experimentally study transcription and translation, we use a commercially available cell-free protein expression system comprising all the purified proteins essential for protein production (PURE), along with a fluorescent RNA aptamer--malachite green aptamer (MGapt), and a green fluorescent protein (deGFP). We observed that the chemical composition of the PURE system significantly impacts MGapt fluorescence, leading to inaccurate RNA calculations. We identify the reducing agent, dithiothreitol (DTT), to address this challenge as a crucial chemical affecting MGapt fluorescence. We propose a model that can reliably model MGapt measurements in commercial PURE. This investigation illuminates the intricate dynamics of MGapt in PURE and emphasizes the necessity of accounting for environmental factors in RNA measurements employing aptamers.
\r\n\r\n\r\nSubsequently, to advance our understanding of a synthetic nucleus and analyze the effects of separating transcription and translation in a cell-free protein expression, we propose and validate a chemical reaction network model for transcription (TX) in PURE. Additionally, we used open-source software to expand an existing translation (TL) model for any arbitrary DNA sequence to create a nearly complete model of TX-TL in PURE. Leveraging this model, we investigate the effect of introducing a synthetic nucleus by modulating the RNA diffusion rate and resource allocation. This detailed model showcases our capability to comprehensively model protein expression in PURE, enabling insights into the efficacy of segregating transcription and translation processes within the artificial cell environment. Lastly, we provide a perspective on the future of synthetic cells with an artificial nucleus and propose further steps to develop the proposed synthetic nucleus model.
", "doi": "10.7907/kvq4-6132", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16087", "collection": "thesis", "collection_id": "16087", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06062023-021337351", "primary_object_url": { "basename": "Caltech_Thesis_Ayush_Pandey.pdf", "content": "final", "filesize": 15175323, "license": "other", "mime_type": "application/pdf", "url": "/16087/4/Caltech_Thesis_Ayush_Pandey.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Modeling Frameworks for Modular and Scalable Biological Circuit Design", "author": [ { "family_name": "Pandey", "given_name": "Ayush", "orcid": "0000-0003-3590-4459", "clpid": "Pandey-Ayush" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Doyle", "given_name": "John Comstock", "orcid": "0000-0002-1828-2486", "clpid": "Doyle-J-C" }, { "family_name": "Pierce", "given_name": "Niles A.", "orcid": "0000-0003-2367-4406", "clpid": "Pierce-N-A" }, { "family_name": "Del Vecchio", "given_name": "Domitilla", "orcid": "0000-0001-6472-8576", "clpid": "DelVecchio-D" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Synthetic biology is a rapidly evolving interdisciplinary field that combines principles from biology, bioengineering, biochemistry, and computational sciences to design and engineer new biological systems for various applications. This thesis focuses on addressing the challenges in engineering large and complex biological circuits. We develop modular modeling frameworks, formal theory, and computer-assisted design (CAD) tools for design and analysis of biological systems at a larger scale.
\r\n\r\nThis thesis introduces a new problem of robustness in structured model reduction of dynamical systems and provides bounds on a robustness distance metric for linear and nonlinear systems. With this theory, we show the discrimination and quantification of different mathematical models, considering resource loading effects in biological circuits.
\r\n\r\nUsing our proposed model reduction robustness theory and its associated software development, we build a modeling, analysis, and parameter identification pipeline. This pipeline is demonstrated through the characterization of DNA recombination enzymes in a cell-free protein expression system. This pipeline is a general approach to systematically develop mathematical models, infer parameters from experimental data, and guide experimental design choices.
\r\n\r\nIdentification of parameters in detailed mathematical models is a major challenge in synthetic biology where only sparse data is available. This prevents the application of our detail-driven modeling approach to larger biological systems. Hence, to address this limitation, we present a formal methods-based approach for specifying and synthesizing implementations for the design of biological circuits. We present a contract-based design framework for synthetic biology. We write formal description of design objectives at a higher level of abstraction without modeling the details of each component. This design framework facilitates the design and prediction of complex synthetic biological circuits at scale.
\r\n\r\nOverall, this thesis contributes to the advancement of synthetic biology by providing novel modeling frameworks, analysis methods, and design approaches. These contributions aim to enable the design and analysis of complex biological systems and foster the systematic engineering of biological circuits.
", "doi": "10.7907/qacp-dw76", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:16453", "collection": "thesis", "collection_id": "16453", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05312024-094443866", "primary_object_url": { "basename": "JGraebener_thesis_1.pdf", "content": "final", "filesize": 26529382, "license": "other", "mime_type": "application/pdf", "url": "/16453/1/JGraebener_thesis_1.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Formal Methods for Test and Evaluation: Reasoning over Tests, Automated Test Synthesis, and System Diagnostics", "author": [ { "family_name": "Graebener", "given_name": "Josefine Berta Marie", "orcid": "0000-0002-1376-0741", "clpid": "Graebener-Josefine-Berta-Marie" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Meiron", "given_name": "Daniel I.", "orcid": "0000-0003-0397-3775", "clpid": "Meiron-D-I" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" }, { "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" } ], "local_group": [ { "literal": "GALCIT" }, { "literal": "div_eng" } ], "abstract": "With the integration of autonomous systems into our everyday lives edging closer to reality, ensuring the safety of these systems is paramount. Part of the safety verification process is a rigorous testing procedure, which currently does not exist for autonomous vehicles. In this thesis, we aim to provide approaches using formal methods to increase the efficiency of testing campaigns.\r\nFirst, we provide a framework based on assume-guarantee contracts to specify tests in the form of a test structure. Using these test structures, we then show how to combine, split, and compare tests. Additionally, we characterize when tests can be combined and when the resulting test requires temporal constraints. Next, we demonstrate the approach on examples and find a strategy for a test agent using winning sets and Monte Carlo tree search.
\r\n\r\nSecond, we present a framework to automatically synthesize a test environment, consisting of static and reactive obstacles, and dynamic test agents. We characterize the desired test behavior in a system and a test objective in the form of a linear temporal logic specification, consisting of sub-tasks commonly used for robotic missions. This test environment must ensure that the test is not impossible (i.e. a correct system can pass the test), but also that every test execution that satisfies the system objective also satisfies the test objective. We use tools from automata theory to construct the virtual product graph that represents all possible test executions, and the virtual system graph, which corresponds to the system's perspective.\r\nWe formulate this routing problem as a network flow optimization on the virtual product graph in the form of a mixed integer linear program for different test environments. We show that this routing problem is NP-hard. We propose a counterexample-guided search using GR(1) synthesis to find a strategy for a test agent. This framework is demonstrated in several examples in simulation and hardware.
\r\n\r\nLastly, we present a framework to diagnose a system-level fault by identifying the component responsible for the failure. We make use of assume-guarantee contracts and Pacti, a tool for compositional system analysis and design, to construct a diagnostics map, which allows us to trace a system-level guarantee to possible causes. We show that this framework can reduce the number of statements that need to be checked in the diagnostics process. We illustrate this framework on several abstract examples and two examples inspired by a real-world autonomous system.
", "doi": "10.7907/4xdc-b988", "publication_date": "2024", "thesis_type": "phd", "thesis_year": "2024" }, { "id": "thesis:15225", "collection": "thesis", "collection_id": "15225", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05292023-181810775", "primary_object_url": { "basename": "Marken_Thesis_Final.pdf", "content": "final", "filesize": 4502877, "license": "other", "mime_type": "application/pdf", "url": "/15225/1/Marken_Thesis_Final.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Experimental and Theoretical Frameworks for Enabling Environmental Synthetic Biology", "author": [ { "family_name": "Marken", "given_name": "John Paul", "orcid": "0000-0001-9696-088X", "clpid": "Marken-John-Paul" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Elowitz", "given_name": "Michael B.", "orcid": "0000-0002-1221-0967", "clpid": "Elowitz-M-B" }, { "family_name": "Hay", "given_name": "Bruce A.", "orcid": "0000-0002-5486-0482", "clpid": "Hay-B-A" }, { "family_name": "Newman", "given_name": "Dianne K.", "orcid": "0000-0003-1647-1918", "clpid": "Newman-D-K" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Although the field of synthetic biology has made great advances toward becoming a mature engineering discipline over its first quarter-century, the vast majority of these efforts have focused on improving the design and performance of genetic circuits intended to operate in well-controlled, laboratory settings. The goal of safely deploying engineered microbes to reliably perform their programmed functions in natural, uncontrolled environments begets its own set of foundational challenges that will require new frameworks that shift our existing mindsets about the way we engineer biological systems.
\r\n\r\nThese frameworks, because they focus on enabling system properties that were not priorities for conventional synthetic biology research, can constitute a new field of research which I refer to as environmental synthetic biology. The central priorities of environmental synthetic biology include (1) developing and characterizing effective ways to introduce engineered biological systems into natural environments, (2) ensuring that the performance of these systems can remain robust and predictable in the face of environmental variability, (3) developing and characterizing ways to control and monitor the behavior of an engineered system after deployment in an inaccessible environment, and (4) developing fundamental architectures to enable autonomous system operation and adaptation within environmental contexts.
\r\n\r\nIn this thesis, I present the initial steps towards the development of three frame- works that address these priorities of environmental synthetic biology. The first framework, described in Chapter 2, demonstrates the potential of using DNA as the substrate for addressable and adaptable intercellular communication in engineered populations. This enables the ability to one day create multicellular systems that can autonomously reconfigure their own architecture in the face of changing environmental conditions. The second framework, described in Chapters 3 and 4, presents a new mathematical representation of biomolecular reaction systems that enables geometric bounds on the space of possible behaviors under all possible configurations for a particular system architecture. The third, ongoing framework emphasizes the importance of explicitly incorporating the physiological state of the host cell into the assessment of a genetic circuit\u2019s behavior by exploring the impact of cellular growth arrest on transcriptional response curves. The preliminary results of this work are presented in Chapter 5.
", "doi": "10.7907/h50w-p058", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:15071", "collection": "thesis", "collection_id": "15071", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12022022-073109279", "primary_object_url": { "basename": "2022_12_05_JTM_Thesis_v037.pdf", "content": "final", "filesize": 8086854, "license": "other", "mime_type": "application/pdf", "url": "/15071/1/2022_12_05_JTM_Thesis_v037.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Engineering and Rapid Prototyping for Biology in Extreme Conditions", "author": [ { "family_name": "Meyerowitz", "given_name": "Joseph Toshiro", "orcid": "0000-0002-3426-0885", "clpid": "Meyerowitz-Joseph-Toshiro" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-3426-0885", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Leadbetter", "given_name": "Jared R.", "orcid": "0000-0002-7033-0844", "clpid": "Leadbetter-J-R" }, { "family_name": "Newman", "given_name": "Dianne K.", "orcid": "0000-0003-1647-1918", "clpid": "Newman-D-K" }, { "family_name": "Phillips", "given_name": "Robert B.", "orcid": "0000-0003-3082-2809", "clpid": "Phillips-R" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "In this thesis we show three projects in which biological systems are engineered for increased robustness to environmental stressors such as toxic small molecules. Several lignocellulose-derived growth inhibitors commonly found in industrial feedstocks for fermentation were used to grow a panel of yeast knockouts for several efflux pumps and detoxifying enzymes. Some specific knockout strains showed slowed growth on specific growth inhibitors, while other knockout strains showed the same growth rate as the wild-type. One efflux pump was identified for vanillin, YHK8, and was overexpressed in yeast. The overexpression strain did not show an improved tolerance to vanillin, and grew more slowly than the wild-type. To regulate the expression of the vanillin pump, a sensor for vanillin was created. The starting enzyme was the wild-type qacR transcription factor, and several variants were generated using computational protein design. The designs were synthesized and tested using in vitro transcription-translation (TX-TL) as part of a rapid prototyping process. This rapid prototyping considerably sped up the design-build-test process. Finally, four bacteria, Pseudomonas synxantha 2-79, Pseudomonas chlororaphis PCL1391, Pseudomonas aureofaciens 30-84, and E. coli are tested against the same lignocellulose growth inhibitors. The Pseudomonas spp. show an improved tolerance to the growth inhibitors. We then develop some ability to engineer and prototype in all three species. A panel of promoter parts were integrated into the P. synxantha genome to produce a collection of test strains. These same promoter parts were also used as DNA templates for TX-TL reactions. The in vivo measurements of promoter strength and in vitro measurements show similar relative strengths between the parts, showing the Pseudomonas-based TX-TL systems can be used for design-build-test activities in these non-model organisms. This alternate approach to developing tolerance, starting with a species that already has a working tolerance to the stressor in question, changes the problem to one of building engineering capabilities in the new chassis.", "doi": "10.7907/9gbb-n831", "publication_date": "2023", "thesis_type": "phd", "thesis_year": "2023" }, { "id": "thesis:14455", "collection": "thesis", "collection_id": "14455", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12212021-193826426", "primary_object_url": { "basename": "Shur-Andrey-2021-thesis-final.pdf", "content": "final", "filesize": 4080541, "license": "other", "mime_type": "application/pdf", "url": "/14455/3/Shur-Andrey-2021-thesis-final.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Serine Integrase-Based Event Recording in E. coli", "author": [ { "family_name": "Shur", "given_name": "Andrey Sergeyvich", "orcid": "0000-0001-9372-6713", "clpid": "Shur-Andrey-Sergeyvich" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Elowitz", "given_name": "Michael B.", "orcid": "0000-0002-1221-0967", "clpid": "Elowitz-M-B" }, { "family_name": "Pierce", "given_name": "Niles A.", "orcid": "0000-0003-2367-4406", "clpid": "Pierce-N-A" }, { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "DNA is a unique molecule that has evolved to serve as the genetic material for life. It seems straightforward to consider this molecule not only as a wonder of the natural world but as a tool for information storage and retrieval. Bacteria have evolved to conserve DNA, but bacteriophages have evolved to specifically integrate their genomes using integrases. In response to viruses, bacteria have evolved the RNA-guided nuclease Cas9 to destroy viral DNA before it can be integrated. The fruits of these evolutionary pressures prove useful to the researcher interested in easily editing DNA. In this work, we have engineered a genetic circuit that can enact specific and controlled genetic changes in response to changing small molecule concentrations. Known DNA sequences can be repeatedly integrated into a synthetic array such that their identity and order encodes information about past small molecule concentrations that the cell has experienced. To accomplish this, we use catalytically inactive CRISPR-Cas9 (dCas9) to bind to and block attachment sites for the integrase Bxb1. Through the co-expression of dCas9 and guide RNA, Bxb1 can be directed to integrate one of two engineered \"ink\" plasmids, which correspond to two orthogonal small molecule inducers whose presence or absence as a function of time can be recorded with this system. Integrase sites present on these plasmids are found to not participate in intramolecular \"deletion\" reactions if closer than 100 bp. Guide RNAs overlapping integrase attachment sites are found to effectively block integrase activity at those sites if the overlap is equal to 9 or 19 base pairs. Other overlap values, including forward or reverse binding result in ineffective integrase activity repression. We develop 8 orthogonal guide RNA sequences capable of binding to and repressing integrase activity at the attP site. Plasmid multimers are sequenced using Oxford Nanopore sequencing and found to follow population-level predictions of event record identity. Single DNA states are found insufficient for identifying past history of events; an ensemble of DNA states at the population level must be used. A modular modeling framework is developed (Global enumeration) to describe this system, and integrated with the existing chemical reaction network creation automation software BioCRNpyler. The modeling framework developed here automatically creates chemical reaction networks based on typical linear DNA-based synthetic biology \"genetic constructs\" and predicts transcripts and proteins produced based on simple transcription/translation rules. Integrase-based recombination events can also be predicted in a recursive way.
", "doi": "10.7907/x4q0-nx18", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14467", "collection": "thesis", "collection_id": "14467", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01042022-184525578", "type": "thesis", "title": "Development and Scaling of Differentiation Circuit Architectures for Improving the Evolutionary Stability of Burdensome Functions in E. coli", "author": [ { "family_name": "Williams", "given_name": "Rory Logan", "orcid": "0000-0003-2605-5790", "clpid": "Williams-Rory-Logan" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Leadbetter", "given_name": "Jared R.", "orcid": "0000-0002-7033-0844", "clpid": "Leadbetter-J-R" }, { "family_name": "Goentoro", "given_name": "Lea A.", "orcid": "0000-0002-3904-0195", "clpid": "Goentoro-L-A" }, { "family_name": "Ismagilov", "given_name": "Rustem F.", "orcid": "0000-0002-3680-4399", "clpid": "Ismagilov-R-F" }, { "family_name": "Bois", "given_name": "Justin S.", "orcid": "0000-0001-7137-8746", "clpid": "Bois-J-S" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "With advances in the sequencing and synthesis of DNA, automation, and computation, we are increasingly able to rapidly and reliably program functions into cells. However, because the functions we engineer cells to perform are often both unnecessary for the cell\u2019s survival and burdensome to cell growth, mutation and natural selection can rapidly lead to loss of function. Though numerous strategies have made headway, improving the evolutionary stability of engineered functions remains a goal of the synthetic biology community. To address this problem generally, we developed a strategy relying on integrase-mediated recombination which allows non-producing progenitor cells to differentiate at a tunable rate, thereby continuously replenishing producer cells expressing the orthogonal T7 RNAP. While this strategy removes selective pressure for mutations inactivating the function of interest in the progenitor cell population, a strategy of terminal differentiation, in which the capacity of differentiated cells to grow is limited, was necessary to prevent the expansion of such mutations in the differentiated cell population. To experimentally implement terminal differentiation, we co-opted the R6K plasmid system, using differentiation to simultaneously activate expression of T7 RNAP, and inactivate expression of \u03c0 protein (an essential factor for R6K plasmid replication), thereby allowing limitation of differentiated cell growth through antibiotic selection. Critically, we demonstrated computationally that terminal differentiation endows the circuit with robustness to mutations which disrupt T7 RNAP driven expression, and to plasmid instability effects that result in decreased expression. Intuitively and computationally identifying the category of mutations which disrupt the differentiation process as the Achilles's heel of terminal differentiation, we developed a redundant architecture using a novel split-\u03c0 protein system which required 2 mutations to break the circuit. We experimentally demonstrated a trade-off between rate of production and duration of function as the differentiation rate is tuned, an increased benefit of terminal differentiation with higher-burden expression, and that redundancy improves the evolutionary stability of the terminal differentiation architecture. Specifically we achieve a maximum of ~2.8x (single-cassette terminal differentiation) and ~4.2x (redundant terminal differentiation) the total fluorescent protein production achieved from comparable high-burden naive expression in which all cells inducibly express T7 RNAP. We further demonstrate differentiation can enable the expression of even toxic functions, and develop a terminal differentiation circuit architecture which will allow the degree of redundancy and therefore the evolutionary stability of the architecture to be scaled to arbitrary degrees.
", "doi": "10.7907/5k67-b636", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14373", "collection": "thesis", "collection_id": "14373", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:09262021-022402778", "primary_object_url": { "basename": "clamons_sam_2021.pdf", "content": "final", "filesize": 16274905, "license": "other", "mime_type": "application/pdf", "url": "/14373/1/clamons_sam_2021.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Three Problems in the Design and Specification of Biomolecular Circuits", "author": [ { "family_name": "Clamons", "given_name": "Samuel Eric", "orcid": "0000-0002-7993-2278", "clpid": "Clamons-Samuel-Eric" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Winfree", "given_name": "Erik", "orcid": "0000-0002-5899-7523", "clpid": "Winfree-E" }, { "family_name": "Rothemund", "given_name": "Paul W. K.", "orcid": "0000-0002-1653-3202", "clpid": "Rothemund-P-W-K" }, { "family_name": "Goentoro", "given_name": "Lea A.", "orcid": "0000-0002-3904-0195", "clpid": "Goentoro-L-A" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Programming biological materials is a daunting challenge. Although part of this challenge is practical -- cloning is difficult, synthesizing DNA is expensive at scale, etc. -- a number of the challenges of bioengineering (and synthetic biology in particular) are problems of design and specification. If we could place arbitrary molecules on a surface with perfect precision, what should we place and where? If we could arbitrarily change the genetic content of a cell, even with perfect knowledge of the function and action of every component, what changes would actually enact the functions we want that cell to have? In this thesis, we explore three specific design and specification challenges at three different levels of abstraction, and demonstrate methods for overcoming them. On the level of design language, we use a specialized class of cellular automaton to probe what chemistry can do when restricted to a surface. On the level of \\textbf{part specification}, we use several models of CRISPR/Cas9-based transcriptional regulators to understand what dynamic functions those regulators can perform and why, and provide some some suggestions for how to engineer such regulators to more robustly perform those functions. On the level of module design, we consider an easy-to-encounter trap in when modeling a replicating DNA species in a CRN-based biocircuit simulation, for which we suggest a simple, flexible, biologically-plausible workaround.
", "doi": "10.7907/9b4h-8f95", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14424", "collection": "thesis", "collection_id": "14424", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:11102021-210013472", "type": "thesis", "title": "Compilation and Inference with Chemical Reaction Networks", "author": [ { "family_name": "Poole", "given_name": "William", "orcid": "0000-0002-2958-6776", "clpid": "Poole-William" } ], "thesis_advisor": [ { "family_name": "Winfree", "given_name": "Erik", "orcid": "0000-0002-5899-7523", "clpid": "Winfree-E" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Thomson", "given_name": "Matthew", "orcid": "0000-0003-1021-1234", "clpid": "Thomson-M-W" }, { "family_name": "Winfree", "given_name": "Erik", "orcid": "0000-0002-5899-7523", "clpid": "Winfree-E" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Phillips", "given_name": "Robert B.", "orcid": "0000-0003-3082-2809", "clpid": "Phillips-R" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "The successful advancement and deployment of technologies in the field of synthetic biology will require sophisticated computational infrastructure coupled with new theoretical ideas in order to more effectively engineer and reverse engineer biochemical networks. This thesis argues that the field of machine learning can inform the development of these underlying principles and techniques. First, software for compiling diverse chemical reaction network models of biological circuits from simple specifications is described. Second, three chemical reaction network implementations of a powerful machine learning model called a Boltzmann machine are analyzed and compared. Third, the class of detailed balanced chemical reaction networks are proven to be capable of probabilistic inference and, when coupled to a driven chemical system, autonomous learning. Finally, the use of machine learning to interpret and understand biological systems is explored in an experimental case study modeling E. coli cell extract metabolism.
", "doi": "10.7907/x3qc-je74", "publication_date": "2022", "thesis_type": "phd", "thesis_year": "2022" }, { "id": "thesis:14115", "collection": "thesis", "collection_id": "14115", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04022021-033321217", "type": "thesis", "title": "Safe and Interpretable Autonomous Systems Design: Behavioral Contracts and Semantic-Based Perception", "author": [ { "family_name": "Cai", "given_name": "Karena Xin", "orcid": "0000-0002-8392-4158", "clpid": "Cai-Karena-Xin" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Chung", "given_name": "Soon-Jo", "orcid": "0000-0002-6657-3907", "clpid": "Chung-Soon-Jo" } ], "thesis_committee": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Chung", "given_name": "Soon-Jo", "orcid": "0000-0002-6657-3907", "clpid": "Chung-Soon-Jo" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "We are on the verge of experiencing a new, integrated society where autonomous vehicles will become a fabric of our everyday lives. And yet, seamless integration of autonomous vehicles into our society will require vehicles to interface safely with humans in an incredibly complex, fast-paced, and dynamic environment. Premature deployment of these new autonomous systems \u2014 without safety guarantees or interpretability of algorithms, could prove catastrophic. How can algorithms governing vehicle behavior be designed in a way that guarantees safety, performance, interpretability and scalability? This is the question this thesis seeks to answer.
\r\n\r\nFirst, we present a framework for architecting the decision-making module of autonomous vehicles so that safety and progress of agents can be formally guaranteed. In particular, all agents are defined to act according to what is termed an assume-guarantee contract, which is broadly defined as a set of behavioral preferences. The first version of the assume-guarantee contract is a behavioral profile, which is a set of ordered rules that agents must use to select actions in a way that is interpretable. With all agents operating according to a behavioral profile, the interactions however, are not necessarily coordinated. We then constrain agent behavior with an additional set of interaction rules. The behavioral profile combined with these additional constraints, are what we term a behavioral protocol. With all agents operating according to a local, decentralized behavioral protocol, we can provide formal proofs of the correctness of agent behavior, i.e. all agents will never collide and agents will make it to their respective destinations. Not only does the protocol so\u00a0defined allow us to make formal guarantees, but it is also designed in a way that scales well in the number of agents and provides interpretability of agent\u00a0behaviors. Safety and progress guarantees are proven and verified in simulation.
\r\n\r\nSecond, we focus on using information from object classifiers to enhance an autonomous vehicle's ability to localize where it is within its environment. The proposed approach for incorporating this semantic information is based on solving the maximum likelihood problem. With a hierarchical formulation, we are not only able to improve upon the accuracy of traditional localization techniques, but we are also able to improve our confidence in the accuracy of object detection classifications. The improvement in robustness and accuracy of these algorithms are shown in simulation.
", "doi": "10.7907/w3m8-es32", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14138", "collection": "thesis", "collection_id": "14138", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05082021-185615529", "primary_object_url": { "basename": "McCardellReed2021thesis.pdf", "content": "final", "filesize": 7370942, "license": "other", "mime_type": "application/pdf", "url": "/14138/7/McCardellReed2021thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Genetic Circuits for the Control of Multi-Strain Bacterial Populations", "author": [ { "family_name": "McCardell", "given_name": "Reed Dillard", "orcid": "0000-0002-0955-3133", "clpid": "McCardell-Reed-Dillard" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Pierce", "given_name": "Niles A.", "orcid": "0000-0003-2367-4406", "clpid": "Pierce-N-A" }, { "family_name": "Orphan", "given_name": "Victoria J.", "orcid": "0000-0002-5374-6178", "clpid": "Orphan-V-J" }, { "family_name": "Ismagilov", "given_name": "Rustem F.", "orcid": "0000-0002-3680-4399", "clpid": "Ismagilov-R-F" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Microbial species rarely exist alone. Nearly everywhere you could think to look, microorganisms of various species live together in harmony. Microbes together in their communities are incredibly powerful actors wherever they are found; they perform small miracles---the conversion of milk into yogurt---and large ones---production of most of the planet's oxygen and organic carbon.
\r\n\r\nOur burgeoning knowledge of microbial life combined with modern technologies to manipulate it create a critical, exciting opportunity to harness microbial power for the betterment of technology, people, and the planet. This thesis presents a body of work which explores the manipulation of microbial communities using the intersectional bio-engineering approach of synthetic biology. We demonstrate how molecular tools evolved by bacteria can be repurposed to create rationally designed systems for controlling features of bacterial populations.
\r\n\r\nWe begin by examining a genetic circuit that caps the size of a bacterial population by coordinating the deaths of population members -- the population capping or \"pop cap\" circuit. Briefly, E. coli cells in the pop cap circuit are engineered to synthesize a chemical -- a quorum sensing (QS) signal -- that reports the density of the population, sense this chemical, and produce the ccdB toxin to destroy themselves in response. The molecular tools that make up this circuit are drawn from organisms across the spectrum of bacterial diversity. Brought together, they create a feedback control circuit that controls population size by causing member cells to die when a target population size has been reached. To improve the performance of this population controller and reduce the influence of the environment on the circuit, we add the aiiA quorum sensing signal degradase to allow the experimenter control over the degradation rate of the QS density signal. Additionally, we explore RNA and protein mechanisms to sequester the death-causing toxin---inactivating it---allowing us to release a population cap. The resulting \"cap and release\" circuit is a flexible motif that can be scaled to control multi-strain populations, expanding the scope of control beyond the single-strain populations regulated by the base pop cap circuit.
\r\n\r\nUsing the scalable cap and release motif, we design a genetic circuit to regulate a multi-strain community. Two different cell strains expressing symmetric, interconnected cap and release systems form the \"A=B\" circuit, so named for its ability to control the composition of the community to a target ratio of A cells to B cells, or Apopulation = \u03b1Bpopulation. Through dynamical system models of the system, we explore the effects of active QS signal degradation on composition control performance and perform a parameter sensitivity analysis of the system to help determine the best method for building a functioning A=B system in the laboratory. We use a high throughput construction and screening protocol to create variants of the A=B system with identical architectures, but slightly differing component production rates. We crown the most successful variant with a series of experiments to determine if it indeed recapitulates our model's predictions for its performance. Our implementation of the A=B circuit can successfully regulate the composition of a community, with interesting additional effects on total population density.
\r\n\r\nThe cap and release and A=B circuits need parts that can do three things: 1) send a signal between cells to communicate information, 2) compare two signals, 3) regulate cell growth or death. We highlight bacteriocins, bacterial protein exotoxins that are released from a producer cell to kill other cells of similar species, as attractive tools for bacterial community engineering both for their multi-functionality and modular protein structure. By themselves, bacteriocins can perform all the functions needed for population control: they transmit themselves between cells, have unique high-affinity sequestering antitoxin proteins, and are toxins to receiver cells. We begin the process of their characterization and usage as synthetic biological \"parts\" by creating non-native expression systems that match native expression strengths. Using these experimenter-controlled systems we design preliminarily test a bacteriocin-based bacterial community control circuit. Additionally, given the E. coli colicin bacteriocins' unique, nearly plug-and-play modular domain structure, we explore possibilities for engineering colicin proteins themselves for increased functional diversity or uses outside of growth regulation.
", "doi": "10.7907/wgpp-vj97", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14052", "collection": "thesis", "collection_id": "14052", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:01132021-065636010", "primary_object_url": { "basename": "Tung Phan Caltech Thesis.pdf", "content": "final", "filesize": 7424375, "license": "other", "mime_type": "application/pdf", "url": "/14052/1/Tung Phan Caltech Thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Contract-Based Design: Theories and Applications", "author": [ { "family_name": "Phan-Minh", "given_name": "Tung", "orcid": "000-0002-1403-5197", "clpid": "Phan-Minh-Tung" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" }, { "family_name": "Doyle", "given_name": "John Comstock", "orcid": "0000-0002-1828-2486", "clpid": "Doyle-J-C" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Most things we know only exist in relation to one another. Their states are strongly coupled due to dependencies that arise from such relations. For a system designer, acknowledging the presence of these dependencies is as crucial to guaranteeing performance as studying them. As the roles played by technology in fields such as transportation, healthcare, and finance continue to be more profound and diverse, modern engineering systems have grown to be more reliant on the integration of technologies across multiple disciplines and their requirements. The need to ensure proper division of labor, integration of system modules, and attribution of legal responsibility calls for a more methodological look into co-design considerations. Originally conceived in computer programming, contract-based reasoning is a design approach whose promise of a formal compositional paradigm is receiving attention from a broader engineering community. Our work is dedicated to narrowing the gap between the theory and application of this yet nascent framework.
\r\n\r\nIn the first half of this dissertation, we introduce a model interface contract theory for input/output automata with guards and a formalization of the directive-response architecture using assume-guarantee contracts and show how these may be used to guide the formal design of a traffic intersection and an automated valet parking system respectively. Next, we address a major drawback of assume-guarantee contracts, i.e., the problem of a void contract due to antecedent failure. Our proposed solution is a reactive version of assume-guarantee contracts that enables direct specification at the assumption and guarantee level along with a novel synthesis algorithm that exposes the effects of failures on the contract structure. This is then used to help optimize, adapt, and robustify our design against an uncertain environment.
\r\n\r\nIn light of ongoing development of autonomous driving technologies and its potential impact on the safety of future transportation, the second half of this work is dedicated to the application of the design-by-contract framework to the distributed control of autonomous vehicles. We start by defining and proving properties of \"assume-guarantee profiles,\" our proposed approach to transparent distributed multi-agent decision making and behavior prediction. Next, we provide a local conflict resolution algorithm in the context of a quasi-simultaneous game which guarantees safety and liveness to the composition of autonomous vehicle systems in this game. Finally, to facilitate the extension of these frameworks to real-life urban driving settings, we also supply an effective method to predict agent behavior that utilizes recent advances in machine learning research.
", "doi": "10.7907/8vp7-kd82", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14111", "collection": "thesis", "collection_id": "14111", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03262021-160841703", "primary_object_url": { "basename": "thesis.pdf", "content": "final", "filesize": 3545856, "license": "other", "mime_type": "application/pdf", "url": "/14111/1/thesis.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Signal Amplification in Synthetic Bacterial Communication", "author": [ { "family_name": "Parkin", "given_name": "James Michael", "orcid": "0000-0002-4058-2338", "clpid": "Parkin-James-Michael" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Winfree", "given_name": "Erik", "orcid": "0000-0002-5899-7523", "clpid": "Winfree-E" }, { "family_name": "Leadbetter", "given_name": "Jared R.", "orcid": "0000-0002-7033-0844", "clpid": "Leadbetter-J-R" }, { "family_name": "Bois", "given_name": "Justin S.", "orcid": "0000-0001-7137-8746", "clpid": "Bois-J-S" }, { "family_name": "Thomson", "given_name": "Matthew", "orcid": "0000-0003-1021-1234", "clpid": "Thomson-M-W" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Synthetic biology will one day enable embedded control of a variety of chemical and biological contexts, from the human gastrointestinal tract to crop roots. Groups of engineered organisms, also known as synthetic consortia, can inhabit niches of interest while monitoring and intervening according to their genetic design. However, the spatial structure of the deployment environments can obstruct coordination between cosortia members. The mechanisms engineered bacteria use to communicate must contend with these adversarial conditions to maximize group performance.
\r\n\r\nCoordination between synthetic bacteria is typically achieved using small molecules that can traverse cell membranes through passive transport. Cell communicate by producing and sensing these small molecules. In cell-cell signaling relationships composed of a sender population and a receiver population, the concentration of signaling molecule sensed by the receiver cells depends on the spatial patterning of the two groups, the geometry of the diffusive environment, and the sender population\u2019s signal secretion rate.
\r\n\r\nTo make sender-receiver communication more robust to these environmental features, we introduce a third consortium strain that transiently amplifies local signaling molecule concentrations. These amplifier cells employ a synchronized pulse-generating circuit built using Lux-type quorum sensing components and an IFFL transcriptional architecture. When applied to sender-receiver consortia growing on semi-solid media, these amplifier cells respond to sender-secreted signaling molecules by contributing a small amount themselves. The support of amplifier cells enables communication over longer distances than can be achieved by sender cells alone and can partially recover coordination in small consortia where the sender population is too small to successfully signal its receiver population alone. We extend these results using simulation to investigate the benefit that amplifier cells confer to consortia of varying complexity.
", "doi": "10.7907/50p8-bd89", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14175", "collection": "thesis", "collection_id": "14175", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05262021-072231177", "primary_object_url": { "basename": "Ren_Caltech_Thesis_v2.pdf", "content": "final", "filesize": 7116984, "license": "other", "mime_type": "application/pdf", "url": "/14175/1/Ren_Caltech_Thesis_v2.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Principles for Designing Robust and Stable Synthetic Microbial Consortia", "author": [ { "family_name": "Ren", "given_name": "Xinying (Cindy)", "orcid": "0000-0002-8852-6722", "clpid": "Ren-Xinying-Cindy" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Doyle", "given_name": "John Comstock", "orcid": "0000-0002-1828-2486", "clpid": "Doyle-J-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" }, { "family_name": "Pierce", "given_name": "Niles A.", "orcid": "0000-0003-2367-4406", "clpid": "Pierce-N-A" }, { "family_name": "Franco", "given_name": "Elisa", "clpid": "Franco-Elisa" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Engineering stable microbial consortia with robust functions are useful in many areas, including bioproduction and human health. Robust and stable properties depend on proper control of dynamics ranging from single cell-level to population-environment interactions. In this thesis, I discuss principles of building microbial consortia with synthetic circuits in two design scenarios.
\r\n\r\nFirst, for one microbial population, strong disturbances in environments often severely perturb cell states and lead to heterogeneous responses. Single cell-level design of control circuits may fail to induce a uniform response as needed. I demonstrate that cell-cell signaling systems can facilitate coordination among cells and achieve robust population-level behaviors. Moreover, I show that heterogeneity can be harnessed for robust adaptation at population-level via a bistable state switch.
\r\n\r\nSecond, multi-pecies consortia are intrinsically unstable due to competitive exclusion. Previous theoretical investigations based on models of pairwise interactions mainly explored what interaction network topology ensures stable coexistence. Yet neglecting detailed interaction mechanisms and spatial context results in contradictory predictions. Focusing on chemical-mediated interaction, I show that detailed mechanisms of chemical consumption/accumulation and chemical-induced growth/death, interaction network topology and spatial structures of environments all are critical factors to maintain stable coexistence. With a two population-system, I demonstrate that the same interaction network topology can exhibit qualitatively different or even opposite behaviors due to interaction mechanisms and spatial conditions.
", "doi": "10.7907/hc8x-3280", "publication_date": "2021", "thesis_type": "phd", "thesis_year": "2021" }, { "id": "thesis:14245", "collection": "thesis", "collection_id": "14245", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06042021-234419803", "primary_object_url": { "basename": "Liana_Merk_CDS_Senior_Thesis_Final.pdf", "content": "final", "filesize": 26069740, "license": "other", "mime_type": "application/pdf", "url": "/14245/1/Liana_Merk_CDS_Senior_Thesis_Final.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Engineering Logical Inflammation Sensing and Secreting Circuit for Gut Modulation", "author": [ { "family_name": "Merk", "given_name": "Liana Noor", "orcid": "0000-0001-9711-954X", "clpid": "Merk-Liana-Noor" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "None", "given_name": "None" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The mammalian gut contains trillions of microbes that interact with host cells and monitor changes in the environment. Opportunistic pathogens exploit environmental conditions to stimulate their growth and virulence, leading to a resurgence of chronic disorders such as inflammatory bowel disease (IBD). Current therapies are effective in less than 30% of patients due to the lack of adherence to prescription schedules and overall, off-target effects. Microbial therapeutics can be engineered to colonize the gut, providing in situ surveillance and conditional disease modulation. However, many current engineered microbes can only respond to single gut environmental factors, limiting their effectiveness. In this work, we implement a previously characterized split activator AND logic gate in the probiotic E. coli strain Nissle 1917. Our system can respond to two input signals: the inflammatory biomarker tetrathionate and a second input signal, IPTG or aTC. We report 4-6 fold induction with minimal leak when both signals are present. We model the dynamics of the AND gate using chemical reaction networks, and by tuning parameters in silico, we identified perturbations that affect our circuit\u2019s selectivity. We then engineer our optimized AND gate to secrete an anti-inflammatory therapeutic cytokine, IL-22, using the hemolysin secretion pathway. We anticipate that our results will prove useful for designing living therapeutics for spatial targeting and signal processing in complex environments.
", "doi": "10.7907/wr7s-6436", "publication_date": "2021", "thesis_type": "senior_major", "thesis_year": "2021" }, { "id": "thesis:14247", "collection": "thesis", "collection_id": "14247", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06052021-045112334", "type": "thesis", "title": "Understanding the Lifetime and Rate of Protein Production in Cell-Free Reactions While Maximizing Energy Use", "author": [ { "family_name": "Roychoudhury", "given_name": "Ankita", "clpid": "Roychoudhury-Ankita" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "None", "given_name": "None" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Liposomes, or vesicles, offer promising applications in fields including biofuel synthesis, drug delivery, and toxin removal. Programmable liposomes can be used for optimal protein synthesis and to prototype genetic technologies. However, one of the major challenges is the short lifetime of protein production. Here, we add metabolites and molecules to cell-free reactions at different times to interrogate their importance. Through this testing, we find that ATP only slightly enhances protein synthesis, and ADP can help a reaction reach steady state faster. We also note that the excess of particular molecules, such as NAD and 3PGA, can halt protein production. With this data, we developed a more accurate chemical reaction network-based model for cell-free reactions. We also begin to study an unexplained discrepancy in protein production between bulk and vesicle dynamics. To quantify protein synthesis, we use E. coli extract and energy buffer, often called cell-free transcription and translation (TXTL), with a chosen DNA template both within vesicles (encapsulated) and without (bulk). We have also been able to uncover fundamental properties of transcription/translation systems. We supplement this data with computational models utilizing chemical reaction networks. We established a vesicle setup with membrane pores and supplemental energy buffer on the outside which increased the efficiency of protein synthesis. By using chemical reaction network models, we have highlighted differences and similarities between models and experiments. With this setup, vesicles can be used for more complicated applications, such as drug delivery or genetic construct testing.", "doi": "10.7907/94ms-b419", "publication_date": "2021", "thesis_type": "senior_minor", "thesis_year": "2021" }, { "id": "thesis:13689", "collection": "thesis", "collection_id": "13689", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04292020-165136662", "type": "thesis", "title": "Scalable Synthesis and Verification: Towards Reliable Autonomy", "author": [ { "family_name": "Dathathri", "given_name": "Sumanth", "clpid": "Dathathri-Sumanth" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" }, { "family_name": "Gao", "given_name": "Sicun", "clpid": "Gao-Sicun" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "We have seen the growing deployment of autonomous systems in our daily life, ranging from safety-critical self-driving cars to dialogue agents. While impactful and impressive, these systems do not often come with guarantees and are not rigorously evaluated for failure cases. This is in part due to the limited scalability of tools available for designing correct-by-construction systems, or verifying them posthoc. Another key limitation is the lack of availability of models for the complex environments with which autonomous systems often have to interact with. In the direction of overcoming these above mentioned bottlenecks to designing reliable autonomous systems, this thesis makes contributions along three fronts.
\r\n\r\nFirst, we develop an approach for parallelized synthesis from linear-time temporal logic Specifications corresponding to the generalized reactivity (1) fragment. We begin by identifying a special case corresponding to singleton liveness goals that allows for a decomposition of the synthesis problem, which facilitates parallelized synthesis. Based on the intuition from this special case, we propose a more generalized approach for parallelized synthesis that relies on identifying equicontrollable states.
\r\n\r\nSecond, we consider learning-based approaches to enable verification at scale for complex systems, and for autonomous systems that interact with black-box environments. For the former, we propose a new abstraction refinement procedure based on machine learning to improve the performance of nonlinear constraint solving algorithms on large-scale problems. For the latter, we present a data-driven approach based on chance-constrained optimization that allows for a system to be evaluated for specification conformance without an accurate model of the environment. We demonstrate this approach on several tasks, including a lane-change scenario with real-world driving data.
\r\n\r\nLastly, we consider the problem of interpreting and verifying learning-based components such as neural networks. We introduce a new method based on Craig's interpolants for computing compact symbolic abstractions of pre-images for neural networks. Our approach relies on iteratively computing approximations that provably overapproximate and underapproximate the pre-images at all layers. Further, building on existing work for training neural networks for verifiability in the classification setting, we propose extensions that allow us to generalize the approach to more general architectures and temporal specifications.
", "doi": "10.7907/4j39-v857", "publication_date": "2020", "thesis_type": "phd", "thesis_year": "2020" }, { "id": "thesis:11129", "collection": "thesis", "collection_id": "11129", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07202018-115217471", "primary_object_url": { "basename": "filippidis_ioannis_2019.pdf", "content": "final", "filesize": 700365, "license": "other", "mime_type": "application/pdf", "url": "/11129/39/filippidis_ioannis_2019.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Decomposing Formal Specifications Into Assume-Guarantee Contracts for Hierarchical System Design", "author": [ { "family_name": "Filippidis", "given_name": "Ioannis", "orcid": "0000-0003-4704-3334", "clpid": "Filippidis-Ioannis" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" }, { "family_name": "Holzmann", "given_name": "Gerard J.", "clpid": "Holzmann-G-J" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Specifications for complex engineering systems are typically decomposed into specifications for individual subsystems in a way that ensures they are implementable and simpler to develop further. We describe a method to algorithmically construct specifications for components that should 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.\r\nTo identify these variables, we parametrize the information flow between components.
\r\n\r\n\r\nThe specifications are written in the Temporal Logic of Actions, TLA+, with liveness properties restricted to an implication of conjoined recurrence properties, known as GR(1). We study whether GR(1) contracts exist in the presence of full information, and prove that memoryless GR(1) contracts that preserve safety do not always exist, whereas contracts in GR(1) with history-determined variables added do exist. We observe that timed stutter-invariant specifications of open-systems in general require GR(2) liveness properties for expressing them.
\r\n\r\n\r\nWe formalize a definition of realizability in TLA+, and define an operator for forming open-systems from closed-systems, based on a variant of the while-plus operator. The resulting open-system properties are realizable when expected to be. We compare stepwise implication operators from the literature, and establish relations between them, and examine the arity required for expressing these operators. We examine which symmetric combinations of stepwise implication and implementation kind avoid circular dependence, and show that only Moore components specified by strictly causal stepwise implication avoid circular dependence.
\r\n\r\n\r\nThe proposed approach relies on symbolic algorithms for computing specifications. To convert the generated specifications from binary decision diagrams to readable formulas over integer variables, we symbolically solve a minimal covering problem. We implemented an algorithm for minimal covering over lattices originally proposed for two-level logic minimization. We formalized the computation of essential elements and cyclic core that is part of this algorithm, and machine-checked the proofs of safety properties using a proof assistant. Proofs supporting the thesis are organized as TLA+ modules in appendices.
", "doi": "10.7907/Z9Q52MTD", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:11161", "collection": "thesis", "collection_id": "11161", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08262018-213846283", "primary_object_url": { "basename": "vipul_singhal_thesis_2018.pdf", "content": "final", "filesize": 5525152, "license": "other", "mime_type": "application/pdf", "url": "/11161/1/vipul_singhal_thesis_2018.pdf", "version": "v8.0.0" }, "type": "thesis", "title": "Modeling, Computation, and Characterization to Accelerate the Development of Synthetic Gene Circuits in Cell-Free Extracts", "author": [ { "family_name": "Singhal", "given_name": "Vipul", "orcid": "0000-0003-1670-1824", "clpid": "Singhal-Vipul" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Winfree", "given_name": "Erik", "clpid": "Winfree-E" }, { "family_name": "Goentoro", "given_name": "Lea A.", "clpid": "Goentoro-L-A" }, { "family_name": "Thomson", "given_name": "Matthew", "clpid": "Thomson-M-W" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Synthetic biology may be defined as an attempt at using engineering principles to design and build novel biological functionalities. An important class of such functionalities involves the bottom up design of genetic networks (or 'circuits') to control cellular behavior. Performing design iterations on these circuits in vivo is often a time consuming process. One approach that has been developed to address these long design times is to use E. coli cell extracts as simplified circuit prototyping environments. The analogy with similar approaches in engineering, such as prototyping using wind tunnels and breadboards, may be extended by developing accompanying computer aided design tools. In this thesis, we discuss the development of computational and mathematical tools to accelerate circuit prototyping in the TX-TL cell free prototyping platform, and demonstrate some applications of these tools.
\r\n\r\nWe start by discussing the problem of reducing circuit behavior variability between different batches of TX-TL cell extracts. To this end, we demonstrate a model-based methodology for calibrating extract batches, and for using the calibrations to 'correct' the behavior of genetic circuits between batches. We also look at the interaction of this methodology with the phenomenon of parameter non-identifiability, which occurs when the parameter identification inverse problem has multiple solutions. In particular, we derive conditions under which parameter non-identifiability does not hinder our modeling objectives, and subsequently demonstrate the use of such non-identifiable models in performing data variability reduction.
\r\n\r\nNext, we describe txtlsim, a MATLAB Simbiology based toolbox for automatically generating models of genetic circuits in TX-TL, and for using these models for part characterization and circuit behavior prediction. Large genetic circuits can have non-negligible resource usage needs, leading to unintended interactions between circuit nodes arising due to the loading of cellular machinery, transcription factors or other regulatory elements. The usage of consumable resources like nucleotides and amino acids can also have non-trivial effects on complex genetic circuits. These types of effects are handled by the modeling framework of txtlsim in a natural way.
\r\n\r\nWe also highlight mcmc-simbio, a smaller toolbox within txtlsim for performing concurrent Bayesian parameter inference on Simbiology models. Concurrent inference here means that a common set of parameters can be identified using data from an ensemble of different circuits and experiments, with each experiment informing a subset of the parameters. The combination of the concurrence feature with the fact that Markov chain Monte Carlo based Bayesian inference methods allow for the direct visualization of parameter non-identifiability enables the design of ensembles of experiments that reduce such non-identifiability.
\r\n\r\nFinally, we end with a method for performing model order reduction on transcription and translation elongation models while maintaining the ability of these models to track resource consumption. We show that due to their network topology, our models cannot be brought into the two-timescale form of singular perturbation theory when written in species concentration coordinates. We identify a coordinate system in which singular perturbation theory may be applied to chemical reaction networks more naturally, and use this to achieve the desired model reduction.
", "doi": "10.7907/g31j-ch52", "publication_date": "2019", "thesis_type": "phd", "thesis_year": "2019" }, { "id": "thesis:10543", "collection": "thesis", "collection_id": "10543", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10242017-193520989", "primary_object_url": { "basename": "fragoso_anthony_2018.pdf", "content": "final", "filesize": 12857622, "license": "other", "mime_type": "application/pdf", "url": "/10543/1/fragoso_anthony_2018.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Egospace Motion Planning Representations for Micro Air Vehicles", "author": [ { "family_name": "Fragoso", "given_name": "Anthony Thomas", "orcid": "0000-0002-5805-9668", "clpid": "Fragoso-Anthony-Thomas" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "McKeon", "given_name": "Beverley J.", "clpid": "McKeon-B-J" }, { "family_name": "Chung", "given_name": "Soon-Jo", "clpid": "Chung-Soon-Jo" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Matthies", "given_name": "Larry H.", "clpid": "Matthies-L-H" } ], "local_group": [ { "literal": "GALCIT" }, { "literal": "div_eng" } ], "abstract": "Navigation of micro air vehicles (MAVs) in unknown environments is a complex sensing and trajectory generation task, particularly at high velocities. In this work, we introduce an efficient sense-and-avoid pipeline that compactly represents range measurements from multiple sensors, trajectory generation, and motion planning in a 2.5\u2013dimensional projective data structure called an egospace representation. Egospace coordinates generalize depth image obstacle representations and are a particularly convenient choice for configuration flat mobile robots, which are differentially flat in their configuration variables and include a number of commonly used MAV plant models. After characterizing egospace obstacle avoidance for robots with trivial dynamics and establishing limits on applicability and performance, we generalize to motion planning over full configuration flat dynamics using motion primitives expressed directly in egospace coordinates. In comparison to approaches based on world coordinates, egospace uses the natural sensor geometry to combine the benefits of a multi-resolution and multi-sensor representation architecture into a single simple and efficient layer.\r\nWe also present an experimental implementation, based on perception with stereo vision and an egocylinder obstacle representation, that demonstrates the specialization of our theoretical results to particular mission scenarios. The natural pixel parameterization of the egocylinder is used to quickly identify dynamically feasible maneuvers onto radial paths, expressed directly in egocylinder coordinates, that enable finely detailed planning at extreme ranges within milliseconds. We have implemented our obstacle avoidance pipeline with an Asctec Pelican quadcopter, and demonstrate the efficiency of our approach experimentally with a set of challenging field scenarios. The scalability potential of our system is discussed in terms of sensor horizon, actuation, and computational limitations and the speed limits that each imposes, and its generality to more challenging environments with multiple moving obstacles is developed as an immediate extension to the static framework.", "doi": "10.7907/Z9GX48RJ", "publication_date": "2018", "thesis_type": "phd", "thesis_year": "2018" }, { "id": "thesis:10401", "collection": "thesis", "collection_id": "10401", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08302017-121452132", "type": "thesis", "title": "Engineering Biosynthetic Pathways in Cell-Free Systems for Sustainability and Chemical Innovation\r ", "author": [ { "family_name": "Wu", "given_name": "Yong Yi", "orcid": "0000-0002-5401-3662", "clpid": "Wu-Yong-Yi" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Tirrell", "given_name": "David A.", "clpid": "Tirrell-D-A" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "clpid": "Shapiro-M-G" }, { "family_name": "Culler", "given_name": "Stephanie J.", "clpid": "Culler-S-J" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "This work presents the cell-free transcription-translation (TX-TL) system as a research and development platform for renewable synthesis and molecular discovery. TX-TL is easy to use and provides a biomolecular breadboard for the rapid prototyping and engineering of biosynthetic pathways. This work has validated the capabilities of the cell-free TX-TL system for simultaneous protein expression and chemical synthesis. Specifically, this work shows that TX-TL supports the conversion of intermediates from carbohydrate metabolism and amino acids into valuable compounds. Metabolic flux through cofactor dependent pathways confirms that active cofactor metabolism is occurring in TX-TL. This work has also demonstrated the industrial relevance of TX-TL through exploring design space of a biosynthetic pathway for improved product yield and expanding substrate scope of another biosynthetic pathway.
\r\n\r\nCurrent methods for assembling biosynthetic pathways in microorganisms require a process of repeated trial and error and have long design-build-test cycles. We describe the use of a cell-free transcription-translation (TX-TL) system as a biomolecular breadboard for the rapid engineering of the 1,4-butanediol (BDO) pathway. In this work, we have verified enzyme expression and enzyme activity and identified the conversion of 4-hydroxybutyrate to downstream metabolites as the pathway bottleneck. We demonstrate the reliability of using linear DNA in TX-TL as a tool for engineering biological systems by undertaking a careful characterization of its transcription and translation capabilities and provide a detailed analysis of its metabolic output. Pathway constructs of varying pathway enzyme expression levels are tested in TX-TL and in vivo to identify correlations between the two systems, and we find that the production of BDO is correlated to the expression of enzyme ald in both systems. The use of TX-TL to survey the design space of the BDO pathway enables rapid tuning of pathway enzyme expression levels for improved product yield. Different pathway combinations are also tested in TX-TL for its application in pathway ranking. Leveraging TX-TL to screen enzyme variants for improved catalytic activity accelerates design iterations that can be directly applied to in vivo strain development.
\r\n\r\nTX-TL simulates a customizable cellular environment that can be controlled by manipulating pH, changing cellular components, or adding exogenous substrates. By adding linear DNA encoding individual enzymes of the violacein pathway and tryptophan analogs in TX-TL reactions, we have discovered new violacein analogs. TX-TL enables rapid production of natural product analogs with diverse substitution, which allows small-scale biosynthesis of potential drug candidates and offers a new platform for drug discovery. This work also presents TX-TL as a platform for protein engineering. Residues targeted for site-saturated mutagenesis were identified with protein-ligand docking. Linear DNAs of individual enzyme mutants were added into TX-TL reactions to screen for improved enzyme variant. Screening result indicates vioE mutant Y17H reduces byproduct formation and redirects metabolic flux towards target metabolites. Protein engineering for improved enzyme activity can further expand the substrate scope of a natural product pathway and result with more natural product analogs that can be applied for medical applications.
\r\n\r\nThis work demonstrates that the cell-free TX-TL system can become a valuable tool that complements the process of engineering biosynthesis in the whole cell in vivo system or the purified protein in vitro system. Future engineering and development of the TX-TL system can further expand the chemical space for biosynthesis.
\r\n", "doi": "10.7907/Z99W0CN1", "publication_date": "2018", "thesis_type": "phd", "thesis_year": "2018" }, { "id": "thesis:10606", "collection": "thesis", "collection_id": "10606", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12132017-121914940", "type": "thesis", "title": "Application, Computation, and Theory for Synthetic Gene Circuits", "author": [ { "family_name": "Swaminathan", "given_name": "Anandh", "orcid": "0000-0001-9935-6530", "clpid": "Swaminathan-Anandh" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Elowitz", "given_name": "Michael B.", "clpid": "Elowitz-M-B" }, { "family_name": "Goentoro", "given_name": "Lea A.", "clpid": "Goentoro-L-A" }, { "family_name": "Beck", "given_name": "James L.", "clpid": "Beck-J-L" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The field of synthetic gene circuits is concerned with engineering novel gene expression dynamics into organisms. This field, a subset of synthetic biology, was started almost two decades ago with the creation of two synthetic circuits: a bistable toggle switch and an oscillator. From the very outset, modeling has played a role in the development of synthetic circuits. However, modeling has been used to gain qualitative insight into dynamics, and actual quantitative modeling has been lagging behind.
\r\n\r\nParameters for quantitative models for biological systems often cannot be adequately estimated from measured data, because far too many sets of parameters can produce the same set of limited measured outputs. Additionally, models for synthetic gene circuits are often not correct the first time, and iterating on cycles of modeling and parameter estimation is difficult. Finally, there is a gap between development of modeling and system identification tools and their application to experiments on actual synthetic gene circuits.
\r\n\r\nThis thesis attempts to work towards addressing these issues with quantitative modeling for synthetic gene circuits. First, we derive theoretical conditions for identifiability of stochastic linear systems from heterogenous types of measurement data. These identifiability conditions can provide insight into what type of model to use and what measurements to collect in order to ensure that the resulting model can be identified.
\r\n\r\nSecond, we develop a software package for fast and flexible modeling and parameter estimation for synthetic gene circuits. The user can input models into our software using a simple text format and perform simulations of all types at optimized speeds. By inputting measured experimental data along with the model, the software can be used to perform Bayesian parameter estimation in an automated manner. To bridge the gap between computation and application, we apply this software to parameter estimation of DNA recombinase dynamics using real experimental data collected in an in vitro cell extract.
\r\n\r\nFinally, we use modeling to guide the design of an improved single gene synthetic oscillator. While the original synthetic genetic oscillator contained three genes, we show that a simple circuit with a single gene can produce robust and synchronized oscillations across a population.
\r\n\r\nOur results constitute an additional step towards the incorporation of quantitative modeling and parameter inference as part of the design-build-test cycle for synthetic gene circuits.
", "doi": "10.7907/Z9833Q67", "publication_date": "2018", "thesis_type": "phd", "thesis_year": "2018" }, { "id": "thesis:11021", "collection": "thesis", "collection_id": "11021", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06042018-171639726", "primary_object_url": { "basename": "Baetica-Ania-Ariadna.pdf", "content": "final", "filesize": 3821497, "license": "other", "mime_type": "application/pdf", "url": "/11021/1/Baetica-Ania-Ariadna.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Design, Analysis, And Computational Methods For Engineering Synthetic Biological Networks", "author": [ { "family_name": "Baetica", "given_name": "Ania-Ariadna", "orcid": "0000-0003-0421-8181", "clpid": "Baetica-Ania-Ariadna" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Pierce", "given_name": "Niles A.", "clpid": "Pierce-N-A" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Munsky", "given_name": "Brian", "clpid": "Munsky-Brian" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis advances our understanding of three important aspects of biological systems engineering: analysis, design, and computational methods. First, biological circuit design is necessary to engineer biological systems that behave consistently and follow our design specifications. We contribute by formulating and solving novel problems in stochastic biological circuit design. Second, computational methods for solving biological systems are often limited by the nonlinearity and high dimensionality of the system\u2019s dynamics. This problem is particularly extreme for the parameter identification of stochastic, nonlinear systems. Thus, we develop a method for parameter identification that relies on data-driven stochastic model reduction. Finally, biological system analysis encompasses understanding the stability, performance, and robustness of these systems, which is critical for their implementation. We analyze a sequestration feedback motif for implementing biological control.
\r\n\r\nFirst, we discuss biological circuit design for the stationary and the transient distributional responses of stochastic biochemical systems. Noise is often indispensable to key cellular activities, such as gene expression, necessitating the use of stochastic models to capture their dynamics. The chemical master equation is a commonly used stochastic model that describes how the probability distribution of a chemically reacting system varies with time. Here we design the distributional response of these stochastic models by formulating and solving it as a constrained optimization problem.
\r\n\r\nSecond, we analyze the stability and the performance of a biological controller implemented by a sequestration feedback network motif. Sequestration feedback networks have been implemented in synthetic biology using an array of biological parts. However, their properties of stability and performance are poorly understood. We provide insight into the stability and performance of sequestration feedback networks. Additionally, we provide guidelines for the implementation of sequestration feedback networks.
\r\n\r\nThird, we develop computational methods for the parameter identification of stochastic models of biochemical reaction networks. It is often not possible to find analytic solutions to problems where the dynamics of the underlying biological circuit are stochastic, nonlinear or both. Stochastic models are often challenging due to their high dimensionality and their nonlinearity, which further limits the availability of analytical tools. To address these challenges, we develop a computational method for data-driven stochastic model reduction and we use it to perform parameter identification. Last, we provide concluding remarks and future research directions.
", "doi": "10.7907/98qt-zv92", "publication_date": "2018", "thesis_type": "phd", "thesis_year": "2018" }, { "id": "thesis:10091", "collection": "thesis", "collection_id": "10091", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03082017-163613964", "primary_object_url": { "basename": "Guo_Shaobin_2017_thesis.pdf", "content": "final", "filesize": 27841341, "license": "other", "mime_type": "application/pdf", "url": "/10091/1/Guo_Shaobin_2017_thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Prototyping Diverse Synthetic Biological Circuits in a Cell-Free Transcription-Translation System", "author": [ { "family_name": "Guo", "given_name": "Shaobin", "orcid": "0000-0001-9736-4078", "clpid": "Guo-Shaobin" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Elowitz", "given_name": "Michael B.", "clpid": "Elowitz-M-B" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Goentoro", "given_name": "Lea A.", "clpid": "Goentoro-L-A" }, { "family_name": "Sternberg", "given_name": "Paul W.", "clpid": "Sternberg-P-W" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Synthetic biological circuits are the foundation for the ultimate goals of controlling cells and building artificial cells from the ground up. To get closer to these goals in a more efficient way, we utilize a cell-free transcription-translation system to help perfect biological circuits for the simplicity, freedom, and convenience that the system offers. In this thesis, we demonstrate three distinct aspects of biological circuits in a cell-free transcription-translation system: circuit dynamics, phosphorylation, and membrane proteins. We start with a simple feedforward circuit, which shows dynamic responses to the input. We first prototype the feedforward circuit in the cell-free system with the aid of mathematical modeling. Then, based on the knowledge learned from prototyping, we successfully implement the circuit in cells. Not only do we show that a circuit with dynamics can be prototyped in the cell- free system, but we also test a more complicated circuit involving a phosphorylation cycle. The phosphorylation-based insulator circuit is prototyped and then a model created for the circuit is shown to be identifiable in the cell-free system. To further expand the capability of the cell-free system, we demonstrate that biologically active membrane proteins can be generated in the cell-free system with engineering, suggesting that even biological circuits requiring membrane proteins can be prototyped in the system. These results help advance our knowledge of both biological circuits and the cell-free transcription-translation system, and bring us one step closer to our ultimate goals of implementing control theory in synthetic biology.", "doi": "10.7907/Z9CR5RDK", "publication_date": "2017", "thesis_type": "phd", "thesis_year": "2017" }, { "id": "thesis:10323", "collection": "thesis", "collection_id": "10323", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06082017-194534497", "primary_object_url": { "basename": "Anu_Thubagere_BBE.pdf", "content": "final", "filesize": 18346331, "license": "other", "mime_type": "application/pdf", "url": "/10323/1/Anu_Thubagere_BBE.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Programming Complex Behavior in DNA-based Molecular Circuits and Robots", "author": [ { "family_name": "Thubagere Jagadeesh", "given_name": "Anupama", "clpid": "Thubagere-Jagadeesh-Anu" } ], "thesis_advisor": [ { "family_name": "Qian", "given_name": "Lulu", "clpid": "Qian-Lulu" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Rothemund", "given_name": "Paul W. K.", "clpid": "Rothemund-P-W-K" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "clpid": "Shapiro-M-G" }, { "family_name": "Qian", "given_name": "Lulu", "clpid": "Qian-Lulu" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Integrated electronic circuits, like those found in cellphones and computers, are ubiquitous in our information-driven society. The success of electronics has, in part, been due its modular architecture that enables individual components to be independently improved while the overall device functionality remains unchanged. Over the last two decades the emerging field of dynamic DNA nanotechnology has been trying to apply the underlying philosophy of electronics to biochemical circuits. DNA nanotechnology employs rationally designed DNA molecules as building blocks of biochemical circuits that can, in principle, enable powerful applications like diagnostics and therapeutics.
\r\n\r\nResearchers in the field of DNA nanotechnology have developed simple elements to construct biomolecular systems with desired functions. They have also developed molecular compilers for defining design principles. The cost of DNA synthesis has decreased by over three orders of magnitude in the past decade. This has lead to a non-trivial number of small scale circuits, like DNA-based logic gates and chemical oscillators, being implemented. However, the scalability of this approach has yet to be clearly demonstrated. n this thesis, we will discuss our main contributions to facilitating the advancement of DNA nanotechnology by developing systematic approaches for constructing modular DNA building blocks. These modules can be used to construct biochemical circuits and molecular robotic systems. The performance of the modules can be individually tuned and integrated into large-scale systems.
\r\n\r\nUsing automated circuit-design software and cheap unpurified DNA, we demonstrated the design and construction of a complex synthetic biochemical circuit consisting of 78 distinct DNA species. The circuit is capable of computing the transition rules of a cell updating its state based on its neighboring cells, defined in a classic computational model called cellular automata. Using a bottom-up approach, we first characterized the component necessary for basic Boolean logic computation. We then systematically integrated more circuit elements and eventually constructed the full circuit. By developing a systematic procedure for building DNA-based circuits using unpurified components, we significantly simplified the experimental procedure. By using unpurified DNA components, we reduced the cost and technical barrier for circuit construction, thus making the design and synthesis of complex DNA circuits accessible to even novice researchers.
\r\n\r\nNext we demonstrated a cargo sorting DNA nano-robot, using a simple algorithm and modular building blocks. The DNA robot has a leg and two foot domains for exploring a two-dimensional DNA origami surface, and an arm and hand domain for picking up randomly located cargos and dropping them off at their designated locations. It is completely autonomous and is programmed to perform a random walk without requiring an external energy source. Further, we demonstrated sorting multiple copies of two distinct cargo species on the same origami. Additionally, by compartmentalizing each sorting task on a single origami, we showed that two distinct sorting tasks can be implemented on different origami simultaneously in the same test tube. The recognition of a cargo is embedded in its destination, therefore it is possible to scale up the system simply by having multiple types of cargos. The same robot design can be used for performing multiple instances of distinct tasks in parallel. The different modules can be integrated to perform diverse functions, including applications in time-release targeted therapeutics.
", "doi": "10.7907/Z9WD3XMS", "publication_date": "2017-06-16", "thesis_type": "phd", "thesis_year": "2017" }, { "id": "thesis:9705", "collection": "thesis", "collection_id": "9705", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05082016-170628018", "primary_object_url": { "basename": "20160509_Hsiao_Victoria_2016.pdf", "content": "final", "filesize": 67580263, "license": "other", "mime_type": "application/pdf", "url": "/9705/1/20160509_Hsiao_Victoria_2016.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Synthetic Circuits for Feedback and Detection in Bacteria", "author": [ { "family_name": "Hsiao", "given_name": "Victoria", "orcid": "0000-0001-9297-1522", "clpid": "Hsiao-Victoria" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Elowitz", "given_name": "Michael B.", "clpid": "Elowitz-M-B" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Pierce", "given_name": "Niles A.", "clpid": "Pierce-N-A" }, { "family_name": "Rothemund", "given_name": "Paul W. K.", "clpid": "Rothemund-P-W-K" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Synthetic biology, by co-opting molecular machinery from existing organisms, can be used as a tool for building new genetic systems from scratch, for understanding natural networks through perturbation, or for hybrid circuits that piggy-back on existing cellular infrastructure. Although the toolbox for genetic circuits has greatly expanded in recent years, it is still difficult to separate the circuit function from its specific molecular implementation. In this thesis, we discuss the function-driven design of two synthetic circuit modules, and use mathematical models to understand the fundamental limits of circuit topology versus operating regimes as determined by the specific molecular implementation. First, we describe a protein concentration tracker circuit that sets the concentration of an output protein relative to the concentration of a reference protein. The functionality of this circuit relies on a single negative feedback loop that is implemented via small programmable protein scaffold domains. We build a mass-action model to understand the relevant timescales of the tracking behavior and how the input/output ratios and circuit gain might be tuned with circuit components. Second, we design an event detector circuit with permanent genetic memory that can record order and timing between two chemical events. This circuit was implemented using bacteriophage integrases that recombine specific segments of DNA in response to chemical inputs. We simulate expected population-level outcomes using a stochastic Markov-chain model, and investigate how inferences on past events can be made from differences between single-cell and population-level responses. Additionally, we present some preliminary investigations on spatial patterning using the event detector circuit as well as the design of stationary phase promoters for growth-phase dependent activation. These results advance our understanding of synthetic gene circuits, and contribute towards the use of circuit modules as building blocks for larger and more complex synthetic networks.", "doi": "10.7907/Z9WD3XJW", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9794", "collection": "thesis", "collection_id": "9794", "cite_using_url": "https://resolver.caltech.edu/CaltechThesis:05272016-145559554", "primary_object_url": { "basename": "Yeung-Enoch-2016-thesis_final.pdf", "content": "final", "filesize": 12581127, "license": "other", "mime_type": "application/pdf", "url": "/9794/1/Yeung-Enoch-2016-thesis_final.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Reverse Engineering and Quantifying Context Effects in Synthetic Gene Networks", "author": [ { "family_name": "Yeung", "given_name": "Enoch Ho-Yee", "orcid": "0000-0001-7630-7429", "clpid": "Yeung-Enoch-Ho-Yee" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Doyle", "given_name": "John C.", "clpid": "Doyle-J-C" }, { "family_name": "Beck", "given_name": "James L.", "clpid": "Beck-J-L" }, { "family_name": "Goentoro", "given_name": "Lea A.", "clpid": "Goentoro-L-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "In the first part of this thesis, we undertake a quantitative investigation of how compositional context, the spatial arrangement and relative orientation of genes, affects individual gene expression in a genetic network. Taking a synthetic biology approach, we construct a series of simple two-reporter biocircuits, each expressing either an mRNA aptamer or a fluorescent protein, and show that by varying the relative orientation of the two genes we obtain a wide range of gene expression profiles, including context-dependent bimodality. We develop a mathematical model to describe the experimental trends observed based on concepts from DNA supercoiling theory. We validate the model through a series of in vitro supercoiling experiments and show that by relaxing positive supercoiling in the plasmids, we can significantly reduce the context effects in gene expression. Most importantly, these insights provide a framework for understanding how compositional context and supercoiling can impose feedback on the intended architecture of a synthetic gene network. As a proof of concept, we engineer a genetic toggle switch exploiting compositional context effects to improve its threshold detection and memory capabilities.
\r\n\r\nIn the second part of this thesis, we examine a series of theoretical and computational tools from dynamical systems theory that assist in engineering novel biochemical reaction networks. We briefly review the concept of dynamical structure functions and network reconstruction as tools for understanding biochemical reaction networks. In particular, we review the concept of resource-loading, show that resource-loading can lead to coupling interactions among biochemical species, and that by estimating a dynamical structure function from experimental data, it is possible to quantify resource loading effects in practice. We illustrate the importance of knowing these loading effects through several example systems, showing that crosstalk imbalance in feed-forward loops can lead to performance limitations. However, since biochemical reaction networks are generally large, in practice, only portions of the global network can be reconstructed at a time. We show, with a combination of theory, simulation, modeling and experiments, it is possible to reconstruct the dynamical structure function of a large-scale biochemical network using a series of network reconstruction experiments. We then demonstrate how the dynamical structure function can be used to analyze context interference and how these perturbations interfere with performance. We illustrate these ideas with several classes of standard biological networks, e.g. autocatalytic systems, cascade systems, and input-coupled systems.
\r\n\r\nFinally, in the third part of this thesis, we consider models for context interference in stochastic chemical reaction networks. We address the problem of representing a biological system and its environment using a stochastic modeling framework. We first introduce a decomposition of the global chemical reaction system into two systems: a system of interest and its environment. We then present and derive a decomposition of the chemical master equation to achieve a representation describing the dynamics of the system of interest, perturbed by an environmental disturbance. We use this decomposition to model examples of two types of environmental disturbances: the disturbance a system experiences through loading effects from limited resources and the disturbance a system experiences when perturbed by an antibiotic that modifies transcription or translation rates.
", "doi": "10.7907/Z9Z31WM4", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9348", "collection": "thesis", "collection_id": "9348", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12312015-131513787", "primary_object_url": { "basename": "ScottCLivingston-phdthesis2015.pdf", "content": "final", "filesize": 1707051, "license": "other", "mime_type": "application/pdf", "url": "/9348/1/ScottCLivingston-phdthesis2015.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Incremental Control Synthesis for Robotics in the Presence of Temporal Logic Specifications", "author": [ { "family_name": "Livingston", "given_name": "Scott Carlton", "clpid": "Livingston-Scott-Carlton" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Holzmann", "given_name": "Gerard J.", "clpid": "Holzmann-G-J" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents methods for incrementally constructing controllers in the presence of uncertainty and nonlinear dynamics. The basic setting is motion planning subject to temporal logic specifications. Broadly, two categories of problems are treated. The first is reactive formal synthesis when so-called discrete abstractions are available. The fragment of linear-time temporal logic (LTL) known as GR(1) is used to express assumptions about an adversarial environment and requirements of the controller. Two problems of changes to a specification are posed that concern the two major aspects of GR(1): safety and liveness. Algorithms providing incremental updates to strategies are presented as solutions. In support of these, an annotation of strategies is developed that facilitates repeated modifications. A variety of properties are proven about it, including necessity of existence and sufficiency for a strategy to be winning. The second category of problems considered is non-reactive (open-loop) synthesis in the absence of a discrete abstraction. Instead, the presented stochastic optimization methods directly construct a control input sequence that achieves low cost and satisfies a LTL formula. Several relaxations are considered as heuristics to address the rarity of sampling trajectories that satisfy an LTL formula and demonstrated to improve convergence rates for Dubins car and single-integrators subject to a recurrence task.", "doi": "10.7907/Z94Q7RW3", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9831", "collection": "thesis", "collection_id": "9831", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06032016-102336160", "primary_object_url": { "basename": "ipthesis.pdf", "content": "final", "filesize": 1702656, "license": "other", "mime_type": "application/pdf", "url": "/9831/1/ipthesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Robustness, Adaptation, and Learning in Optimal Control", "author": [ { "family_name": "Papusha", "given_name": "Ivan Igorevych", "clpid": "Papusha-Ivan-Igorevych" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Lavretsky", "given_name": "Eugene", "clpid": "Lavretsky-Eugene" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Recent technological advances have opened the door to a wide variety of dynamic control applications, which are enabled by increasing computational power in ever smaller devices. These advances are backed by reliable optimization algorithms that allow specification, synthesis, and embedded implementation of sophisticated learning-based controllers. However, as control systems become more pervasive, dynamic, and complex, the control algorithms governing them become more complex to design and analyze. In many cases, optimal control policies are practically impossible to determine unless the state dimension is small, or the dynamics are simple. Thus, in order to make implementation progress, the control designer must specialize to suboptimal architectures and approximate control. The major engineering challenge in the upcoming decades will be how to cope with the complexity of designing implementable control architectures for these smart systems while certifying their safety, robustness, and performance.
\r\n\r\nThis thesis tackles the design and verification complexity by carefully employing tractable lower and upper bounds on the Lyapunov function, while making connections to robust control, formal synthesis, and machine learning. Specifically, optimization-based upper bounds are used to specify robust controllers, while lower bounds are used to obtain performance bounds and to synthesize approximately optimal policies. Implementation of these bounds depends critically on carrying out learning and optimization in the loop. Examples in aerospace, formal methods, hybrid systems, and networked adaptive systems are given, and novel sources of identifiability and persistence of excitation are discussed.
", "doi": "10.7907/Z9F18WPB", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9880", "collection": "thesis", "collection_id": "9880", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06202016-133637013", "primary_object_url": { "basename": "main.pdf", "content": "submitted", "filesize": 481417, "license": "other", "mime_type": "application/pdf", "url": "/9880/1/main.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Economic Fluctuations and Capitalistic Production: A Case Study in Robustness Constraints", "author": [ { "family_name": "Cruz", "given_name": "Gerardo", "clpid": "Cruz-Gerardo" } ], "thesis_advisor": [ { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "A central pursuit of macroeconomic research is to understand the source of short run variations in aggregate economic variables. To this end, the branch of macroeconomics known as Real Business Cycle (RBC) theory emphasizes the role of disturbances to the real economy while abstracting from nominal variables (e.g. money). According to RBC theory, business cycles are the result of optimal responses to exogenous stochastic disturbances on technology in a structure of capitalistic production. In this report, we contend that the structure of capitalistic production per se constrains the ability of the economy to absorb shocks. That is, even if the feedback behavior in the model is designed to mitigate fluctuation (and is not necessarily optimal relative to some inter-temporal utility), the resulting sensitivity is nevertheless constrained by a lower bound. Moreover, we show that this lower bound is exacerbated with increasing steady state consumption, capital and investment. Concretely, we show that the Ramsey model, linearized about its steady state equilibrium, has a non-minimum phase structure and therefore its sensitivity is constrained by the control theoretic design limits. Moreover, the non-minimum phase zero is given by the inverse of the discount factor. As the discount factor approaches unity, steady state consumption approaches optimal steady state consumption, but the non-minimum phase zero approaches the closed unit circle exacerbating the sensitivity constraints.", "doi": "10.7907/FDCE-MQ31", "publication_date": "2016", "thesis_type": "masters", "thesis_year": "2016" }, { "id": "thesis:9218", "collection": "thesis", "collection_id": "9218", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10132015-121212703", "primary_object_url": { "basename": "jonsson-2016.pdf", "content": "final", "filesize": 5433194, "license": "other", "mime_type": "application/pdf", "url": "/9218/1/jonsson-2016.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Robust Control of Evolutionary Dynamics", "author": [ { "family_name": "Jonsson", "given_name": "Vanessa Danielle", "clpid": "Jonsson-Vanessa-Danielle" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Baltimore", "given_name": "David L.", "clpid": "Baltimore-D-L" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Baltimore", "given_name": "David L.", "clpid": "Baltimore-D-L" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "clpid": "Bjorkman-P-J" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The application of principles from evolutionary biology has long been used to gain new insights into the progression and clinical control of both infectious diseases and neoplasms. This iterative evolutionary process consists of expansion, diversification and selection within an adaptive landscape - species are subject to random genetic or epigenetic alterations that result in variations; genetic information is inherited through asexual reproduction and strong selective pressures such as therapeutic intervention can lead to the adaptation and expansion of resistant variants. These principles lie at the center of modern evolutionary synthesis and constitute the primary reasons for the development of resistance and therapeutic failure, but also provide a framework that allows for more effective control.
\r\n\r\nA model system for studying the evolution of resistance and control of therapeutic failure is the treatment of chronic HIV-1 infection by broadly neutralizing antibody (bNAb) therapy. A relatively recent discovery is that a minority of HIV-infected individuals can produce broadly neutralizing antibodies, that is, antibodies that inhibit infection by many strains of HIV. Passive transfer of human antibodies for the prevention and treatment of HIV-1 infection is increasingly being considered as an alternative to a conventional vaccine. However, recent evolution studies have uncovered that antibody treatment can exert selective pressure on virus that results in the rapid evolution of resistance. In certain cases, complete resistance to an antibody is conferred with a single amino acid substitution on the viral envelope of HIV.
\r\n\r\nThe challenges in uncovering resistance mechanisms and designing effective combination strategies to control evolutionary processes and prevent therapeutic failure apply more broadly. We are motivated by two questions: Can we predict the evolution to resistance by characterizing genetic alterations that contribute to modified phenotypic fitness? Given an evolutionary landscape and a set of candidate therapies, can we computationally synthesize treatment strategies that control evolution to resistance?
\r\n\r\nTo address the first question, we propose a mathematical framework to reason about evolutionary dynamics of HIV from computationally derived Gibbs energy fitness landscapes -- expanding the theoretical concept of an evolutionary landscape originally conceived by Sewall Wright to a computable, quantifiable, multidimensional, structurally defined fitness surface upon which to study complex HIV evolutionary outcomes.
\r\n\r\nTo design combination treatment strategies that control evolution to resistance, we propose a methodology that solves for optimal combinations and concentrations of candidate therapies, and allows for the ability to quantifiably explore tradeoffs in treatment design, such as limiting the number of candidate therapies in the combination, dosage constraints and robustness to error. Our algorithm is based on the application of recent results in optimal control to an HIV evolutionary dynamics model and is constructed from experimentally derived antibody resistant phenotypes and their single antibody pharmacodynamics. This method represents a first step towards integrating principled engineering techniques with an experimentally based mathematical model in the rational design of combination treatment strategies and offers predictive understanding of the effects of combination therapies of evolutionary dynamics and resistance of HIV. Preliminary in vitro studies suggest that the combination antibody therapies predicted by our algorithm can neutralize heterogeneous viral populations despite containing resistant mutations.
", "doi": "10.7907/Z9NP22CH", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:9191", "collection": "thesis", "collection_id": "9191", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10012015-221355676", "primary_object_url": { "basename": "SunZacharyZhipeng2016thesis.pdf", "content": "final", "filesize": 45522801, "license": "other", "mime_type": "application/pdf", "url": "/9191/1/SunZacharyZhipeng2016thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "An in vitro Biomolecular Breadboard for Prototyping Synthetic Biological Circuits", "author": [ { "family_name": "Sun", "given_name": "Zachary Zhipeng", "orcid": "0000-0002-9425-2924", "clpid": "Sun-Zachary-Zhipeng" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Elowitz", "given_name": "Michael B.", "clpid": "Elowitz-M-B" }, { "family_name": "Baltimore", "given_name": "David L.", "clpid": "Baltimore-D-L" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Noireaux", "given_name": "Vincent", "clpid": "Noireaux-V" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Biomolecular circuit engineering is critical for implementing complex functions in vivo, and is a baseline method in the synthetic biology space. However, current methods for conducting biomolecular circuit engineering are time-consuming and tedious. A complete design-build-test cycle typically takes weeks' to months' time due to the lack of an intermediary between design ex vivo and testing in vivo. In this work, we explore the development and application of a \"biomolecular breadboard\" composed of an in-vitro transcription-translation (TX-TL) lysate to rapidly speed up the engineering design-build-test cycle. We first developed protocols for creating and using lysates for conducting biological circuit design. By doing so we simplified the existing technology to an affordable ($0.03/uL) and easy to use three-tube reagent system. We then developed tools to accelerate circuit design by allowing for linear DNA use in lieu of plasmid DNA, and by utilizing principles of modular assembly. This allowed the design-build-test cycle to be reduced to under a business day. We then characterized protein degradation dynamics in the breadboard to aid to implementing complex circuits. Finally, we demonstrated that the breadboard could be applied to engineer complex synthetic circuits in vitro and in vivo. Specifically, we utilized our understanding of linear DNA prototyping, modular assembly, and protein degradation dynamics to characterize the repressilator oscillator and to prototype novel three- and five-node negative feedback oscillators both in vitro and in vivo. We therefore believe the biomolecular breadboard has wide application for acting as an intermediary for biological circuit engineering.", "doi": "10.7907/Z9TB14TW", "publication_date": "2016", "thesis_type": "phd", "thesis_year": "2016" }, { "id": "thesis:8865", "collection": "thesis", "collection_id": "8865", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05182015-163708506", "primary_object_url": { "basename": "delossantos_elc_2015_thesis.pdf", "content": "final", "filesize": 11163927, "license": "other", "mime_type": "application/pdf", "url": "/8865/1/delossantos_elc_2015_thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Expanding the Toolkit for Synthetic Biology: Frameworks for Native-like Non-natural Gene Circuits", "author": [ { "family_name": "Cornejo de los Santos", "given_name": "Emmanuel Lorenzo", "clpid": "Cornejo-de-los-Santos-Emmanuel-Lorenzo-Cornejo" } ], "thesis_advisor": [ { "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" } ], "thesis_committee": [ { "family_name": "Tirrell", "given_name": "David A.", "orcid": "0000-0003-3175-4596", "clpid": "Tirrell-D-A" }, { "family_name": "Elowitz", "given_name": "Michael B.", "orcid": "0000-0002-1221-0967", "clpid": "Elowitz-M-B" }, { "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" } ], "local_group": [ { "literal": "div_bbe" } ], "abstract": "Synthetic biology combines biological parts from different sources in order to engineer non-native, functional systems. While there is a lot of potential for synthetic biology to revolutionize processes, such as the production of pharmaceuticals, engineering synthetic systems has been challenging. It is oftentimes necessary to explore a large design space to balance the levels of interacting components in the circuit. There are also times where it is desirable to incorporate enzymes that have non-biological functions into a synthetic circuit. Tuning the levels of different components, however, is often restricted to a fixed operating point, and this makes synthetic systems sensitive to changes in the environment. Natural systems are able to respond dynamically to a changing environment by obtaining information relevant to the function of the circuit. This work addresses these problems by establishing frameworks and mechanisms that allow synthetic circuits to communicate with the environment, maintain fixed ratios between components, and potentially add new parts that are outside the realm of current biological function. These frameworks provide a way for synthetic circuits to behave more like natural circuits by enabling a dynamic response, and provide a systematic and rational way to search design space to an experimentally tractable size where likely solutions exist. We hope that the contributions described below will aid in allowing synthetic biology to realize its potential.", "doi": "10.7907/Z9M61H64", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:8648", "collection": "thesis", "collection_id": "8648", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08282014-165029252", "primary_object_url": { "basename": "Gomez_MarcellaM_Thesis_2015.pdf", "content": "final", "filesize": 12301385, "license": "other", "mime_type": "application/pdf", "url": "/8648/1/Gomez_MarcellaM_Thesis_2015.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "On the Role of Delays in Biological Systems : Analysis and Design", "author": [ { "family_name": "Gomez", "given_name": "Marcella Mary", "clpid": "Gomez-Marcella-Mary" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Beck", "given_name": "James L.", "clpid": "Beck-J-L" }, { "family_name": "Balas", "given_name": "Mark J.", "clpid": "Balas-M-J" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This work quantifies the nature of delays in genetic regulatory networks and their effect on system dynamics. It is known that a time lag can emerge from a sequence of biochemical reactions. Applying this modeling framework to the protein production processes, delay distributions are derived in a stochastic (probability density function) and deterministic setting (impulse function), whilst being shown to be equivalent under different assumptions. The dependence of the distribution properties on rate constants, gene length, and time-varying temperatures is investigated. Overall, the distribution of the delay in the context of protein production processes is shown to be highly dependent on the size of the genes and mRNA strands as well as the reaction rates. Results suggest longer genes have delay distributions with a smaller relative variance, and hence, less uncertainty in the completion times, however, they lead to larger delays. On the other hand large uncertainties may actually play a positive role, as broader distributions can lead to larger stability regions when this formalization of the protein production delays is incorporated into a feedback system.
\r\n\r\nFurthermore, evidence suggests that delays may play a role as an explicit design into existing controlling mechanisms. Accordingly, the reccurring dual-feedback motif is also investigated with delays incorporated into the feedback channels. The dual-delayed feedback is shown to have stabilizing effects through a control theoretic approach. Lastly, a distributed delay based controller design method is proposed as a potential design tool. In a preliminary study, the dual-delayed feedback system re-emerges as an effective controller design.
", "doi": "10.7907/Z9JH3J4W", "publication_date": "2015", "thesis_type": "phd", "thesis_year": "2015" }, { "id": "thesis:8078", "collection": "thesis", "collection_id": "8078", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02172014-121159358", "primary_object_url": { "basename": "wolff_eric_thesis.pdf", "content": "final", "filesize": 2659687, "license": "other", "mime_type": "application/pdf", "url": "/8078/1/wolff_eric_thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Control of Dynamical Systems with Temporal Logic Specifications", "author": [ { "family_name": "Wolff", "given_name": "Eric McKenzie", "clpid": "Wolff-Eric-McKenzie" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Topcu", "given_name": "Ufuk", "clpid": "Topcu-U" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis is motivated by safety-critical applications involving autonomous air, ground, and space vehicles carrying out complex tasks in uncertain and adversarial environments. We use temporal logic as a language to formally specify complex tasks and system properties. Temporal logic specifications generalize the classical notions of stability and reachability that are studied in the control and hybrid systems communities. Given a system model and a formal task specification, the goal is to automatically synthesize a control policy for the system that ensures that the system satisfies the specification. This thesis presents novel control policy synthesis algorithms for optimal and robust control of dynamical systems with temporal logic specifications. Furthermore, it introduces algorithms that are efficient and extend to high-dimensional dynamical systems.
\r\n\r\nThe first contribution of this thesis is the generalization of a classical linear temporal logic (LTL) control synthesis approach to optimal and robust control. We show how we can extend automata-based synthesis techniques for discrete abstractions of dynamical systems to create optimal and robust controllers that are guaranteed to satisfy an LTL specification. Such optimal and robust controllers can be computed at little extra computational cost compared to computing a feasible controller.
\r\n\r\nThe second contribution of this thesis addresses the scalability of control synthesis with LTL specifications. A major limitation of the standard automaton-based approach for control with LTL specifications is that the automaton might be doubly-exponential in the size of the LTL specification. We introduce a fragment of LTL for which one can compute feasible control policies in time polynomial in the size of the system and specification. Additionally, we show how to compute optimal control policies for a variety of cost functions, and identify interesting cases when this can be done in polynomial time. These techniques are particularly relevant for online control, as one can guarantee that a feasible solution can be found quickly, and then iteratively improve on the quality as time permits.
\r\n\r\nThe final contribution of this thesis is a set of algorithms for computing feasible trajectories for high-dimensional, nonlinear systems with LTL specifications. These algorithms avoid a potentially computationally-expensive process of computing a discrete abstraction, and instead compute directly on the system's continuous state space. The first method uses an automaton representing the specification to directly encode a series of constrained-reachability subproblems, which can be solved in a modular fashion by using standard techniques. The second method encodes an LTL formula as mixed-integer linear programming constraints on the dynamical system. We demonstrate these approaches with numerical experiments on temporal logic motion planning problems with high-dimensional (10+ states) continuous systems.
", "doi": "10.7907/TGFR-SS39", "publication_date": "2014", "thesis_type": "phd", "thesis_year": "2014" }, { "id": "thesis:7991", "collection": "thesis", "collection_id": "7991", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10162013-111333269", "primary_object_url": { "basename": "han_shuo_2014_thesis.pdf", "content": "final", "filesize": 1628283, "license": "other", "mime_type": "application/pdf", "url": "/7991/1/han_shuo_2014_thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Optimal Uncertainty Quantification via Convex Optimization and Relaxation", "author": [ { "family_name": "Han", "given_name": "Shuo", "clpid": "Han-Shuo" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Chandrasekaran", "given_name": "Venkat", "clpid": "Chandrasekaran-V" }, { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" }, { "family_name": "Low", "given_name": "Steven H.", "clpid": "Low-S-H" }, { "family_name": "Owhadi", "given_name": "Houman", "clpid": "Owhadi-H" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Many engineering applications face the problem of bounding the expected value of a quantity of interest (performance, risk, cost, etc.) that depends on stochastic uncertainties whose probability distribution is not known exactly. Optimal uncertainty quantification (OUQ) is a framework that aims at obtaining the best bound in these situations by explicitly incorporating available information about the distribution. Unfortunately, this often leads to non-convex optimization problems that are numerically expensive to solve.
\r\n\r\nThis thesis emphasizes on efficient numerical algorithms for OUQ problems. It begins by investigating several classes of OUQ problems that can be reformulated as convex optimization problems. Conditions on the objective function and information constraints under which a convex formulation exists are presented. Since the size of the optimization problem can become quite large, solutions for scaling up are also discussed. Finally, the capability of analyzing a practical system through such convex formulations is demonstrated by a numerical example of energy storage placement in power grids.
\r\n\r\nWhen an equivalent convex formulation is unavailable, it is possible to find a convex problem that provides a meaningful bound for the original problem, also known as a convex relaxation. As an example, the thesis investigates the setting used in Hoeffding's inequality. The naive formulation requires solving a collection of non-convex polynomial optimization problems whose number grows doubly exponentially. After structures such as symmetry are exploited, it is shown that both the number and the size of the polynomial optimization problems can be reduced significantly. Each polynomial optimization problem is then bounded by its convex relaxation using sums-of-squares. These bounds are found to be tight in all the numerical examples tested in the thesis and are significantly better than Hoeffding's bounds.
", "doi": "10.7907/X00K-T615", "publication_date": "2014", "thesis_type": "phd", "thesis_year": "2014" }, { "id": "thesis:7789", "collection": "thesis", "collection_id": "7789", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05312013-103940337", "primary_object_url": { "basename": "Xu_Huan_Thesis_2013.pdf", "content": "final", "filesize": 16950376, "license": "other", "mime_type": "application/pdf", "url": "/7789/1/Xu_Huan_Thesis_2013.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Design, Specification, and Synthesis of Aircraft Electric Power Systems Control Logic", "author": [ { "family_name": "Xu", "given_name": "Huan", "clpid": "Xu-Huan" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" }, { "family_name": "Holzmann", "given_name": "Gerard J.", "clpid": "Holzmann-G-J" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Cyber-physical systems integrate computation, networking, and physical processes. Substantial research challenges exist in the design and verification of such large-scale, distributed sensing, ac- tuation, and control systems. Rapidly improving technology and recent advances in control theory, networked systems, and computer science give us the opportunity to drastically improve our approach to integrated flow of information and cooperative behavior. Current systems rely on text-based spec- ifications and manual design. Using new technology advances, we can create easier, more efficient, and cheaper ways of developing these control systems. This thesis will focus on design considera- tions for system topologies, ways to formally and automatically specify requirements, and methods to synthesize reactive control protocols, all within the context of an aircraft electric power system as a representative application area.
\r\n\r\nThis thesis consists of three complementary parts: synthesis, specification, and design. The first section focuses on the synthesis of central and distributed reactive controllers for an aircraft elec- tric power system. This approach incorporates methodologies from computer science and control. The resulting controllers are correct by construction with respect to system requirements, which are formulated using the specification language of linear temporal logic (LTL). The second section addresses how to formally specify requirements and introduces a domain-specific language for electric power systems. A software tool automatically converts high-level requirements into LTL and synthesizes a controller.
\r\n\r\nThe final sections focus on design space exploration. A design methodology is proposed that uses mixed-integer linear programming to obtain candidate topologies, which are then used to synthesize controllers. The discrete-time control logic is then verified in real-time by two methods: hardware and simulation. Finally, the problem of partial observability and dynamic state estimation is ex- plored. Given a set placement of sensors on an electric power system, measurements from these sensors can be used in conjunction with control logic to infer the state of the system.
", "doi": "10.7907/QDJN-BB72", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7700", "collection": "thesis", "collection_id": "7700", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05122013-221658522", "primary_object_url": { "basename": "Dabby_Nadine_2013_complete_thesis.pdf", "content": "final", "filesize": 41643872, "license": "other", "mime_type": "application/pdf", "url": "/7700/50/Dabby_Nadine_2013_complete_thesis.pdf", "version": "v8.0.0" }, "type": "thesis", "title": "Synthetic Molecular Machines for Active Self-Assembly: Prototype Algorithms, Designs, and Experimental Study", "author": [ { "family_name": "Dabby", "given_name": "Nadine L.", "clpid": "Dabby-Nadine-L" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Barr", "given_name": "Alan H.", "clpid": "Barr-A-H" }, { "family_name": "Pierce", "given_name": "Niles A.", "clpid": "Pierce-N-A" }, { "family_name": "Shimojo", "given_name": "Shinsuke", "clpid": "Shimojo-S" }, { "family_name": "Stojanovic", "given_name": "Milan N.", "clpid": "Stojanovic-M-N" }, { "family_name": "Fygenson", "given_name": "Deborah K.", "clpid": "Fygenson-D-K" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Computer science and electrical engineering have been the great success story of the twentieth century. The neat modularity and mapping of a language onto circuits has led to robots on Mars, desktop computers and smartphones. But these devices are not yet able to do some of the things that life takes for granted: repair a scratch, reproduce, regenerate, or grow exponentially fast\u2013all while remaining functional.
\r\n\r\nThis thesis explores and develops algorithms, molecular implementations, and theoretical proofs in the context of \u201cactive self-assembly\u201d of molecular systems. The long-term vision of active self-assembly is the theoretical and physical implementation of materials that are composed of reconfigurable units with the programmability and adaptability of biology\u2019s numerous molecular machines. En route to this goal, we must first find a way to overcome the memory limitations of molecular systems, and to discover the limits of complexity that can be achieved with individual molecules.
\r\n\r\nOne of the main thrusts in molecular programming is to use computer science as a tool for figuring out what can be achieved. While molecular systems that are Turing-complete have been demonstrated [Winfree, 1996], these systems still cannot achieve some of the feats biology has achieved.
\r\n\r\nOne might think that because a system is Turing-complete, capable of computing \u201canything,\u201d that it can do any arbitrary task. But while it can simulate any digital computational problem, there are many behaviors that are not \u201ccomputations\u201d in a classical sense, and cannot be directly implemented. Examples include exponential growth and molecular motion relative to a surface.
\r\n\r\n\r\nPassive self-assembly systems cannot implement these behaviors because (a) molecular motion relative to a surface requires a source of fuel that is external to the system, and (b) passive systems are too slow to assemble exponentially-fast-growing structures. We call these behaviors \u201cenergetically incomplete\u201d programmable behaviors. This class of behaviors includes any behavior where a passive physical system simply does not have enough physical energy to perform the specified tasks in the requisite amount of time.
\r\n\r\n\r\nAs we will demonstrate and prove, a sufficiently expressive implementation of an \u201cactive\u201d molecular self-assembly approach can achieve these behaviors. Using an external source of fuel solves part of the the problem, so the system is not \u201cenergetically incomplete.\u201d But the programmable system also needs to have sufficient expressive power to achieve the specified behaviors. Perhaps surprisingly, some of these systems do not even require Turing completeness to be sufficiently expressive.
\r\n\r\n\r\nBuilding on a large variety of work by other scientists in the fields of DNA nanotechnology, chemistry and reconfigurable robotics, this thesis introduces several research contributions in the context of active self-assembly.
\r\n\r\n\r\nWe show that simple primitives such as insertion and deletion are able to generate complex and interesting results such as the growth of a linear polymer in logarithmic time and the ability of a linear polymer to treadmill. To this end we developed a formal model for active-self assembly that is directly implementable with DNA molecules. We show that this model is computationally equivalent to a machine capable of producing strings that are stronger than regular languages and, at most, as strong as context-free grammars. This is a great advance in the theory of active self- assembly as prior models were either entirely theoretical or only implementable in the context of macro-scale robotics.
\r\n\r\n\r\nWe developed a chain reaction method for the autonomous exponential growth of a linear DNA polymer. Our method is based on the insertion of molecules into the assembly, which generates two new insertion sites for every initial one employed. The building of a line in logarithmic time is a first step toward building a shape in logarithmic time. We demonstrate the first construction of a synthetic linear polymer that grows exponentially fast via insertion. We show that monomer molecules are converted into the polymer in logarithmic time via spectrofluorimetry and gel electrophoresis experiments. We also demonstrate the division of these polymers via the addition of a single DNA complex that competes with the insertion mechanism. This shows the growth of a population of polymers in logarithmic time. We characterize the DNA insertion mechanism that we utilize in Chapter 4. We experimentally demonstrate that we can control the kinetics of this re- action over at least seven orders of magnitude, by programming the sequences of DNA that initiate the reaction.
\r\n\r\n\r\nIn addition, we review co-authored work on programming molecular robots using prescriptive landscapes of DNA origami; this was the first microscopic demonstration of programming a molec- ular robot to walk on a 2-dimensional surface. We developed a snapshot method for imaging these random walking molecular robots and a CAPTCHA-like analysis method for difficult-to-interpret imaging data.
", "doi": "10.7907/T0ZG-PA07", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7724", "collection": "thesis", "collection_id": "7724", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05182013-191132413", "primary_object_url": { "basename": "caltech_thesis_pete_trautman_small.pdf", "content": "final", "filesize": 11230460, "license": "other", "mime_type": "application/pdf", "url": "/7724/1/caltech_thesis_pete_trautman_small.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Robot Navigation in Dense Crowds: Statistical Models and Experimental Studies of Human Robot Cooperation", "author": [ { "family_name": "Trautman", "given_name": "Peter", "clpid": "Trautman-Peter" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Krause", "given_name": "R. Andreas", "clpid": "Krause-R-A" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Beck", "given_name": "James L.", "clpid": "Beck-J-L" }, { "family_name": "Krause", "given_name": "R. Andreas", "clpid": "Krause-R-A" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis explores the problem of mobile robot navigation in dense human crowds. We begin by considering a fundamental impediment to classical motion planning algorithms called the freezing robot problem: once the environment surpasses a certain level of complexity, the planner decides that all forward paths are unsafe, and the robot freezes in place (or performs unnecessary maneuvers) to avoid collisions. Since a feasible path typically exists, this behavior is suboptimal. Existing approaches have focused on reducing predictive uncertainty by employing higher fidelity individual dynamics models or heuristically limiting the individual predictive covariance to prevent overcautious navigation. We demonstrate that both the individual prediction and the individual predictive uncertainty have little to do with this undesirable navigation behavior. Additionally, we provide evidence that dynamic agents are able to navigate in dense crowds by engaging in joint collision avoidance, cooperatively making room to create feasible trajectories. We accordingly 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. Navigation naturally emerges as a statistic of this distribution.
\r\n\r\nMost importantly, we empirically validate our models in the Chandler dining hall at Caltech during peak hours, and in the process, carry out the first extensive quantitative study of robot navigation in dense human crowds (collecting data on 488 runs). The multiple goal interacting Gaussian processes algorithm performs comparably with human teleoperators in crowd densities nearing 1 person/m2, while a state of the art noncooperative planner exhibits unsafe behavior more than 3 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/m2. We also show that our noncooperative planner or our reactive planner capture the salient characteristics of nearly any dynamic navigation algorithm. For inclusive validation purposes, we show that either our non-interacting planner or our reactive planner captures the salient characteristics of nearly any existing 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.
\r\n\r\nFinally, we produce a large database of ground truth pedestrian crowd data. We make this ground truth database publicly available for further scientific study of crowd prediction models, learning from demonstration algorithms, and human robot interaction models in general.
\r\n", "doi": "10.7907/BHGM-0C65", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7863", "collection": "thesis", "collection_id": "7863", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06072013-095239958", "primary_object_url": { "basename": "Venturelli-O-S-2013-thesis.pdf", "content": "final", "filesize": 15828338, "license": "other", "mime_type": "application/pdf", "url": "/7863/13/Venturelli-O-S-2013-thesis.pdf", "version": "v7.0.0" }, "type": "thesis", "title": "Role of Feedback and Dynamics of a Gene Regulatory Network", "author": [ { "family_name": "Venturelli", "given_name": "Ophelia Shalini", "clpid": "Venturelli-Ophelia-Shalini" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Phillips", "given_name": "Robert B.", "orcid": "0000-0003-3082-2809", "clpid": "Phillips-R" }, { "family_name": "Elowitz", "given_name": "Michael B.", "orcid": "0000-0002-1221-0967", "clpid": "Elowitz-M-B" }, { "family_name": "Deshaies", "given_name": "Raymond Joseph", "orcid": "0000-0002-3671-9354", "clpid": "Deshaies-R-J" }, { "family_name": "El-Samad", "given_name": "Hana", "clpid": "El-Samad-H" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "Cells exhibit a diverse repertoire of dynamic behaviors. These dynamic functions are implemented by circuits of interacting biomolecules. Although these regulatory networks function deterministically by executing specific programs in response to extracellular signals, molecular interactions are inherently governed by stochastic fluctuations. This molecular noise can manifest as cell-to-cell phenotypic heterogeneity in a well-mixed environment. Single-cell variability may seem like a design flaw but the coexistence of diverse phenotypes in an isogenic population of cells can also serve a biological function by increasing the probability of survival of individual cells upon an abrupt change in environmental conditions. Decades of extensive molecular and biochemical characterization have revealed the connectivity and mechanisms that constitute regulatory networks. We are now confronted with the challenge of integrating this information to link the structure of these circuits to systems-level properties such as cellular decision making. To investigate cellular decision-making, we used the well studied galactose gene-regulatory network in Saccharomyces cerevisiae. We analyzed the mechanism and dynamics of the coexistence of two stable on and off states for pathway activity. We demonstrate that this bimodality in the pathway activity originates from two positive feedback loops that trigger bistability in the network. By measuring the dynamics of single-cells in a mixed sugar environment, we observe that the bimodality in gene expression is a transient phenomenon. Our experiments indicate that early pathway activation in a cohort of cells prior to galactose metabolism can accelerate galactose consumption and provide a transient increase in growth rate. Together these results provide important insights into strategies implemented by cells that may have been evolutionary advantageous in competitive environments. \r\n", "doi": "10.7907/WGK3-Y839", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:7248", "collection": "thesis", "collection_id": "7248", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10282012-082208075", "primary_object_url": { "basename": "main_dissertation-caltech-oct28.pdf", "content": "final", "filesize": 24248874, "license": "other", "mime_type": "application/pdf", "url": "/7248/4/main_dissertation-caltech-oct28.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Bootstrapping Vehicles: A Formal Approach to Unsupervised Sensorimotor Learning Based on Invariance", "author": [ { "family_name": "Censi", "given_name": "Andrea", "clpid": "Censi-Andrea" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Soatto", "given_name": "Stefano", "clpid": "Soatto-Stefano" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Abu-Mostafa", "given_name": "Yaser S.", "clpid": "Abu-Mostafa-Y-S" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Could a \"brain in a jar\" be able to control an unknown robotic body to which it is connected, and use it to achieve useful tasks, without any prior assumptions on the body's sensors and actuators? Other than of purely intellectual interest, this question is relevant to the medium-term challenges of robotics: as the complexity of robotics applications grows, automated learning techniques might reduce design effort and increase the robustness and reliability of the solutions. In this work, the problem of \"bootstrapping\" is studied in the context of the Vehicles universe, which is an idealization of simple mobile robots, after the work of Braitenberg. The first thread of results consists in analyzing such simple sensorimotor cascades and proposing models of varying complexity that can be learned from data. The second thread regards how to properly formalize the notions of \"absence of assumptions\", as a particular form of invariance that the bootstrapping agent must satisfy, and proposes some invariance-based design techniques.", "doi": "10.7907/PWVS-2Q74", "publication_date": "2013", "thesis_type": "phd", "thesis_year": "2013" }, { "id": "thesis:6718", "collection": "thesis", "collection_id": "6718", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10192011-161454857", "type": "thesis", "title": "Analysis, Design, and in vitro Implementation of Robust Biochemical Networks", "author": [ { "family_name": "Franco", "given_name": "Elisa", "clpid": "Franco-Elisa" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Winfree", "given_name": "Erik", "clpid": "Winfree-E" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Winfree", "given_name": "Erik", "clpid": "Winfree-E" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Rothemund", "given_name": "Paul W. K.", "clpid": "Rothemund-P-W-K" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The functionalities of every living organism are wired in the biochemical interactions among proteins, nucleic acids, and all the other molecules that constitute life's building blocks. Understanding the general design principles of this \"hardware of life\" is an exciting and challenging task for modern bioengineers. In this thesis, I focus on the topic of molecular network robustness: I investigate several design rules guaranteeing desired functionalities in specific systems, despite their components variability. Experimental verifications of such design schemes are carried out using \\emph{in vitro} transcriptional circuits, a minimal analogue of cellular genetic networks.
\r\n \r\nThe first problem I consider is flux control, which is a fundamental feature for the correct performance of biochemical systems. I describe a simple model problem where two reagents bind stoichiometrically to form an output product. In the absence of any regulation, imbalances in the reagent production rates can cause accumulation of unused molecules, and limit the output flow. To match the reagents' flux robustly with respect to the open loop rates, I propose the use of negative or positive feedback schemes that rely on competitive binding. Such schemes are modeled through ordinary differential equations and implemented using transcriptional circuits; data are presented showing the performance of the two approaches.
\r\n \r\nThe second topic I examine is the functional robustness of interconnected networks. Molecular devices characterized in isolation may lose their properties once interconnected. This challenge is illustrated with a case study: a synthetic transcriptional clock is used to time conformational changes in a molecular nanomachine called DNA tweezers. Mass conservation introduces parasitic interactions that perturb the oscillator trajectories proportionally to the total amount of tweezers \"load\". To overcome this problem, we can use a transcriptional switch that acts as a buffer amplifier, achieving signal propagation and at the same time reducing the perturbations on the source of signal.
\r\n\r\nFinally, I describe a general class of control-theoretic methods to analyze structural robustness in natural biological systems. Using Lyapunov theory and set invariance, the stability properties of several well-known case studies are analytically demonstrated. The key feature of this analysis is its reliance on parameter-independent models, which only capture essential dynamic interactions between molecular species.
\r\n \r\n", "doi": "10.7907/1C3S-FA59", "publication_date": "2012-06", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:6749", "collection": "thesis", "collection_id": "6749", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12102011-161913831", "primary_object_url": { "basename": "DionysiosBarmpoutis-PhDThesis.pdf", "content": "final", "filesize": 1147053, "license": "other", "mime_type": "application/pdf", "url": "/6749/1/DionysiosBarmpoutis-PhDThesis.pdf", "version": "v6.0.0" }, "type": "thesis", "title": "Network Structure Optimization with Applications to Minimizing Variance and Crosstalk", "author": [ { "family_name": "Barmpoutis", "given_name": "Dionysios", "clpid": "Barmpoutis-Dionysios" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Abu-Mostafa", "given_name": "Yaser S.", "clpid": "Abu-Mostafa-Y-S" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis provides a unified methodology for analyzing structural properties of graphs, along with their applications. In the last several years, the field of complex networks has been extensively studied, and it is now well understood that the way a large network is built is closely intertwined with its function. Structural properties have an impact on the function of the network, and the form of many systems has been evolved in order to optimize for given functions. Despite the great progress, particularly in how structural attributes affect the various network functions, there is a significant gap in the quantitative study of how much these properties can change in a network without a significant impact on the functionality of the system, or what the bounds of these structural attributes are. Here, we find and analytically prove tight bounds of global graph properties, as well as the form of the graphs that achieve these bounds. The attributes studied include the network efficiency, radius, diameter, average distance, betweenness centrality, resistance distance, and average clustering. All of these qualities have a direct impact on the function of the network, and finding the graph that optimizes one or more of them is of interest when designing a large system. In addition, we measure how sensitive these properties are with respect to random rewirings or addition of new edges, since designing a network with a given set of constraints may include a lot of trade-offs. This thesis also studies properties that are of interest in both natural and engineered networks, such as maximum immunity to crosstalk interactions and random noise. We are primarily focused on networks where information is transmitted through a means that is accessible by all the individual units of the network and the interactions among the different entities that comprise it do not necessarily have a dedicated mechanism that facilitates information transmission, or isolates them from other parts of the network. Two examples of this class are biological and chemical reaction networks. Such networks suffer from unwanted crosstalk interactions when two or more units spuriously interact with each other. In addition, they are subject to random fluctuations in their output, both due to noisy inputs and because of the random variance of their parameters. These two types of randomness affect the behavior of the system in ways that are intrinsically different. We examine the network topologies that accentuate or alleviate the effect of random variance in the network for both directed and undirected graphs, and find that increasing the crosstalk among different parts reduces the output variance but also contributes to a slower response.\r\n", "doi": "10.7907/ER8Y-ZK49", "publication_date": "2012", "thesis_type": "phd", "thesis_year": "2012" }, { "id": "thesis:7150", "collection": "thesis", "collection_id": "7150", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06082012-142445518", "type": "thesis", "title": "Peak-Seeking Controller for Real-Time Mobile Satellite Tracking", "author": [ { "family_name": "Karol", "given_name": "Robert Frederick", "clpid": "Karol-Robert-Frederick" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "None", "given_name": "None" } ], "local_group": [ { "literal": "GALCIT" }, { "literal": "Senior Undergraduate Thesis Prize" }, { "literal": "div_eng" } ], "abstract": "Increasingly tightened restrictions on antenna beam-width force the use of higher performance hardware in gimbaled satellite communication transceivers. The need for more precise hardware is forcing the price of gimbal-mounted satellites antennas higher. In addition to the increased cost, as more satellites are launched every year, the demand for antenna systems which can receive data from the new satellites grows. Although algorithms capable of tracking a satellite with a mobile antenna have been developed and characterized in detail, instabilities in the system and cross-axis eects degrade the performance. Since an increase in tracking capability would be most benecial if it did not require extensive hardware changes, this project focuses on improvements to the conical scanning algorithm. An algorithm which is one of the oldest, and most common mobile satellite tracking system implementations. Initial work was done on developing and characterizing a new estimator which could be used while continuing to scan the antenna with as few software modications as possible. After successful development, work was done to eliminate the induced scanning motion and gain observability in the system using nothing but the noise inherent in the system.", "doi": "10.7907/CCW3-V522", "publication_date": "2012", "thesis_type": "senior_minor", "thesis_year": "2012" }, { "id": "thesis:6510", "collection": "thesis", "collection_id": "6510", "cite_using_url": "https://resolver.caltech.edu/CaltechThesis:06082011-191034348", "primary_object_url": { "basename": "sbfuller_dissertation2011.pdf", "content": "final", "filesize": 16285464, "license": "other", "mime_type": "application/pdf", "url": "/6510/1/sbfuller_dissertation2011.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Steady as She Goes: Visual Autocorrelators and Antenna-Mediated Airspeed Feedback in the Control of Flight Dynamics in Fruit Flies and Robotics ", "author": [ { "family_name": "Fuller", "given_name": "Sawyer Buckminster", "clpid": "Fuller-Sawyer-Buckminster" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Dickinson", "given_name": "Michael H.", "clpid": "Dickinson-M-H" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Straw", "given_name": "Andrew", "clpid": "Straw-A" }, { "family_name": "Dickinson", "given_name": "Michael H.", "clpid": "Dickinson-M-H" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Achieving agile autonomous flight by an insect-sized micro aerial vehicle (MAV) will require improved technology that is radically smaller, lighter, and more power-efficient. One animal that has solved the problem is the fly, a virtuoso among insect flyers whose nervous system can perform sophisticated aerial maneuvers under severe computational constraints. This thesis is concerned with understanding and emulating the dynamics of the fly's feedback control system. Because vision is noisy and information rich, processing time may a problem for a fast-moving MAV or fly. By tracking the fruit fly Drosophila melanogaster in free flight in gusts of wind, I found that they incorporate feedback from wind-sensing antennae in a fast feedback loop that dampens the forward-flight dynamics. The slower dynamics are easier to control for long-delay visual feedback, making the fly more robust to the limitations of its visual system. Using the fly as inspiration, I designed a minimal, visual autocorrelation based controller that used a small array of visual sensors to stabilize a fan-actuated hovercraft robot in a narrow corridor. Using a model for correlators developed for the robot, I showed that a uniform array of visual correlators was sufficient to explain the free-flight velocity regulation behavior of flies, rather than a different model. In addition to illustrating the benefits of concurrent scientific analysis and engineering synthesis, the results give new insight into how to control small biological and man-made flying vehicles using limited, noisy sensors.", "doi": "10.7907/Z3D0-GG27", "publication_date": "2011", "thesis_type": "phd", "thesis_year": "2011" }, { "id": "thesis:6391", "collection": "thesis", "collection_id": "6391", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05132011-113642762", "primary_object_url": { "basename": "Thesis_Caltech.pdf", "content": "final", "filesize": 3285748, "license": "other", "mime_type": "application/pdf", "url": "/6391/1/Thesis_Caltech.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Large-Scale Complex Systems: From Antenna Circuits to Power Grids", "author": [ { "family_name": "Lavaei", "given_name": "Javad", "clpid": "Lavaeiyanesi-Javad" } ], "thesis_advisor": [ { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Low", "given_name": "Steven H.", "clpid": "Low-S-H" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This dissertation is motivated by the lack of scalable methods for the analysis and synthesis of different large-scale complex systems appearing in electrical and computer engineering. The systems of interest in this work are power networks, analog circuits, antenna systems, communication networks and distributed control systems. By combining theories from control and optimization, the high-level objective is to develop new design tools and algorithms that explicitly exploit the physical properties of these practical systems (e.g., passivity of electrical elements or sparsity of network topology). To this end, the aforementioned systems are categorized intro three classes of systems, and then studied in Parts I, II, and III of this dissertation, as explained below:
\r\n\r\nPower networks: In Part I of this work, the operation planning of power networks using efficient algorithms is studied. The primary focus is on the optimal power flow (OPF) problem, which has been studied by the operations research and power communities in the past 50 years with little success. In this part, it is shown that there exists an efficient method to solve a practical OPF problem along with many other energy-related optimization problems such as dynamic OPF or security-constrained OPF. The main reason for the successful convexification of these optimization problems is also identified to be the physical properties of a power circuit, especially the passivity of transmission lines.
\r\n\r\nCircuits and systems: Motivated by different applications in power networks, electromagnetics and optics, Part II of this work studies the fundamental limits associated with the synthesis of a particular type of linear circuit. It is shown that the optimal design of the parameters of this type of circuit can be performed in polynomial time if the circuit is passive and there are sufficient number of controllable (unknown) parameters. This result introduces a trade-off between the design simplicity and the implementation complexity for an important class of linear circuits. As an application of this methodology, the design of smart antennas is also studied; the goal is to devise an intelligent wireless communication device in order to avoid co-channel interference, power consumption in undesired directions and security issues. Since the existing smart antennas are either hard to program or hard to implement, a new type of smart antenna is synthesized by utilizing tools from algebraic geometry, control, communications, and circuits, which is both easy to program and easy to implement.
\r\n \r\nDistributed computation: The first problem tackled in Part III of this work is a very simple type of distributed computation, referred to as quantized consensus, which aims to compute the average of a set of numbers using a distributed algorithm subject to a quantization error. It is shown that quantized consensus is reached by means of a recently proposed gossip algorithm, and the convergence time of the algorithm is also derived. The second problem studied in Part III is a more advanced type of distributed computation, which is the distributed resource allocation problem for the Internet. The existing distributed resource allocation algorithms aim to maximize the utility of the network only at the equilibrium point and ignore the transient behavior of the network. To address this issue, it is shown that optimal control theory provides powerful tools for designing distributed resource allocation algorithms with a guaranteed real-time performance.
\r\n\r\nThe results of this work can all be integrated to address real-world interdisciplinary problems, such as the design of the next generation of the electrical power grid, named the Smart Grid.
\r\n\r\n", "doi": "10.7907/CM46-5R54", "publication_date": "2011", "thesis_type": "phd", "thesis_year": "2011" }, { "id": "thesis:6441", "collection": "thesis", "collection_id": "6441", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05252011-164957222", "primary_object_url": { "basename": "Moore_thesis.pdf", "content": "final", "filesize": 9726477, "license": "other", "mime_type": "application/pdf", "url": "/6441/1/Moore_thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Discrete Mechanics and Optimal Control for Space Trajectory Design", "author": [ { "family_name": "Moore", "given_name": "Ashley", "clpid": "Moore-Ashley" } ], "thesis_advisor": [ { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Desbrun", "given_name": "Mathieu", "clpid": "Desbrun-M" }, { "family_name": "Ortiz", "given_name": "Michael", "clpid": "Ortiz-M" }, { "family_name": "Ober-Blobaum", "given_name": "Sina", "clpid": "Ober-Blobaum-S" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Space trajectory design is often achieved through a combination of dynamical systems theory and optimal control. The union of trajectory design techniques utilizing invariant manifolds of the planar circular restricted three-body problem and the optimal control scheme Discrete Mechanics and Optimal Control (DMOC) facilitates the design of low-energy trajectories in the N-body problem. In particular, DMOC is used to optimize a trajectory from the Earth to the Moon in the 4-body problem, removing the mid-course change in velocity usually necessary for such a trajectory while still exploiting the structure from the invariant manifolds.
\r\n\r\nThis thesis also focuses on how to adapt DMOC, a method devised with a constant step size, for the highly nonlinear dynamics involved in trajectory design. Mesh refinement techniques that aim to reduce discretization errors in the solution and energy evolution and their effect on DMOC optimization are explored and compared with trajectories created using time adaptive variational integrators.
\r\n\r\nFurthermore, a time adaptive form of DMOC is developed that allows for a variable step size that is updated throughout the optimization process. Time adapted DMOC is based on a discretization of Hamilton's principle applied to the time adapted Lagrangian of the optimal control problem. Variations of the discrete action of the optimal control Lagrangian lead to discrete Euler-Lagrange equations that can be enforced as constraints for a boundary value problem. This new form of DMOC leads to the accurate and efficient solution of optimal control problems with highly nonlinear dynamics. Time adapted DMOC is tested on several space trajectory problems including the elliptical orbit transfer in the 2-body problem and the reconfiguration of a cubesat.
\r\n", "doi": "10.7907/ZXTG-V056", "publication_date": "2011", "thesis_type": "phd", "thesis_year": "2011" }, { "id": "thesis:5864", "collection": "thesis", "collection_id": "5864", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05272010-153304667", "primary_object_url": { "basename": "main.pdf", "content": "final", "filesize": 3350152, "license": "other", "mime_type": "application/pdf", "url": "/5864/1/main.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Formal Methods for Design and Verification of Embedded Control Systems: Application to an Autonomous Vehicle", "author": [ { "family_name": "Wongpiromsarn", "given_name": "Tichakorn", "clpid": "Wongpiromsarn-Tichakorn" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" }, { "family_name": "Holzmann", "given_name": "Gerard J.", "clpid": "Holzmann-G-J" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The design of reliable embedded control systems inherits the difficulties involved in designing both control systems and distributed (concurrent) computing systems. Design bugs in these systems may arise from the unforeseen interactions among the computing, communication and control subsystems. Motivated by the difficulties of finding this type of design bugs, this thesis develops mathematical frameworks, based on formal methods, to facilitate the design and analysis of such embedded systems. An expressive specification language of linear temporal logic (LTL) is used to specify the desired system properties. The practicality of the proposed frameworks is demonstrated through autonomous vehicle case studies and autonomous urban driving problems.
\r\n\r\nOur approach incorporates methodology from computer science and control, including model checking, theorem proving, synthesis of digital designs, reachability analysis, Lyapunov-type methods and receding horizon control. This thesis consists of two complementary parts, namely, verification and design. First, we introduce Periodically Controlled Hybrid Automata (PCHA), a subclass of hybrid automata that abstractly captures a common design pattern in embedded control systems. New sufficient conditions that exploit the structure of PCHAs in order to simplify their invariant verification are presented.
\r\n\r\nAlthough the aforementioned technique simplifies an invariant verification of PCHAs, finding a proper invariant remains a challenging problem. To complement the verification efforts, in the second part of the thesis, we present a methodology for automatic synthesis of embedded control software that provides a formal guarantee of system correctness, with respect to its desired properties expressed in linear temporal logic. The correctness of the system is guaranteed even in the presence of an adversary (typically arising from changes in the environments), disturbances and modeling errors. A receding horizon framework is proposed to alleviate the associated computational complexity of LTL synthesis. The effectiveness of this framework is demonstrated through the autonomous urban driving problems.
\r\n", "doi": "10.7907/XZ3X-7V51", "publication_date": "2010", "thesis_type": "phd", "thesis_year": "2010" }, { "id": "thesis:3252", "collection": "thesis", "collection_id": "3252", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-08272008-121822", "primary_object_url": { "basename": "Ling_Shi_thesis.pdf", "content": "final", "filesize": 1526490, "license": "other", "mime_type": "application/pdf", "url": "/3252/1/Ling_Shi_thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Resource Optimization for Networked Estimator with Guaranteed Estimation Quality", "author": [ { "family_name": "Shi", "given_name": "Ling", "clpid": "Shi-Ling" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" }, { "family_name": "Johansson", "given_name": "Karl Henrik", "clpid": "Johansson-K-H" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Advances in fabrication, modern sensor and communication technologies, and computer architecture have enabled a variety of new networked sensing and control applications. However, many difficulties are inherent with these systems, for example, the constrained communication and computation capabilities, and limited energy resources, which are frequently seen in a wireless sensor network. As a consequence, the networks typically induce many new issues such as limited bandwidth, packet loss, and delay. Estimation and control over such networks thus require new design paradigms beyond traditional sampled-data control, as the aforementioned constraints undoubtedly affect system performance or even stability. In this thesis work, I consider the problem of state estimation over networks. As communication, computation, and energy are scarce resources in such networks, I focus on optimizing the use of them. When the state estimation is carried out over a sensor network, I consider the problem of minimizing the sensor energy usage and maximizing the network lifetime. When the state estimation is carried out over a packet-delaying network, I consider the problem of minimizing the buffer length at the remote state estimator. In each scenario, a certain desired level of estimation quality is guaranteed.\r\n", "doi": "10.7907/DTCJ-BN07", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:3823", "collection": "thesis", "collection_id": "3823", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09292008-204618", "primary_object_url": { "basename": "Akellythesis090408.pdf", "content": "final", "filesize": 1100957, "license": "other", "mime_type": "application/pdf", "url": "/3823/1/Akellythesis090408.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "A Constitutive Relation for Shape-Memory Alloys", "author": [ { "family_name": "Kelly", "given_name": "Alex", "clpid": "Kelly-Alex" } ], "thesis_advisor": [ { "family_name": "Bhattacharya", "given_name": "Kaushik", "clpid": "Bhattacharya-K" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Bhattacharya", "given_name": "Kaushik", "clpid": "Bhattacharya-K" }, { "family_name": "Ravichandran", "given_name": "Guruswami", "clpid": "Ravichandran-G" }, { "family_name": "Greer", "given_name": "Julia R.", "clpid": "Greer-J-R" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The novel nonlinear thermoelastic behavior of shape-memory alloys (SMAs) makes them increasingly desirable as components in many advanced technological applications. In order to incorporate these materials into engineering designs, it is important to develop an understanding of their constitutive response. The purpose of this thesis is to develop a constitutive model of shape-memory polycrystals that is faithful to the underlying micromechanics while remaining simple enough for utility in engineering analysis and design.
\r\n\r\nWe present a model in which the material microstructure is represented macroscopically as a recoverable transformation strain that is constrained by the texture of the polycrystal. The point of departure in this model is the recognition that the mechanics of the onset of martensitic transformation are fundamentally different from those of its saturation. Consequently, the constraint on the set of recoverable strains varies throughout the transformation process. The effects of constraint geometry on the constitutive response of SMAs are studied. Several well known properties of SMAs are demonstrated. Finally the model is simply implemented in a commercial finite-element package as a proof of the concept.
\r\n", "doi": "10.7907/YMT5-AX47", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:2271", "collection": "thesis", "collection_id": "2271", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05292009-111937", "primary_object_url": { "basename": "thesis.pdf", "content": "final", "filesize": 5631440, "license": "other", "mime_type": "application/pdf", "url": "/2271/11/thesis.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Safety Verification and Failure Analysis of Goal-Based Hybrid Control Systems", "author": [ { "family_name": "Braman", "given_name": "Julia Marie Badger", "clpid": "Braman-Julia-Marie-Badger" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Beck", "given_name": "James L.", "clpid": "Beck-J-L" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The success of complex autonomous robotic systems depends on the quality and correctness of their fault tolerant control systems. A goal-based approach to fault tolerant control, which is modeled after a software architecture developed at the Jet Propulsion Laboratory, uses networks of goals to control autonomous systems. The complex conditional branching of the control program makes safety verification necessary. Three novel verification methods are presented. In the first, goal networks are converted to linear hybrid automata via a bisimulation. The converted automata can then be verified against an unsafe set of conditions using an existing symbolic model checker such as PHAVer. Due to the complexity issues that result from this method, a design for verification software tool, the SBT Checker, was developed to create goal networks that have state-based transitions. Goal networks that have state-based transitions can be converted to hybrid automata whose locations' invariants contain all information necessary to determine the transitions between the locations. An original verification software called InVeriant can then be used to find unsafe locations of linear hybrid systems based on the locations\u2019 invariants and rate conditions, which are compared to the unsafe set of conditions. The reachability of the unsafe locations depends only on the reachability of the states of the state variables constrained in the locations' invariants from those state variables' initial conditions. In cases where this reachability condition is not trivially true, the software efficiently searches for a path to the unsafe locations using properties of the system. The third verification method is the calculation of the failure probability of the verified hybrid control system due to state estimation uncertainty, which is extremely important in autonomous systems that rely heavily on the state estimates made from sensor measurements. Finally, two significant example goal network control programs, one for a complex rover and another for a proposed aerobot mission to Titan, a moon of Saturn, are verified using the three techniques presented.", "doi": "10.7907/3H42-BF56", "publication_date": "2009", "thesis_type": "phd", "thesis_year": "2009" }, { "id": "thesis:1664", "collection": "thesis", "collection_id": "1664", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05072008-131735", "primary_object_url": { "basename": "Carson_Thesis_1sided.pdf", "content": "final", "filesize": 1904222, "license": "other", "mime_type": "application/pdf", "url": "/1664/1/Carson_Thesis_1sided.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Robust Model Predictive Control with a Reactive Safety Mode", "author": [ { "family_name": "Carson", "given_name": "John Maurice, III", "clpid": "Carson-John-Maurice-III" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "MacMynowski", "given_name": "Douglas G.", "clpid": "MacMynowski-D-G" }, { "family_name": "Acikmese", "given_name": "Behcet", "clpid": "Acikmese-B" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Acikmese", "given_name": "Behcet", "clpid": "Acikmese-B" }, { "family_name": "MacMynowski", "given_name": "Douglas G.", "clpid": "MacMynowski-D-G" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Control algorithms suitable for online implementation in engineering applications, such as aerospace and mechanical vehicles, often require adherence to physical state and control constraints. Additionally, the chosen algorithms must provide robustness to uncertainty affecting both the system dynamics and the constraints. As further autonomy is built into these systems, the algorithms must be capable of blending multiple operational modes without violating the intrinsic constraints. Further, for real-time applications, the implemented control algorithms must be computationally efficient and reliable. The research in this thesis approaches these application needs by building upon the framework of MPC (Model Predictive Control).
\r\n\r\nThe MPC algorithm makes use of a nominal dynamics model to predict and optimize the response of a system under the application of a feedforward control policy, which is computed online in a finite-horizon optimization problem. The MPC algorithm is quite general and can be applied to linear and nonlinear systems and include explicit state and control constraints. The finite-horizon optimization is advantageous given the finite online computational capabilities in practical applications. Further, recursively re-solving the finite-horizon optimization in a compressing- or receding-horizon manner provides a form of closed-loop control that updates the feedforward control policy by setting the nominal state at re-solve to the current actual state. However, uncertainty between the nominal model and the actual system dynamics, along with constraint uncertainty can cause feasibility, and hence, robustness issues with the traditional MPC algorithm.
\r\n\r\nIn this thesis, an R-MPC (Robust and re-solvable MPC) algorithm is developed for uncertain nonlinear systems to address uncertainty affecting the dynamics. The R-MPC control policy consists of two components: the feedforward component that is solved online as in traditional MPC; and a separate feedback component that is determined offline, based on a characterization of the uncertainty between the nominal model and actual system. The addition of the feedback policy generates an invariant tube that ensures the actual system trajectories remain in the proximity of the nominal feedforward trajectory for all time. Further, this tube provides a means to theoretically guarantee continued feasibility and thus re-solvability of the R-MPC algorithm, both of which are required to guarantee asymptotic stability.
\r\n\r\nTo address uncertainty affecting the state constraints, an SR-MPC (Safety-mode augmented R-MPC) algorithm is developed that blends a reactive safety mode with the R-MPC algorithm for uncertain nonlinear systems. The SR-MPC algorithm has two separate operational modes: standard mode implements a modified version of the R-MPC algorithm to ensure asymptotic convergence to the origin; safety mode, if activated, guarantees containment within an invariant set about a safety reference for all time. The standard mode modifies the R-MPC algorithm with a special constraint to ensure safety-mode availability at any time. The safety-mode control is provided by an offline designed control policy that can be activated at any time during standard mode. The separate, reactive safety mode provides robustness to unexpected state-constraint changes; e.g., other vehicles crossing/stopping in the feasible path, or unexpected ground proximity in landing scenarios.
\r\n\r\nExplicit design methods are provided for implementation of the R-MPC and SR-MPC algorithms on a class of systems with uncertain nonlinear terms that have norm-bounded derivatives. Further, a discrete SR-MPC algorithm is developed that is more broadly applicable to real engineering systems. The discrete algorithm is formulated as a second-order cone program that can be solved online in a computationally efficient manner by using interior-point algorithms, which provide convergence guarantees in finite time to a prescribed level of accuracy.
\r\n\r\nThis discrete SR-MPC algorithm is demonstrated in simulation of a spacecraft descent toward a small asteroid where there is an uncertain gravity model, as well as errors in the expected surface altitude. Further, realistic effects such as control-input uncertainty, sensor noise, and unknown disturbances are included to further demonstrate the applicability of the discrete SR-MPC algorithm in a realistic implementation.
", "doi": "10.7907/S0VN-VE35", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:682", "collection": "thesis", "collection_id": "682", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-02192008-153449", "type": "thesis", "title": "Real-Time Trajectory Generation for Constrained Nonlinear Dynamical Systems Using Non-Uniform Rational B-Spline Basis Functions", "author": [ { "family_name": "Flores Contreras", "given_name": "Melvin Estuardo", "clpid": "Flores-Contreras-Melvin-Estuardo" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Milam", "given_name": "Mark B.", "clpid": "Milam-M-B" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The thesis describes a new method for obtaining minimizers for optimal control problems whose minima serve as control policies for guiding nonlinear dynamical systems to achieve prescribed goals under imposed trajectory and actuator constraints. One of the major contributions of the present work resides in the approximation of such minimizers by piecewise polynomial functions expressed in terms of a linear combination of non-uniform rational B-spline (NURBS) basis functions and the judicious exploitation of the properties of the resulting NURBS curves to improve the computational effort often associated with solving optimal control problems for constrained dynamical systems.
\r\n\r\nIn particular, by exploiting the two structures combined in a NURBS curve, NURBS basis functions and an associated union of overlapping polytopes constructed from the coefficients of the linear combination, we are able to separate an optimal control problem into two subproblems | guidance and obstacle avoidance, making the original problem tractable. This is accomplished by laying out the union of overlapping polytopes in such a way that they delineate a section of space that avoids all obstacles and then manipulating the NURBS basis functions to obtain trajectories that are guaranteed to remain bounded by this section of space without explicitly including the conjunction of disjunctions naturally induced from obstacles into the guidance problem.
\r\n\r\nIn addition, we show how one can construct systematically a feasible region that corresponds to a NURBS parameterization starting from an ordered union of pairwise adjacently overlapping nonempty compact convex sets. Specifically, we show how to setup a nonlinear programming problem to solve for the feasible region in terms of an ordered union of pairwise adjacently overlapping polytopes with nonempty interiors by maximizing the sum of their volumes and starting from a feasible region described by an ordered union of pairwise adjacently overlapping nonempty convex compact simi-algebraic sets. Finally, we show how this strategy can be implemented practically for an autonomous system traversing an urban environment.
\r\n\r\nFinally, this work culminated in the filing of patent US20070179685 on behalf of Northrop Grumman for the Space Technology sector and in the development of the NURBS-based OTG software package. This C++ package contains the theoretical results of this thesis in the form of an object-oriented implementation optimized for real-time trajectory generation.
\r\n\r\n", "doi": "10.7907/TK01-9X60", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:4374", "collection": "thesis", "collection_id": "4374", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-11022007-104734", "primary_object_url": { "basename": "waydo-thesis-final-oneside.pdf", "content": "final", "filesize": 5568170, "license": "other", "mime_type": "application/pdf", "url": "/4374/1/waydo-thesis-final-oneside.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Explicit Object Representation by Sparse Neural Codes", "author": [ { "family_name": "Waydo", "given_name": "Stephen J.", "clpid": "Waydo-Stephen-J" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Koch", "given_name": "Christof", "orcid": "0000-0001-6482-8067", "clpid": "Koch-C" } ], "thesis_committee": [ { "family_name": "Koch", "given_name": "Christof", "orcid": "0000-0001-6482-8067", "clpid": "Koch-C" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Olshausen", "given_name": "Bruno", "clpid": "Olshausen-B" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Perona", "given_name": "Pietro", "orcid": "0000-0002-7583-5809", "clpid": "Perona-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Neurons have been identified in the human medial temporal lobe (MTL) that display a strong selectivity for only a few stimuli (such as familiar individuals or landmark buildings) out of perhaps 100 presented to the test subject. While highly selective for a particular object or category, these cells are remarkably insensitive to different presentations (i.e., different poses and views) of their preferred stimulus. This invariant, sparse, and explicit representation of the world may be crucial to the transformation of complex visual stimuli into more abstract memories. In this thesis I first discuss the issue of how best to quantify sparseness, particularly in very sparse systems where biases are significant, and show the results of this analysis applied to human MTL data. I also provide an overview of existing results from other investigators on measuring sparseness both elsewhere along the primate visual pathway and in selected other sensory processing systems. From there I move into the computational realm. Sparse coding as a computational constraint applied to the representation of natural images has been shown to produce receptive fields strikingly similar to those observed in mammalian primary visual cortex. I apply sparse coding as a model for processing further along the visual hierarchy: not directly to images but rather to an invariant feature-based representation of images analogous to that found in the inferotemporal cortex. This combination of sparseness and invariance naturally leads to explicit category representation. That is, by exposing the model to different images drawn from different categories, units develop that respond selectively to different categories. After extending an existing model of sparse coding and providing some mathematical analysis of its operation, I show results obtained by applying this method both to unsupervised category discovery in images and to differentiation between images of different individuals.\r\n", "doi": "10.7907/1XY7-2H19", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:5073", "collection": "thesis", "collection_id": "5073", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-12192007-153619", "primary_object_url": { "basename": "MSE_thesis.pdf", "content": "final", "filesize": 1506285, "license": "other", "mime_type": "application/pdf", "url": "/5073/2/MSE_thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Managing Information in Networked and Multi-Agent Control Systems", "author": [ { "family_name": "Epstein", "given_name": "Michael Steven", "clpid": "Epstein-Michael-Steven" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "MacMynowski", "given_name": "Douglas G.", "clpid": "MacMynowski-D-G" }, { "family_name": "Chandy", "given_name": "K. Mani", "clpid": "Chandy-K-M" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Traditional feedback control systems give little attention to issues associated with the flow of information through the feedback loop. Typically implemented with dedicated communication links that deliver nearly precise, reliable and non-delayed information, researchers have not needed to concern themselves with issues related to quantized, delayed and even lost information. With the advent of newer technologies and application areas that pass information through non-reliable networks, these issues can not be ignored. In recent years the field of Networked Control Systems (NCS) has emerged to describe situations where these issues are present. The research in this field focuses on quantifying performance degradations in the presence of network effects and proposing algorithms for managing the information flow to counter those negative effects. In this thesis I propose and analyze algorithms for managing information flow for several NCS scenarios; state estimation with lossy measurement signals, using input buffers to reduce the frequency of communication with a remote plant, and performing state estimation when control signals are transmitted to a remote plant via a lossy communication link with no acknowledgement signal at the estimator. Multi-agent coordinated control systems serve as a prime example of an emerging area of feedback control systems that utilize feedback loops with information passed through possibly imperfect communication networks. In these systems, agents use a communication network to exchange information in order to achieve a desired global objective. Hence managing the information flow has a direct impact on the performance of the system. I also explore this area by focusing on the problem of multi-agent average consensus. I propose an algorithm based on a hierarchical decomposition of the communication topology to speed up the time to convergence. For all these topics I focus on designing intuitive algorithms that intelligently manage the information flow and provide analysis and simulations to illustrate their effectiveness.\r\n", "doi": "10.7907/84NT-9N46", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:5976", "collection": "thesis", "collection_id": "5976", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07212010-164605005", "primary_object_url": { "basename": "Thesis_report.pdf", "content": "final", "filesize": 1080757, "license": "other", "mime_type": "application/pdf", "url": "/5976/1/Thesis_report.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Nonlinear Three-Dimensional Trajectory Following: Simulation and Application", "author": [ { "family_name": "Hines", "given_name": "George Herbert", "clpid": "Hines-George-Herbert" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "None", "given_name": "None" } ], "local_group": [ { "literal": "GALCIT" }, { "literal": "div_eng" } ], "abstract": "In light of recent military requirements for unmanned and autonomous vehicles, research into methods of designing arbitrary three-dimensional trajectories and controlling aircraft along them has become vital. In this report, we explore two methods of nonlinear control for the purpose of following three-dimensional trajectories and paths. First, prior work on a dynamic feedback linearization exploiting the differential flatness of the ideal airplane is adapted with the intent of implementing it on a physical testbed in MIT\u2019s Realtime indoor Autonomous Vehicle test ENvironment (RAVEN), but poor behavior\u2014both in simulation and in hardware\u2014under moderate levels of joint parameter uncertainty thwarted attempts at implementation. Additionally, the differential flatness technique in its pure form follows trajectories, which are sometimes inferior intuitively and practically to paths. In the context of unmanned air vehicle (UAV) flight in gusty environments, this motivated the extension of prior work on two-dimensional path following to three-dimensions, and simulations are presented in which the fully nonlinear controller derived from differential flatness follows a trajectory that is generated dynamically from a path. The three-dimensional path-following logic is actually implemented in RAVEN, and results are presented that demonstrate good vertical rise time in response to a step input and centimeter accuracy in vertical and lateral tracking. Future directions are proposed.", "doi": "10.7907/YE4Q-FV39", "publication_date": "2008", "thesis_type": "senior_minor", "thesis_year": "2008" }, { "id": "thesis:10642", "collection": "thesis", "collection_id": "10642", "cite_using_url": "https://resolver.caltech.edu/CaltechThesis:01112018-113614173", "primary_object_url": { "basename": "ZhonglinJZhangThesis_seniorthesis.pdf", "content": "final", "filesize": 3735532, "license": "other", "mime_type": "application/pdf", "url": "/10642/1/ZhonglinJZhangThesis_seniorthesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Identification of Lagrangian Coherent Structures Around Swimming Jellyfish from Experimental Time-Series Data", "author": [ { "family_name": "Zhang", "given_name": "Zhonglin Johnny", "clpid": "Zhang-Zhonglin-Johnny" } ], "thesis_advisor": [ { "family_name": "Dabiri", "given_name": "John O.", "clpid": "Dabiri-J-O" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "GALCIT" }, { "literal": "div_eng" } ], "abstract": "The unique body kinematics of jellyfish embodies the most intriguing form of biological propulsion, which makes jellyfish a promising resource for developing new locomotion systems. Instead of the conventional Eulerian method, we take an unprecedented Lagrangian approach by tracking individual fluid particles around a swimming jellyfish over a finite time interval. Specifically, we utilize the Lagrangian coherent structures (LCS) in the flow field to investigate the flow characteristics around a jellyfish. LCS are separatrices or invariant manifolds, which separate the flow field into distinct regions. To locate the LCS in the flow, we employ the concept of the finite-time Lyapunov Exponent (FTLE), which measures the rate at which particles diverge from each other, and LCS are identified as the high-value ridges in the FTLE field. This method is implemented and validated by analysis on two-dimensional vortex dipole flow, two-dimensional experimental time-series data, and Hill\u2019s vortex sphere. This method is expected to extract LCS from three-dimensional experimental time-series data.", "doi": "10.7907/KK45-ZV02", "publication_date": "2008", "thesis_type": "senior_minor", "thesis_year": "2008" }, { "id": "thesis:2320", "collection": "thesis", "collection_id": "2320", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05302008-141602", "primary_object_url": { "basename": "00_mjdunlop_complete_thesis.pdf", "content": "final", "filesize": 4934029, "license": "other", "mime_type": "application/pdf", "url": "/2320/1/00_mjdunlop_complete_thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Dynamics and Correlated Noise in Gene Regulation", "author": [ { "family_name": "Dunlop", "given_name": "Mary Julia", "orcid": "0000-0002-9261-8216", "clpid": "Dunlop-Mary-Julia" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "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": "Elowitz", "given_name": "Michael B.", "orcid": "0000-0002-1221-0967", "clpid": "Elowitz-M-B" }, { "family_name": "Phillips", "given_name": "Robert B.", "orcid": "0000-0003-3082-2809", "clpid": "Phillips-R" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Gene regulatory interactions are context dependent, active in some cell types or cellular states but not in others. In this thesis we present a method for determining when a regulatory link is active given temporal measurements of gene expression. Correlations in time-series data are used to determine how genes influence each other and their causal relationships. Natural stochastic noise is shown to aid in the process of network identification by perturbing the expression of genes; the speed and direction at which the noisy signal propagates shows how the network is connected. Cross correlation functions are used to reveal time-delayed correlations.
\r\n\r\nWe develop a stochastic model of gene expression and show that by measuring correlations in cellular noise, it is possible to infer network activity and temporal properties of gene regulation. Using a linearized version of the model, we introduce a method for analytically deriving cross correlation functions for arbitrary networks. These results are validated experimentally using a synthetic gene circuit in E. coli bacteria. Single-cell time-lapse microscopy is used to measure noisy expression of multiple genes over time. Extending this work to natural systems, we study feed-forward loops and determine that certain classes of feed-forward loops are more robust to noise and parameter variations that others. Noise in two naturally occurring feed-forward loops involved in galactose utilization is measured experimentally and it is shown that neither is actively regulating its target in the conditions tested.
", "doi": "10.7907/AC8V-6S05", "publication_date": "2008", "thesis_type": "phd", "thesis_year": "2008" }, { "id": "thesis:3625", "collection": "thesis", "collection_id": "3625", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09182006-162259", "primary_object_url": { "basename": "Thesis_ZJ_Caltech_07.pdf", "content": "final", "filesize": 1131131, "license": "other", "mime_type": "application/pdf", "url": "/3625/1/Thesis_ZJ_Caltech_07.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Coordinated Control for Networked Multi-Agent Systems", "author": [ { "family_name": "Jin", "given_name": "Zhipu", "clpid": "Jin-Zhipu" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "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" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" }, { "family_name": "Doyle", "given_name": "John Comstock", "orcid": "0000-0002-1828-2486", "clpid": "Doyle-J-C" }, { "family_name": "Ho", "given_name": "Tracey C.", "clpid": "Ho-Tracey" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Coordination in networked multi-agent systems attracts significant interest in the realm of engineering. Typical examples include formations of unmanned aerial vehicles, automated highway systems, and sensor networks. One common feature for these systems is that coordinated behaviors are exhibited by interactions among agents where information exchange and manipulation are necessary. In this work, three relevant issues are investigated in detail: uniform strategy for multi-agent formation control, fast-converging consensus protocols, and packet-based state estimation over communication networks.
\r\n\r\nFormation control of multi-agent systems involves harmony among local controller design, interaction topology analysis, and objective agreement among networked agents. We propose a novel control strategy so that each agent responds to neighbors' behaviors as well as acts towards the global goal. Thus, information flows for local interactions and global objective synchronization are studied separately. Using the tools from signal flow graphs and algebraic graph theory, we show that this new strategy eases the design of local controllers by relaxing stabilizing conditions. Robustness against the link failure and scalable disturbance resistance are also discussed based on small-gain theory. Experimental results on the Caltech multi-vehicle wireless testbed are provided to verify the feasibility and efficiency of this control strategy.
\r\n\r\nConsensus protocols over communication networks are used to achieve agreement among agents. One important issue is the convergence speed. We propose multi-hop relay protocols for fast consensus seeking. Without physically changing the topology of the communication network, this type of distributed protocol increases the algebraic connectivity by employing multi-hop paths in the network. We also investigate the convergence behaviors of consensus protocols with communication delays. It is interesting that, the faster the protocol converges, the more sensitive it is to the delay. This tradeoff is identified when we investigate delay margins of multi-hop relay protocols using the frequency sweep method.
\r\n\r\nEfficiently estimating the states of other agents over communication links is also discussed in this work. When information flows in the network, packet-based data is normally not retransmitted in order to satisfy real-time requirements. Thus, packet drops and random delays are inevitable. In this context, observation data that the estimator can receive is intermittent. In order to decrease the chance of losing packets and efficiently using the limited bandwidth, we introduce multiple description source codes to manipulate the data before transmission. Using modified algebraic Riccati equations, we show that multiple description codes improve the performance of Kalman filters over a large set of packet-dropping scenarios. This problem is also generalized to the case where observation data has an independent and identical static distribution over a finite set of observation noise. Moreover, Kalman filtering with bursty packet drops is also discussed based on the two-state Markov chain model.
", "doi": "10.7907/ZRAD-XN95", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:2336", "collection": "thesis", "collection_id": "2336", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05312007-024822", "primary_object_url": { "basename": "THC_thesis.pdf", "content": "final", "filesize": 2999095, "license": "other", "mime_type": "application/pdf", "url": "/2336/1/THC_thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Intelligent Information-Gathering: Using Control for Sensing and Decision-Making", "author": [ { "family_name": "Chung", "given_name": "Timothy Hahn Deut", "clpid": "Chung-Timothy-Hahn-Deut" } ], "thesis_advisor": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Antonsson", "given_name": "Erik K.", "clpid": "Antonsson-E-K" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Information is everywhere and evolving, which necessitates both deliberate and efficient processing to acquire a good understanding of the dynamic situation, environment, or system of interest. Intelligent agents such as autonomous mobile sensors can control the way they gather information and thereby take advantage of feedback to improve the quality of that information. This approach reflects a shift from traditional \"sensing for control\" notions to \"control for sensing\" methods for addressing information-based objectives. This thesis presents several algorithms for distributed sensing tasks in the context of a team of mobile sensing agents. Applications of these types of mobile sensor networks include target tracking, dynamic environment monitoring, and distributed classification. These methods point beyond the use of sensory data for control and toward a framework for using control to improve information-based decisions made by intelligent agents. The sequential decision-theoretic framework presented herein has relevant applications in engineered systems such as search and rescue using a robotic team, as well as potential connections to natural systems including search strategies in the human vision system.", "doi": "10.7907/V5S4-4197", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:3157", "collection": "thesis", "collection_id": "3157", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-08172006-130145", "primary_object_url": { "basename": "main.pdf", "content": "final", "filesize": 2051167, "license": "other", "mime_type": "application/pdf", "url": "/3157/1/main.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Distributed Estimation and Control in Networked Systems", "author": [ { "family_name": "Gupta", "given_name": "Vijay", "clpid": "Gupta-Vijay" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" }, { "family_name": "Bruck", "given_name": "Jehoshua", "clpid": "Bruck-J" }, { "family_name": "Schulman", "given_name": "Leonard J.", "clpid": "Schulman-L-J" }, { "family_name": "Vaidyanathan", "given_name": "P. P.", "clpid": "Vaidyanathan-P-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Rapid advances in information processing, communication and sensing technologies have enabled more and more devices to be provided with embedded processors, networking capabilities and sensors. For the field of estimation and control, it is now possible to consider an architecture in which many simple components communicate and cooperate to achieve a joint team goal. This distributed (or networked) architecture promises much in terms of performance, reliability and simplicity of design; however, at the same time, it requires extending the traditional theories of control, communication and computation and, in fact, looking at a unified picture of the three fields. A systematic theory of how to design distributed systems is currently lacking.
\r\n\r\nThis dissertation takes the first steps towards understanding the effects of imperfect information flow in distributed systems from an estimation and control perspective and coming up with new design principles to counter these effects. Designing networked systems is difficult because such systems challenge two basic assumptions of traditional control theory - presence of a central node with access to all the information about the system and perfect transmission of information among components. We formulate and solve many problems that deal with the removal of one, or both, of these assumptions. The chief idea explored in this dissertation is the joint design of information flow and the control law. While traditional control design has concentrated on calculating the optimal control input by assuming a particular information flow between the components, our approach seeks to synthesize the optimal information flow along with the optimal control law that satisfies the constraints of the information flow. Thus besides the question of 'What should an agent do?', the questions of 'Whom should an agent talk to?', 'What should an agent communicate?', 'When should an agent communicate?' and so on also have to be answered. The design of the information flow represents an important degree of freedom available to the system designer that has hitherto largely been ignored. As we demonstrate in the dissertation, the joint design of information flow and the optimal control input satisfying the constraints of that information flow yields large improvements in performance over simply trying to fit traditional design theories on distributed systems.
\r\n\r\nWe begin by formulating a distributed control problem in which many agents in a formation need to cooperate to minimize a joint cost function. We provide numerical algorithms to synthesize the optimal constrained control law that involve solving linear equations only and hence are free from numerical issues plaguing the other approaches proposed in the literature. We then provide and analyze a model to understand the issue of designing the topology according to which the agents interact. The results are very surprising since there are cases when allowing communication to happen between two agents may, in fact, be detrimental to the performance.
\r\n\r\nWe then move on to consider the effects of communication channels on control performance. To counter such effects, we propose the idea of encoding information for the purpose of estimation and control prior to transmission. Although information theoretic techniques are not possible in our problem, we are able to solve for a recursive yet optimal encoder / decoder structure in many cases. This information flow design oriented approach has unique advantages such as being optimal for any packet drop pattern, being able to include the effect of known but random delays easily, letting us escape the limits set by reliability for transmission of data across a network by using intermediate nodes as 'repeaters' similar to a digital communication network and so on.
\r\n\r\nWe finally take a look at combining the effects of multiple sources of information and communication channels on estimation and control. We look at a distributed estimation problem in which, at every time step, only a subset out of many sensors can transmit information to the estimator. This is also a representative resource allocation problem. We propose the idea of stochastic communication patterns that allows us to include the effects of communication channels explicitly during system design. Thus, instead of tree-search based algorithms proposed in the literature, we provide stochastic scheduling algorithms that can take into account the random packet drop effect of the channels. We also consider a distributed control problem with switching topologies and solve for the optimal controller. The tools that we develop are applicable to many other scenarios and we demonstrate some of them in the dissertation.
\r\n\r\nAlong the way, we look at many other related problems in the dissertation. As an example, we provide initial results about the issue of robustness of a distributed system design to a malfunctioning agent. This notion is currently lacking in the control and estimation community, but has to be a part of any effective theory for designing networked or distributed systems.
", "doi": "10.7907/KWN2-X741", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:1897", "collection": "thesis", "collection_id": "1897", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05202007-135411", "primary_object_url": { "basename": "thesis_main.pdf", "content": "final", "filesize": 1027735, "license": "other", "mime_type": "application/pdf", "url": "/1897/1/thesis_main.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Geometrical Analysis of Spatio-temporal Planning Problems", "author": [ { "family_name": "Tiwari", "given_name": "Abhishek", "clpid": "Tiwari-Abhishek" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Hassibi", "given_name": "Babak", "clpid": "Hassibi-B" }, { "family_name": "Jeffcoat", "given_name": "David E.", "clpid": "Jeffcoat-D-E" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "In this thesis I represent and analyze spatially and temporally constrained multi-agent planning problems using tools from geometry and advanced calculus. The two problems considered in this thesis are multi-agent rendezvous and dynamic sensor coverage. Together, these problems encompass the cooperation, constraint representation,and task scheduling aspects of multi-agent planning problems. I have represented the constraint of the rendezvous problem on the phase space and shown that the fulfilment of rendezvous constraints is equivalent to certain conical regions being invariant. Alternatively, for the dynamic coverage problem, the constraints can be adequately represented on the uncertainty space and sensor motion laws can be obtained by partitioning the uncertainty space and making decisions based on which partition the uncertainty lies in. I have examined convergence behavior of sensor motion under such laws.", "doi": "10.7907/917G-MJ20", "publication_date": "2007", "thesis_type": "phd", "thesis_year": "2007" }, { "id": "thesis:7330", "collection": "thesis", "collection_id": "7330", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12122012-095010036", "primary_object_url": { "basename": "thesis_cds_chunhui.pdf", "content": "final", "filesize": 703304, "license": "other", "mime_type": "application/pdf", "url": "/7330/1/thesis_cds_chunhui.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Improving Situational Awareness in RoboFlag", "author": [ { "family_name": "Gu", "given_name": "Chunhui", "clpid": "Gu-Chunhui" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "None", "given_name": "None" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Situational awareness in competitive games has started to attract increasing attention in the control community. It studies how a robot identifies, understands and predicts the significant factors around it, which is essential for effective decision making and performance in any complex and dynamic environment. In this thesis, we investigate the situational awareness problems in RoboFlag, a highly dynamic testbed that comprises a mixture of offense and defense games between two robotic teams. To improve situational awareness in RoboFlag, we want to solve two main problems. (1) Real-time position estimation given limited sensing capability. (2) Optimal decision-making strategy based on position estimation.
\r\n\r\nMonte Carlo Localization (MCL), a statistical method based on particle representations of probability densities moving sequentially in discrete time, has been shown as an effective and time-efficient method for reliable position estimation, especially when the dynamics of the system and the environment are nonlinear and non-Gaussian, such as RoboFlag. In this thesis, a dynamic weight map, Hospitability Map (H-Map), that measures the ability of a target to move and maneuver at each location of the field, has been applied to MCL to enhance the efficiency and accuracy of MCL in resampling phase. Empirical results illustrate that H-Map based MCL method improves situational awareness in Roboflag by providing reliable position prediction and enhancing decisionmaking performance.
", "doi": "10.7907/9PEH-B582", "publication_date": "2006", "thesis_type": "senior_minor", "thesis_year": "2006" }, { "id": "thesis:2014", "collection": "thesis", "collection_id": "2014", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05242006-190748", "primary_object_url": { "basename": "cremean_thesis.pdf", "content": "final", "filesize": 4480525, "license": "other", "mime_type": "application/pdf", "url": "/2014/1/cremean_thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "System Architectures and Environment Modeling for High-Speed Autonomous Navigation", "author": [ { "family_name": "Cremean", "given_name": "Lars Br\u00f6r", "clpid": "Cremean-Lars-Br\u00f6r" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Antonsson", "given_name": "Erik K.", "clpid": "Antonsson-E-K" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Successful high-speed autonomous navigation requires integration of tools from robotics, control theory, computer vision, and systems engineering. This thesis presents work that develops and combines these tools in the context of navigating desert terrain.
\r\n\r\nA comparative analysis of reactive, behavior-based, and deliberative control architectures provides important guidelines for design of robotic systems. These guidelines depend on the particular task and environment of the vehicle. Two important factors are identified which guide an effective choice between these architectures: dynamic feasibility for the vehicle, and predictability of the environment. This is demonstrated by parallels to control theory, illustrative examples, simulations, and analysis of Bob and Alice---Caltech's full-scale autonomous ground vehicle entries in the 2004 and 2005 Grand Challenge races, respectively.
\r\n\r\nFurther, new model-based methods are developed for constructing and maintaining estimates of terrain elevation and road geometry. These are demonstrated in simulation and in fully autonomous operation of Alice, including accurate detection and tracking of the centerline of desert roads at speeds up to 5 m/s. Finally, Alice's navigation architecture is presented in full along with experimental results that demonstrate its capabilities.
", "doi": "10.7907/8HT2-N165", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:10641", "collection": "thesis", "collection_id": "10641", "cite_using_url": "https://resolver.caltech.edu/CaltechThesis:01112018-111923389", "primary_object_url": { "basename": "Gillula_Jeremy-thesis.pdf", "content": "final", "filesize": 1014774, "license": "other", "mime_type": "application/pdf", "url": "/10641/1/Gillula_Jeremy-thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "A Probabilistic Framework for Real-Time Mapping on an Unmanned Ground Vehicle", "author": [ { "family_name": "Gillula", "given_name": "Jeremy Hugh", "orcid": "0000-0003-1800-8222", "clpid": "Gillula-Jeremy-Hugh" } ], "thesis_advisor": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" } ], "thesis_committee": [ { "family_name": "None", "given_name": "None" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "In the course of preparing for the 2005 DARPA Grand Challenge, an off-road race for autonomous vehicles, a group of undergraduates from Caltech developed a set of deterministic algorithms for performing sensor fusion on maps generated by different range sensors on a mobile robot. That framework had serious limitations, however, including \"disappearing\" obstacles and lack of confidence data associated with features in the maps. In this thesis, we present a probabilistic framework that attempts to solve some of these problems by using error models of two typical types of range sensors, as well as by making use of Kalman filtering techniques from control theory to fuse the resulting measurements into an accurate digital elevation map. Our results indicate that this probabilistic framework has several advantages over the determinisic framework used by Team Caltech in the 2005 Grand Challenge.", "doi": "10.7907/SXNY-XG55", "publication_date": "2006", "thesis_type": "senior_minor", "thesis_year": "2006" }, { "id": "thesis:2735", "collection": "thesis", "collection_id": "2735", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06262006-171822", "primary_object_url": { "basename": "thesis_master.pdf", "content": "final", "filesize": 676842, "license": "other", "mime_type": "application/pdf", "url": "/2735/1/thesis_master.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Distributed Gradient Systems and Dynamic Coordination", "author": [ { "family_name": "Spanos", "given_name": "Demetri Polychronis", "clpid": "Spanos-Demetri-Polychronis" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Low", "given_name": "Steven H.", "clpid": "Low-S-H" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Many systems comprised of interconnected sub-units exhibit coordinated behaviors; social groups, networked computers, financial markets, and numerous biological systems come to mind. There has been long-standing interest in developing a scientific understanding of coordination, both for explanatory power in the natural and economic sciences, and also for constructive power in engineering and applied sciences. This thesis is an abstract study of coordination, focused on developing a systematic \"design theory\" for producing interconnected systems with specifiable coordinated behavior; this is in contrast to the bulk of previous work on this subject, in which any design component has been primarily ad-hoc.
\r\n\r\nThe main theoretical contribution of this work is a geometric formalism in which to cast distributed systems. This has numerous advantages and \"naturally\" parametrizes a wide class of distributed interaction mechanisms in a uniform way. We make use of this framework to present a model for distributed optimization, and we introduce the distributed gradient as a general design tool for synthesizing dynamics for distributed systems. The distributed optimization model is a useful abstraction in its own right and motivates a definition for a distributed extremum. As one might expect, the distributed gradient is zero at a distributed extremum, and the dynamics of a distributed gradient flow must converge to a distributed extremum. This forms the basis for a wide variety of designs, and we are in fact able to recover a widely studied distributed averaging algorithm as a very special case.
\r\n\r\nWe also make use of our geometric model to introduce the notion of coordination capacity; intuitively, this is an upper bound on the \"complexity\" of coordination that is feasible given a particular distributed interaction structure. This gives intuitive results for local, distributed, and global control architectures, and allows formal statements to be made regarding the possibility of \"solving\" certain optimization problems under a particular distributed interaction model.
\r\n\r\nFinally, we present a number of applications to illustrate the theoretical approach presented; these range from \"standard\" distributed systems tasks (leader election and clock synchronization) to more exotic tasks like graph coloring, distributed account balancing, and distributed statistical computations.
", "doi": "10.7907/D1NJ-KF96", "publication_date": "2006", "thesis_type": "phd", "thesis_year": "2006" }, { "id": "thesis:2147", "collection": "thesis", "collection_id": "2147", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05272005-113928", "primary_object_url": { "basename": "Thesis.pdf", "content": "final", "filesize": 752980, "license": "other", "mime_type": "application/pdf", "url": "/2147/1/Thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "State Estimation in Multi-Agent Decision and Control Systems", "author": [ { "family_name": "Del Vecchio", "given_name": "Domitilla", "clpid": "Del-Vecchio-Domitilla" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Klavins", "given_name": "Eric", "clpid": "Klavins-E" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "his thesis addresses the problem of estimating the state in multi-agent decision and control systems. In particular, a novel approach to state estimation is developed that uses partial order theory in order to overcome some of the severe computational complexity issues arising in multi-agent systems. Within this approach, state estimation algorithms are developed that enjoy provable convergence properties and are scalable with the number of agents.
\r\n\r\nThe dynamic evolution of the systems under study are characterized by the interplay of continuous and discrete variables. Continuous variables usually represent physical quantities such as position, velocity, voltage, and current, while the discrete variables usually represent quantities internal to the decision protocol that are used for coordination, communication, and control. Within the proposed state estimation approach, the estimation of continuous and discrete variables is developed in the same mathematical framework as a joint continuous-discrete space is considered for the estimator. This way, the dichotomy between the continuous and discrete world is overcome for the purpose of state estimation.
\r\n\r\nApplication examples are considered, which include the state estimation in competitive multi-robot systems and in multi-agent discrete event systems, and the monitoring of distributed environments.
", "doi": "10.7907/SAX3-ED56", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:2163", "collection": "thesis", "collection_id": "2163", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05272005-165938", "primary_object_url": { "basename": "jf_cit_phdthesis.pdf", "content": "final", "filesize": 4884172, "license": "other", "mime_type": "application/pdf", "url": "/2163/1/jf_cit_phdthesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Coarse Analysis of Multiscale Systems: Diffuser Flows, Charged Particle Motion, and Connections to Averaging Theory", "author": [ { "family_name": "Fung", "given_name": "Jimmy", "orcid": "0000-0002-6612-2209", "clpid": "Fung-Jimmy" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Ortiz", "given_name": "Michael", "orcid": "0000-0001-5877-4824", "clpid": "Ortiz-M" }, { "family_name": "Gharib", "given_name": "Morteza", "orcid": "0000-0003-0754-4193", "clpid": "Gharib-M" }, { "family_name": "Colonius", "given_name": "Tim", "orcid": "0000-0003-0326-3909", "clpid": "Colonius-T" } ], "local_group": [ { "literal": "GALCIT" }, { "literal": "div_eng" } ], "abstract": "We describe a technique for the efficient computation of the dominant-scale dynamics of a fluid system when only a high-fidelity simulation is available. Such a technique is desirable when governing equations for the dominant scales are unavailable, when model reduction is impractical, or when the original high-fidelity computation is expensive. We adopt the coarse analysis framework proposed by I. G. Kevrekidis (Comm. Math. Sci. 2003), where a computational superstructure is designed to use short-time, high-fidelity simulations to extract the dominant features for a multiscale system. We apply this technique to compute the dominant features of the compressible flow through a planar diffuser. We apply the proper orthogonal decomposition to classify the dominant and subdominant scales of diffuser flows. We derive a suitable coarse projective Adams-Bashforth time integration routine and apply it to compute averaged diffuser flows. The results include accurate tracking of the dominant-scale dynamics for a range of parameter values for the computational superstructure. These results demonstrate that coarse analysis methods are useful for solving fluid flow problems of a multiscale nature.
\r\n\r\nIn order to elucidate the behavior of coarse analysis techniques, we make comparisons to averaging theory. To this end, we derive governing equations for the average motion of charged particles in a magnetic field in a number of different settings. First, we apply a novel procedure, inspired by WKB theory and Whitham averaging, to average the variational principle. The resulting equations are equivalent to the guiding center equations for charged particle motion; this marks an instance where averaging and variational principles commute. Secondly, we apply Lagrangian averaging techniques, previously applied in fluid mechanics, to derive averaged equations. Making comparisons to the WKB/Whitham-style derivation allows for the necessary closure of the Lagrangian averaging formulation. We also discuss the Hamiltonian setting and show that averaged Hamiltonian systems may be derivable using concepts from coarse analysis. Finally, we apply a prototypical coarse analysis procedure to the system of charged particles and generate trajectories that resemble guiding center trajectories. We make connections to perturbation theory to derive guidelines for the design of coarse analysis techniques and comment on the prototypical coarse analysis application.
", "doi": "10.7907/wn0z-gn57", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:5225", "collection": "thesis", "collection_id": "5225", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06072005-163739", "primary_object_url": { "basename": "thesis.pdf", "content": "final", "filesize": 4892392, "license": "other", "mime_type": "application/pdf", "url": "/5225/2/thesis.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Bio-Inspired Visuomotor Convergence in Navigation and Flight Control Systems", "author": [ { "family_name": "Humbert", "given_name": "James Sean", "orcid": "0000-0002-0863-875X", "clpid": "Humbert-James-Sean" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "MacMynowski", "given_name": "Douglas G.", "clpid": "MacMynowski-D-G" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Dickinson", "given_name": "Michael H.", "clpid": "Dickinson-M-H" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Insects exhibit incredibly robust closed loop flight dynamics in the face of uncertainties. A fundamental principle contributing to this unparalleled behavior is rapid processing and convergence of visual sensory information to flight motor commands via spatial wide-field integration, accomplished by retinal motion pattern sensitive interneurons (LPTCs) in the lobula plate portion of the visual ganglia. Within a control-theoretic framework, an inner product model for wide-field integration of retinal image flow is developed, representing the spatial decompositions performed by LPTCs in the insect visuomotor system. A rigorous characterization of the information available from this visuomotor convergence technique for motion within environments exhibiting non-homogeneous spatial distributions is performed, establishing the connection between retinal motion sensitivity shape and closed loop behavior. The proposed output feedback methodology is shown to be sufficient to give rise to experimentally observed insect navigational heuristics, including forward speed regulation, obstacle avoidance, hovering, and terrain following behaviors. Hence, extraction of global retinal motion cues through computationally efficient wide-field integration processing provides a novel and promising methodology for utilizing visual sensory information in autonomous robotic navigation and flight control applications.\r\n", "doi": "10.7907/T5QZ-QS18", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:2198", "collection": "thesis", "collection_id": "2198", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05282004-170123", "primary_object_url": { "basename": "WBDdissertation.pdf", "content": "final", "filesize": 1540394, "license": "other", "mime_type": "application/pdf", "url": "/2198/1/WBDdissertation.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Distributed Receding Horizon Control of Multiagent Systems", "author": [ { "family_name": "Dunbar", "given_name": "William Bruce", "orcid": "0000-0002-0913-318X", "clpid": "Dunbar-William-Bruce" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Hickey", "given_name": "Jason J.", "clpid": "Hickey-J-J" }, { "family_name": "Shamma", "given_name": "Jeff", "clpid": "Shamma-J" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Multiagent systems arise in several domains of engineering. Examples include arrays of mobile sensor networks for aggregate imagery, autonomous highways, and formations of unmanned aerial vehicles. In these contexts, agents are governed by vehicle dynamics and often constraints, and the control objective is achieved by cooperation. Cooperation refers to the agreement of the agents to 1) have a common objective with neighboring agents, with the objective typically decided offline, and 2) share information online to realize the objective. To be viable, the control approach for multiagent systems should be distributed, for autonomy of the individual agents and for scalability and improved tractability over centralized approaches.
\r\n\r\nOptimization-based techniques are suited to multiagent problems, in that such techniques can admit very general objectives. Receding horizon control is an optimization-based approach that is applicable when dynamics and constraints on the system are present. Several researchers have recently explored the use of receding horizon control to achieve multi-vehicle objectives. In most cases, the common objective is formulated, and the resulting control law implemented, in a centralized way.
\r\n\r\nThis dissertation provides a distributed implementation of receding horizon control with guaranteed convergence and performance comparable to a centralized implementation. To begin with, agents are presumed to be individually governed by heterogeneous dynamics, modelled by a nonlinear ordinary differential equation. Coupling between agents occurs in a generic quadratic cost function of a single optimal control problem. The distributed implementation is generated by decomposition of the single optimal control problem into local problems, and the inclusion of local compatibility constraints in each local problem. The coordination requirements are globally synchronous timing and local information exchanges between neighboring agents. For sufficiently fast update times, the distributed implementation is proven to be asymptotically stabilizing. Extensions for handling inter-agent coupling constraints and partially synchronous timing are also explored. The venue of multi-vehicle formation stabilization demonstrates the efficacy of the implementation in numerical experiments. Given the generality of the receding horizon control mechanism, there is great potential for the implementation presented here in dynamic and constrained distributed systems.
", "doi": "10.7907/1N74-MZ62", "publication_date": "2004", "thesis_type": "phd", "thesis_year": "2004" }, { "id": "thesis:2378", "collection": "thesis", "collection_id": "2378", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06022003-114340", "primary_object_url": { "basename": "mbmthesis_ds.pdf", "content": "final", "filesize": 3135332, "license": "other", "mime_type": "application/pdf", "url": "/2378/1/mbmthesis_ds.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Real-Time Optimal Trajectory Generation for Constrained Dynamical Systems", "author": [ { "family_name": "Milam", "given_name": "Mark Bradley", "clpid": "Milam-Mark-Bradley" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Hauser", "given_name": "John", "clpid": "Hauser-J" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "With the advent of powerful computing and efficient computational algorithms, real-time solutions to constrained optimal control problems are nearing a reality. In this thesis, we develop a computationally efficient Nonlinear Trajectory Generation (NTG) algorithm and describe its software implementation to solve, in real-time, nonlinear optimal trajectory generation problems for constrained systems. NTG is a nonlinear trajectory generation software package that combines nonlinear control theory, B-spline basis functions, and nonlinear programming. We compare NTG with other numerical optimal control problem solution techniques, such as direct collocation, shooting, adjoints, and differential inclusions.
\r\n\r\nWe demonstrate the performance of NTG on the Caltech Ducted Fan testbed. Aggressive, constrained optimal control problems are solved in real-time for hover-to-hover, forward flight, and terrain avoidance test cases. Real-time trajectory generation results are shown for both the two-degree of freedom and receding horizon control designs. Further experimental demonstration is provided with the station-keeping, reconfiguration, and deconfiguration of micro-satellite formation with complex nonlinear constraints. Successful application of NTG in these cases demonstrates reliable real-time trajectory generation, even for highly nonlinear and non-convex systems. The results are among the first to apply receding horizon control techniques for agile flight in an experimental setting, using representative dynamics and computation.
", "doi": "10.7907/1X68-E370", "publication_date": "2003", "thesis_type": "phd", "thesis_year": "2003" }, { "id": "thesis:1304", "collection": "thesis", "collection_id": "1304", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-04082003-180353", "primary_object_url": { "basename": "thesis.pdf", "content": "final", "filesize": 40124312, "license": "other", "mime_type": "application/pdf", "url": "/1304/1/thesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Time-Dependent Dynamical Systems and Geophysical Flows", "author": [ { "family_name": "Lekien", "given_name": "Francois Paul", "clpid": "Lekien-Francois-Paul" } ], "thesis_advisor": [ { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Leonard", "given_name": "Anthony", "clpid": "Leonard-A" }, { "family_name": "Haller", "given_name": "George", "clpid": "Haller-G" }, { "family_name": "Mezic", "given_name": "Igor", "clpid": "Mezic-I" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents a dynamical systems approach to transport and mixing in geophysical flows. First, new algorithms are developed that allow one to study a dynamical system that is described in a variety of ways such as by means of observational data or numerical simulations of differential equations.
\r\n\r\nNext, methods available to study non-autonomous systems, such as hyperbolic trajectories and Lagrangian coherent structures, are developed. These concepts are applied to examples of interests: Monterey Bay, the coast of Florida and the circulation in the North Atlantic. Combining accurate current measurements and recent developments in dynamical systems theory provides new and original answers to many problems, such as the minimization of the impact of released contaminants in a coastal area or the optimization of the coverage by a group of drifters.
\r\n\r\nThe appendices give details about MANGEN, a software package developed to produce the numerical results of this thesis. Some projects that make use of its algorithms, such as the dissociation rate of a molecule and efficient space mission design, are also described.
", "doi": "10.7907/A83E-VZ73", "publication_date": "2003", "thesis_type": "phd", "thesis_year": "2003" }, { "id": "thesis:4207", "collection": "thesis", "collection_id": "4207", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-10222002-115711", "primary_object_url": { "basename": "mgthesis.pdf", "content": "final", "filesize": 3074987, "license": "other", "mime_type": "application/pdf", "url": "/4207/1/mgthesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Modeling and Control of Epitaxial Thin Film Growth", "author": [ { "family_name": "Gallivan", "given_name": "Martha Anne", "orcid": "0000-0002-7036-776X", "clpid": "Gallivan-Martha-Anne" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Goodwin", "given_name": "David G.", "clpid": "Goodwin-D-G" }, { "family_name": "Atwater", "given_name": "Harry Albert", "clpid": "Atwater-H-A" }, { "family_name": "Hunt", "given_name": "Melany L.", "clpid": "Hunt-M-L" }, { "family_name": "Christofides", "given_name": "Panagiotis D.", "clpid": "Christofides-P-D" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Thin film deposition is a manufacturing process in which tolerances may approach the size of individual atoms. The final film is highly sensitive to the processing conditions, which can be intentionally manipulated to control film properties. A lattice model of surface evolution during thin film growth captures many important features, including the nucleation and growth of clusters of atoms and the propagation of atomic-height steps. The dimension of this probabilistic master equation is too large to directly simulate for any physically realistic domain, and instead stochastic realizations of the lattice model are obtained with kinetic Monte Carlo simulations.
\r\n\r\nIn this thesis simpler representations of the master equation are developed for use in analysis and control. The static map between macroscopic process conditions and microscopic transition rates is first analyzed. In the limit of fast periodic process parameters, the surface responds only to the mean transition rates, and, since the map between process parameters and transition rates is nonlinear, new effective combinations of transition rates may be generated. These effective rates are the convex hull of the set of instantaneous rates.
\r\n\r\nThe map between transition rates and expected film properties is also studied. The dimension of a master equation can be reduced by eliminating or grouping configurations, yielding a reduced-order master equation that approximates the original one. A linear method for identifying the coefficients in a master equation is then developed, using only simulation data. These concepts are extended to generate low-order master equations that approximate the dynamic behavior seen in large Monte Carlo simulations. The models are then used to compute optimal time-varying process parameters.
\r\n\r\nThe thesis concludes with an experimental and modeling study of germanium film growth, using molecular beam epitaxy and reflection high-energy electron diffraction. Growth under continuous and pulsed flux is compared in experiment, and physical parameters for the lattice model are extracted. The pulsing accessible in the experiment does not trigger a change in growth mode, which is consistent with the Monte Carlo simulations. The simulations are then used to suggest other growth strategies to produce rougher or smoother surfaces.
", "doi": "10.7907/FXZB-XT91", "publication_date": "2003", "thesis_type": "phd", "thesis_year": "2003" }, { "id": "thesis:4230", "collection": "thesis", "collection_id": "4230", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-10242005-105000", "primary_object_url": { "basename": "Fax_ja_2002.pdf", "content": "final", "filesize": 6899741, "license": "other", "mime_type": "application/pdf", "url": "/4230/1/Fax_ja_2002.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Optimal and Cooperative Control of Vehicle Formations", "author": [ { "family_name": "Fax", "given_name": "Joseph Alexander", "clpid": "Fax-Joseph-Alexander" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Hickey", "given_name": "Jason J.", "clpid": "Hickey-J-J" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Control of vehicle formations has emerged as a topic of significant interest to the controls community. In applications such as microsatellites and underwater vehicles, formations have the potential for greater functionality and versatility than individual vehicles. In this thesis, we investigate two topics relevant to control of vehicle formations: optimal vehicle control and cooperative control.\r\n\r\nThe framework of optimal control is often employed to generate vehicle trajectories. We use tools from geometric mechanics to specialize the two classical approaches to optimal control, namely the calculus of variations and the Hamilton-Jacobi-Bellman (HJB) equation, to the case of vehicle dynamics. We employ the formalism of the covariant derivative, useful in geometric representations of vehicle dynamics, to relate variations of position to variations of velocity. When variations are computed in this setting, the evolution of the adjoint variables is shown to be governed by the covariant derivative, thus inheriting the geometric structure of the vehicle dynamics. To simplify the HJB equation, we develop the concept of time scalability enjoyed by many vehicle systems. We employ this property to eliminate time from the HJB equation, yielding a purely spatial PDE whose solution supplies both finite-time optimal trajectories and a time-invariant stabilizing control law.\r\n\r\nCooperation among vehicles in formation depends on intervehicle communication. However, vehicle communication is often subject to disruption, especially in an adversarial setting. We apply tools from graph theory to relate the topology of the communication network to formation stability. We prove a Nyquist criterionthat uses the eigenvalues of the graph Laplacian matrix to determine the effect of the graph 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 states that formation stability is achieved if the information flow is stable for the given graph and if the local controller stabilizes the vehicle. The information flow can be rendered highly robust to changes in the graph, thus enabling tight formation control despite limitations in intervehicle communication capability.", "doi": "10.7907/M4N7-AK02", "publication_date": "2002", "thesis_type": "phd", "thesis_year": "2002" }, { "id": "thesis:2989", "collection": "thesis", "collection_id": "2989", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-07312002-091923", "primary_object_url": { "basename": "thesis.pdf", "content": "final", "filesize": 2313008, "license": "other", "mime_type": "application/pdf", "url": "/2989/1/thesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Control of Multiple Model Systems", "author": [ { "family_name": "Murphey", "given_name": "Todd David", "clpid": "Murphey-Todd-David" } ], "thesis_advisor": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" }, { "family_name": "Antonsson", "given_name": "Erik K.", "clpid": "Antonsson-E-K" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Perona", "given_name": "Pietro", "orcid": "0000-0002-7583-5809", "clpid": "Perona-P" }, { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis considers the control of multiple model systems. These are systems for which only one model out of some finite set of models gives the system dynamics at any given time. In particular, the model that gives the system dynamics can change over time. This thesis covers some of the theoretical aspects of these systems, including controllability and stabilizability. As an application, ``overconstrained' mechanical systems are modeled as multiple model systems. Examples of such systems include distributed manipulation problems such as microelectromechanical systems and many wheeled vehicles such as the Sojourner vehicle of the Mars Pathfinder mission. Such systems are typified by having more Pfaffian constraints than degrees of freedom. Conventional classical motion planning and control theories do not directly apply to overconstrained systems. Control issues for two examples are specifically addressed. The first example is distributed manipulation. Distributed manipulation systems control an object's motion through contact with a high number of actuators. Stability results are shown for such systems and control schemes based on these results are implemented on a distributed manipulation test-bed. The second example is that of overconstrained vehicles, of which the Mars rover is an example. The nonlinear controllability test for multiple model systems is used to answer whether a kinematic model of the rover is or is not controllable.", "doi": "10.7907/17Q7-Y019", "publication_date": "2002", "thesis_type": "phd", "thesis_year": "2002" }, { "id": "thesis:2544", "collection": "thesis", "collection_id": "2544", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06112002-132034", "primary_object_url": { "basename": "aththesis.pdf", "content": "final", "filesize": 4110318, "license": "other", "mime_type": "application/pdf", "url": "/2544/1/aththesis.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Self-Organized Robotic System Design and Autonomous Odor Localization", "author": [ { "family_name": "Hayes", "given_name": "Adam Thomas", "clpid": "Hayes-Adam-Thomas" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Goodman", "given_name": "Rodney M.", "clpid": "Goodman-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Koch", "given_name": "Christof", "orcid": "0000-0001-6482-8067", "clpid": "Koch-C" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" }, { "family_name": "Perona", "given_name": "Pietro", "orcid": "0000-0002-7583-5809", "clpid": "Perona-P" }, { "family_name": "Goodman", "given_name": "Rodney M.", "clpid": "Goodman-R-M" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis presents a methodology for designing self-organized autonomous robotic systems and demonstrates how this process can be applied to the problem of finding the source of an airborne odor plume. The design methodology is applicable to other task domains and the resulting odor localization system extends the state of the art.\r\n\r\nThe design procedure centers on the ability to define a specific task performance metric, systematically evaluate performance in a realistic environment, and define abstract relationships between system parameters and system performance. Once such relationships have been experimentally validated in a test environment, they can be used to guide the design of a deployable system. Because this process relies heavily on evaluative feedback, this work emphasizes the development of tools that allow the collection of accurate performance data. It presents a reliable multiple robot test-bed and some task-enabling sensory hardware, as well as validation of the sensory and kinematic models used in simulation. Also, a reinforcement learning methodology is described that provides consistent optimization performance while minimizing the amount of required evaluation.\r\n\r\nThe design methodology is applied to the task of odor localization. Specifically, this thesis analyzes a basic collective search task and derives the optimal group size and expected performance bounds for random and coordinated search. It also investigates a set of biologically inspired behaviors that permit an agent to traverse an odor plume to its source and describes the common characteristics of successful algorithms. One of these algorithms is implemented on the real test-bed and in simulation to verify that plume traversal is taking place and that the use of multiple collaborating robots can expand the reachable performance space. Collective search and plume traversal are then combined (along with egocentric source declaration) into the full odor localization task which is optimized in simulation. Then, following the design methodology, a model is presented which can aid in the prediction of performance and choice of algorithm parameters in more complex environments. Finally, a flocking behavior is designed, and the addition of this flocking behavior to the plume tracing algorithm is shown to produce a more capable system", "doi": "10.7907/KH16-XH33", "publication_date": "2002", "thesis_type": "phd", "thesis_year": "2002" }, { "id": "thesis:6161", "collection": "thesis", "collection_id": "6161", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:10262010-112027161", "type": "thesis", "title": "Receding horizon control of nonlinear systems: a control Lyapunov function approach", "author": [ { "family_name": "Jadbabaie", "given_name": "Ali", "clpid": "Jadbabaie-A" } ], "thesis_advisor": [ { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "With the advent of faster and cheaper computers, optimization based control methodologies have become a viable candidate for control of nonlinear systems. Over the past twenty years, a group of such control schemes have been successfully used in the process control industry where the processes are either intrinsically stable or have very large time constants.
\r\n\r\nThe purpose of this thesis is to provide a theoretical framework for synthesis of a class of optimization based control schemes, known as receding horizon control techniques for nonlinear systems such as unmanned aerial vehicles.
\r\n\r\nIt is well known that unconstrained infinite horizon optimal control may be used to construct a stabilizing controller for a nonlinear system. In this thesis, we show that similar stabilization results may be achieved using unconstrained finite horizon optimal control. The key idea is to approximate the tail of the infinite horizon cost-to-go using, as terminal cost, an appropriate control Lyapunov function (CLF). A CLF can be thought of as generalization of the concept of a Lyapunov function to systems with inputs.
\r\n\r\nRoughly speaking, the terminal CLF should provide an (incremental) upper bound on the cost. In this fashion, important stability characteristics may be retained without the use of terminal constraints such as those employed by a number of other researchers. The absence of constraints allows a significant speedup in computation.
\r\n\r\nFurthermore, it is shown that in order to guarantee stability, it suffices to satisfy an improvement property, thereby relaxing the requirement that truly optimal trajectories be found.
\r\n\r\nWe provide a complete analysis of the stability and region of attraction/operation properties of receding horizon control strategies that utilize finite horizon approximations in the proposed class. It is shown that the guaranteed region of operation contains that of the CLF controller and may be made as large as desired by increasing the optimization horizon (restricted, of course, to the infinite horizon domain). Moreover, it is easily seen that both CLF and infinite horizon optimal control approaches are limiting cases of our receding horizon strategy. The key results are illustrated using a familiar example, the inverted pendulum, as well as models of the Caltech ducted fan at hover and forward flight, where significant improvements in guaranteed region of operation and cost are noted.
\r\n\r\nWe also develop an optimization based scheme for generation of aggressive trajectories for hover and forward flight models of the Caltech ducted fan experiment, using a technique known as trajectory morphing. The main idea behind trajectory morphing is to develop a simplified model of the nonlinear system and solve the trajectory generation problem for that model. The resulting trajectory is then used as a reference in a receding horizon optimization scheme to generate trajectories of the original nonlinear system. Several aggressive trajectories are obtained in this fashion for the forward flight model of the Caltech ducted fan experiment.
", "doi": "10.7907/CRHD-3202", "publication_date": "2001", "thesis_type": "phd", "thesis_year": "2001" }, { "id": "thesis:2753", "collection": "thesis", "collection_id": "2753", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06282005-103901", "primary_object_url": { "basename": "Wang_y_2000.pdf", "content": "final", "filesize": 8520722, "license": "other", "mime_type": "application/pdf", "url": "/2753/1/Wang_y_2000.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Effects of actuator limits in bifurcation control with applications to active control of fluid instabilities in turbomachinery", "author": [ { "family_name": "Wang", "given_name": "Yong", "clpid": "Wang-Yong" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Paduano", "given_name": "James D.", "clpid": "Paduano-J-D" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Culick", "given_name": "Fred E. C.", "clpid": "Culick-F-E-C" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Feedback stabilization is one of the most dominant issues in modern control theory. The validity of linear control design is based on the assumption that the system is stabilizable. With rapid broadening of control applications to complex systems during the past two decades, the attainability of linear stabilizability sometimes has to compromise with system constraints and affordability of distributed actuation. The goal of this thesis is to tackle some of the problems in control of nonequilibrium behavior and to apply the theory to active control of fluid instabilities in gas turbine engines.\r\n\r\nWe consider two of the simplest nontrivial scenarios in local smooth feedback stabilization: the steady-state case, when the linearly unstabilizable eigenvalue is zero; and the Hopf case, when the unstabilizable eigenvalues are a pair of pure imaginary numbers. Under certain nondegeneracy conditions, we give explicit algebraic conditions for stabilizability. And when the system is stabilizable, the stabilizing feedback can be explicitly constructed.\r\n\r\nThe problem of local smooth feedback stabilization for systems with critical unstabilizable modes is closely related to bifurcation control. Under certain nondegeneracy conditions, a steady-state/Hopf bifurcation can be turned into a supercritical pitchfork/Hopf bifurcation if and only if the system is locally stabilizable at the bifurcation point. Algebraic necessary and sufficient conditions are derived under which the criticality of a simple steady-state or Hopf bifurcation can be changed to supercritical by a smooth feedback. The effects of magnitude saturation, bandwidth, and rate limits are important issues in control engineering. We give qualitative estimates of the region of attraction to the stabilized bifurcating equilibrium/periodic orbits under these constraints.\r\n\r\nWe apply the above theoretical results to the Moore-Greitzer model in active control of rotating stall and surge in gas turbine engines. Though linear stabilizability can be achieved using distributed actuation, it limits the practical usefulness due to considerations of affordability and reliability. On the other hand, simple but practically promising actuation schemes such as outlet bleed valves, a couple of air injectors, and magnetic bearings will make the system loss of linear stabilizability, thus the control design becomes a challenging task. The above mentioned results in bifurcation stabilization can be applied to these cases. We analyze the effects of magnitude and rate saturations in active stall and surge control using bleed valves and magnetic bearings using the Moore-Greitzer model. The analytical formulas for bleed valve actuation give good qualitative predictions when compared with experiments. Our conclusion is that these constraints are serious limiting factors in stall control and must be addressed in practical implementation to the aircraft engines.", "doi": "10.7907/229f-f376", "publication_date": "2000", "thesis_type": "phd", "thesis_year": "2000" }, { "id": "thesis:785", "collection": "thesis", "collection_id": "785", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-02272008-083453", "primary_object_url": { "basename": "Yeung_ch_1999.pdf", "content": "final", "filesize": 7060334, "license": "other", "mime_type": "application/pdf", "url": "/785/1/Yeung_ch_1999.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Nonlinear control of rotating stall and surge with axisymmetric bleed and air injection on axial flow compressors", "author": [ { "family_name": "Yeung", "given_name": "Chung-hei (Simon)", "clpid": "Yeung-C-S" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Culick", "given_name": "Fred E. C.", "clpid": "Culick-F-E-C" }, { "family_name": "Gavalas", "given_name": "George R.", "clpid": "Gavalas-G-R" }, { "family_name": "Flagan", "given_name": "Richard C.", "clpid": "Flagan-R-C" }, { "family_name": "Caughey", "given_name": "Thomas Kirk", "clpid": "Caughey-T-K" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "The study of compressor instabilities in gas turbine engines has received much attention in recent ears. In particular, rotating stall and surge are major causes of problems ranging from component stress and lifespan reduction to engine explosion. In this thesis, modeling and control of rotating stall and surge using bleed valve and air injection is studied and validated on a low speed, single stage, axial compressor at Caltech.\n\nBleed valve control of stall is achieved only when the compressor characteristic is actuated, due to the fast growth rate of the stall cell compared to the rate limit of the valve. Furthermore, experimental results show that the actuator rate requirement for stall control is reduced by a factor of fourteen via compressor characteristic actuation. Analytical expressions based on low order models (2-3 states) and a high fidelity simulation (37 states) tool are developed to estimate the minimum rate requirement of a bleed valve for control of stall. A comparison of the tools to experiments show a good qualitative agreement, with increasing quantitative accuracy as the complexity of the underlying model increases.\n\nAir injection control of stall and surge is also investigated. Simultaneous control of stall and surge is achieved using axisymmetric air injection. Three cases with different injector back pressure are studied. Surge control via binary air injection is achieved in all three cases. Simultaneous stall and surge control is achieved for two of the cases, but is not achieved for the lowest authority case. This is consistent with previous results for control of stall with axisymmetric air injection without a plenum attached.\n\nNon\u2014axisymmetric air injection control of stall and surge is also studied. Three existing control algorithms found in literature are modeled and analyzed. A three\u2014state model is obtained for each algorithm. For two cases, conditions for linear stability and bifurcation criticality on control of rotating stall are derived and expressed in terms of implementation\u2014oriented variables such as number of injectors. For the third case, bifurcation criticality conditions are not obtained due to complexity, though linear stability property is derived. A theoretical comparison between the three algorithms is made, via the use of low\u2014order models, to investigate pros and cons of the algorithms in the context of operability.\n\nThe effects of static distortion on the compressor facility at Caltech is characterized experimentally. Results consistent with literature are obtained. Simulations via a high fidelity model (34 states) are also performed and show good qualitative as well as quantitative agreement to experiments. A non\u2014axisymmetric pulsed air injection controller for stall is shown to be robust to static distortion.", "doi": "10.7907/1wef-gp10", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:540", "collection": "thesis", "collection_id": "540", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-02072008-100242", "primary_object_url": { "basename": "Bullo_f_1999.pdf", "content": "final", "filesize": 5715647, "license": "other", "mime_type": "application/pdf", "url": "/540/1/Bullo_f_1999.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Nonlinear control of mechanical systems : a Riemannian geometry approach", "author": [ { "family_name": "Bullo", "given_name": "Francesco", "clpid": "Bullo-F" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Perona", "given_name": "Pietro", "clpid": "Perona-P" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Nonlinear control of mechanical systems is a challenging discipline that lies at the intersection between control theory and geometric mechanics. This thesis sheds new light on this interplay while investigating motion control problems for Lagrangian systems. Both stability and motion planning aspects are treated within a unified framework that accounts for a large class of devices such as robotic manipulators, autonomous vehicles and locomotion systems.\n\nOne distinguishing feature of mechanical systems is the number of control forces. For systems with as many input forces as degrees of freedom, many control problems are tractable. One contribution of this thesis is a set of trajectory tracking controllers designed via the notions of configuration and velocity error. The proposed approach includes as special cases a variety of results on joint and workspace control of manipulators as well as on attitude and position control of vehicles.\n\nWhenever fewer input forces are available than degrees of freedom, various control questions arise. The main contribution of this thesis is the design of motion algorithms for vehicles, i.e., rigid bodies moving in Euclidean space. First, an algebraic controllability analysis characterizes the set of reachable configurations and velocities for a system starting at rest. Then, provided a certain controllability condition is satisfied, various motion algorithms are proposed to perform tasks such as short range reconfiguration and hovering.\n\nFinally, stabilization techniques for underactuated systems are investigated. The emphasis is on relative equilibria, i.e., steady motions for systems that have a conserved momentum. Local exponential stabilization is achieved via an appropriate splitting of the control authority.", "doi": "10.7907/xrak-3409", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:784", "collection": "thesis", "collection_id": "784", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-02272008-083040", "primary_object_url": { "basename": "Shapiro_b_1999.pdf", "content": "final", "filesize": 6931204, "license": "other", "mime_type": "application/pdf", "url": "/784/1/Shapiro_b_1999.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Passive control of flutter and forced response in bladed disks via mistuning", "author": [ { "family_name": "Shapiro", "given_name": "Benjamin", "clpid": "Shapiro-B" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Mistuning or blade to blade variation in jet-engine bladed-disks can lead to large changes in engine performance. Even the small random mistuning associated with manufacturing tolerances can significantly change both stability boundaries and forced response. This thesis addresses two questions. Analysis: given any mistuning (random or intentional), what is the resulting change in performance? And passive control: can intentional mistuning be used to improve stability and forced response in a robust manner? \n\nA general framework based on symmetry arguments and eigenvalue/vector perturbations is presented to answer both questions. Symmetry constrains all facets of mistuning behaviour and provides simplifications for both the analysis and control problems. This is combined with the eigenvalue/vector perturbation which captures the nonlinear mistuning dependence and solves the analysis problem. It is shown that intentional mistuning can provide robust damping and so guarantee improved stability and forced response under fixed manufacturing tolerances. Results are demonstrated on a high-fidelity low-order model derived from computational-fluid-dynamic data.", "doi": "10.7907/1xae-bn33", "publication_date": "1999", "thesis_type": "phd", "thesis_year": "1999" }, { "id": "thesis:3105", "collection": "thesis", "collection_id": "3105", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-08122005-152639", "primary_object_url": { "basename": "Kelly_sd_1998.pdf", "content": "final", "filesize": 17181627, "license": "other", "mime_type": "application/pdf", "url": "/3105/1/Kelly_sd_1998.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "The mechanics and control of robotic locomotion with applications to aquatic vehicles", "author": [ { "family_name": "Kelly", "given_name": "Scott D.", "clpid": "Kelly-S-D" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Caughey", "given_name": "Thomas Kirk", "clpid": "Caughey-T-K" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This work illuminates the utility of a theory of locomotion rooted in geometric mechanics and nonlinear control. We regard the internal configuration of a deformable body, together with its position and orientation in ambient space, as a point in a trivial principal fiber bundle over the manifold of body deformations. We obtain connections on such bundles which describe the nonholonomic constraints, conservation laws, and force balances to which certain propulsors are subject, and contruct and analyze control-affine normal forms for different classes of systems. We examine the applicability of results involving geometric phases to the practical computation of trajectories for systems described by single connections. We propose a model for planar carangiform swimming based on reduced Euler-Lagrange equations for the interaction of a rigid body and an incompressible fluid, accounting for the generation of thrust due to vortex shedding through controlled coupling terms. We investigate the correct form of this coupling experimentally with a robotic propulsor, comparing its observed behavior with that predicted numerically.\r\n", "doi": "10.7907/50M3-1529", "publication_date": "1998", "thesis_type": "phd", "thesis_year": "1998" }, { "id": "thesis:206", "collection": "thesis", "collection_id": "206", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-01162008-152619", "primary_object_url": { "basename": "Vanelli_ca_1997.pdf", "content": "final", "filesize": 3758809, "license": "other", "mime_type": "application/pdf", "url": "/206/1/Vanelli_ca_1997.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Autonomous Reorientation of a Maneuver-Limited Spacecraft Under Simple Pointing Constraints", "author": [ { "family_name": "Vanelli", "given_name": "Charles Anthony", "clpid": "Vanelli-Charles-Anthony" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "orcid": "0000-0002-5785-7481", "clpid": "Murray-R-M" }, { "family_name": "Antonsson", "given_name": "Erik K.", "clpid": "Antonsson-E-K" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "orcid": "0000-0002-3091-540X", "clpid": "Burdick-J-W" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This report presents techniques for using discrete finite rotations to reorient a spacecraft from a given initial attitude to a final attitude which satisfies a specified aiming objective. The objective may be a fully specified final orientation or it may require that the spacecraft direct an instrument along a certain direction. Constraints are also imposed on the allowable intermediate orientations that the spacecraft may assume during the course of the maneuver, representing the operational requirements of onboard instrumentation. The algorithms presented consider solutions that will achieve the desired objective with only one or two slew maneuvers, although they may be easily extended to consider more complicated solutions requiring additional maneuvers.", "doi": "10.7907/kap2-6n63", "publication_date": "1997", "thesis_type": "engd", "thesis_year": "1997" }, { "id": "thesis:2845", "collection": "thesis", "collection_id": "2845", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-07102006-085216", "primary_object_url": { "basename": "Behnken_rl_1997.pdf", "content": "final", "filesize": 7945357, "license": "other", "mime_type": "application/pdf", "url": "/2845/1/Behnken_rl_1997.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Nonlinear Control and Modeling of Rotating Stall in an Axial Flow Compressor", "author": [ { "family_name": "Behnken", "given_name": "Robert Louis", "clpid": "Behnken-Robert-Louis" } ], "thesis_advisor": [ { "family_name": "Brennen", "given_name": "Christopher E.", "clpid": "Brennen-C-E" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "Caltech Distinguished Alumni Award" }, { "literal": "div_eng" } ], "abstract": "This thesis focuses on understanding the use of air injection as a means of controlling rotating stall in an axial flow compressor, involving modeling, dynamical systems analysis, and experimental investigations.
\r\n\r\nThe first step towards this understanding was the development of a low order model for air injection control, the starting point of which was the Moore and Greitzer model for axial flow compressors. The Moore and Greitzer model was extended to include the effects of air injection and bifurcation analysis was performed to determine how the closed loop system dynamics are different from those of the open loop system. This low order model was then used to determine the optimal placement of the air injection actuators.
\r\n\r\nExperimental work focused on verifying that the low order model, developed for air injection actuation, qualitatively captured the behavior of the Caltech compressor rig. Open loop tests were performed to determine how the placement of the air injectors on the rig affected the performance of the compressor. The positioning of the air injectors that provided the greatest control authority were used in the development of air injection controllers for rotating stall. The controllers resulted in complete elimination of the hysteresis associated with rotating stall. The use of a throttle actuator for the control of the surge dynamics was investigated, and then combined with an air injection controller for rotating stall; the resulting controller performed quite well in throttle disturbance rejection tests.
\r\n\r\nA higher order model was developed to qualitatively match the experimental results with a simulation. The results of this modeling effort compared quite well with the experimental results for the open loop behavior of the Caltech rig. The details of how the air injection actuators affect the compressor flow were included in this model, and the simulation predicted the same optimal controller that was developed through experimentation.
\r\n\r\nThe development of the higher order model also included the investigation of systematic methods for determining the simulation parameters. Based on experimental measurements of compression system transients, the open loop simulation parameters were identified, including values for the compressor performance characteristic in regions where direct measurements were not possible. These methods also provided information on parameters used in the modeling of the pressure rise delivered by the compressor under unsteady flow conditions.
", "doi": "10.7907/ke8m-n471", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:214", "collection": "thesis", "collection_id": "214", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-01172008-092801", "primary_object_url": { "basename": "Sur_s_1997.pdf", "content": "final", "filesize": 8719654, "license": "other", "mime_type": "application/pdf", "url": "/214/1/Sur_s_1997.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Robotic manipulation with flexible link fingers", "author": [ { "family_name": "Sur", "given_name": "Sudipto", "clpid": "Sur-S" } ], "thesis_advisor": [ { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Robots with structural flexibility provide an attractive alternative to rigid robots for many of the new and evolving applications in robotics. In certain applications their use is unavoidable. The increased complexity in modeling and control of such robots is offset by desirable performance enhancements in some respects. In this thesis we present a singular perturbation approach for modeling, analysis and control of robots with flexibility. As our singular perturbation approach does not treat the flexible manipulator as a perturbation of the rigid manipulator, it can treat significant flexibility, beyond the linear range. Analysis based on this approach leads to some provably stable control laws for the hybrid position and force control of flexible-link manipulators. The analysis is done in the framework of a single robot manipulator in a constrained motion task. Simulations and experimental results are presented for this case. To show applicability of the results to more general and complex systems with flexibilities we also present experimental data from a planar, two-fingered, reconfigurable grasping setup which allows rigid and flexible configurations. The aim of the experimentation is to show the applicability of the control laws and analysis developed, and to determine the performance enhancements resulting from the introduction of flexibility. Experimental data is analysed to show the tradeoffs between controller complexity and performance enhancement as we deal with greater flexibility. Various performance criteria are set up and experimental results are discussed within their framework. We conclude that large flexibility can be controlled without too much additional effort, has performance comparable to that of rigid robots, and possesses enhancing properties which make it appealing for use in certain types of applications.", "doi": "10.7907/RVP5-Q254", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:191", "collection": "thesis", "collection_id": "191", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-01152008-082733", "primary_object_url": { "basename": "Rathinam_m_1997.pdf", "content": "final", "filesize": 6515859, "license": "other", "mime_type": "application/pdf", "url": "/191/1/Rathinam_m_1997.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Differentially flat nonlinear control systems", "author": [ { "family_name": "Rathinam", "given_name": "Muruhan", "clpid": "Rathinam-M" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Differentially flat systems are underdetermined systems of (nonlinear) ordinary differential equations (ODEs) whose solution curves are in smooth one-one correspondence with arbitrary curves in a space whose dimension equals the number of equations by which the system is underdetermined. For control systems this is the same as the number of inputs. The components of the map from the system space to the smaller dimensional space are referred to as the flat outputs. Flatness allows one to systematically generate feasible trajectories in a relatively simple way. Typically the flat outputs may depend on the original independent and dependent variablesterms of which the ODEs are written as well as finitely many derivatives of the dependent variables. Flatness of systems underdetermined by one equation is completely characterised by Elie Cartan's work. But for general underdetermined systems no complete characterisation of flatness exists.\n\nIn this dissertation we describe two different geometric frameworks for studying flatness and provide constructive methods for deciding the flatness of certain classes of nonlinear systems and for finding these flat outputs if they exist. We first introduce the concept of \"absolute equivalence\" due to Cartan and define flatness in this frame work. We provide a method of testing for the flatness of systems, which involves making a guess for all but one of the flat outputs after which the problem is reduced to the case solved by Cartan. Secondly we present an alternative geometric approach to flatness which uses \"jet bundles\" and present a theorem which partially characterises flat outputs that depend only on the original variables but not on their derivatives, for the case of systems described by two independent one-forms in arbitrary number of variables. Finally, for the class of Lagrangian mechanical systems whose number of control inputs is one less than the number of degrees of freedom, we provide a characterisation of flat outputs that depend only on the configuration variables, but not on their derivatives. This characterisation makes use of the Riemannian metric provided by the kinetic energy of the system.\n", "doi": "10.7907/k7pm-hs13", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:212", "collection": "thesis", "collection_id": "212", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-01172008-085534", "primary_object_url": { "basename": "VanNieuwstadt_mj_1997.pdf", "content": "final", "filesize": 8063098, "license": "other", "mime_type": "application/pdf", "url": "/212/1/VanNieuwstadt_mj_1997.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Trajectory generation for nonlinear control systems", "author": [ { "family_name": "Van Nieuwstadt", "given_name": "Michiel Jacques", "clpid": "Van-Nieuwstadt-M-J" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "This thesis explores the paradigm of two degree of freedom design for nonlinear control systems. In two degree of freedom design one generates an explicit trajectory for state and input around which the system is linearized. Linear techniques are then used to stabilize the system around the nominal trajectory and to deal with uncertainty. This approach allows the use of the wealth of tools in linear control theory to stabilize a system in the face of uncertainty, while exploiting the non-linearities to increase performance. Indeed, this thesis shows through simulations and experiments that the generation of a nominal trajectory allows more aggressive tracking in mechanical systems.\r\n\r\nThe generation of trajectories for general systems involves the solution of two point boundary value problems which are hard to solve numerically. For the special class of differentially flat systems there exists a unique correspondence between trajectories in the output space and the full state and input space. This allows us to generate trajectories in the lower dimensional output, space where we don't have differential constraints, and subsequently map these to the full state and input space through an algebraic procedure. No differential equations have to be solved in this process. This thesis gives a definition of differential flatness in terms of differential geometry, and proves some properties of flat systems. In particular, it is shown that differential flatness is equivalent to dynamic feedback linearizability in an open and dense set.\r\n\r\nThis dissertation focuses on differentially flat systems. We describe some interesting trajectory generation problems for these systems, and present software to solve them. We also present algorithms and software for real time trajectory generation, that allow a computational tradeoff between stability and performance. We prove convergence for a rather general class of desired trajectories. If a system is not differentially flat we can approximate it with a differentially flat system, and extend the techniques for flat systems. The various extensions for approximately flat systems are validated in simulation and experiments on a thrust vectored aircraft. A system may exhibit a two layer structure where the outer layer is a flat system, and the inner system is not. We call this structure outer flatness. We investigate trajectory generation for these systems and present theorems on the type of tracking we can achieve. We validate the outer flatness approach on a model helicopter in simulations and experiment.\r\n", "doi": "10.7907/9X7P-A431", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:54", "collection": "thesis", "collection_id": "54", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-01072008-082023", "primary_object_url": { "basename": "Tierno_je_1996.pdf", "content": "final", "filesize": 6392136, "license": "other", "mime_type": "application/pdf", "url": "/54/1/Tierno_je_1996.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "A computational approach to nonlinear system analysis", "author": [ { "family_name": "Tierno", "given_name": "Jorge E.", "clpid": "Tierno-J-E" } ], "thesis_advisor": [ { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Unknown", "given_name": "Unknown" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Most practical control systems have significant nonlinear components. However, these systems are typically analyzed either through robustness analysis of their linearizations, or through extensive simulation of their nonlinear models. Other forms of analysis of nonlinear systems have not as yet led to computationally tractable solutions. The aim of this thesis is to extend the analysis methodology for linear systems given by the structured singular value framework to nonlinear systems. We study the question: Given an uncertain nonlinear system, driven by a nominal command signal over a finite time horizon, and subject to bounded noise, norm bounded feedback components, and uncertain parameters, how far from the nominal trajectory will the actual trajectory be? In order to inherit the properties of the structured singular value, we will use the 2-norm as measure for noise signals and undermodeled feedback components. As is the case for robustness analysis of linear systems, we can only find efficient computation algorithms for upper and lower bounds to the answer to this question.\n\nTo compute the lower bound we develop a power algorithm similar to the one developed for the structured singular value. Since, as was the case for linear systems, the algorithm is not guaranteed to converge in general, its analysis has to be done empirically. We test this algorithm by applying it to simulations of real systems and show that it performs better than other available optimization methods. To develop an upper bound, we study a class of rational nonlinear systems. We show that for problems in this class, an uncertain, constrained linear system can be constructed that achieves the same performance level. Upper bounds on the performance of these systems can be computed by solving linear matrix inequalities. Finally, we study extensions that can be obtained to these analysis methods when the system is linear but time varying.\n", "doi": "10.7907/4txk-p492", "publication_date": "1996", "thesis_type": "phd", "thesis_year": "1996" }, { "id": "thesis:4139", "collection": "thesis", "collection_id": "4139", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-10172007-104556", "primary_object_url": { "basename": "M'Closkey_rt_1995.pdf", "content": "final", "filesize": 6682073, "license": "other", "mime_type": "application/pdf", "url": "/4139/1/M'Closkey_rt_1995.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Exponential stabilization of driftless nonlinear control systems", "author": [ { "family_name": "M'Closkey", "given_name": "Robert Thomas", "clpid": "M-Closkey-R-R" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Doyle", "given_name": "John Comstock", "clpid": "Doyle-J-C" }, { "family_name": "Wiggins", "given_name": "Stephen R.", "clpid": "Wiggins-S-R" }, { "family_name": "Caughey", "given_name": "Thomas Kirk", "clpid": "Caughey-T-K" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document.\n\nThis dissertation lays the foundation for practical exponential stabilization of driftless control systems. Driftless systems have the form,\n\n[...].\n\nSuch systems arise when modeling mechanical systems with nonholonomic constraints. In engineering applications it is often required to maintain the mechanical system around a desired configuration. This task is treated as a stabilization problem where the desired configuration is made an asymptotically stable equilibrium point. The control design is carried out on an approximate system. The approximation process yields a nilpotent set of input vector fields which, in a special coordinate system, are homogeneous with respect to a non-standard dilation. Even though the approximation can be given a coordinate-free interpretation, the homogeneous structure is useful to exploit. Since implementing a controller requires choosing a coordinate system, there are extra benefits to be gained by choosing coordinates in which the approximation is homogeneous. The feedbacks are required to be homogeneous functions and thus preserve the homogeneous structure in the closed-loop system. The stability achieved is called p-exponential stability. This extended notion of exponential stability is required since the feedback, and hence the closed-loop system, is not Lipschitz. However, it is shown that the convergence rate of a Lipschitz closed-loop driftless system cannot be bounded by an exponential envelope.\n\nThe synthesis methods generate feedbacks which are not smooth on [...]. The solutions of the closed-loop system are proven to be unique in this case. In addition, for many driftless systems the control inputs are often velocities. A more appropriate formulation of the stabilization problem has the control law specifying forces instead of velocities. We have extended the kinematic velocity controllers to controllers which command forces and still p-exponentially stabilize the system. \n\nPerhaps the ultimate justification of the methods proposed in this thesis are the experimental results. The experiments demonstrate the superior convergence performance of the p-exponential stabilizers versus traditional smooth feedbacks. The experiments also highlight the importance of transformation conditioning in the feedbacks. Other design issues, such as scaling the measured states to eliminate hunting, are discussed. The methods and problems in this thesis bring the practical control of strongly nonlinear systems one step closer.\n", "doi": "10.7907/7myb-h217", "publication_date": "1995", "thesis_type": "phd", "thesis_year": "1995" }, { "id": "thesis:2875", "collection": "thesis", "collection_id": "2875", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-07132006-143133", "primary_object_url": { "basename": "Lewis_ad_1995.pdf", "content": "final", "filesize": 7123017, "license": "other", "mime_type": "application/pdf", "url": "/2875/1/Lewis_ad_1995.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Aspects of geometric mechanics and control of mechanical systems", "author": [ { "family_name": "Lewis", "given_name": "Andrew David", "clpid": "Lewis-A-D" } ], "thesis_advisor": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" } ], "thesis_committee": [ { "family_name": "Murray", "given_name": "Richard M.", "clpid": "Murray-R-M" }, { "family_name": "Marsden", "given_name": "Jerrold E.", "clpid": "Marsden-J-E" }, { "family_name": "Burdick", "given_name": "Joel Wakeman", "clpid": "Burdick-J-W" }, { "family_name": "Caughey", "given_name": "Thomas Kirk", "clpid": "Caughey-T-K" } ], "local_group": [ { "literal": "div_eng" } ], "abstract": "Many interesting control systems are mechanical control systems. In spite of this, there has not been much effort to develop methods which use the special structure of mechanical systems to obtain analysis tools which are suitable for these systems. In this dissertation we take the first steps towards a methodical treatment of mechanical control systems.\n\nFirst we develop a framework for analysis of certain classes of mechanical control systems. In the Lagrangian formulation we study \"simple mechanical control systems\" whose Lagrangian is \"kinetic energy minus potential energy.\" We propose a new and useful definition of controllability for these systems and obtain a computable set of conditions for this new version of controllability. We also obtain decompositions of simple mechanical systems in the case when they are not controllable. In the Hamiltonian formulation we study systems whose control vector fields are Hamiltonian. We obtain decompositions which describe the controllable and uncontrollable dynamics. In each case, the dynamics are shown to be Hamiltonian in a suitably general sense.\n\nNext we develop intrinsic descriptions of Lagrangian and Hamiltonian mechanics in the presence of external inputs. This development is a first step towards a control theory for general Lagrangian and Hamiltonian control systems. Systems with constraints are also studied. We first give a thorough overview of variational methods including a comparison of the \"nonholonomic\" and \"vakonomic\" methods. We also give a generalised definition for a constraint and, with this more general definition, we are able to give some preliminary controllability results for constrained systems.\n", "doi": "10.7907/CHWF-M421", "publication_date": "1995", "thesis_type": "phd", "thesis_year": "1995" } ]