ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- Creators: Pedrielli, Giulia
Description
The success of genetically-modified T-cells in treating hematological malignancies has accelerated the research timeline for Chimeric Antigen Receptor-T (CAR-T) cell therapy. Since there are only two approved products (Kymriah and Yescarta), the process knowledge is limited. This leads to a low efficiency at manufacturing stage with serious challenges corresponding to high cost and scalability. In addition, the individualized nature of the therapy limits inventory and creates a high risk of product loss due to supply chain failure. The sector needs a new manufacturing paradigm capable of quickly responding to individualized demands while considering complex system dynamics.
The research formulates the problem of Chimeric Antigen Receptor-T (CAR-T) manufacturing design, understanding the performance for large scale production of personalized therapies. The solution looks to develop a simulation environment for bio-manufacturing systems with single-use equipment. The result is BioMan: a discrete-event simulation model that considers the role of therapy's individualized nature, type of processing and quality-management policies on process yield and time, while dealing with the available resource constraints simultaneously. The tool will be useful to understand the impact of varying factor inputs on Chimeric Antigen Receptor-T (CAR-T) cell manufacturing and will eventually facilitate the decision-maker to finalize the right strategies achieving better processing, high resource utilization, and less failure rates.
The research formulates the problem of Chimeric Antigen Receptor-T (CAR-T) manufacturing design, understanding the performance for large scale production of personalized therapies. The solution looks to develop a simulation environment for bio-manufacturing systems with single-use equipment. The result is BioMan: a discrete-event simulation model that considers the role of therapy's individualized nature, type of processing and quality-management policies on process yield and time, while dealing with the available resource constraints simultaneously. The tool will be useful to understand the impact of varying factor inputs on Chimeric Antigen Receptor-T (CAR-T) cell manufacturing and will eventually facilitate the decision-maker to finalize the right strategies achieving better processing, high resource utilization, and less failure rates.
ContributorsSharma, Gaurav (Author) / Pedrielli, Giulia (Thesis advisor) / Fainekos, Georgios (Committee member) / Fowler, John (Committee member) / Arizona State University (Publisher)
Created2020
Description
Complex systems appear when interaction among system components creates emergent behavior that is difficult to be predicted from component properties. The growth of Internet of Things (IoT) and embedded technology has increased complexity across several sectors (e.g., automotive, aerospace, agriculture, city infrastructures, home technologies, healthcare) where the paradigm of cyber-physical systems (CPSs) has become a standard. While CPS enables unprecedented capabilities, it raises new challenges in system design, certification, control, and verification. When optimizing system performance computationally expensive simulation tools are often required, and search algorithms that sequentially interrogate a simulator to learn promising solutions are in great demand. This class of algorithms are black-box optimization techniques. However, the generality that makes black-box optimization desirable also causes computational efficiency difficulties when applied real problems. This thesis focuses on Bayesian optimization, a prominent black-box optimization family, and proposes new principles, translated in implementable algorithms, to scale Bayesian optimization to highly expensive, large scale problems. Four problem contexts are studied and approaches are proposed for practically applying Bayesian optimization concepts, namely: (1) increasing sample efficiency of a highly expensive simulator in the presence of other sources of information, where multi-fidelity optimization is used to leverage complementary information sources; (2) accelerating global optimization in the presence of local searches by avoiding over-exploitation with adaptive restart behavior; (3) scaling optimization to high dimensional input spaces by integrating Game theoretic mechanisms with traditional techniques; (4) accelerating optimization by embedding function structure when the reward function is a minimum of several functions. In the first context this thesis produces two multi-fidelity algorithms, a sample driven and model driven approach, and is implemented to optimize a serial production line; in the second context the Stochastic Optimization with Adaptive Restart (SOAR) framework is produced and analyzed with multiple applications to CPS falsification problems; in the third context the Bayesian optimization with sample fictitious play (BOFiP) algorithm is developed with an implementation in high-dimensional neural network training; in the last problem context the minimum surrogate optimization (MSO) framework is produced and combined with both Bayesian optimization and the SOAR framework with applications in simultaneous falsification of multiple CPS requirements.
ContributorsMathesen, Logan (Author) / Pedrielli, Giulia (Thesis advisor) / Candan, Kasim (Committee member) / Fainekos, Georgios (Committee member) / Gel, Esma (Committee member) / Montgomery, Douglas (Committee member) / Zabinsky, Zelda (Committee member) / Arizona State University (Publisher)
Created2021