Matching Items (133)
Description
Over the past 20 years, the fields of synthetic biology and synthetic biosystems engineering have grown into mature disciplines, leading to significant breakthroughs in cancer research, diagnostics, cell-based medicines, biochemical production, etc. Application of mathematical modelling to biological and biochemical systems have not only given great insight into how these systems function, but also have lent enough predictive power to aid in the forward-engineering of synthetic constructs. However, progress has been impeded by several modes of context-dependence unique to biological and biochemical systems that are not seen in traditional engineering disciplines, resulting in the need for lengthy design-build-test cycles before functional prototypes are generated.In this work, two of these universal modes of context dependence – resource competition and growth feedback –their effects on synthetic gene circuits and potential control mechanisms, are studied and characterized. Results demonstrate that a novel competitive control architecture can be utilized to mitigate the effects of winner-take-all resource competition (a form of context dependence where distinct gene modules influence each other by competing over a shared pool of transcriptional/translational resources) in synthetic gene circuits and restore circuits to their intended function. Application of the fluctuation-dissipation theorem and rigorous stochastic simulations demonstrate that realistic resource constraints present in cells at the transcriptional and translational levels influence noise in gene circuits in a nonmonotonic fashion, either increasing or decreasing noise depending on the transcriptional/translational capacity.
Growth feedback on the other hand links circuit function to cellular growth rate via increased protein dilution rate during exponential growth phase. This in turn can result in the collapse of bistable gene circuits as the accelerated dilution rate forces switches in a high stable state to fall to a low stable state. Mathematical modelling and experimental data demonstrate that application of repressive links can insulate sensitive parts of gene circuits against growth-fluctuations and can in turn increase the robustness of multistable circuits in growth contexts.
The results presented in this work aid in the accumulation of understanding of biological and biochemical context dependence, and corresponding control strategies and design principles engineers can utilize to mitigate these effects.
ContributorsStone, Austin (Author) / Tian, Xiao-jun (Thesis advisor) / Wang, Xiao (Committee member) / Smith, Barbara (Committee member) / Kuang, Yang (Committee member) / Cheng, Albert (Committee member) / Arizona State University (Publisher)
Created2023
Description
This thesis focuses on the turbulent bluff body wakes in incompressible and compressible flows. An incompressible wake flow past an axisymmetric body of revolution at a diameter-based Reynolds number Re=5000 is investigated via a direct numerical simulation. It is followed by the development of a compressible solver using a split-form discontinuous Galerkin spectral element method framework with shock capturing. In the study on incompressible wake flows, three dominant coherent vortical motions are identified in the wake: the vortex shedding motion with the frequency of St=0.27, the bubble pumping motion with St=0.02, and the very-low-frequency (VLF) motion originated in the very near wake of the body with the frequencies St=0.002 and 0.005. The very-low-frequency motion is associated with a slow precession of the wake barycenter. The vortex shedding pattern is demonstrated to follow a reflectional symmetry breaking mode, with the detachment location rotating continuously and making a full circle over one vortex shedding period. The VLF radial motion with St=0.005 originates as m = 1 mode, but later transitions into m = 2 mode in the intermediate wake. Proper orthogonaldecomposition (POD) and dynamic mode decomposition (DMD) are further performed to analyze the spatial structure associated with the dominant coherent motions. Results of the POD and DMD analysis are consistent with the results of the azimuthal Fourier analysis. To extend the current incompressible code to be able to solve compressible flows, a computational methodology is developed using a high-order approximation for the compressible Navier-Stokes equations with discontinuities. The methodology is based on a split discretization framework with a summation-by-part operator. An entropy viscosity method and a subcell finite volume method are implemented to capture discontinuities. The developed high-order split-form with shock-capturing methodology is subject to a series of evaluation on cases from subsonic to hypersonic, from one-dimensional to three dimensional. The Taylor-Green vortex case and the supersonic sphere wake case show the capability to handle three-dimensional turbulent flows without and with the presence of shocks. It is also shown that higher-order approximations yield smaller errors than lower-order approximations, for the same number of total degrees of freedom.
ContributorsZhang, Fengrui (Author) / Peet, Yulia (Thesis advisor) / Kostelich, Eric (Committee member) / Kim, Jeonglae (Committee member) / Hermann, Marcus (Committee member) / Adrian, Ronald (Committee member) / Arizona State University (Publisher)
Created2022
Description
There is a need in the ecology literature to have a discussion about the fundamental theories from which population dynamics arises. Ad hoc model development is not uncommon in the field often as a result of a need to publish rapidly and frequently. Ecologists and statisticians like Robert J. Steidl and Kenneth P Burnham have called for a more deliberative approach they call "hard thinking". For example, the phenomena of population growth can be captured by almost any sigmoid function. The question of which sigmoid function best explains a data set cannot be answered meaningfully by statistical regression since that can only speak to the validity of the shape. There is a need to revisit enzyme kinetics and ecological stoichiometry to properly justify basal model selection in ecology. This dissertation derives several common population growth models from a generalized equation. The mechanistic validity of these models in different contexts is explored through a kinetic lens. The behavioral kinetic framework is then put to the test by examining a set of biologically plausible growth models against the 1968-1995 elk population count data for northern Yellowstone. Using only this count data, the novel Monod-Holling growth model was able to accurately predict minimum viable population and life expectancy despite both being exogenous to the model and data set. Lastly, the elk/wolf data from Yellowstone was used to compare the validity of the Rosenzweig-MacArthur and Arditi-Ginzburg models. They both were derived from a more general model which included both predator and prey mediated steps. The Arditi-Ginzburg model was able to fit the training data better, but only the Rosenzweig-MacArthur model matched the validation data. Accounting for animal sexual behavior allowed for the creation of the Monod-Holling model which is just as simple as the logistic differential equation but provides greater insights for conservation purposes. Explicitly acknowledging the ethology of wolf predation helps explain the differences in predictive performances by the best fit Rosenzweig-MacArthur and Arditi-Ginzburg models. The behavioral kinetic framework has proven to be a useful tool, and it has the ability to provide even further insights going forward.
ContributorsPringle, Jack Andrew McCracken (Author) / Anderies, John M (Thesis advisor) / Kuang, Yang (Committee member) / Milner, Fabio (Committee member) / Arizona State University (Publisher)
Created2022
Description
Ecology has been an actively studied topic recently, along with the rapid development of human microbiota-based technology. Scientists have made remarkable progress using bioinformatics tools to identify species and analyze composition. However, a thorough understanding of interspecies interactions of microbial ecosystems is still lacking, which has been a significant obstacle in the further development of related technologies. In this work, a genetic circuit design principle with synthetic biology approaches is developed to form two-strain microbial consortia with different inter-strain interactions. The microbial systems are well-defined and inducible. Co-culture experiment results show that our microbial consortia behave consistently with previous ecological knowledge and thus serves as excellent model systems to simulate ecosystems with similar interactions. Colony patterns also emerge when co-culturing multiple species on solid media. With the engineered microbial consortia, image-processing based methods were developed to quantify the shape of co-culture colonies and distinguish microbial consortia with different interactions. Factors that affect the population ratios were identified through induction and variations in the inoculation process. Further time-lapse experiments revealed the basic rules of colony growth, composition variation, patterning, and how spatial factors impact the co-culture colony.
ContributorsChen, Xingwen (Author) / Wang, Xiao (Thesis advisor) / Kuang, Yang (Committee member) / Tian, Xiaojun (Committee member) / Brafman, David (Committee member) / Plaisier, Christopher (Committee member) / Arizona State University (Publisher)
Created2022
Description
The mutual inhibition between synthetic gene circuits and cell growth produces growth feedback in the host-circuit system. Previous studies have demonstrated that the growth feedback has an marked impact on the molecular dynamics of the host-circuit system. However, the complexity of the growth feedback effect is not fully understood. A theoretical framework was developed to study the dynamics of the coupling between growth feedback and synthetic gene circuits. The study’s results reveal three major points about the impact of growth feedback. First, a nonlinear emergent behavior mediated by growth feedback. The unexpected behavior depends on the dynamic ribosome allocation between gene circuit expression and host cell growth. Second, the emergence and loss of unexpected qualitative states on the host-circuit system generated by ultrasensitive growth feedback. Third, the growth feedback-induced cooperativity behavior in synthetic gene modules competing for resources. In addition, growth feedback attenuated the winner-takes-all rules on resource competition between the two self-activating modules. These results demonstrate that growth feedback plays an important role in the host-circuit system’s molecular dynamics. Characterizing general principles from the effect of growth facilitates the ability to minimize or even harness unexpected gene expression behaviors derived from the effect of growth feedback.
ContributorsMelendez-Alvarez, Juan Ramon (Author) / Tian, Xiaojun (Thesis advisor) / Wang, Xiao (Committee member) / Kuang, Yang (Committee member) / Arizona State University (Publisher)
Created2022
Description
In the last two decades, fantasy sports have grown massively in popularity. Fantasy football in particular is the most popular fantasy sport in the United States. People spend hours upon hours every year building, researching, and perfecting their teams to compete with others for money or bragging rights. One problem, however, is that National Football League (NFL) players are human and will not perform the same as they did last week or last season. Because of this, there is a need to create a machine learning model to help predict when players will have a tough game or when they can perform above average. This report discusses the history and science of fantasy football, gathering large amounts of player data, manipulating the information to create more insightful data points, creating a machine learning model, and how to use this tool in a real-world situation. The initial model created significantly accurate predictions for quarterbacks and running backs but not receivers and tight ends. Improvements significantly increased the accuracy by reducing the mean average error to below one for all positions, resulting in a successful model for all four positions.
ContributorsCase, Spencer (Author) / Johnson, Jarod (Co-author) / Kostelich, Eric (Thesis director) / Zhuang, Houlong (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Mechanical and Aerospace Engineering Program (Contributor)
Created2023-05
Description
The main purpose of this project is to create a method for determining the absolute position of an accelerometer. Acceleration and angular speed were obtained from an accelerometer attached to a vehicle as it moves around. As the vehicle moves to collect information the orientation of the accelerometer changes, so a rotation matrix is applied to the data based on the angular change at each time. The angular change and distance are obtained by using the trapezoidal approximation of the integrals. This method was first validated by using simple sets of "true" data which are explicitly known sets of data to compare the results to. Then, an analysis of how different time steps and levels of noise affect the error of the results was performed to determine the optimal time step of 0.1 sec that was then used for the actual tests. The tests that were performed were: a stationary test for uses of calibration, a straight line test to verify a simple test, and a closed loop test to test the accuracy. The graphs for these tests give no indication of the actual paths, so the final results can only show that the data from the accelerometer is too noisy and inaccurate for this method to be used by this sensor. The future work would be to test different ways to get more accurate data and then use it to verify this methods. These ways could include using more sensors to interpolate the data, reducing noise by using a different sensor, or adding a filter. Then, if this method is considered accurate enough, it could be implemented into control systems.
ContributorsHorner, Devon (Author) / Kostelich, Eric (Thesis director) / Crook, Sharon (Committee member) / Barrett, The Honors College (Contributor) / Mechanical and Aerospace Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2023-05
Description
High-dimensional systems are difficult to model and predict. The underlying mechanisms of such systems are too complex to be fully understood with limited theoretical knowledge and/or physical measurements. Nevertheless, redcued-order models have been widely used to study high-dimensional systems, because they are practical and efficient to develop and implement. Although model errors (biases) are inevitable for reduced-order models, these models can still be proven useful to develop real-world applications. Evaluation and validation for idealized models are indispensable to serve the mission of developing useful applications. Data assimilation and uncertainty quantification can provide a way to assess the performance of a reduced-order model. Real data and a dynamical model are combined together in a data assimilation framework to generate corrected model forecasts of a system. Uncertainties in model forecasts and observations are also quantified in a data assimilation cycle to provide optimal updates that are representative of the real dynamics. In this research, data assimilation is applied to assess the performance of two reduced-order models. The first model is developed for predicting prostate cancer treatment response under intermittent androgen suppression therapy. A sequential data assimilation scheme, the ensemble Kalman filter (EnKF), is used to quantify uncertainties in model predictions using clinical data of individual patients provided by Vancouver Prostate Center. The second model is developed to study what causes the changes of the state of stratospheric polar vortex. Two data assimilation schemes: EnKF and ES-MDA (ensemble smoother with multiple data assimilation), are used to validate the qualitative properties of the model using ECMWF (European Center for Medium-Range Weather Forecasts) reanalysis data. In both studies, the reduced-order model is able to reproduce the data patterns and provide insights to understand the underlying mechanism. However, significant model errors are also diagnosed for both models from the results of data assimilation schemes, which suggests specific improvements of the reduced-order models.
ContributorsWu, Zhimin (Author) / Kostelich, Eric (Thesis advisor) / Moustaoui, Mohamed (Thesis advisor) / Jones, Chris (Committee member) / Espanol, Malena (Committee member) / Platte, Rodrigo (Committee member) / Arizona State University (Publisher)
Created2021
Description
Communicating with computers through thought has been a remarkable achievement in recent years. This was made possible by the use of Electroencephalography (EEG). Brain-computer interface (BCI) relies heavily on Electroencephalography (EEG) signals for communication between humans and computers. With the advent ofdeep learning, many studies recently applied these techniques to EEG data to perform various tasks like emotion recognition, motor imagery classification, sleep analysis, and many more.
Despite the rise of interest in EEG signal classification, very few studies have explored the MindBigData dataset, which collects EEG signals recorded at the stimulus of seeing a digit and thinking about it. This dataset takes us closer to realizing the idea of mind-reading or communication via thought. Thus classifying these signals into the respective digit that the user thinks about is a challenging task. This serves as a motivation to study this dataset and apply existing deep learning techniques to study it.
Given the recent success of transformer architecture in different domains like Computer Vision and Natural language processing, this thesis studies transformer architecture for EEG signal classification. Also, it explores other deep learning
techniques for the same. As a result, the proposed classification pipeline achieves comparable performance with the existing methods.
ContributorsMuglikar, Omkar Dushyant (Author) / Wang, Yalin (Thesis advisor) / Liang, Jianming (Committee member) / Venkateswara, Hemanth (Committee member) / Arizona State University (Publisher)
Created2021
Description
Statistical Shape Modeling is widely used to study the morphometrics of deformable objects in computer vision and biomedical studies. There are mainly two viewpoints to understand the shapes. On one hand, the outer surface of the shape can be taken as a two-dimensional embedding in space. On the other hand, the outer surface along with its enclosed internal volume can be taken as a three-dimensional embedding of interests. Most studies focus on the surface-based perspective by leveraging the intrinsic features on the tangent plane. But a two-dimensional model may fail to fully represent the realistic properties of shapes with both intrinsic and extrinsic properties. In this thesis, severalStochastic Partial Differential Equations (SPDEs) are thoroughly investigated and several methods are originated from these SPDEs to try to solve the problem of both two-dimensional and three-dimensional shape analyses. The unique physical meanings of these SPDEs inspired the findings of features, shape descriptors, metrics, and kernels in this series of works. Initially, the data generation of high-dimensional shapes, here, the tetrahedral meshes, is introduced. The cerebral cortex is taken as the study target and an automatic pipeline of generating the gray matter tetrahedral mesh is introduced. Then, a discretized Laplace-Beltrami operator (LBO) and a Hamiltonian operator (HO) in tetrahedral domain with Finite Element Method (FEM) are derived. Two high-dimensional shape descriptors are defined based on the solution of the heat equation and Schrödinger’s equation. Considering the fact that high-dimensional shape models usually contain massive redundancies, and the demands on effective landmarks in many applications, a Gaussian process landmarking on tetrahedral meshes is further studied. A SIWKS-based metric space is used to define a geometry-aware Gaussian process. The study of the periodic potential diffusion process further inspired the idea of a new kernel call the geometry-aware convolutional kernel. A series of Bayesian learning methods are then introduced to tackle the problem of shape retrieval and classification. Experiments of every single item are demonstrated. From the popular SPDE such as the heat equation and Schrödinger’s equation to the general potential diffusion equation and the specific periodic potential diffusion equation, it clearly shows that classical SPDEs play an important role in discovering new features, metrics, shape descriptors and kernels. I hope this thesis could be an example of using interdisciplinary knowledge to solve problems.
ContributorsFan, Yonghui (Author) / Wang, Yalin (Thesis advisor) / Lepore, Natasha (Committee member) / Turaga, Pavan (Committee member) / Yang, Yezhou (Committee member) / Arizona State University (Publisher)
Created2021