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Description
Adaptive therapy utilizes competitive interactions between resistant and sensitive cells by keeping some sensitive cells to control tumor burden with the aim of increasing overall survival and time to progression. The use of adaptive therapy to treat breast cancer, ovarian cancer, and pancreatic cancer in preclinical models has shown significant results in controlling tumor growth. The purpose of this thesis is to draft a protocol to study adaptive therapy in a preclinical model of breast cancer on MCF7, estrogen receptor-positive, cells that have evolved resistance to fulvestrant and palbociclib (MCF7 R). In this study, we used two protocols: drug dose adjustment and intermittent therapy. The MCF7 R cell lines were injected into the mammary fat pads of 11-month-old NOD/SCID gamma (NSG) mice (18 mice) which were then treated with gemcitabine.<br/>The results of this experiment did not provide complete information because of the short-term treatments. In addition, we saw an increase in the tumor size of a few of the treated mice, which could be due to the metabolism of the drug at that age, or because of the difference in injection times. Therefore, these adaptive therapy protocols on hormone-refractory breast cancer cell lines will be repeated on young, 6-week old mice by injecting the cell lines at the same time for all mice, which helps the results to be more consistent and accurate.
ContributorsConti, Aviona (Author) / Maley, Carlo (Thesis director) / Blattman, Joseph (Committee member) / Seyedi, Sareh (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Coherent vortices are ubiquitous structures in natural flows that affect mixing and transport of substances and momentum/energy. Being able to detect these coherent structures is important for pollutant mitigation, ecological conservation and many other aspects. In recent years, mathematical criteria and algorithms have been developed to extract these coherent structures in turbulent flows. In this study, we will apply these tools to extract important coherent structures and analyze their statistical properties as well as their implications on kinematics and dynamics of the flow. Such information will aide representation of small-scale nonlinear processes that large-scale models of natural processes may not be able to resolve.
ContributorsCass, Brentlee Jerry (Author) / Tang, Wenbo (Thesis director) / Kostelich, Eric (Committee member) / Department of Information Systems (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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
Advancements to a dual scale Large Eddy Simulation (LES) modeling approach for immiscible turbulent phase interfaces are presented. In the dual scale LES approach, a high resolution auxiliary grid, used to capture a fully resolved interface geometry realization, is linked to an LES grid that solves the filtered Navier-Stokes equations. Exact closure of the sub-filter interface terms is provided by explicitly filtering the fully resolved quantities from the auxiliary grid. Reconstructing a fully resolved velocity field to advance the phase interface requires modeling several sub-filter effects, including shear and accelerational instabilities and phase change. Two sub-filter models were developed to generate these sub-filter hydrodynamic instabilities: an Orr-Sommerfeld model and a Volume-of-Fluid (VoF) vortex sheet method. The Orr-Sommerfeld sub-filter model was found to be incompatible with the dual scale approach, since it is unable to generate interface rollup and a process to separate filtered and sub-filter scales could not be established. A novel VoF vortex sheet method was therefore proposed, since prior vortex methods have demonstrated interface rollup and following the LES methodology, the vortex sheet strength could be decomposed into its filtered and sub-filter components. In the development of the VoF vortex sheet method, it was tested with a variety of classical hydrodynamic instability problems, compared against prior work and linear theory, and verified using Direct Numerical Simulations (DNS). An LES consistent approach to coupling the VoF vortex sheet with the LES filtered equations is presented and compared against DNS. Finally, a sub-filter phase change model is proposed and assessed in the dual scale LES framework with an evaporating interface subjected to decaying homogeneous isotropic turbulence. Results are compared against DNS and the interplay between surface tension forces and evaporation are discussed.
ContributorsGoodrich, Austin Chase (Author) / Herrmann, Marcus (Thesis advisor) / Dahm, Werner (Committee member) / Kim, Jeonglae (Committee member) / Huang, Huei-Ping (Committee member) / Kostelich, Eric (Committee member) / Arizona State University (Publisher)
Created2023
Description
A moving overlapping mesh methodology that achieves spectral accuracy in space and up to second-order accuracy in time is developed for solution of unsteady incompressible flow equations in three-dimensional domains. The targeted applications are in aerospace and mechanical engineering domains and involve problems in turbomachinery, rotary aircrafts, wind turbines and others. The methodology is built within the dual-session communication framework initially developed for stationary overlapping meshes. The methodology employs semi-implicit spectral element discretization of equations in each subdomain and explicit treatment of subdomain interfaces with spectrally-accurate spatial interpolation and high-order accurate temporal extrapolation, and requires few, if any, iterations, yet maintains the global accuracy and stability of the underlying flow solver. Mesh movement is enabled through the Arbitrary Lagrangian-Eulerian formulation of the governing equations, which allows for prescription of arbitrary velocity values at discrete mesh points.
The stationary and moving overlapping mesh methodologies are thoroughly validated using two- and three-dimensional benchmark problems in laminar and turbulent flows. The spatial and temporal global convergence, for both methods, is documented and is in agreement with the nominal order of accuracy of the underlying solver.
Stationary overlapping mesh methodology was validated to assess the influence of long integration times and inflow-outflow global boundary conditions on the performance. In a turbulent benchmark of fully-developed turbulent pipe flow, the turbulent statistics are validated against the available data.
Moving overlapping mesh simulations are validated on the problems of two-dimensional oscillating cylinder and a three-dimensional rotating sphere. The aerodynamic forces acting on these moving rigid bodies are determined, and all results are compared with published data. Scaling tests, with both methodologies, show near linear strong scaling, even for moderately large processor counts.
The moving overlapping mesh methodology is utilized to investigate the effect of an upstream turbulent wake on a three-dimensional oscillating NACA0012 extruded airfoil. A direct numerical simulation (DNS) at Reynolds Number 44,000 is performed for steady inflow incident upon the airfoil oscillating between angle of attack 5.6 and 25 degrees with reduced frequency k=0.16. Results are contrasted with subsequent DNS of the same oscillating airfoil in a turbulent wake generated by a stationary upstream cylinder.
The stationary and moving overlapping mesh methodologies are thoroughly validated using two- and three-dimensional benchmark problems in laminar and turbulent flows. The spatial and temporal global convergence, for both methods, is documented and is in agreement with the nominal order of accuracy of the underlying solver.
Stationary overlapping mesh methodology was validated to assess the influence of long integration times and inflow-outflow global boundary conditions on the performance. In a turbulent benchmark of fully-developed turbulent pipe flow, the turbulent statistics are validated against the available data.
Moving overlapping mesh simulations are validated on the problems of two-dimensional oscillating cylinder and a three-dimensional rotating sphere. The aerodynamic forces acting on these moving rigid bodies are determined, and all results are compared with published data. Scaling tests, with both methodologies, show near linear strong scaling, even for moderately large processor counts.
The moving overlapping mesh methodology is utilized to investigate the effect of an upstream turbulent wake on a three-dimensional oscillating NACA0012 extruded airfoil. A direct numerical simulation (DNS) at Reynolds Number 44,000 is performed for steady inflow incident upon the airfoil oscillating between angle of attack 5.6 and 25 degrees with reduced frequency k=0.16. Results are contrasted with subsequent DNS of the same oscillating airfoil in a turbulent wake generated by a stationary upstream cylinder.
ContributorsMerrill, Brandon Earl (Author) / Peet, Yulia (Thesis advisor) / Herrmann, Marcus (Committee member) / Huang, Huei-Ping (Committee member) / Kostelich, Eric (Committee member) / Calhoun, Ronald (Committee member) / Arizona State University (Publisher)
Created2016
Description
Predicting resistant prostate cancer is critical for lowering medical costs and improving the quality of life of advanced prostate cancer patients. I formulate, compare, and analyze two mathematical models that aim to forecast future levels of prostate-specific antigen (PSA). I accomplish these tasks by employing clinical data of locally advanced prostate cancer patients undergoing androgen deprivation therapy (ADT). I demonstrate that the inverse problem of parameter estimation might be too complicated and simply relying on data fitting can give incorrect conclusions, since there is a large error in parameter values estimated and parameters might be unidentifiable. I provide confidence intervals to give estimate forecasts using data assimilation via an ensemble Kalman Filter. Using the ensemble Kalman Filter, I perform dual estimation of parameters and state variables to test the prediction accuracy of the models. Finally, I present a novel model with time delay and a delay-dependent parameter. I provide a geometric stability result to study the behavior of this model and show that the inclusion of time delay may improve the accuracy of predictions. Also, I demonstrate with clinical data that the inclusion of the delay-dependent parameter facilitates the identification and estimation of parameters.
ContributorsBaez, Javier (Author) / Kuang, Yang (Thesis advisor) / Kostelich, Eric (Committee member) / Crook, Sharon (Committee member) / Gardner, Carl (Committee member) / Nagy, John (Committee member) / Arizona State University (Publisher)
Created2017
Description
Efforts to treat prostate cancer have seen an uptick, as the world’s most commoncancer in men continues to have increasing global incidence. Clinically, metastatic
prostate cancer is most commonly treated with hormonal therapy. The idea behind
hormonal therapy is to reduce androgen production, which prostate cancer cells
require for growth. Recently, the exploration of the synergistic effects of the drugs
used in hormonal therapy has begun. The aim was to build off of these recent
advancements and further refine the synergistic drug model. The advancements I
implement come by addressing biological shortcomings and improving the model’s
internal mechanistic structure. The drug families being modeled, anti-androgens,
and gonadotropin-releasing hormone analogs, interact with androgen production in a
way that is not completely understood in the scientific community. Thus the models
representing the drugs show progress through their ability to capture their effect
on serum androgen. Prostate-specific antigen is the primary biomarker for prostate
cancer and is generally how population models on the subject are validated. Fitting
the model to clinical data and comparing it to other clinical models through the
ability to fit and forecast prostate-specific antigen and serum androgen is how this
improved model achieves validation. The improved model results further suggest that
the drugs’ dynamics should be considered in adaptive therapy for prostate cancer.
prostate cancer is most commonly treated with hormonal therapy. The idea behind
hormonal therapy is to reduce androgen production, which prostate cancer cells
require for growth. Recently, the exploration of the synergistic effects of the drugs
used in hormonal therapy has begun. The aim was to build off of these recent
advancements and further refine the synergistic drug model. The advancements I
implement come by addressing biological shortcomings and improving the model’s
internal mechanistic structure. The drug families being modeled, anti-androgens,
and gonadotropin-releasing hormone analogs, interact with androgen production in a
way that is not completely understood in the scientific community. Thus the models
representing the drugs show progress through their ability to capture their effect
on serum androgen. Prostate-specific antigen is the primary biomarker for prostate
cancer and is generally how population models on the subject are validated. Fitting
the model to clinical data and comparing it to other clinical models through the
ability to fit and forecast prostate-specific antigen and serum androgen is how this
improved model achieves validation. The improved model results further suggest that
the drugs’ dynamics should be considered in adaptive therapy for prostate cancer.
ContributorsReckell, Trevor (Author) / Kostelich, Eric (Thesis advisor) / Kuang, Yang (Committee member) / Mahalov, Alex (Committee member) / Arizona State University (Publisher)
Created2020
Description
The central purpose of this work is to investigate the large-scale, coherent structures that exist in turbulent Rayleigh-Bénard convection (RBC) when the domain is large enough for the classical ”wind of turbulence” to break down. The study exclusively focuses on the structures that from when the RBC geometry is a cylinder. A series of visualization studies, Fourier analysis and proper orthogonal decomposition are employed to qualitatively and quantitatively inspect the large-scale structures’ length and time scales, spatial organization, and dynamic properties. The data in this study is generated by direct numerical simulation to resolve all the scales of turbulence in a 6.3 aspect-ratio cylinder at a Rayleigh number of 9.6 × 107 and Prandtl number of 6.7. Single and double point statistics are compared against experiments and several resolution criteria are examined to verify that the simulation has enough spatial and temporal resolution to adequately represent the physical system.
Large-scale structures are found to organize as roll-cells aligned along the cell’s side walls, with rays of vorticity pointing toward the core of the cell. Two different large- scale organizations are observed and these patterns are well described spatially and energetically by azimuthal Fourier modes with frequencies of 2 and 3. These Fourier modes are shown to be dominant throughout the entire domain, and are found to be the primary source for radial inhomogeneity by inspection of the energy spectra. The precision with which the azimuthal Fourier modes describe these large-scale structures shows that these structures influence a large range of length scales. Conversely, the smaller scale structures are found to be more sensitive to radial position within the Fourier modes showing a strong dependence on physical length scales.
Dynamics in the large-scale structures are observed including a transition in the global pattern followed by a net rotation about the central axis. The transition takes place over 10 eddy-turnover times and the subsequent rotation occurs at a rate of approximately 1.1 degrees per eddy-turnover. These time-scales are of the same order of magnitude as those seen in lower aspect-ratio RBC for similar events and suggests a similarity in dynamic events across different aspect-ratios.
Large-scale structures are found to organize as roll-cells aligned along the cell’s side walls, with rays of vorticity pointing toward the core of the cell. Two different large- scale organizations are observed and these patterns are well described spatially and energetically by azimuthal Fourier modes with frequencies of 2 and 3. These Fourier modes are shown to be dominant throughout the entire domain, and are found to be the primary source for radial inhomogeneity by inspection of the energy spectra. The precision with which the azimuthal Fourier modes describe these large-scale structures shows that these structures influence a large range of length scales. Conversely, the smaller scale structures are found to be more sensitive to radial position within the Fourier modes showing a strong dependence on physical length scales.
Dynamics in the large-scale structures are observed including a transition in the global pattern followed by a net rotation about the central axis. The transition takes place over 10 eddy-turnover times and the subsequent rotation occurs at a rate of approximately 1.1 degrees per eddy-turnover. These time-scales are of the same order of magnitude as those seen in lower aspect-ratio RBC for similar events and suggests a similarity in dynamic events across different aspect-ratios.
ContributorsSakievich, Philip Sakievich (Author) / Peet, Yulia (Thesis advisor) / Adrian, Ronald (Committee member) / Squires, Kyle (Committee member) / Herrmann, Marcus (Committee member) / Kostelich, Eric (Committee member) / Arizona State University (Publisher)
Created2017