Matching Items (214)
Description
Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and includes chemotherapy, radiation therapy, and surgical removal if the tumor is surgically accessible. Treatment seldom results in a significant increase in longevity, partly due to the lack of precise information regarding tumor size and location. This lack of information arises from the physical limitations of MR and CT imaging coupled with the diffusive nature of glioblastoma tumors. GBM tumor cells can migrate far beyond the visible boundaries of the tumor and will result in a recurring tumor if not killed or removed. Since medical images are the only readily available information about the tumor, we aim to improve mathematical models of tumor growth to better estimate the missing information. Particularly, we investigate the effect of random variation in tumor cell behavior (anisotropy) using stochastic parameterizations of an established proliferation-diffusion model of tumor growth. To evaluate the performance of our mathematical model, we use MR images from an animal model consisting of Murine GL261 tumors implanted in immunocompetent mice, which provides consistency in tumor initiation and location, immune response, genetic variation, and treatment. Compared to non-stochastic simulations, stochastic simulations showed improved volume accuracy when proliferation variability was high, but diffusion variability was found to only marginally affect tumor volume estimates. Neither proliferation nor diffusion variability significantly affected the spatial distribution accuracy of the simulations. While certain cases of stochastic parameterizations improved volume accuracy, they failed to significantly improve simulation accuracy overall. Both the non-stochastic and stochastic simulations failed to achieve over 75% spatial distribution accuracy, suggesting that the underlying structure of the model fails to capture one or more biological processes that affect tumor growth. Two biological features that are candidates for further investigation are angiogenesis and anisotropy resulting from differences between white and gray matter. Time-dependent proliferation and diffusion terms could be introduced to model angiogenesis, and diffusion weighed imaging (DTI) could be used to differentiate between white and gray matter, which might allow for improved estimates brain anisotropy.
ContributorsAnderies, Barrett James (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Stepien, Tracy (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Compressed sensing magnetic resonance spectroscopic imaging (MRSI) is a noninvasive and in vivo potential diagnostic technique for cancer imaging. This technique undersamples the distribution of specific cancer biomarkers within an MR image as well as changes in the temporal dimension and subsequently reconstructs the missing data. This technique has been shown to retain a high level of fidelity even with an acceleration factor of 5. Currently there exist several different scanner types that each have their separate analytical methods in MATLAB. A graphical user interface (GUI) was created to facilitate a single computing platform for these different scanner types in order to improve the ease and efficiency with which researchers and clinicians interact with this technique. A GUI was successfully created for both prospective and retrospective MRSI data analysis. This GUI retained the original high fidelity of the reconstruction technique and gave the user the ability to load data, load reference images, display intensity maps, display spectra mosaics, generate a mask, display the mask, display kspace and save the corresponding spectra, reconstruction, and mask files. Parallelization of the reconstruction algorithm was explored but implementation was ultimately unsuccessful. Future work could consist of integrating this parallelization method, adding intensity overlay functionality and improving aesthetics.
ContributorsLammers, Luke Michael (Author) / Kodibagkar, Vikram (Thesis director) / Hu, Harry (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
This study investigates how the patient-provider relationship between lesbian, gay, and bisexual women and their healthcare providers influences their access to, utilization of, and experiences within healthcare environments. Nineteen participants, ages 18 to 34, were recruited using convenience and snowball sampling. Interviews were conducted inquiring about their health history and their experiences within the healthcare system in the context of their sexual orientation. The data collected from these interviews was used to create an analysis of the healthcare experiences of those who identify as queer. Although the original intention of the project was to chronicle the experiences of LGB women specifically, there were four non-binary gender respondents who contributed interviews. In an effort to not privilege any orientation over another, the respondents were collectively referred to as queer, given the inclusive and an encompassing nature of the term. The general conclusion of this study is that respondents most often experienced heterosexism rather than outright homophobia when accessing healthcare. If heterosexism was present within the healthcare setting, it made respondents feel uncomfortable with their providers and less likely to inform them of their sexuality even if it was medically relevant to their health outcomes. Gender, race, and,socioeconomic differences also had an effect on the patient-provider relationship. Non-binary respondents acknowledged the need for inclusion of more gender options outside of male or female on the reporting forms often seen in medical offices. By doing so, medical professionals are acknowledging their awareness and knowledge of people outside of the binary gender system, thus improving the experience of these patients. While race and socioeconomic status were less relevant to the context of this study, it was found that these factors have an affect on the patient-provider relationship. There are many suggestions for providers to improve the experiences of queer patients within the healthcare setting. This includes nonverbal indications of acknowledgement and acceptance, such as signs in the office that indicate it to be a queer friendly space. This will help in eliminating the fear and miscommunication that can often happen when a queer patient sees a practitioner for the first time. In addition, better education on medically relevant topics to queer patients, is necessary in order to eliminate disparities in health outcomes. This is particularly evident in trans health, where specialized education is necessary in order to decrease poor health outcomes in trans patients. Future directions of this study necessitate a closer look on how race and socioeconomic status have an effect on a queer patient's relationship with their provider.
ContributorsRajan, Sindhu (Co-author) / Bradley, Arianna (Co-author) / Larson, Michelle (Co-author) / Alvarado, Aimee (Co-author) / Ingram-Waters, Mary (Thesis director) / Arnold, Michelle (Committee member) / School of Molecular Sciences (Contributor) / School of Social Transformation (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / College of Public Service and Community Solutions (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Netflix has positioned itself at the forefront of the future of television with its original programming, which has been rolled out in greater and more frequent amounts just in the last couple of years. The streaming service has already experimented with creativity in ways most other shows and creators haven't, playing with the pacing of overall seasons as well as the length of episodes. So, too, Netflix has been at the forefront of increasing visibility for minority characters on television. Many of its shows incorporate racially diverse casts and depict lots of LGBTQ characters, a refreshingly realistic view of the world that many of its viewers have always lived in but haven't yet witnessed on television. Visibility and representation are critical concepts for analyzing minority characters on television. It is important for diverse characters to be seen, first and foremost, but also to be seen in positive or at least realistic lights. Care must be taken to avoid fulfilling stereotypes or tropes, and attention must be paid to what has happened to other characters who have come before. However, many of Netflix's portrayals of these characters, particularly bisexual characters, leave much to be desired. With the original dramas House of Cards, Hemlock Grove, Orange is the New Black, and Sense8, all of which include characters who identify as or behave bisexually, Netflix has been reluctant to use the specific word bisexual to describe characters, and many don't even identify their sexuality with a synonym for the term. Many of the bisexual characters that I identified died or were killed on the shows, and nearly all of them fulfilled stereotypes or tropes in some way. There were multiple scenes of threesomes or other distinctly kinky sexual encounters, which served to exoticize bisexuality and distance it from the more normatively viewed identities of heterosexuality and homosexuality. Ultimately, while Netflix's original programming has offered increased visibility to bisexual characters, it has yet to reflect the real community it seeks to portray. In particular, Netflix's refusal to label characters as bisexual is frustrating and limiting. It can be argued that this is a progressive move toward more ideas of sexual fluidity and a post-modern lack of sexual labels, but there are not enough depictions of identified bisexual characters on television yet for this to make sense. Until bisexual characters and their identities are not invisibilized or stigmatized, more work has to be done to ensure that bisexual people are represented fairly and accurately on television and in all media.
ContributorsKoerth, Kimberly Marie (Author) / Himberg, Julia (Thesis director) / Sturges, Robert (Committee member) / Department of English (Contributor) / College of Public Service and Community Solutions (Contributor) / Walter Cronkite School of Journalism and Mass Communication (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Magnetic resonance imaging (MRI) of changes in metabolic activity in tumors and metabolic abnormalities can provide a window to understanding the complex behavior of malignant tumors. Both diagnostics and treatment options can be improved through the further comprehension of the processes that contribute to tumor malignancy and growth. By detecting and disturbing this activity through personalized treatments, it is the hope to provide better diagnostics and care to patients. Experimenting with multicellular tumor spheroids (MCTS) allows for a rapid, inexpensive and convenient solution to studying multiple in vitro tumors. High quality magnetic resonance images of small samples, such as spheroid, however, are difficult to achieve with current radio frequency coils. In addition, in order for the information provided by these scans to accurately represent the interactions and metabolic activity in vivo, there is a need for a perfused vascular network. A perfused vascular network has the potential to improve metabolic realism and particle transport within a tumor spheroid. By creating a more life-like cancer model and allowing the progressive imaging of metabolic functions of such small samples, a better, more efficient mode of studying metabolic activity in cancer can be created and research efforts can expand. The progress described in this paper attempts to address both of these current shortcomings of metabolic cancer research and offers potential solutions, while acknowledging the potential of future work to improve cancer research with MCTS.
ContributorsTobey, John Paul (Author) / Kodibagkar, Vikram (Thesis director) / Sadleir, Rosalind (Committee member) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The combination of immunohistochemical (IHC) stainings and optical microscopy has allowed for the visualization of specific microscopic structures within tissue; however, limitations in light and antibody penetration mitigate the scale on which these images can be taken (Alshammari et al, 2016; Marx, 2014). Tissue clearing, specifically the removal of lipids to improve sample transparency, solves the former weakness well, but does not improve antibody penetration significantly (Chung et al, 2013; Treweek et al, 2015). Therefore, there is a need to equalize the maximum depth that light can pass through a section with the depth at which there is recognizable fluorescence. This is particularly important when staining blood vessels as traditional size limitations exclusively allows for cross sectional visualization. Passive CLARITY Technique (PACT) has been at the forefront of tissue clearing protocols, utilizing an acrylamide hydrogel solution to maintain structure and sodium dodecyl sulfate to wash out lipids (Tomer et al, 2014). PACT is limited in its ability to clear larger sections and is not conducive to IHC antibody diffusion (Treweek et al, 2015). In order to circumvent these drawbacks, CUBIC was developed as an alternative passive protocol, aimed at being scalable to any tissue size (Richardson, 2015; Susaki et al, 2015). This study compared the effectiveness of both protocols in high and low lipid tissues in the context of blood vessel staining efficacy. Upon initial comparison, it became apparent that there was a statistically significant difference in mean DAPI intensity at all depths, up to 200 micrometers, between CUBIC and PACT \u2014 the former showcasing brighter stainings. Moreover, it was found that PACT does not remove erythrocytes from the tissue meaning that their auto-fluorescence is seen during imaging. Therefore, for blood vessel stainings, only CUBIC was optimized and quantitatively analyzed. In both tissue conditions as well as for two stainings, DAPI and fibronectin (FNCT), optimized CUBIC demonstrated a statistically significant difference from standard CUBIC with regards to mean fluorescent intensity.
ContributorsSidhu, Gurpaul Singh (Author) / VanAuker, Michael (Thesis director) / Kodibagkar, Vikram (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Climate change is one of the most pressing issues affecting the world today. One of the impacts of climate change is on the transmission of mosquito-borne diseases (MBDs), such as West Nile Virus (WNV). Climate is known to influence vector and host demography as well as MBD transmission. This dissertation addresses the questions of how vector and host demography impact WNV dynamics, and how expected and likely climate change scenarios will affect demographic and epidemiological processes of WNV transmission. First, a data fusion method is developed that connects non-autonomous logistic model parameters to mosquito time series data. This method captures the inter-annual and intra-seasonal variation of mosquito populations within a geographical location. Next, a three-population WNV model between mosquito vectors, bird hosts, and human hosts with infection-age structure for the vector and bird host populations is introduced. A sensitivity analysis uncovers which parameters have the most influence on WNV outbreaks. Finally, the WNV model is extended to include the non-autonomous population model and temperature-dependent processes. Model parameterization using historical temperature and human WNV case data from the Greater Toronto Area (GTA) is conducted. Parameter fitting results are then used to analyze possible future WNV dynamics under two climate change scenarios. These results suggest that WNV risk for the GTA will substantially increase as temperature increases from climate change, even under the most conservative assumptions. This demonstrates the importance of ensuring that the warming of the planet is limited as much as possible.
ContributorsMancuso, Marina (Author) / Milner, Fabio A (Thesis advisor) / Kuang, Yang (Committee member) / Kostelich, Eric (Committee member) / Eikenberry, Steffen (Committee member) / Manore, Carrie (Committee member) / Arizona State University (Publisher)
Created2023
Description
Allogeneic islet transplantation has the potential to reverse Type 1 Diabetes in patients. However, limitations such as chronic immunosuppression, islet donor numbers, and islet survival post-transplantation prevent the widespread application of allogeneic islet transplantation as the treatment of choice. Macroencapsulation devices have been widely used in allogeneic islet transplantation due to their capability to shield transplanted cells from the immune system as well as provide a supportive environment for cell viability, but macroencapsulation devices face oxygen transport challenges as their geometry increases from preclinical to clinical scales. The goal of this work is to generate complex 3D hydrogel macroencapsulation devices with sufficient oxygen transport to support encapsulated cell survival and generate these devices in a way that is accessible in the clinic as well as scaled manufacturing. A 3D-printed injection mold has been developed to generate hydrogel-based cell encapsulation devices with spiral geometries. The spiral geometry of the macroencapsulation device facilitates greater oxygen transport throughout the whole device resulting in improved islet function in vivo in a syngeneic rat model. A computational model of the oxygen concentration within macroencapsulation devices, validated by in vitro analysis, predicts that cells and islets maintain a greater viability and function in the spiral macroencapsulation device. To further validate the computational model, pO2 Reporter Composite Hydrogels (PORCH) are engineered to enable spatiotemporal measurement of oxygen tension within macroencapsulation devices using the Proton Imaging of Siloxanes to map Tissue Oxygenation Levels (PISTOL) magnetic resonance imaging approach. Overall, a macroencapsulation device geometry designed via computational modeling of device oxygen gradients and validated with magnetic resonance (MR) oximetry imaging enhances islet function and survival for islet transplantation.
ContributorsEmerson, Amy (Author) / Weaver, Jessica (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Sadleir, Rosalind (Committee member) / Stabenfeldt, Sarah (Committee member) / Wang, Kuei-Chun (Committee member) / Arizona State University (Publisher)
Created2023
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
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