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Description
Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, or amyotrophic lateral sclerosis are defined by the loss of several types of neurons and glial cells within the central nervous system (CNS). Combatting these diseases requires a robust population of relevant cell types that can be employed in cell therapies, drug screening, or patient specific disease modeling. Human induced pluripotent stem cells (hiPSC)-derived neural progenitor cells (hNPCs) have the ability to self-renew indefinitely and differentiate into the various neuronal and glial cell types of the CNS. In order to realize the potential of hNPCs, it is necessary to develop a xeno-free scalable platform for effective expansion and differentiation. Previous work in the Brafman lab led to the engineering of a chemically defined substrate—vitronectin derived peptide (VDP), which allows for the long-term expansion and differentiation of hNPCs. In this work, we use this substrate as the basis for a microcarrier (MC)-based suspension culture system. Several independently derived hNPC lines were cultured on MCs for multiple passages as well as efficiently differentiated to neurons. Finally, this MC-based system was used in conjunction with a low shear rotating wall vessel (RWV) bioreactor for the integrated, large-scale expansion and neuronal differentiation of hNPCs. Finally, VDP was shown to support the differentiation of hNPCs into functional astrocytes. Overall, this fully defined and scalable biomanufacturing system will facilitate the generation of hNPCs and their derivatives in quantities necessary for basic and translational applications.
ContributorsMorgan, Daylin (Author) / Brafman, David (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2018
Description
Calcium imaging is a well-established, non-invasive or minimally technique designed to study the electrical signaling neurons. Calcium regulates the release of gliotransmitters in astrocytes. Analyzing astrocytic calcium transients can provide significant insights into mechanisms such as neuroplasticity and neural signal modulation.
In the past decade, numerous methods have been developed to analyze in-vivo calcium imaging data that involves complex techniques such as overlapping signals segregation and motion artifact correction. The hypothesis used to detect calcium signal is the spatiotemporal sparsity of calcium signal, and these methods are unable to identify the passive cells that are not actively firing during the time frame in the video. Statistics regarding the percentage of cells in each frame of view can be critical for the analysis of calcium imaging data for human induced pluripotent stem cells derived neurons and astrocytes.
The objective of this research is to develop a simple and efficient semi-automated pipeline for analysis of in-vitro calcium imaging data. The region of interest (ROI) based image segmentation is used to extract the data regarding intensity fluctuation caused by calcium concentration changes in each cell. It is achieved by using two approaches: basic image segmentation approach and a machine learning approach. The intensity data is evaluated using a custom-made MATLAB that generates statistical information and graphical representation of the number of spiking cells in each field of view, the number of spikes per cell and spike height.
In the past decade, numerous methods have been developed to analyze in-vivo calcium imaging data that involves complex techniques such as overlapping signals segregation and motion artifact correction. The hypothesis used to detect calcium signal is the spatiotemporal sparsity of calcium signal, and these methods are unable to identify the passive cells that are not actively firing during the time frame in the video. Statistics regarding the percentage of cells in each frame of view can be critical for the analysis of calcium imaging data for human induced pluripotent stem cells derived neurons and astrocytes.
The objective of this research is to develop a simple and efficient semi-automated pipeline for analysis of in-vitro calcium imaging data. The region of interest (ROI) based image segmentation is used to extract the data regarding intensity fluctuation caused by calcium concentration changes in each cell. It is achieved by using two approaches: basic image segmentation approach and a machine learning approach. The intensity data is evaluated using a custom-made MATLAB that generates statistical information and graphical representation of the number of spiking cells in each field of view, the number of spikes per cell and spike height.
ContributorsBhandarkar, Siddhi Umesh (Author) / Brafman, David (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Tian, Xiaojun (Committee member) / Arizona State University (Publisher)
Created2019
Description
A global warming of two degrees Celsius is predicted to drive almost half the world's lizard populations to extinction. Currently, the Phoenix metropolitan region in Arizona, USA, is an average of 3 oC warmer than the surrounding desert. Using a bare lot as a control, I placed copper lizard models with data loggers in several vegetation and irrigation treatments that represent the dominant backyard landscaping styles in Phoenix (grassy mesic with mist irrigation, drip irrigated xeric, unirrigated native, and a hybrid style known as oasis). Lizard activity time in summer is currently restricted to a few hours in un-irrigated native desert landscaping, while heavily irrigated grass and shade trees allow for continual activity during even the hottest days. Maintaining the existing diversity of landscaping styles (as part of an ongoing mitigation strategy targeted at humans) will be beneficial for lizards.
Fourteen native lizard species inhabit the desert surrounding Phoenix, AZ, USA, but only two species persist within heavily developed areas. This pattern is best explained by a combination of socioeconomic status, land cover, and location. Lizard diversity is highest in affluent areas and lizard abundance is greatest near large patches of open desert. The percentage of building cover has a strong negative impact on both diversity and abundance. Despite Phoenix's intense urban heat island effect, which strongly constrains the potential activity and microhabitat use of lizards in summer, thermal patterns have not yet impacted their distribution and relative abundance at larger scales.
Fourteen native lizard species inhabit the desert surrounding Phoenix, AZ, USA, but only two species persist within heavily developed areas. This pattern is best explained by a combination of socioeconomic status, land cover, and location. Lizard diversity is highest in affluent areas and lizard abundance is greatest near large patches of open desert. The percentage of building cover has a strong negative impact on both diversity and abundance. Despite Phoenix's intense urban heat island effect, which strongly constrains the potential activity and microhabitat use of lizards in summer, thermal patterns have not yet impacted their distribution and relative abundance at larger scales.
ContributorsAckley, Jeffrey (Author) / Wu, Jianguo (Thesis advisor) / Sullivan, Brian (Thesis advisor) / Myint, Soe (Committee member) / DeNardo, Dale (Committee member) / Angilletta Jr., Michael (Committee member) / Arizona State University (Publisher)
Created2015
Description
This study uses the Weather Research and Forecasting (WRF) model to simulate and predict the changes in local climate attributed to the urbanization for five desert cities. The simulations are performed in the fashion of climate downscaling, constrained by the surface boundary conditions generated from high resolution land-use maps. For each city, the land-use maps of 1985 and 2010 from Landsat satellite observation, and a projected land-use map for 2030, are used to represent the past, present, and future. An additional set of simulations for Las Vegas, the largest of the five cities, uses the NLCD 1992 and 2006 land-use maps and an idealized historical land-use map with no urban coverage for 1900.
The study finds that urbanization in Las Vegas produces a classic urban heat island (UHI) at night but a minor cooling during the day. A further analysis of the surface energy balance shows that the decrease in surface Albedo and increase effective emissivity play an important role in shaping the local climate change over urban areas. The emerging urban structures slow down the diurnal wind circulation over the city due to an increased effective surface roughness. This leads to a secondary modification of temperature due to the interaction between the mechanical and thermodynamic effects of urbanization.
The simulations for the five desert cities for 1985 and 2010 further confirm a common pattern of the climatic effect of urbanization with significant nighttime warming and moderate daytime cooling. This effect is confined to the urban area and is not sensitive to the size of the city or the detail of land cover in the surrounding areas. The pattern of nighttime warming and daytime cooling remains robust in the simulations for the future climate of the five cities using the projected 2030 land-use maps. Inter-city differences among the five urban areas are discussed.
The study finds that urbanization in Las Vegas produces a classic urban heat island (UHI) at night but a minor cooling during the day. A further analysis of the surface energy balance shows that the decrease in surface Albedo and increase effective emissivity play an important role in shaping the local climate change over urban areas. The emerging urban structures slow down the diurnal wind circulation over the city due to an increased effective surface roughness. This leads to a secondary modification of temperature due to the interaction between the mechanical and thermodynamic effects of urbanization.
The simulations for the five desert cities for 1985 and 2010 further confirm a common pattern of the climatic effect of urbanization with significant nighttime warming and moderate daytime cooling. This effect is confined to the urban area and is not sensitive to the size of the city or the detail of land cover in the surrounding areas. The pattern of nighttime warming and daytime cooling remains robust in the simulations for the future climate of the five cities using the projected 2030 land-use maps. Inter-city differences among the five urban areas are discussed.
ContributorsKamal, Samy (Author) / Huang, Huei-Ping (Thesis advisor) / Anderson, James (Thesis advisor) / Herrmann, Marcus (Committee member) / Calhoun, Ronald (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2015
Description
Several debilitating neurological disorders, such as Alzheimer's disease, stroke, and spinal cord injury, are characterized by the damage or loss of neuronal cell types in the central nervous system (CNS). Human neural progenitor cells (hNPCs) derived from human pluripotent stem cells (hPSCs) can proliferate extensively and differentiate into the various neuronal subtypes and supporting cells that comprise the CNS. As such, hNPCs have tremendous potential for disease modeling, drug screening, and regenerative medicine applications. However, the use hNPCs for the study and treatment of neurological diseases requires the development of defined, robust, and scalable methods for their expansion and neuronal differentiation. To that end a rational design process was used to develop a vitronectin-derived peptide (VDP)-based substrate to support the growth and neuronal differentiation of hNPCs in conventional two-dimensional (2-D) culture and large-scale microcarrier (MC)-based suspension culture. Compared to hNPCs cultured on ECMP-based substrates, hNPCs grown on VDP-coated surfaces displayed similar morphologies, growth rates, and high expression levels of hNPC multipotency markers. Furthermore, VDP surfaces supported the directed differentiation of hNPCs to neurons at similar levels to cells differentiated on ECMP substrates. Here it has been demonstrated that VDP is a robust growth and differentiation matrix, as demonstrated by its ability to support the expansions and neuronal differentiation of hNPCs derived from three hESC (H9, HUES9, and HSF4) and one hiPSC (RiPSC) cell lines. Finally, it has been shown that VDP allows for the expansion or neuronal differentiation of hNPCs to quantities (>1010) necessary for drug screening or regenerative medicine purposes. In the future, the use of VDP as a defined culture substrate will significantly advance the clinical application of hNPCs and their derivatives as it will enable the large-scale expansion and neuronal differentiation of hNPCs in quantities necessary for disease modeling, drug screening, and regenerative medicine applications.
ContributorsVarun, Divya (Author) / Brafman, David (Thesis advisor) / Nikkhah, Mehdi (Committee member) / Stabenfeldt, Sarah (Committee member) / Arizona State University (Publisher)
Created2016
Description
The Kilombero Valley lies at the intersection of a network of protected areas that cross Tanzania. The wetlands and woodlands of the Valley, as well as the forest of surrounding mountains are abundant in biodiversity and are considered to be critical areas for conservation. This area, however, is also the home to more than a half million people, primarily poor smallholder farmers. In an effort to support the livelihoods and food security of these farmers and the larger Tanzanian population, the country has recently targeted a series of programs to increase agricultural production in the Kilombero Valley and elsewhere in the country. Bridging concepts and methods from land change science, political ecology, and sustainable livelihoods, I present an integrated assessment of the linkages between development and conservation efforts in the Kilombero Valley and the implications for food security.
This dissertation uses three empirical studies to understand the process of development in the Kilombero Valley and to link the priorities and perceptions of conservation and development efforts to the material outcomes in food security and land change. The first paper of this dissertation examines the changes in land use in the Kilombero Valley between 1997 and 2014 following the privatization of agriculture and the expansion of Tanzania’s Kilimo Kwanza program. Remote sensing analysis reveals a two-fold increase in agricultural area during this short time, largely at the expense of forest. Protected areas in some parts of the Valley appear to be deterring deforestation, but rapid agricultural growth, particularly surrounding a commercial rice plantation, has led to loss of extant forest and sustained habitat fragmentation. The second paper focuses examines livelihood strategies in the Valley and claims regarding the role of agrobiodiversity in food security.
The results of household survey reveal no difference or lower food security among households that diversify their agricultural activities. Some evidence, however, emerges regarding the importance of home gardens and crop diversification for dietary diversity. The third paper considers the competing discourses surrounding conservation and development in the Kilombero Valley. Employing q-method, this paper discerns four key viewpoints among various stakeholders in the Valley. While there are some apparently intractable distinctions between among these discourses, consensus regarding the importance of wildlife corridors and the presence of boundary-crossing individuals provide the promise of collaboration and compromise.
ContributorsConnors, John Patrick (Author) / Turner, Billie Lee (Thesis advisor) / Eakin, Hallie (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2015
Description
The quality of real-world visual content is typically impaired by many factors including image noise and blur. Detecting and analyzing these impairments are important steps for multiple computer vision tasks. This work focuses on perceptual-based locally adaptive noise and blur detection and their application to image restoration.
In the context of noise detection, this work proposes perceptual-based full-reference and no-reference objective image quality metrics by integrating perceptually weighted local noise into a probability summation model. Results are reported on both the LIVE and TID2008 databases. The proposed metrics achieve consistently a good performance across noise types and across databases as compared to many of the best very recent quality metrics. The proposed metrics are able to predict with high accuracy the relative amount of perceived noise in images of different content.
In the context of blur detection, existing approaches are either computationally costly or cannot perform reliably when dealing with the spatially-varying nature of the defocus blur. In addition, many existing approaches do not take human perception into account. This work proposes a blur detection algorithm that is capable of detecting and quantifying the level of spatially-varying blur by integrating directional edge spread calculation, probability of blur detection and local probability summation. The proposed method generates a blur map indicating the relative amount of perceived local blurriness. In order to detect the flat
ear flat regions that do not contribute to perceivable blur, a perceptual model based on the Just Noticeable Difference (JND) is further integrated in the proposed blur detection algorithm to generate perceptually significant blur maps. We compare our proposed method with six other state-of-the-art blur detection methods. Experimental results show that the proposed method performs the best both visually and quantitatively.
This work further investigates the application of the proposed blur detection methods to image deblurring. Two selective perceptual-based image deblurring frameworks are proposed, to improve the image deblurring results and to reduce the restoration artifacts. In addition, an edge-enhanced super resolution algorithm is proposed, and is shown to achieve better reconstructed results for the edge regions.
In the context of noise detection, this work proposes perceptual-based full-reference and no-reference objective image quality metrics by integrating perceptually weighted local noise into a probability summation model. Results are reported on both the LIVE and TID2008 databases. The proposed metrics achieve consistently a good performance across noise types and across databases as compared to many of the best very recent quality metrics. The proposed metrics are able to predict with high accuracy the relative amount of perceived noise in images of different content.
In the context of blur detection, existing approaches are either computationally costly or cannot perform reliably when dealing with the spatially-varying nature of the defocus blur. In addition, many existing approaches do not take human perception into account. This work proposes a blur detection algorithm that is capable of detecting and quantifying the level of spatially-varying blur by integrating directional edge spread calculation, probability of blur detection and local probability summation. The proposed method generates a blur map indicating the relative amount of perceived local blurriness. In order to detect the flat
ear flat regions that do not contribute to perceivable blur, a perceptual model based on the Just Noticeable Difference (JND) is further integrated in the proposed blur detection algorithm to generate perceptually significant blur maps. We compare our proposed method with six other state-of-the-art blur detection methods. Experimental results show that the proposed method performs the best both visually and quantitatively.
This work further investigates the application of the proposed blur detection methods to image deblurring. Two selective perceptual-based image deblurring frameworks are proposed, to improve the image deblurring results and to reduce the restoration artifacts. In addition, an edge-enhanced super resolution algorithm is proposed, and is shown to achieve better reconstructed results for the edge regions.
ContributorsZhu, Tong (Author) / Karam, Lina (Thesis advisor) / Li, Baoxin (Committee member) / Bliss, Daniel (Committee member) / Myint, Soe (Committee member) / Arizona State University (Publisher)
Created2016
Description
The combination of rapid urban growth and climate change places stringent constraints on multisector sustainability of cities. Green infrastructure provides a great potential for mitigating anthropogenic-induced urban environmental problems; nevertheless, studies at city and regional scales are inhibited by the deficiency in modelling the complex transport coupled water and energy inside urban canopies. This dissertation is devoted to incorporating hydrological processes and urban green infrastructure into an integrated atmosphere-urban modelling system, with the goal to improve the reliability and predictability of existing numerical tools. Based on the enhanced numerical tool, the effects of urban green infrastructure on environmental sustainability of cities are examined.
Findings indicate that the deployment of green roofs will cool the urban environment in daytime and warm it at night, via evapotranspiration and soil insulation. At the annual scale, green roofs are effective in decreasing building energy demands for both summer cooling and winter heating. For cities in arid and semiarid environments, an optimal trade-off between water and energy resources can be achieved via innovative design of smart urban irrigation schemes, enabled by meticulous analysis of the water-energy nexus. Using water-saving plants alleviates water shortage induced by population growth, but comes at the price of an exacerbated urban thermal environment. Realizing the potential water buffering capacity of urban green infrastructure is crucial for the long-term water sustainability and subsequently multisector sustainability of cities. Environmental performance of urban green infrastructure is determined by land-atmosphere interactions, geographic and meteorological conditions, and hence it is recommended that analysis should be conducted on a city-by-city basis before actual implementation of green infrastructure.
Findings indicate that the deployment of green roofs will cool the urban environment in daytime and warm it at night, via evapotranspiration and soil insulation. At the annual scale, green roofs are effective in decreasing building energy demands for both summer cooling and winter heating. For cities in arid and semiarid environments, an optimal trade-off between water and energy resources can be achieved via innovative design of smart urban irrigation schemes, enabled by meticulous analysis of the water-energy nexus. Using water-saving plants alleviates water shortage induced by population growth, but comes at the price of an exacerbated urban thermal environment. Realizing the potential water buffering capacity of urban green infrastructure is crucial for the long-term water sustainability and subsequently multisector sustainability of cities. Environmental performance of urban green infrastructure is determined by land-atmosphere interactions, geographic and meteorological conditions, and hence it is recommended that analysis should be conducted on a city-by-city basis before actual implementation of green infrastructure.
ContributorsYang, Jiachuan (Author) / Wang, Zhihua (Thesis advisor) / Kaloush, Kamil (Committee member) / Myint, Soe (Committee member) / Huang, Huei-Ping (Committee member) / Mascaro, Giuseppe (Committee member) / Arizona State University (Publisher)
Created2016
Description
Ephemeral streams in Arizona that are perpendicularly intersected by the Central Arizona Project (CAP) canal have been altered due to partial or complete damming of the stream channel. The dammed upstream channels have experienced decades long cycles of sediment deposition and waterlogging during storm events causing the development of "green-up" zones. This dissertation examines the biogeomorphological effects of damming ephemeral streams caused by the CAP canal by investigating: (1) changes in the preexisting spatial cover of riparian vegetation and how these changes are affected by stream geometry; (2) green-up initiation and evolution; and (3) changes in plant species and community level changes. To the author's knowledge, this is the only study that undertakes an interdisciplinary approach to understanding the environmental responses to anthropogenically-altered ephemeral stream channels. The results presented herein show that vegetation along the upstream section increased by an average of 200,872 m2 per kilometer of the CAP canal over a 28 year period. Vegetation growth was compared to channel widths which share a quasi-linear relationship. Remote sensing analysis of Landsat TM images using an object-oriented approach shows that riparian vegetation cover gradually increased over 28 years. Field studies reveal that the increases in vegetation are attributed to the artificial rise in local base-level upstream created by the canal, which causes water to spill laterally onto the desert floor. Vegetation within the green-up zone varies considerably in comparison to pre-canal construction. Changes are most notable in vegetation community shifts and abundance. The wettest section of the green-up zone contains the greatest density of woody plant stems, the greatest vegetation volume, and a high percentage of herbaceous cover. Vegetation within wetter zones changed from a tree-shrub to a predominantly tree-herb assemblage, whereas desert shrubs located in zones with intermediate moisture have developed larger stems. Results from this study lend valuable insight to green-up processes associated with damming ephemeral streams, which can be applied to planning future canal or dam projects in drylands. Also, understanding the development of the green-up zones provide awareness to potentially avoiding flood damage to infrastructure that may be unknowingly constructed within the slow-growing green-up zone.
ContributorsHamdan, Abeer (Author) / Schmeeckle, Mark (Thesis advisor) / Myint, Soe (Thesis advisor) / Dorn, Ronald (Committee member) / Stromberg, Juliet (Committee member) / Arizona State University (Publisher)
Created2014
Description
Neurotoxicology has historically focused on substances that directly damage nervous tissue. Behavioral assays that test sensory, cognitive, or motor function are used to identify neurotoxins. But, the outcomes of behavioral assays may also be influenced by the physiological status of non-neural organs. Therefore, toxin induced damage to non- neural organs may contribute to behavioral modifications. Heavy metals and metalloids are persistent environmental pollutants and induce neurological deficits in multiple organisms. However, in the honey bee, an important insect pollinator, little is known about the sublethal effects of heavy metal and metalloid toxicity though they are exposed to these toxins chronically in some environments. In this thesis I investigate the sublethal effects of copper, cadmium, lead, and selenium on honey bee behavior and identify potential mechanisms mediating the behavioral modifications. I explore the honey bees’ ability to detect these toxins, their sensory perception of sucrose following toxin exposure, and the effects of toxin ingestion on performance during learning and memory tasks. The effects depend on the specific metal. Honey bees detect and reject copper containing solutions, but readily consume those contaminated with cadmium and lead. And, exposure to lead may alter the sensory perception of sucrose. I also demonstrate that acute selenium exposure impairs learning and long-term memory formation or recall. Localizing selenium accumulation following chronic exposure reveals that damage to non-neural organs and peripheral sensory structures is more likely than direct neurotoxicity. Probable mechanisms include gut microbiome alterations, gut lining
damage, immune system activation, impaired protein function, or aberrant DNA methylation. In the case of DNA methylation, I demonstrate that inhibiting DNA methylation dynamics can impair long-term memory formation, while the nurse-to- forager transition is not altered. These experiments could serve as the bases for and reference groups of studies testing the effects of metal or metalloid toxicity on DNA methylation. Each potential mechanism provides an avenue for investigating how neural function is influenced by the physiological status of non-neural organs. And from an ecological perspective, my results highlight the need for environmental policy to consider sublethal effects in determining safe environmental toxin loads for honey bees and other insect pollinators.
damage, immune system activation, impaired protein function, or aberrant DNA methylation. In the case of DNA methylation, I demonstrate that inhibiting DNA methylation dynamics can impair long-term memory formation, while the nurse-to- forager transition is not altered. These experiments could serve as the bases for and reference groups of studies testing the effects of metal or metalloid toxicity on DNA methylation. Each potential mechanism provides an avenue for investigating how neural function is influenced by the physiological status of non-neural organs. And from an ecological perspective, my results highlight the need for environmental policy to consider sublethal effects in determining safe environmental toxin loads for honey bees and other insect pollinators.
ContributorsBurden, Christina Marie (Author) / Amdam, Gro (Thesis advisor) / Smith, Brian H. (Thesis advisor) / Gallitano-Mendel, Amelia (Committee member) / Harrison, Jon (Committee member) / Vu, Eric (Committee member) / Arizona State University (Publisher)
Created2016