Matching Items (93)
Description
Anthropogenic land use has irrevocably transformed the natural systems on which humankind relies. Understanding where, why, and how social and economic processes drive globally-important land-use changes, from deforestation to urbanization, has advanced substantially. Illicit and clandestine activities--behavior that is intentionally secret because it breaks formal laws or violates informal norms--are poorly understood, however, despite the recognition of their significant role in land change. This dissertation fills this lacuna by studying illicit and clandestine activity and quantifying its influence on land-use patterns through examining informal urbanization in Mexico City and deforestation Central America. The first chapter introduces the topic, presenting a framework to examine illicit transactions in land systems. The second chapter uses data from interviews with actors involved with land development in Mexico City, demonstrating how economic and political payoffs explain the persistence of four types of informal urban expansion. The third chapter examines how electoral politics influence informal urban expansion and land titling in Mexico City using panel regression. Results show land title distribution increases just before elections, and more titles are extended to loyal voters of the dominant party in power. Urban expansion increases with electoral competition in local elections for borough chiefs and legislators. The fourth chapter tests and confirms the hypothesis that narcotrafficking has a causal effect on forest loss in Central America from 2001-2016 using two proxies of narcoactivity: drug seizures and events from media reports. The fifth chapter explores the spatial signature and pattern of informal urban development. It uses a typology of urban informality identified in chapter two to hypothesize and demonstrate distinct urban expansion patterns from satellite imagery. The sixth and final chapter summarizes the role of illicit and clandestine activity in shaping deforestation and urban expansion through illegal economies, electoral politics, and other informal transactions. Measures of illicit and clandestine activity should--and could--be incorporated into land change models to account for a wider range of relevant causes. This dissertation shines a new light on the previously hidden processes behind ever-easier to detect land-use patterns as earth observing satellites increase spatial and temporal resolution.
ContributorsTellman, Elizabeth (Author) / Turner II, Billie L (Thesis advisor) / Eakin, Hallie (Thesis advisor) / Janssen, Marco (Committee member) / Alba, Felipe de (Committee member) / Jain, Meha (Committee member) / Arizona State University (Publisher)
Created2019
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
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
This dissertation examines the various factors and processes that have been proposed as explanations for the spread of agriculture in the west Mediterranean. The expansion of the Neolithic in the west Mediterranean (the Impresso-Cardial Neolithic) is characterized by a rapid spread of agricultural subsistence and material culture from the southern portion of the Italian peninsula to the western coast of the Iberian peninsula. To address this unique case, four conceptual models of Neolithic spread have been proposed: the Wave of Advance, the Capillary Spread Model, the Maritime Pioneer Colonization Model and the Dual Model. An agent-based model, the Cardial Spread Model, was built to simulate each conceptual spread model in a spatially explicit environment for comparison with evidence from the archaeological record. Chronological information detailing the arrival of the Neolithic was used to create a map of the initial arrival of the Neolithic (a chronosurface) throughout the study area. The results of each conceptual spread model were then compared to the chronosurface in order to evaluate the relative performance of each conceptual model of spread. These experiments suggest that both the Dual and Maritime Pioneer Colonization models best fit the available chronological and spatial distribution of the Impresso-Cardial Neolithic.
For the purpose of informing agent movement and improving the fit of the conceptual spread models, a variety of paleoenvironmental maps were tested within the Cardial Spread Model. The outcome of these experiments suggests that topographic slope was an important factor in settlement location and that rivers were important vectors of transportation for early Neolithic migration. This research demonstrates the application of techniques rare to archaeological analysis, agent-based modeling and the inclusion of paleoenvironmental information, and provides a valuable tool that future researchers can utilize to further evaluate and fabricate new models of Neolithic expansion.
For the purpose of informing agent movement and improving the fit of the conceptual spread models, a variety of paleoenvironmental maps were tested within the Cardial Spread Model. The outcome of these experiments suggests that topographic slope was an important factor in settlement location and that rivers were important vectors of transportation for early Neolithic migration. This research demonstrates the application of techniques rare to archaeological analysis, agent-based modeling and the inclusion of paleoenvironmental information, and provides a valuable tool that future researchers can utilize to further evaluate and fabricate new models of Neolithic expansion.
ContributorsBergin, Sean M (Author) / Barton, Michael (Thesis advisor) / Janssen, Marco (Committee member) / Coudart, Anick (Committee member) / Arizona State University (Publisher)
Created2016
Description
The closer integration of the world economy has yielded many positive benefits including the worldwide diffusion of innovative technologies and efficiency gains following the widening of international markets. However, closer integration also has negative consequences. Specifically, I focus on the ecology and economics of the spread of species and pathogens. I approach the problem using theoretical and applied models in ecology and economics. First, I use a multi-species theoretical network model to evaluate the ability of dispersal to maintain system-level biodiversity and productivity. I then extend this analysis to consider the effects of dispersal in a coupled social-ecological system where people derive benefits from species. Finally, I estimate an empirical model of the foot and mouth disease risks of trade. By combining outbreak and trade data I estimate the disease risks associated with the international trade in live animals while controlling for the biosecurity measures in place in importing countries and the presence of wild reservoirs. I find that the risks associated with the spread and dispersal of species may be positive or negative, but that this relationship depends on the ecological and economic components of the system and the interactions between them.
ContributorsShanafelt, David William (Author) / Perrings, Charles (Thesis advisor) / Fenichel, Eli (Committee member) / Richards, Timorthy (Committee member) / Janssen, Marco (Committee member) / Collins, James (Committee member) / Arizona State University (Publisher)
Created2016
Description
The coordination of group behavior in the social insects is representative of a broader phenomenon in nature, emergent biological complexity. In such systems, it is believed that large-scale patterns result from the interaction of relatively simple subunits. This dissertation involved the study of one such system: the social foraging of the ant Temnothorax rugatulus. Physically tiny with small population sizes, these cavity-dwelling ants provide a good model system to explore the mechanisms and ultimate origins of collective behavior in insect societies. My studies showed that colonies robustly exploit sugar water. Given a choice between feeders unequal in quality, colonies allocate more foragers to the better feeder. If the feeders change in quality, colonies are able to reallocate their foragers to the new location of the better feeder. These qualities of flexibility and allocation could be explained by the nature of positive feedback (tandem run recruitment) that these ants use. By observing foraging colonies with paint-marked ants, I was able to determine the `rules' that individuals follow: foragers recruit more and give up less when they find a better food source. By altering the nutritional condition of colonies, I found that these rules are flexible - attuned to the colony state. In starved colonies, individual ants are more likely to explore and recruit to food sources than in well-fed colonies. Similar to honeybees, Temmnothorax foragers appear to modulate their exploitation and recruitment behavior in response to environmental and social cues. Finally, I explored the influence of ecology (resource distribution) on the foraging success of colonies. Larger colonies showed increased consistency and a greater rate of harvest than smaller colonies, but this advantage was mediated by the distribution of resources. While patchy or rare food sources exaggerated the relative success of large colonies, regularly (or easily found) distributions leveled the playing field for smaller colonies. Social foraging in ant societies can best be understood when we view the colony as a single organism and the phenotype - group size, communication, and individual behavior - as integrated components of a homeostatic unit.
ContributorsShaffer, Zachary (Author) / Pratt, Stephen C (Thesis advisor) / Hölldobler, Bert (Committee member) / Janssen, Marco (Committee member) / Fewell, Jennifer (Committee member) / Liebig, Juergen (Committee member) / Arizona State University (Publisher)
Created2014
Description
In Latin America food insecurity is still prevailing in those regions where extreme poverty and political instability are common. Tseltal communities are experiencing changes due to religious conversions and the incursion of external political institutions. These changes have diminished the importance of traditional reciprocal and redistributive institutions that historically have been essential for personal and community survival. This dissertation investigated the impact that variations on governance systems and presence of reciprocal and distributional exchanges have on the food security status of communities. Qualitative data collected in four communities through 117 free lists and 117 semi-structured interviews was used to elaborate six scales that correspond to the traditional and civic authority system and to inter-community and intra-community reciprocity and redistribution. I explore the relationship that the scores of four communities on those scales have on the food security status of their inhabitants based on their results on the National Health and Nutrition Survey 2012. Findings from this study suggest that in marginalized communities that many scientists would described as experiencing market failure, participation in inter-community reciprocal, intra-community reciprocal and intra-community redistribution are better predictors of food security than enrollment in food security programs. Additionally, communities that participated the most in these non-market mechanisms have stronger traditional institutions. In contrast, communities that participated more in inter-community redistribution scored higher on the civic authority scale, are enrolled in more food aid programs, but are less food secure.
ContributorsDe La Torre Pacheco, Sindy Yaneth (Author) / Janssen, Marco (Thesis advisor) / Eakin, Hallie (Committee member) / BurnSilver, Shauna (Committee member) / Arizona State University (Publisher)
Created2015
Description
The portability of genetic tools from one organism to another is a cornerstone of synthetic biology. The shared biological language of DNA-to-RNA-to-protein allows for expression of polypeptide chains in phylogenetically distant organisms with little modification. The tools and contexts are diverse, ranging from catalytic RNAs in cell-free systems to bacterial proteins expressed in human cell lines, yet they exhibit an organizing principle: that genes and proteins may be treated as modular units that can be moved from their native organism to a novel one. However, protein behavior is always unpredictable; drop-in functionality is not guaranteed.
My work characterizes how two different classes of tools behave in new contexts and explores methods to improve their functionality: 1. CRISPR/Cas9 in human cells and 2. quorum sensing networks in Escherichia coli.
1. The genome-editing tool CRISPR/Cas9 has facilitated easily targeted, effective, high throughput genome editing. However, Cas9 is a bacterially derived protein and its behavior in the complex microenvironment of the eukaryotic nucleus is not well understood. Using transgenic human cell lines, I found that gene-silencing heterochromatin impacts Cas9’s ability to bind and cut DNA in a site-specific manner and I investigated ways to improve CRISPR/Cas9 function in heterochromatin.
2. Bacteria use quorum sensing to monitor population density and regulate group behaviors such as virulence, motility, and biofilm formation. Homoserine lactone (HSL) quorum sensing networks are of particular interest to synthetic biologists because they can function as “wires” to connect multiple genetic circuits. However, only four of these networks have been widely implemented in engineered systems. I selected ten quorum sensing networks based on their HSL production profiles and confirmed their functionality in E. coli, significantly expanding the quorum sensing toolset available to synthetic biologists.
My work characterizes how two different classes of tools behave in new contexts and explores methods to improve their functionality: 1. CRISPR/Cas9 in human cells and 2. quorum sensing networks in Escherichia coli.
1. The genome-editing tool CRISPR/Cas9 has facilitated easily targeted, effective, high throughput genome editing. However, Cas9 is a bacterially derived protein and its behavior in the complex microenvironment of the eukaryotic nucleus is not well understood. Using transgenic human cell lines, I found that gene-silencing heterochromatin impacts Cas9’s ability to bind and cut DNA in a site-specific manner and I investigated ways to improve CRISPR/Cas9 function in heterochromatin.
2. Bacteria use quorum sensing to monitor population density and regulate group behaviors such as virulence, motility, and biofilm formation. Homoserine lactone (HSL) quorum sensing networks are of particular interest to synthetic biologists because they can function as “wires” to connect multiple genetic circuits. However, only four of these networks have been widely implemented in engineered systems. I selected ten quorum sensing networks based on their HSL production profiles and confirmed their functionality in E. coli, significantly expanding the quorum sensing toolset available to synthetic biologists.
ContributorsDaer, René (Author) / Haynes, Karmella (Thesis advisor) / Brafman, David (Committee member) / Nielsen, David (Committee member) / Kiani, Samira (Committee member) / Arizona State University (Publisher)
Created2017
Description
Synthetic gene networks have evolved from simple proof-of-concept circuits to
complex therapy-oriented networks over the past fifteen years. This advancement has
greatly facilitated expansion of the emerging field of synthetic biology. Multistability is a
mechanism that cells use to achieve a discrete number of mutually exclusive states in
response to environmental inputs. However, complex contextual connections of gene
regulatory networks in natural settings often impede the experimental establishment of
the function and dynamics of each specific gene network.
In this work, diverse synthetic gene networks are rationally designed and
constructed using well-characterized biological components to approach the cell fate
determination and state transition dynamics in multistable systems. Results show that
unimodality and bimodality and trimodality can be achieved through manipulation of the
signal and promoter crosstalk in quorum-sensing systems, which enables bacterial cells to
communicate with each other.
Moreover, a synthetic quadrastable circuit is also built and experimentally
demonstrated to have four stable steady states. Experiments, guided by mathematical
modeling predictions, reveal that sequential inductions generate distinct cell fates by
changing the landscape in sequence and hence navigating cells to different final states.
Circuit function depends on the specific protein expression levels in the circuit.
We then establish a protein expression predictor taking into account adjacent
transcriptional regions’ features through construction of ~120 synthetic gene circuits
(operons) in Escherichia coli. The predictor’s utility is further demonstrated in evaluating genes’ relative expression levels in construction of logic gates and tuning gene expressions and nonlinear dynamics of bistable gene networks.
These combined results illustrate applications of synthetic gene networks to
understand the cell fate determination and state transition dynamics in multistable
systems. A protein-expression predictor is also developed to evaluate and tune circuit
dynamics.
complex therapy-oriented networks over the past fifteen years. This advancement has
greatly facilitated expansion of the emerging field of synthetic biology. Multistability is a
mechanism that cells use to achieve a discrete number of mutually exclusive states in
response to environmental inputs. However, complex contextual connections of gene
regulatory networks in natural settings often impede the experimental establishment of
the function and dynamics of each specific gene network.
In this work, diverse synthetic gene networks are rationally designed and
constructed using well-characterized biological components to approach the cell fate
determination and state transition dynamics in multistable systems. Results show that
unimodality and bimodality and trimodality can be achieved through manipulation of the
signal and promoter crosstalk in quorum-sensing systems, which enables bacterial cells to
communicate with each other.
Moreover, a synthetic quadrastable circuit is also built and experimentally
demonstrated to have four stable steady states. Experiments, guided by mathematical
modeling predictions, reveal that sequential inductions generate distinct cell fates by
changing the landscape in sequence and hence navigating cells to different final states.
Circuit function depends on the specific protein expression levels in the circuit.
We then establish a protein expression predictor taking into account adjacent
transcriptional regions’ features through construction of ~120 synthetic gene circuits
(operons) in Escherichia coli. The predictor’s utility is further demonstrated in evaluating genes’ relative expression levels in construction of logic gates and tuning gene expressions and nonlinear dynamics of bistable gene networks.
These combined results illustrate applications of synthetic gene networks to
understand the cell fate determination and state transition dynamics in multistable
systems. A protein-expression predictor is also developed to evaluate and tune circuit
dynamics.
ContributorsWu, Fuqing (Author) / Wang, Xiao (Thesis advisor) / Haynes, Karmella (Committee member) / Marshall, Pamela (Committee member) / Nielsen, David (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2017