VictorJuiz/thesis huggingface dataset:
Injectable Hydrogels Enhance Cellular Transplantations for Spinal Cord Injury Repair
Keywords:  Department of Biology
Spinal cord injury (SCI)
graft
regeneration
Olfactory Ensheathing Glia (OEG)
hydrogel
encapsulation
cellular transplantation
Stanford University
Thesis

Approximately 12,000 new spinal cord injuries (SCI) occur in the US each year, and less than 1% of SCI patients have full neurological recovery. Current treatments for SCI are limited to reducing inflammation and preventing further degradation. As such, developing a regenerative therapy for SCI would be transformational. The cellular transplantation of olfactory ensheathing glia (OEG) has been shown to be a potential solution, but developing an efficient cell-delivery and engraftment mechanism for transplantation remains a significant challenge. Previous studies have suggested that cell delivery within a carrier gel may increase cell viability, but a majority of these gels suffer from critical limitations that prevent their translation to clinical use. A recently developed family of hydrogels called Sheer-thinning Hydrogel for Injectable Encapsulation and Long-term Delivery (SHIELD) that are biocompatible, customizable, and reproducible may provide a more translatable and optimized solution to enhance transplantation for SCI repair. Here we assay in vitro the behavior of OEGs encapsulated in SHIELD and demonstrate that these hydrogels are capable of protecting and supporting the OEGs. Metabolic activity and cell death assays along with fluorescence immunocytochemistry show that the cells are healthier when encapsulated within SHIELD compared to cell-only controls. OEG delivery in vivo was also shown to be enhanced when encapsulated with SHIELD. These results suggest that encapsulating OEGs in the hydrogel prior to transplantation is an attractive strategy to increase the efficacy of cellular transplantations and may serve to significantly increase functional regeneration in SCI repair. In the future, SHIELD may increase the efficacy of a variety of cell-based therapies.
Innate immune decision-making [electronic resource] : insights from single-cell dynamic responses
Keywords: Bioengineering.

The innate immune system is the body's ﬁrst response to infection and gateway to an inﬂammatory or adaptive immune response. Many of the receptor and signaling pathways involved in the innate immune system have been delineated in great detail, including those recognizing microorganism-speciﬁc molecular patterns and damage or stress signals released in response to infection. But relatively little is known about how speciﬁcity to diﬀerent pathogens is conferred within a class of microorganisms. This thesis is dedicated to achieving a better understanding of the innate immune system and its speciﬁc and self-limited response to pathogens, namely bacterial infection. Using a combination of microscopy and single-cell dynamics, computational modeling, and multiplex assays, we were able to gain insight into how the innate immune response is coordinated. We show that innate immune system function is more speciﬁc to pathogens than previously thought, that the response consists of variable and invariable dynamic aspects, and that the innate immune system can employ combinatorial synergies to amplify its response to dangerous microbes. These ﬁndings may provide clues to how many immunodeﬁciencies and autoimmune diseases develop and may inform the design of novel vaccine adjuvants and immunotherapies.
Innovation in the global economy [electronic resource]
Keywords: Economics.

International migration and international trade are two major components of the current globalization process. Their impact on the global economy has been studied extensively. This dissertation explores how international migration and trade influence global innovative activities. In particular, I study the trade flow and migration of skilled workers from developing countries to the U.S., and how such flows affect the U.S. as well as the source countries. In the first chapter, I study the migration of science and engineering (S& E) workers from non-OECD (i.e., developing) countries to the US. In particular, I evaluate the impact of such brain drain on both the US and the source countries using a multi-country endogenous growth model. The proposed framework introduces and quantifies a "frontier growth effect" of skilled migration: migrants from developing countries create more frontier knowledge in the U.S., and the non-rivalrous knowledge diffuses to all countries. In particular, each source country is able to adopt technology invented by migrants from other countries, a previously ignored externality of skilled migration. I quantify the model by matching both micro and macro moments, and then consider counterfactuals wherein U.S. immigration policy changes. My results suggest that a policy -- which doubles the number of immigrants from every non-OECD country -- would boost U.S. productivity growth by 0.1 percentage point per year, and improve average welfare in the U.S. by 3.3%. Such a policy can also benefit the source countries because of the "frontier growth effect". Taking India as an example source country, I find that the same policy would lead to faster long-run growth and a 0.9% increase in average welfare in India. This welfare gain in India is largely the result of additional non-Indian migrants, indicating the significance of the previously overlooked externality. The second chapter is co-authored with Kaiji Gong. We analyze the impact of rising Chinese import competition on innovative activities in the U.S. We adopt a similar identification strategy as in Autor et al. (2013), whereby we use Compustat firm-level data and industry- level trade data to exploit cross-industry variation in exposure to import competition. We find that U.S. firms on average reduce R& D investment when faced with more import com- petition from China. The negative effect is driven by smaller firms and highly leveraged firms. When we weight the firms by their initial sizes, the average impact of import com- petition became insignificant. Our findings cannot fully be explained by a simple story of negative demand shock. Further empirical exploration is needed to identify the channels through which import competition affects firm's R& D investment.
Integrated decision support tool for nested, spatially-scaled urban recycled water infrastructure planning [electronic resource]
Keywords: Civil and Environmental Engineering.

Globally, the main drivers for expansion of water reuse are: 1) Increasing water demand to support industrial and population growth; 2) Water scarcity and droughts, particularly in arid and semi-arid regions; and 3) Environmental protection and enhancement. Development of water reuse systems that can address these various drivers is complex. Here, we introduce an integrated decision-support software tool for planning of water reuse infrastructure using multiple weighted criteria. The main contributions of this research are: 1. A high level decision methodology that selects the combination of centralized and satellite resource (water/energy) recovery and reuse systems that best balances monetary and non-monetary criteria. A case study for the Palo Alto wastewater catchment is used to demonstrate the methodology. 2. Development and implementation of decision support software components: 1) a Locator for satellite treatment and wastewater scalping facilities, 2) a Calculator for water and organic mass balances, 3) a Calculator for recycled water and sewer costs and incentive, and 4) a pipeline Designer. The designer is used to identify near-minimum-cost pipeline routes for multiple users, and accounts for existing configurations, environmental or social constraints, and trade-offs in pipeline length, construction methods, and traffic congestion during construction. In addition, the designer optimizes pipe diameters, pipe pressure classes, pump station locations, and pumping energy and includes the theoretical additional capacity of each pipe, facilitating future expansion. To illustrate the utility of the designer, a case study was conducted for the City of Palo Alto, CA. 3. An Integrator that combines the above software components and adds capability for wastewater treatment process selection to enable nested, spatially-scaled, urban recycled water reuse system design. This decision support tool is applied to a case study of Golden, CO.
Intelligent urban traffic signal control using multiagent reinforcement learning [electronic resource]
Keywords: Civil and Environmental Engineering.

Urban traffic management plays an important role in building smart and sustainable cities, from social, economical, and environmental points of view. However, modern traffic signal control systems have no been significantly improved over the last four decades despite extensive studies conducted in urban transportation research. One major reason is that most traditional signal control models rely heavily on statistical assumptions and heuristic criteria, which cannot support adaptive microscopic signal controls, while most proposed intelligent signal control methods are not robust and scalable enough for managing real-world large-scale urban traffic flows. This thesis proposes a systematic and realistic approach for implementing reinforcement learning (RL) to design adaptive, optimal, and scalable intelligent urban signal control systems. The direct adoption of existing RL models is impractical for large-scale signal control because of the extremely high computational complexity of learning and searching of control policies. To overcome this difficulty, this thesis proposes a practical multiagent RL framework that is scalable for large-scale traffic signal control, by applying various approximation methods. These methods are developed from three major perspectives: (1) integrating heuristic rules in traditional urban transportation studies to reduce the complexity of control policy searching; (2) applying state-of-the-art supervised learning techniques to achieve efficient feature extraction and Q-function approximation; and (3) implementing distributed control techniques to achieve effective communication and coordination in large-scale traffic networks. To evaluate the performance of this MARL framework, various numerical experiments are conducted in microscopic traffic simulations. The results demonstrate that proposed MARL methods outperform the major traditional and intelligent signal control methods, with a linear computational time complexity which is acceptable for real-world applications.
Inter-colony variation in harvester ant foraging behavior in response to weather conditions
Keywords:  Department of Biology
reaction norms
collective behavior
Thesis

Individuals of the same species differ in reaction norms, responding to environmental cues in distinct ways. Reaction norms describe the range of phenotypes a single genotype can produce, depending on the environment. In this study, we investigate reaction norms in foraging behavior of red harvester ant colonies (Pogonomyrmex barbatus) in response to weather conditions. We aim to build on previous research that has suggested that both foraging intensity and foraging regulation are affected by weather (Gordon, Dektar, and Pinter-wollman 2013; Azc and Kovacs 2007). At a field site near Rodeo, NM, we compared data from 2 years on the foraging behavior of 4 colonies, and examined the relation of foraging behavior to temperature and humidity. We statistically examined the correlation between weather conditions and foraging rate by quantifying foraging behavior of each day using 4 metrics: average rate of outgoing foragers, maximum rate of outgoing foragers, total outgoing foragers, and the difference between outgoing and incoming foragers. We found that colonies varied in their foraging behavior relative to each other in the same weather conditions, and differed in their sensitivity to varying weather conditions. Exploring the behavioral plasticity of colonies as they integrate environmental cues helps us understand more about the regulation of collective behavior.
Interrogation of viscoelastic protein layers at bubble interfaces [electronic resource]
Keywords: Chemical Engineering.

From a cup of creamed coffee to the salty spray of seawater, fluid-fluid interfaces exist everywhere in our lives. Simple fluid-fluid interfaces can be described by a scalar surface tension, but adherence of amphiphilic species such as small molecule surfactants, particles, and macromolecules, and the consequent formation of interfacial microstructures, results in the formation of a complex interface that is inadequately described by a simple surface tension. The scope of the thesis will wholly focus on complex air-aqueous solution interfaces, the presence of which can be undesirable, for example, in the form of isolated bubbles entrained in pharmaceutical processing flows, or desirable, as the foams for beverages and consumer products. Furthermore, the focus is on proteins at the air-aqueous solution interface which form a viscoelastic protein layer. The first project examines the aggregation of a proprietary monoclonal (mAb) molecule under interfacial deformations by investigating the mechanical response of mAb-adsorbed interfaces to dilatational strains and by characterizing particles ejected from dilatationally-compressed surfaces with spectroscopic and microscopic techniques. The project also introduces the interfacial dilatational rheometer that underpins much of the work and demonstrates its capabilities in studying the stability of product formulations. The second part of the thesis examines the influence of rheological surface elasticity on thin film entrainment within foams for bovine serum albumin (BSA) protein-adsorbed interfaces. The results of the latter study could be beneficial for industries interested in developing a framework for predicting bulk foam characteristics, such as liquid foam density, from interfacial and bulk liquid properties.
Inventing an American political tradition [electronic resource] : how John Locke became "America's philosopher"
Keywords: History.

Inventing an American Political Tradition elucidates the trans-Atlantic influence of the seventeenth-century English philosopher John Locke on American thought and culture from before the American Revolution through the Civil Rights Movement. It tells the story of how and why Americans transformed Locke, best known to them in the eighteenth and nineteenth centuries as an epistemologist of the Scientific Revolution, into "America's Philosopher" in the twentieth century—the supposed founder in his Second Treatise of a distinctly American liberal democratic political tradition resting on property rights, individual liberty, freedom of religious practice, and representative government. This dissertation is the first study of Locke's place in American intellectual and political life across multiple centuries.
Investigating contemporary questions in climate science from a modern statistical perspective [electronic resource]
Keywords: Environmental Earth System Science.

The recent "hiatus" in global warming has been the subject of much scrutiny and debate, both in the scientific community and in the public discourse. The implications of the alleged hiatus call into question the reliability of climate models and the need for mitigating anthropogenic contributions to warming. The observed change in the relationship between temperature and atmospheric carbon dioxide concentrations during the hiatus period has also raised questions regarding model-based estimates of climate sensitivity. The aim of this dissertation is to make sense of some of the current compelling questions in climate science in a rigorous way. An important component in this is to develop and apply modern statistical methodology, with the explicit goal of informing the scientific debate. We formally consider the hypothesis of a recent "hiatus" in global warming with the aid of quantitative statistical methods. We also investigate the related assertion that despite increase in greenhouse gas concentrations, temperatures have not followed suit. We develop a general methodology to test for a difference between two populations, even when one population has a fixed, small sample size. The method applies quite generally, as we are able to account for arbitrary temporal dependence in the data without explicitly modeling the temporal structure (under minimal stationarity assumptions). We additionally consider two scientific hypotheses that consider surface warming at a regional scale. Appropriate statistical methods are used to account for multiple hypothesis testing, temporal dependence, and spatial dependence.
Investigating the biophysical mechanisms of integrin-based adhesion at the cellular and single-molecule level [electronic resource]
Keywords: Chemical Engineering.

Integrins mediate cell adhesion to the extracellular matrix and enable the construction of complex, multicellular organisms, yet fundamental aspects of integrin-based adhesion remain poorly understood. Notably, recent estimates of the load experienced by integrins span two orders of magnitude, a discrepancy arising from limitations inherent to existing techniques. Thus, it is unclear if integrin-based adhesion, and by extension mechanotransduction, reflects a disproportionate contribution by only a few integrins bearing large forces, or is instead a collective phenomenon reflecting the cumulative output of many weaker interactions. We used FRET-based molecular tension sensors (MTSs) to directly measure the distribution of forces experienced by individual integrins in living cells. We find that the majority of integrins transmit relatively modest forces of less than 7 pN, and that a large proportion of these integrins bear minimal loads of less than 3 pN. This finding suggests that most integrins are tensioned to well below their load-bearing capacities. In addition, load-bearing integrins are not exclusively localized to adhesion structures; integrins exerting low forces outside of discernible adhesions contribute a significant fraction of the cell's total traction and are sufficient for maintaining adhesion. Further, we developed MTSs presenting the full fibronectin type III 9th and 10th domains which includes the synergy site, a secondary binding site thought to reinforce the fibronectin- α5β1 integrin bond. Our data indicate that the synergy site does not increase the force per integrin, but does increase the relative contribution of α5β1 integrin in mediating adhesion. Further, our data indicate that the synergy site is critical for the cell's ability to resist detachment when exposed to externally applied load. In total, these data suggest that a substantial population of bound but minimally tensioned integrins, aided by synergy site-mediated mechanical reinforcement, can provide cells and tissues with physical resiliency. Finally, we tested the hypothesis that loads are apportioned differently on distinct integrin types (here, α5β1 and αv-class). Surprisingly, our data indicate minimal differences in the amount of force transmitted by either α5β1 and αv-class integrins. Instead, our data are consistent with a model in which different integrin subtypes play distinct roles in organizing adhesion structure and dynamics.
Investigating the effects of beta1-adrenergic receptor agonist and antagonist administration on microglia in a mouse model of Alzheimer’s disease
Keywords:  Department of Biology
Biology
Neuroscience
Alzheimer's Disease
Alzheimer's
Microglia
Thesis

The beta1-adrenergic receptor agonist xamoterol has been shown to rescue cognitive deficits, downregulate pro-inflammatory cytokine production (TNF-α, CD74, and CD14) and decrease amyloid beta accumulation in Alzheimer’s disease (AD) mouse model. Nevertheless, given these previous results, the cellular mechanism of action and neuronal/glial correlates responsible for xamoterol’s AD-therapeutic effects are not well characterized. Furthermore, few studies have looked at microglia in the context of AD. In this study, a beta1-adrenergic receptor agonist (xamoterol) and antagonist (metoprolol) were separately administered to wildtype mice and amyloid precursor protein-overexpressing Alzheimer’s disease (AD) mouse model, and drug effects on microglial cellular density and Iba1 immunoreactivity (obtained through cell counts and immunohistochemical quantification of Iba1, a marker of activated microglia) were determined for hippocampal and cortical regions of the brain. Xamoterol was shown to have no significant effect on microglial density in either transgenic or wildtype animals. Furthermore, metoprolol administration mildly suppressed microglial cellular populations in dentate gyrus in both transgenic and wildtype animals, relative to saline-dosed controls. Altogether, these data suggest that beta1-adrenergic receptor antagonism leads to downregulated microglial populations for both wildtype and transgenic AD mice, while receptor agonism has no effect on microglial populations. Data from this study also do not support the role of a microglial-density-dependent mechanism of action in xamoterol’s activity as a therapeutic drug in AD mouse model.
Investigating the effects of chemical composition and surface structure of catalysts on the electrochemical reduction of carbon dioxide [electronic resource]
Keywords: Chemical Engineering.

The elimination of our dependence on fossil fuel sources is strongly motivated by the non renewable nature of these resources and the mounting evidence of their connection to anthropogenic climate change. Such a shift away from the use of fossil fuels could be facilitated by the electrochemical reduction of CO2, as it could allow for a sustainable process by which renewable energy from wind and solar are used directly in the production of fuels and chemicals. However, one key barrier to its utilization is the lack of effective catalysts that make the process energy efficient and selective. In order to develop effective catalysts for the process, fundamental understanding of the catalytic reaction must be established. To this end, the relation between catalyst properties and catalytic performance was investigated in this thesis. In order to obtain fundamental insights into the chemical processes occurring at the catalyst surfaces during CO2 electroreduction, we first investigated a broad group of transition metals. The potential-dependent activity and selectivity of CO2 electroreduction on each metal were characterized, which allowed for the observation of trends across the metals investigated. Using these results and theory, key factors affecting the catalytic performance for CO2 electroreduction were elucidated along with insights for the design of better catalysts. The catalyst property-performance relation was further probed through surface modification schemes such as alloying and surface structure engineering. Key observations from these investigations include: the enhancement in the activity for CO2 electroreduction to further reduced products on a AgZn alloy compared to pure Ag and pure Zn, the composition dependence of the catalytic performance of a PdxIny alloy system, and the surface structure-dependence of the product selectivity among further reduced products on Cu thin films. These results highlight the importance of control over chemical composition and surface structure of the catalyst surface, and contribute toward the design of effective catalysts.