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Species-Specific Regulation of Human Oligodendrocyte Precursor Cells Homeostasis
No full textM.S.Oligodendrocyte precursor cells (OPCs) represent the most numerous population of stem/progenitor cells in the adult human brain. Upon activation, adult OPCs divide and generate new oligodendrocytes in response to neuronal activity and following demyelination. The molecular mechanisms that govern OPC homeostasis remain poorly defined, but in vivo imaging studies have revealed that these processes are governed by their local environment such that differentiation or death of an OPC is followed by compensatory division of a neighboring OPC. However following transplantation, human OPCs (hOPCs) continuing to divide in the presence of murine OPCs (mOPC). This suggests the presence of a species-specific signal that regulates hOPC proliferation and implicates species-mismatch as a mechanism underlying the success of xenografted OPCs for myelin repair. In order to characterize the molecular mechanisms, we developed an in vitro model in which mCherry-expressing primary hOPCs were cultured either alone or in the presence of mOPCs or hOPCs (Chapter 3). As observed following transplantation, hOPC proliferation was inhibited by coculture with hOPCs but not by mOPCs. Conversely, mOPC proliferation was halted by coculture with either species OPCs. The species-specific inhibition of proliferation was dependent on cell-cell signaling as coculture with fixed hOPCs relieved the inhibitory effect. Importantly, reduced hOPC proliferation was not associated with oligodendrocyte differentiation. This cell-cell signal exhibited cell-type specificity as coculture with human astrocytes-like cells did not substantially block hOPC proliferation. We next established that the hOPC-derived signal was likely soluble using discontinuous transwell cultures and conditioned media. Proteome analysis (LC-MS and IonStar) was utilized to identify several candidates that may mediate this inhibitory effect (Chapter 4). We identified six candidate proteins which were relatively enriched in hOPC conditioned media and predicted to be actively secreted (SignalP). To determine whether these proteins could influence hOPC proliferation, we exposed hOPCs to individual recombinant proteins as well as the combination of all of the candidates. IGFBP2 was the sole recombinant protein capable of reducing hOPC proliferation and individually exerted an equivalent effect to the combination of all candidates. Interestingly, IGFBP2 exhibited a species-specific effect, in that human IGFBP2 (hIGFBP2) blocked proliferation but mouse IGFBP2 did not. Moreover, following infection with a lentivirus encoding the GCaMP6s calcium reporter, we observed that only hIGFBP2 induced increased calcium oscillations in a similar manner to high-density hOPC culture. While additional loss-of-function experiments are necessary, these findings strongly suggest that IGFBP2 released by hOPC exerts an anti-proliferative effect in high-density culture. In Chapter 5, to investigate the specific downstream signaling pathways that are influenced by hOPC coculture, we performed RNA-seq of mCherry+ hOPCs following coculture and FACS isolation. The expression profile of mCherry+ hOPCs indicated that coculture with either hOPCs, mOPCs, or human astrocyte-like cells exhibited a distinct transcriptional profile. Consistent with our earlier results, co-culture with hOPC induced genes associated with inhibition of proliferation. Intriguingly, while coculture did not induce O4+ oligodendrocyte differentiation in mCherry+ cells, we noted significant upregulation of several genes associated with both oligodendrocyte and astrocyte differentiation. These changes were associated with the downregulation of several negative regulators of the MAP kinase pathway, suggesting possible activation of this pathway. Notably, coculture regardless of cell identity induced a profound downregulation of cholesterol biosynthesis pathways. The successful characterization of homeostatic signals that regulate hOPC proliferation will allow us to define novel therapeutic strategies to promote cell engraftment in the context of human demyelination and, potentially, overcome the inhibitory environment that prevents efficient endogenous remyelination in multiple sclerosis.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Optimal Control of Differentially Flat Systems
No full textPh.D.The aim of this dissertation is to examine optimal control of a class of system known as differentially flat systems. These are systems in which the states and inputs can be expressed as functions of an output vector and its derivatives. The flat outputs can be described as components of the mapping from the system space to a smaller dimensional space. This property allows one to systematically generate feasible trajectories in a relatively simple way. Using this property, optimal control formulations can be transformed into a Linear Programming problem (LP) or a Nonlinear Programming problem (NLP) hence making it more tractable. In this dissertation an overview of differentially flat systems is given, stating the conditions needed for a system to be differentially flat. Examples to illustrate how the optimal control problem is transformed to a nonlinear or linear programming problem is discussed before highlighting the shortcomings of differential flatness. Polynomial chaos, a tool used in uncertainty quantification is discussed to serve as a surrogate model for uncertainty propagation for differentially flat system. Also, the Bonferroni Approximation used in rewriting probabilistic constraints in deterministic form is also discussed in this work. A case study of finding an efficient way of flying fixed wing Unmanned Aerial Vehicles motivated by locomotion observed in birds and sea mammals is presented with emphasis on how differential flatness makes solving the problem easier. This new approach to optimal flight of Unmanned Aerial Vehicle is known as periodic flight. A test to determine if optimal periodic flight results in a better cost compared to optimal steady state flight known as the Π test is also discussed. The concept of differential flatness is explored to solve the optimal control path planning towards finding the desired periodic trajectories which will optimize either the range, power or endurance of UAVs for both translation and loiter trajectories. Another case study which seeks to find an optimal trajectory that minimizes the vibration in the load of UAV with suspended load using the concept of differential flatness is also examined. The optimal solution obtained from the differential flatness formulation is compared to the solution from other standard vibration mitigation methods. The resulting solutions are validated with experiments for both point-to-point trajectory and a waypoint based trajectory. Also, a method of dealing with time invariant parametric uncertainties in this class of systems using polynomial chaos is also presented. The method seeks to find a robust feedforward controller for differentially flat system without the need for feedback. It is also shown that for flat linear systems, the polynomial chaos surrogate model is also flat. The surrogate model is then used in a chance constraint optimization. A single mass spring damper and two mass spring damper systems are used to illustrate the proposed method.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
“In/Visibility Crises: Transnational Correctives and the Happiness of Black Women in Francophone Prose Fiction and Dramatic Film”
No full textPh.D.This project is a broad reflection on the visibility of the self, reexamined through transnational experiences black women have lived, fictionalized, and theorized in francophone contexts. Weaving together fiction, nonfiction, and theory from postcolonial francophone contexts, with theoretical works in anglophone spaces, this project considers how and why the crisis of material and subjective in/visibility that black women have experienced, and their corresponding experiences with happiness, have been made central in fiction. I focus largely on prose fiction and dramatic film, because the intimate narration and visceral imagery they offer become resonance chambers for attempting to convey the crises of in/visibility that black women live. They also help audiences to begin to conceptualize the transnational correctives black women seek to assemble as they migrate across the conflicts of global spaces. I argue that such works, along with documentary films and free verse poetry, weave to longstanding black feminist and black womanist practices of theorizing the eclipsed presence of black women in the canons of fiction and thought, and in particular of francophone work of and by women in global spaces. For such reasons, this project turns to comparative readings of twentieth- and twenty-first century works, in order to tease out how diverse migrations of black women trouble and expose dangerous hegemonies of global "North" and "South" spaces. Through its emphasis on black female protagonists, the project also spotlights how black women are regularly forced into in/visibility, as they are resiliently forge recourse (successfully and unsuccessfully) through transnational correctives to their crises.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Separation Anxieties: Laws of Sex and Race in the American Unconscious, 1865-1939
No full textPh.D.This dissertation engages with the legal crisis leading up to and following the ratification of the Fourteenth Amendment (1868) through an analysis of law, prohibition, and taboo in the works of Elizabeth Cady Stanton, Sutton E. Griggs, and Pauline E. Hopkins. In order to understand the intractability of sexism and racism to constitutional or legal reform, this project draws on literature as a necessary supplement to the law, and as a site at which the "other scene" of law can be deduced from the contradictions and anxieties internal to white male American culture. Following Sigmund Freud’s reconstruction of the murder of the primal father in Moses and Monotheism (1939) from the traces of its coverup in what would become Hebrew law and culture, this dissertation argues that the blatant hypocrisy of anti-miscegenation laws in the period following the Civil War can be read as a coverup of the nearly ubiquitous crime of rape under U.S. slavery. In contrast to a tendency within psychoanalytic theory to read the Freudian reconstruction as a hypothetical fabrication, I emphasize that these scenes of subjection under chattel slavery are not myths that found the law, but lived historical realities made into quasi-myths through the very function of law. This project contends that we can reimagine the real at stake in Freud’s reconstruction by applying his theoretical model to the post-bellum and post-Reconstruction eras of American life, where the rise of anti-miscegenation law actively repressed—and thus made primal—a history of sexual and racial mixings.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
A Critical Analysis of the Savoy-Sarr Report (The Restitution of African Cultural Heritage: Toward a New Relational Ethics)
No full textM.A.This thesis is a critical analysis of The Restitution of African Cultural Heritage: Toward a New Relational Ethics, commonly referred to as the Savoy-Sarr Report. The report addresses the call for the return of the cultural heritage of Sub-Saharan Africa from France, but incorporates the collections of other institutions. This thesis contends that while the report strives to separate from the political on the grounds of a morally superior argument, it is unable to do so given its commission by the French government, and the fact that the institutions under discussion rely predominantly on the funding of their respective local and national governments. By analyzing two areas of proposed restitution within the report, the former Kingdom of Benin and the former Empire of Mali, this thesis seeks to highlight why the blanket measures of the Savoy-Sarr report are unsustainable and why the adoption of a case by case evaluation of restitution is the best way of ensuring the survival of cultural heritage.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
The Direct and Indirect Effects of School Climate on the School Completion of Students with ADHD
No full textM.A.This study examined the direct and indirect effects of school climate on the likelihood of students with ADHD graduating high school. Data from the High school Longitudinal Study of 2009 was used to answer the research questions. To examine both the indirect and direct effects, structural equation modeling was used. School climate had a significant direct effect on the likelihood of students with ADHD graduating high school. This effect was positive; students who attended a school with a more positive school climate were more likely to graduate. School climate also had a significant, positive indirect effect on graduation through math self-efficacy, school engagement, and math achievement. These findings suggest that school climate effects the likelihood of students with ADHD graduating through multiple paths.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
A Nuisance-Free Inference Procedure Accounting for the Unknown Missingness Mechanism
No full textPh.D.This thesis is motivated by the difficulty of handling missing data in patient-reported outcomes (PRO) and electronic health records (EHR), where the missingness has been well documented as missing not at random (MNAR), or statistically termed as nonignorable. One key challenge in these situations is that, a correct statistical model for the missingness mechanism is extremely difficult, if not infeasible, to specify. To circumvent, we will generally regard the whole problem as a semiparametric model where, other than the parameter of interest, this annoying missingness mechanism is treated as a nuisance nonparametric component. The parameter of interest could come from a commonly-used regression model such as linear regression or logistic regression, depending on the interpretability of the scientific problem. The key idea of this dissertation is to use the conditional likelihoods so that the nonparametric mechanism is completely canceled out through the conditioning arguments. We apply our methodology to a children’s mental health study where the response variable is a PRO and the parameter of interest is from a logistic regression model. We also apply our methodology to the study of the Medical Information Mart for Intensive Care III (MIMIC-III), where the parameter of interest is from a linear regression model. Especially in this latter application, due to the vast amount of available explanatory variables in the EHR system, we also consider the problem of how to statistically solve the high dimensionality issue which includes the variable selection and the post-selection inference. We also conduct comprehensive simulation studies to demonstrate the finite sample performance of our proposed methodology as well as its comparison to some currently existing methods, when the data generation process is known.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Structural Modeling of a Medium Density Fiberboard Tessellated Beam
No full textM.S.Structural-Architectural Tessellated (TeSA) systems are composed of repeated tiles that can interconnect, be designed to have load carrying capacity, and are aesthetically pleasing. TeSA systems may localize damage to few tiles when subjected to extreme leads, and hence may facilitate easier or faster reparability, and contribute to resilience. This research investigates the behavior of a simply supported TeSA beam made of Medium Density Fiberboard (MDF) using numerical methods. Finite Element (FE) analysis was performed and the results were validated using experimental data. The FE analysis incorporated gaps and interaction between tiles. The results showed that contact properties and gap size between tiles affected load-displacement relationship and strain of the TeSA beam. The pressure-overclosure relationship for contact properties and gap size were calibrated using the global load-displacement response obtained from testing. Incorporation of large deformations (geometric nonlinearity) in the analyses did not affect the results significantly. Beams with varying friction coefficient between tiles, load and support bearing width, Poisson's ratio and aspect ratios were also analyzed. The results showed that TeSA beams had smaller stiffness than solid beams with similar dimensions. The outcomes of this research can be used to make recommendations for modeling of TeSA structures in other applications such as reinforced concrete shear walls in buildings.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Fabrication of Micron Scale Test Structures for Magneto-Electric Chromia (Cr2O3) Thin Films
No full textM.S.Chromium oxide (Cr2O3) is one of the few magneto-electric (ME) oxides with insulating behavior which exhibits voltage-controlled magnetization switching at room temperature. It has the potential for faster switching speeds compared to existing magnetization switching technologies. The insulating behavior allows for low energy voltage-controlled switching. This particular characteristic has made chromia (Cr2O3) an emerging candidate for post-CMOS energy efficient spintronic devices. Although successful voltage-controlled magnetic switching is demonstrated in bulk Cr2O3 crystals, it remains a significant challenge to demonstrate the same in the thin films needed for device applications. Recently, ME switching has been reported in thin films, however the response was measured with magneto-optic effect. In this study, we propose to study the switching of thin film chromia using electrical methods. Our first objective is to measure Capacitance-Voltage (C-V) characteristics of the proposed device structure at room temperature in the presence of a magnetic field. This measurement should show a ferroelectric behavior which is expected from ME effect. Our device structure consists of Cr2O3/conducting Vanadium Oxide (V2O3) grown on insulating sapphire (Al2O3) substrate. Cr2O3 films with V2O3 bottom conductor showed lower leakage current compared to Pd or Pt bottom contacts which is already reported by recent studies. However, the thin films are not insulating enough for capacitance measurement. Previous work has shown that the leakage is due to conducting pinholes. A smaller area device has less chance of intersecting a leakage pinhole, hence has lower leakage current density. In this work, we developed a new fabrication method to form micron to nanoscale test structures, which will enable capacitance measurements. We used chlorine-based Reactive Ion Etching (RIE) technique to etch Cr2O3 and stop on V2O3 layer. Next, we formed contacts on the top (Cr2O3) and bottom (V2O3) layer. Using this device structure, we can measure the high frequency response by measuring S-parameters. We demonstrated the complete fabrication process that showed low background capacitance. However, the devices did not show any ME effect due to the RIE damage of the bottom electrode (V2O3) which made it insulating.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Seismic Resilience Quantification for a Set of Buildings
No full textM.S.In recent years, the topic of resilience has caught the attention of the structural engineering community. Several approaches have been proposed through the years to quantify resilience for various infrastructure systems, but quantifying the resilience of buildings, and groups of buildings, remains challenging. Here, research was conducted to investigate the effectiveness of three different approaches proposed to quantify resilience, based on results from performance-based assessments. The proposed approaches use repair costs, occupancy levels, and asset values as the functionality measures to quantify resilience. Resilience indexes are quantified for four different example buildings using the three approaches. Performance-based assessments of the buildings are performed following the procedures of the Federal Emergency Management Agency (FEMA) P-58 document using an intensity-based method and the simplified analysis procedures. The proposed methodology by the Resilience-based Earthquake Design Initiative Rating System (REDi), to account for downtimes due to delays calculated from the FEMA P-58 assessments, are incorporated in the resilience quantification for the four example buildings. The delays due to downtimes are included in the computation of resilience index considering two scenarios based on different impeding factors. Resilience is quantified for a range of different spectral accelerations. Casualties for the range of spectral accelerations considering different collapse modes for the four example buildings are presented. The individual results for each building are also combined using a weight-based approach to quantify the resilience index for an archetype city block. The influence of contractor availability and collapse probability in the resilience indexes for a set of buildings is investigated. The findings presented here are useful both from the perspective of quantifying the resilience of a community on the basis of its building assets, as well as for possible inclusion into broader integrated framework that aims to quantify community resilience.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*