VictorJuiz/thesis huggingface dataset:
Effect of Innate Immune Collectin Surfactant Protein D and Adaptive Immune Protein IgM on Enhancing Clearance of Late Apoptotic Cells by Alveolar Macrophages

The innate immune protein surfactant protein (SP-) D is a carbohydrate binding protein that was originally isolated from mucosal lung tissues. Recently, studies show that SP-D binds to antibodies, including immunoglobulin M (IgM), which interacts with late apoptotic cells. Here we focus on the interaction between SP-D and IgM as they pertain to late apoptotic cell clearance. We hypothesized that the three-way interaction between IgM, SP-D and late apoptotic cells is functionally applicable to clearing late apoptotic cells from the lungs, thereby reducing lung inflammation. We show that SP-D binds to IgM and that IgM binds to the late apoptotic subclass of dying cells. We demonstrate that IgM and SP-D can both bind to late apoptotic cells in mutually distinct regions while also displaying some regional overlap. We show evidence that during LPS-induced lung inflammation both IgM and SP-D levels are elevated and this corresponds to an augmentation of apoptotic cell clearance. We illustrate that the protein interaction of IgM and SP-D is functionally relevant to apoptotic cell clearance in the lungs by showing that late apoptotic cells coated in IgM and/or SP-D are cleared more efficiently than control cells, by alveolar macrophages in vivo. Our ex vivo studies further show that these cells internalize apoptotic cells by engulfing very small particles released from the dying cells. We then showed that IgM preferentially directs the engulfment of small particles (~1 μm) by macrophages, in an apparent size-specific antibody-dependent particle clearance function. Our data reveals a novel relationship amongst IgM, SP-D, apoptotic cells, and alveolar macrophages that contributes to our understanding of apoptotic cell clearance, which may be used in the future to generate strategies addressing apoptotic cell accumulation or clearance deficiency in disease.

Keywords: lung
collectin
SP-D
IgM
alveolar macrophage
apoptotic cell
surfactant
lung disease
innate immune
natural IgM
clearance
phagocytosis
inflammation
small particle
Advisor: Palaniyar, Nades
A Climate Model of the Deep (Neoproterozoic) Past

It has been commonly recognized that a series of global glaciation events occurred during the late Neoproterozoic Era (800 - 540 million years ago (Ma)). However, the extent of these glaciations continues to be hotly debated, namely whether the whole Earth was ice covered (ie. a “hard snowball”) or only the continents were fully ice covered but the oceans were not (“slushball/soft snowball”). Through a combination of climate modeling and carbon cycle modeling, I have investigated the plausibility of the “soft snowball” Earth hypothesis. It is demonstrated that the flow of land ice is critical to the formation of a “soft snowball”, such that low latitude land ice must be generated through ice transported from high latitudes. In order for a climate state of this kind to be realizable, continental fragments at low latitude must be well connected to those at high latitude, and the high latitude continents must be sufficiently extensive that a large ice sheet may initiate and subsequently flow to low latitude. It is found that these constraints are satisfied by the most accurate available continental reconstruction for both the initial Sturtian glaciation of the late Neoproterozoic and the subsequent Marinoan event. It is furthermore proposed that the alternative “hard snowball” hypothesis would have been prevented by a negative feedback due to the enhanced remineralization of dissolved organic carbon (DOC) in the ocean due to increased oxygen solubility in seawater at lower temperature. This process would release CO2 to the atmosphere, thus counteracting the initial climate cooling. I have also carried out detailed simulations in which an explicit model of the carbon cycle is coupled to the ice-sheet coupled climate model to investigate this feedback quantitatively. It is found that the remineralization of the DOC does indeed provide a strong negative feedback that counteracts climate cooling. The action of this feedback not only prevents the descent of the climate into a hard snowball state, but also enables the model to re-produce the δ13C carbon isotopic anomalies observed to accompany Neoproterozoic glacial events. The resistance of this carbon cycle coupled climate system to descent into a “hard snowball” state is further tested against stochastic perturbations, and shown to be robust in the presence of such influence.

Keywords: Snowball Earth
Neoproterozoic
Paleoclimate
Carbon cycle
Advisor: Peltier, William Richard
Expansion and Equality in Access to Chinese Higher Education: A Cultural Perspective

This study is a sequential multi-methods research effort which examines the issue of equality in Chinese higher education after the recent expansion, and explores how educational equality has been shaped by policies which reflected the shifting value orientations of the government since 1949. Quantitative methods were used to discover the current patterns of educational equality. The dataset is derived from a survey carried out under a project supported by the Social Sciences and Humanities Research Council of Canada. Logistic regressions were conducted to discover the relations between students’ social background characteristics and their likelihood of studying in different part of the differentiated higher education system. The findings show that while overall access has increased greatly, advantaged groups have maintained their advantage in gaining entry to higher status universities and attractive disciplines. The study went deeper to explore the changing patterns of educational equality through historical analysis of policy using the lens of culture, since social phenomena are context-based and culture is a deep yet decisive force which has previously been given inadequate attention in relation to this issue. Applying a multidisciplinary approach, an indigenous analytical framework was developed which identified six dimensions of culture relating to educational equality, and Chinese cultural values were then organized along these dimensions. This framework was used to explain the results of the quantitative analysis at a deeper level. It was also used to construct ideal types of elitism and populism as a means of analyzing the historical process of policy change. The study found that policies regarding educational equality swung between these two poles in post 1949 China, due to an internal tension in the Chinese cultural value system which was in turn stimulated or provoked by diverse external influences. Four major modes were identified: politically restrained elitism, politically restrained populism, inclusive elitism, and a tendency toward harmony. This approach represents an original attempt to develop an indigenous framework to interpret educational equality through a cultural lens. The dissertation also seeks to contribute to knowledge and theory development in the comparative research on educational equality more widely, and to provide insights that may inform policy making.

Keywords: higher education
equality
access
China
cultural analysis
indigenous
Advisor: Hayhoe, Ruth
Solute-solvent Interactions in Folded and Unfolded Proteins

This thesis is devoted to understanding solute-solvent interactions in folded and unfolded proteins. To this end, we have studied partial molar volume, Vo, and adiabatic compressibility, KoS, of 20 amino acid side chains using low weight molecular model compounds, N-acetyl amino acid amide and its derivatives, between 18 oC and 55 oC. We used our data to develop an additive scheme for calculating the partial specific volume and adiabatic compressibility of fully extended polypeptide chains as a function of pH and temperature. We compared our calculated volumetric characteristics of the fully extended conformations of apocytochrome c and apomyoglobin with the experimental values measured in neutral pH (for apocytochrome c) or acidic pH (for apomyoglobin). The comparison between the calculated and experimental volumetric characteristics suggested that neither apocytochrome c nor apomyoglobin are fully unfolded and retain solvent-inaccessible amino acid residues. To study cosolvent-solute interactions, we determined Vo and KoS of amino acid side chains and glycyl units as a function of urea concentration. We analyzed these data within the framework of a statistical thermodynamic formalism to determine the association constants, k, for the reaction in which urea binds to each of the amino acid side chains and the glycyl unit replacing two water molecules in solvation shell. Our determined k range from 0.04 to 0.39 M with the average of 0.16 ± 0.09 M. There was no apparent correlation between the values of k and the ratio of polar to nonpolar solvent accessible surface areas. This study supports a direct interaction model in which urea denatures a protein by concerted action via favorable interactions with a wide range of protein groups. In addition, we have presented buffer ionization effect on the volume of protein denaturation could be significant with the potential to affect not only its magnitude but also its sign using a pressure perturbation calorimetric technique. Our results identified buffer ionization as an important determinant of protein transition volume that needs to be carefully taken into account. Results described in this work provide fundamental understanding of solute-solvent interaction in both folded and unfolded proteins.

Keywords: volumetric properties
solute-solvent interactions
Advisor: Chalikian, Tigran
Adsorption of Alkaline Copper Quat Components in Wood-mechanisms and Influencing Factors

Mechanisms of adsorption of alkaline copper quat (ACQ) components in wood were investigated with emphasis on: copper chemisorption, copper physisorption, and quat adsorption. Various factors were investigated that could affect the adsorption of individual ACQ components in red pine wood. Copper chemisorption in wood was affected by ligand types coordinating with Cu and the stability of the Cu-ligand complexes in solution. For Cu-monoethanolamine (Cu-Mea) system, the prevailing active solvent species at the solution pH, [Cu(Mea)2-H]+ complexes with wood acid sites and loses one Mea molecule through a ligand exchange reaction. The amount of adsorbed Cu was closely related to the cation exchange capacity of wood. An increase in Mea/Cu ratio increased the proportion of the uncharged Cu-Mea complex and resulted in decreased Cu chemisorption in wood. Copper precipitation is also an important Cu fixation mechanisms of Cu-amine treated wood. X-ray diffraction analysis revealed that in vitro precipitated Cu was a mixture of copper carbonates (azurite and malachite) and possibly Cu2O. Higher concentration Cu-amine solutions retarded the Cu precipitation to a lower pH because of higher free amine in the preservative-wood system. The changes in zeta potential of wood in relationship to the quaternary ammonium (alkyldimethylbenzylammonium chloride: ADBAC) adsorption isotherm showed two different adsorption mechanisms for quat in wood: ion exchange reaction at low concentration and additional aggregation form of adsorption by hydrophobic interaction at high concentration. Because of the aggregation effect, when wood was treated with ACQ, high amounts of ADBAC were concentrated near the surface creating a steep gradient with depth. This aggregated ADBAC was easily leached out while the ion exchanged ADBAC had high leaching resistance. Free Mea and Cu of ACQ components appeared to compete with ADBAC for the same bonding sites in wood.

Keywords: ACQ
Alkaline copper quat
amine
chemisorption
cation exchange capacity
copper precipitation
hydrophobic interaction
ion exchange
ligand exchange
micelle
physisorption
Quat
quaternary ammonium compound
wood preservatives
Advisor: Cooper, Paul
Three Essays on Total Returns to the Employment Relationship

This dissertation examines the total returns to the employment relationship from a variety of perspectives. In the first chapter, I examine different forms of training and study its influence on individual turnover. My second chapter examines the impact of mandatory volunteer/work experience in high school on the employment and wage decisions of youths. In my final chapter, I examine flexible work hours as a moderator in the relationship between workplace strategy and organizational performance. The first chapter highlights the importance of the type of training provided to the employee in order to avoid voluntary turnover. I compare the impact of institutional training compared to course training on voluntary turnover. Estimates indicate that employees who receive course training are more likely to leave the firm for another job, while employees who receive institutional training are more likely to stay with the firm. The results indicate that different types of training have differential impacts on the employee’s turnover decision. The second chapter utilizes a provincial policy reform that requires either working at a paid job or volunteering as a mandatory high school graduation requirement and examines its impact on employment outcomes. I propose that this reform causes a change in the perceptions of work by individuals which may lead them to sacrifice income for an altruistic purpose. In addition, the low quality of jobs found working or volunteering in high school may result in a distaste for work and hence provide motivation for enrolling in post-secondary education. The empirical results support this argument as the reform resulted in an increased likelihood of high school graduates to pursue post-secondary education, while those who entered the labour force had a lower probability of employment and lower wages. The final chapter examines the generalizeable conditions under which flexible work schedules are beneficial to firm performance. I find that flextime is not a best practice that is applicable across all firm environments. Instead, flextime only increases profitability when implemented within a workforce strategy focused on employees. Conversely, flextime when implemented with a cost-reduction strategy has detrimental effects on firm profits.

Keywords: compensation
employment relationship
Advisor: Gunderson, Morley
Estimating Non-homogeneous Intensity Matrices in Continuous Time Multi-state Markov Models

Multi-State-Markov (MSM) models can be used to characterize the behaviour of categorical outcomes measured repeatedly over time. Kalbfleisch and Lawless (1985) and Gentleman et al. (1994) examine the MSM model under the assumption of time-homogeneous transition intensities. In the context of non-homogeneous intensities, current methods use piecewise constant approximations which are less than ideal. We propose a local likelihood method, based on Tibshirani and Hastie (1987) and Loader (1996), to estimate the transition intensities as continuous functions of time. In particular the local EM algorithm suggested by Betensky et al. (1999) is employed to estimate the in-homogeneous intensities in the presence of missing data. A simulation comparing the piecewise constant method with the local EM method is examined using two different sets of underlying intensities. In addition, model assessment tools such as bandwidth selection, grid size selection, and bootstrapped percentile intervals are examined. Lastly, the method is applied to an HIV data set to examine the intensities with regard to depression scores. Although computationally intensive, it appears that this method is viable for estimating non-homogeneous intensities and outperforms existing methods.

Keywords: Biostatistics
Multi State Models
Ordinal Data
Advisor: Tomlinson, George
"To Make the Negro Anew"; The African American Worker in the Progressive Imagination 1896-1928

This dissertation examines how progressive era social scientists thought about African American workers and their place in the nation’s industrial past, present, and future.Progressives across the color line drew on a common discourse of industrial evolution that linked racial development with labor fitness. Evolutionary science merged with scientific management to create new taxonomies of racial labor fitness. I chart this process from turn of the century actuarial science which defined African Americans as a dying race, to wartime mental and physical testing that acknowledged the Negro as a vital -albeit inferior- part of the nation’s industrial workforce. During this period, African Americans struggled to prove their worth on the shop-floor, the battlefield, and the academy. This thesis contends that the modern Negro type- African Americans as objects of social scientific inquiry- which came of age in the post-World War Two era, was born in the draft boards, factories, trenches, hospitals, and university classrooms of the Progressive Era.

Keywords: African American
Progressivism
Labor
World War One
Evolution
Scientific Management
Advisor: Bender, Daniel
Halpern, Rick
Understanding and Changing the Patient Safety Culture in Canadian Hospitals

Patient safety experts identify changes in culture as critical to creating safer care (Flin, 2007; Leape, 1994; Reason, 1997; Vincent, Taylor-Adams & Stanhope, 1998). Yet there is limited understanding of how to best study, evaluate and make changes to patient safety culture. The literature on organizational culture, safety sciences and health services research suggests varying perspectives on studying culture and an evolving approach to creating tools to measure culture change. This thesis reports two projects. The first project used the Manchester Patient Safety Culture Assessment Tool, the Modified Stanford Instrument, and qualitative interviews to examine whether safety culture profiles varied by research method and instrument used to assess culture. Comparative assessment of the results suggests that while the quantitative measurement tools provide a high level organizational summary of safety issues, the qualitative interviews provide a more fine-grained understanding of the contextual and local features of the culture. The second research project used a multiple case study design to understand what hospitals have learned from trying to improve patient safety culture. Interviews in three organizations were used to determine how these organizations shifted their cultures. Although each organization had different experiences and used varying methods, they all created culture change through the simultaneous implementation of practice, policies and strategic framing of patient safety culture concepts in their everyday work. The third research paper examined how leaders measured changes in patient safety culture. Both leaders and front line workers look to both process measures (e.g., talking about safety and encouraging patient safety activities) together with outcome measures (e.g., adverse events, infection rates, and culture survey results) to evaluate their success in culture change. Overall this dissertation deepens our knowledge of how methods influence our assessment of patient safety culture and how leaders influence culture change. Future research needs to assess in more detail the roles of leaders and middle managers to understand how these individuals are able to reconcile the practice environment challenges while continuing to create a culture of patient safety.

Keywords: patient safety culture
organizational culture
organizational culture change
patient safety culture measurement
Advisor: Baker, G. Ross
Real Robustness Radii and Performance Limitations of LTI Control Systems

In the study of linear time-invariant systems, a number of definitions, such as controllability, observability, not having decentralized fixed modes, minimum phase, etc., have been made. These definitions are highly useful in obtaining existence results for solving various types of control problems, but a drawback to these definitions is that they are binary, which simply determines whether a system is, for instance, either controllable or uncontrollable. In practical situations, however, there are many uncertainties in a system’s parameters caused by linearization, modelling errors, discretizations, and other numerical approximations and/or errors. So knowing that a system is controllable can sometimes be misleading if the controllable system is actually "almost" uncontrollable as a result of such uncertainties. Since an "almost" uncontrollable system poses significant difficulty in designing a quality controller, a continuous measure of controllability, called a controllability radius, is more desirable to use and has been widely studied in the past. The main focus of this thesis is to extend the development behind the controllability radius, with an emphasis on real parametric perturbations, to other definitions, replacing the traditional binary 'yes/no' metrics with continuous measures. We study four topics related to this development. First, we generalize the concept of real perturbation values of a matrix to the cases of matrix pairs and matrix triplets. By doing so, we are able to deal with more general perturbation structures and subsequently study, in addition to standard LTI systems, other types of systems such as LTI descriptor and time-delay systems. Second, we introduce the real decentralized fixed mode (DFM) radius, the real transmission zero at s radius, and the real minimum phase radius, which respectively measure how "close" i) a decentralized LTI system is to having a DFM, ii) a centralized system is to having a transmission zero at a particular point s in the complex plane, and iii) a minimum phase system is to being a nonminimum phase system. These radii are defined in terms of real parametric perturbations, and computable formulas for these radii are derived using a characterization based on real perturbation values and the aforementioned generalizations. Third, we present two efficient algorithms to i) solve the general real perturbation value problem, and ii) evaluate the various real LTI robustness radii introduced in this thesis. Finally as the last topic, we study the ability of a LTI system to achieve high performance control, and characterize the difficulty of achieving high performance control using a new continuous measure called the Toughness Index. A number of examples involving the various measures are studied in this thesis.

Keywords: control systems
linear time-invariant systems
robustness radius
performance limitation
Advisor: Davison, Edward J.