VictorJuiz/thesis huggingface dataset:
Evaluating the Contribution of Immune Gene Variants to Schizophrenia

Schizophrenia is a devastating mental illness of unknown etiology. There is a longstanding theory that dysregulation of the immune system causes schizophrenia in at least a subset of patients. Many schizophrenia patients show hallmarks of immune disease – such as prior infections, presence of autoantibodies, co-occurring autoimmunity, and inflammation – supporting this immune hypothesis. Given that another hallmark of immune disease is the convergence of genetic risk factors on key immune pathways, this thesis evaluates the immune hypothesis of schizophrenia using both focused candidate gene and large-scale genome-wide association study (GWAS) approaches. In study one, we performed a candidate gene study of the neuroinflammatory biomarker TSPO and identified a loss-of-function variant (Thr allele of rs6971 or Ala147Thr) associated with increased antipsychotic-induced weight gain in two independent samples. In study two, we performed conditional analysis of the extended major histocompatibility complex (xMHC) – the strongest region of association in schizophrenia GWASs – and discovered three independent genetic variants explaining the association that do not appear to represent canonical immune genes in the MHC region. In study three we compared enrichment of SNPs representing immune genes in GWASs of schizophrenia and five immune diseases, and found that the genetic architecture of schizophrenia was distinct from diseases of known immune origin. Finally, in study four, we evaluated the extent of shared genetic risk factors for schizophrenia and 19 immune-mediated diseases again using GWAS results. We found evidence of subtle genome-wide sharing of risk alleles for schizophrenia and a subset of five immune diseases, the biological significance of which remains unclear. Taken together these studies indicate a non-genetic etiology for the immune disturbances observed in schizophrenia, and suggest that immune genes and variants conferring risk for immune-mediated diseases do not play a major role in schizophrenia susceptibility. It remains to be seen whether immune processes act as a second non-genetic hit that contributes to disease susceptibility, progression, or treatment outcomes. Whether this is the case is an important question to be addressed by longitudinal studies, particularly given burgeoning interest in the potential use of immunotherapies.

Keywords: Genetic
Genome-wide association study
Immune
Inflammation
Psychiatry
Schizophrenia
Advisor: Kennedy, James L
Knight, Jo
Interactions Between 2009 Pandemic H1N1 Influenza A Virus and Underlying Host Factors Dictate Host Response and Disease Outcome

Host responses and disease during influenza A infection are shaped by multiple interactions between virus and host which may vary considerably between virus strains. The 2009 pandemic H1N1 influenza A (A(H1N1)pdm09) virus was recently introduced in the human population and now persists in worldwide circulation. Distinct clinical manifestations and distribution of severe illness among human cohorts including the young (

Keywords: Adaptive Immunity
A(H1N1)pdm09
Host-Pathogen Interaction
Inflammation
Influenza A
Lung Immunology
Advisor: Kelvin, David J
Code-aided Expectation-maximization and Probabilistic Constellation Shaping for Fiber-optic Communication Systems

This thesis provides signal-processing and constellation shaping algorithms to combat equalizer-enhanced phase-noise and nonlinearity-induced interference in long-haul fiber-optic communication systems. In the first part of this work, an iterative phase-estimation algorithm is designed that combines expectation-maximization (EM) with a soft-input soft-output error control decoder. At 280 Gbit/s, this system doubles the optical system reach, and generally enhances phase-noise tolerance. Among three different 16-point constellations, the 4-4-4-4 ring constellation was found to have the best performance. The laser linewidth tolerance gain is improved further by reducing the code rate. In the second part of this work, this code-aided (CA) EM approach is applied to long-haul systems dominated by nonlinearity-induced interference. Based on laboratory measurements, a second-order autoregressive phase-noise model is proposed, and used to modify the EM regularizer term. Simulation and experimental results show that in a dual-polarization wavelength-division-multiplexed 16 QAM system, launch-power tolerance can be increased by 1.5 dB, and the optical signal-to-noise ratio requirement can be relaxed by 0.3 dB to achieve the same error ratio. The complexity of the CAEM algorithm was found to be about 1/4 of the complexity of digital back-propagation. In the third part of this work, a low complexity probabilistic constellation shaping scheme is proposed to increase the system tolerance to nonlinearity impairments. A theoretical analysis predicts that, with 16 and 64-point constellations, reach improvements of 7% and 10% respectively can be achieved at a mutual information of 3.2 bit/symbol/polarization. Such probabilistic constellation shaping requires minimal added complexity.

Keywords: Constellation shaping
Error control coding
Fiber-optic communication
Machine learning
Nonlinearity
Phase noise
Advisor: Kschischang, Frank R.
Biochar and Wood Ash Impacts on Soil Microbial Community Structure and Biogeochemical Functioning in Managed Ontario Forests

Biochars and wood ash could be used as valuable soil amendments in managed Canadian forests to counteract effects of full-tree harvesting and N deposition, such as soil acidification and nutrient depletion. However, large-scale application cannot be recommended without a thorough assessment of the impacts of these amendments on key aspects of the ecosystem. Characterizing microbial responses is crucial for predicting the overall forest response to biochar and wood ash additions, because soil microbial communities affect ecosystem health and functioning and aboveground plant communities. However, for biochars in particular, the long-term effects on the soil microbial community in temperate forested ecosystems are still unknown. Similarly, while there have been ongoing ash-addition experiments in northern European and South American forests, the variability in microbial responses makes it challenging to extrapolate to other forest types and few field-scale ash addition studies have been conducted in Canadian forests. This thesis examines the effects of adding biochars and wood ash to Great Lakes' St. Lawrence and Boreal forest soils, particularly focusing on changes to the structure of the soil microbial community and its biogeochemical functional ability. In a north-temperate, selection-harvested forest, biochar application had only minor effects on bacterial and fungal community composition, fungi:bacteria ratios, microbial biomass, and microbial C mineralization two years after addition. Ash addition to a clear-cut boreal forest and the same selection-harvested forest had similarly minor effects on microbial community composition and did not alter overall microbial biomass or microbial C mineralization. In a microcosm experiment, biochar and ash addition effects on P bioavailability depended on soil texture and tree species. A comparison of four-year-old biochar particles and adjacent soil showed that even when there were phylogenetic differences between biochar and bulk soil microbial communities, both groups had very similar functional abilities. Across all experiments, site-specific factors played a strong role in chemical and biological responses to biochar and ash addition. However, most observed effects were minor and transient, indicating that biochar and ash can likely be used as soil amendments in these systems without negatively disrupting the soil microbial community.

Keywords: amplicon sequencing
biochar
forests
metagenomics
soil microbial ecology
wood ash
Advisor: Basiliko, Nathan
Fulthorpe, Roberta
From Africa to Europe, Youth and Transnational Migration: Examining the Lived Experiences of Nigerian Migrant Youth in Malta

Innovations in communication and transportation industries have improved and increased the potential for the movement of individuals, commodities, and capitals across international borders as they respond to global environmental and socio-economic stimuli. Extant studies have focused on adult transnational migrants, and youth migration is highlighted only in relation to the adult experiences. However, movement of young adults as independent transnational migrants is an emerging trend in international migration. There is a general lack of awareness on the working and living conditions of youth migrants. This research was therefore informed by the urgent need to understand the migration experiences of youth with the view of protecting young migrants and ensuring that migration leads to their development and those of their home and host countries. The thesis employs data collected with interpretative phenomenological analysis, IPA in a qualitative field study conducted in 2013 in the Republic of Malta to examine the lived experiences of Europe-bound migrant Nigerian youth. By resisting the banal Push and Pull explanations for transnational migration, which literally blames migrants and the countries of origin for current trends in global migration, the thesis advances the understanding of global youth migration from the perspectives of Indigenous world views, anti-colonial, and antiracist theories. It disturbs, and by so doing, unpacks as colonial project, the existing dominant imaginaries around immigrants from the developing world. These imagined mindsets have informed immigration policies and praxis that have continued to generate and sustain the migrant other. The study uncovered the enormous transit and settlement challenges that transnational migrant youth contend with as they are polarized into social and demographic opposites (male and female migrants, legal and illegal, citizen and alien) by the advanced border-surveillance technologies and authorities of receiving states. Within this intersectionality lies migrant struggles and resistance as they aim for the countries of their destination. It therefore concludes by recommending a holistic and multilateral approach to resolving the issues of global youth migration. The approach (es) adopted must include addressing the major driving forces of the 21st century migration, which is social insecurity and economic marginalization.

Keywords: Europe
Experiences
Migration
Nigeria
Transnational
Youth
Advisor: Wane, Njoki
Transformational Learning Experience of RPN to BScN Students in One Program in Ontario

The purpose of this study was to explore the learning experience of students who are transitioning from the Registered Practical Nurse (RPN) to the Registered Nurse (RN) role in Ontario. Recent changes in the educational system now provide the opportunity for RPNs to pursue their Bachelor of Science in Nursing (BScN) in three years. The challenge is to develop programs that recognize the diversity of the RPNs' pre-existing knowledge and cultivate those into more advanced critical thinking and leadership skills required of an RN. To explore their transitioning and transformative learning experiences, a mixed method design was utilized through the use of interviews and King's (2009) learning activity survey (LAS) that identifies factors that contribute to transformational learning. RPN to BScN students enrolled in the program completed the LAS and participated in interviews. Graduates of the program, and faculty who taught in the program also participated in the interviews. During the interviews, factors that contributed and hindered the RPN learner was explored. The factors that triggered opportunities to reflect critically upon previously held beliefs were key nursing concepts that added value to their existing knowledge. Faculty, peer support and specific learning activities also contributed to their change in thinking. The challenges revealed by the students and graduates were: balancing multiple responsibilities, disappointment with faculty, overall program challenges, being integrated with the generic students, and role confusion. The faculty interviews resulted in two major themes that were: respect and admiration for the RPN, and challenges teaching the RPN learner. This study concluded that the RPN to BScN learner in this study represented the mature students who are older and have greater responsibilities in relationship to family and work than traditional students. Their diverse nursing backgrounds brought a wealth of knowledge to the classroom that needed to be challenged in different ways to facilitate a change in perspective. Exploration of RPN to BScN program curriculum should be reviewed and revised to ensure this learnerâ s needs are being met. Transformative learning provided a viable theoretical lens that educators can use to create optimal learning experiences for the RPN learner.

Keywords: BScN program
Mature Learner
Mixed Method
RPN to BScN learner
Transformational Learning
Advisor: Janzen, Katharine
Roman de l'Artiste et Valeurs chez George Sand

Dans cette thèse nous examinons le Künstlerroman (le roman de l’artiste) de George Sand en tant que lieu d’un investissement intellectuel complexe qui permet à la romancière à la fois de résoudre une crise identitaire, causée par le statut problématique de femme auteur à son époque, et de mettre en place une axiologie provocatrice qui déstabilise les étalons esthétiques, romanesques et socioculturels contemporains. Nous démontrons, dans un premier temps, comment l’exploitation des structures et des topoï du Künstlerroman dans Lettres d’un voyageur rend possible une représentation (dans la culture) de la Bildung au féminin, phénomène réputé difficile, même impossible dans la littérature du XIXe siècle. Dans un deuxième temps, nous examinons les notions, importantes pour le discours esthétique romantique, de l’idéal, de l’interprétation artistique, telles que les réfracte le Künstlerroman de Sand en les juxtaposant avec la réflexion sur le statut social de l’artiste (de la femme artiste). Une analyse de l’effet-valeur qui se dégage de plusieurs récits représentatifs sandiens (Les maîtres mosaïstes, Pauline, Consuelo, Les maîtres sonneurs) démontre comment la figure de l’artiste, figure créatrice s’il en est une, est utilisée pour produire des récits où de nouvelles significations culturelles apparaissent, de nouvelles relations normatives se forment. Traversé par l’Histoire, mais aspirant à laisser sa propre marque sur elle, le roman de l’artiste sandien met en avant les figures inexistantes dans le roman de l’artiste de ses contemporains : les femmes génies, les paysans artistes, tout en célébrant le savoir-faire des artisans. Au fil de notre étude, nous constatons que son Künstlerroman apporte d’importantes innovations au genre et à celui du Bildungsroman, tandis que la romancière supplée à une idéologie romantique de la sacralisation de l’Art et de l’Artiste, tout en valorisant à l’extrême ces deux notions, à l’instar de son époque, ce qu’on pourrait appeler la sécularisation de l’art et de l’artiste.

Keywords: Artist
Bildungsroman
George Sand
K端nstlerroman
Poetics
Values
Advisor: Michelucci, Pascal
Temperature and Pressure Retrievals and Mitigation of the Impact of Dust for a High-resolution Fourier Transform Spectrometer Mission to Mars

On the path to sending a Fourier transform spectrometer (FTS) to Mars to measure the trace gas composition of the atmosphere, several critical elements of the analysis routine need to be adapted from Earth to Mars observation. I have developed new algorithms and software for retrieving vertical profiles of temperature and pressure from infrared spectra, and created interferograms simulating observations at Mars in the presence of dust. The temperature and pressure retrieval algorithm exploits the temperature dependence of absorption lines in \coo vibration rotation bands. It was applied to terrestrial spectra from the Atmospheric Chemistry Experiment (ACE) FTS, a solar occultation instrument in orbit since 2003, and the basis for the instrument selected for a Mars mission. ACE-FTS makes multiple spectral measurements during an occultation, separated in altitude by 1.5-5 km, and ten CO2 bands are analyzed at each altitude, each with a different usable altitude range. I present an inter-comparison of temperature profiles retrieved from ACE-FTS using my algorithm and that of the ACE Science Team, and from the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC, coincident within 1.5 hours and 150 km). Compared to the ACE-FTS standard product, my retrievals exhibit mean differences between -5 and +2 K and compared to COSMIC, mean differences are between -4 and +1 K. A solar occultation FTS vertically scans the limb of the atmosphere continuously, and so the optical path for a Mars observation will move through layers of varying dust levels during a single interferogram acquisition, resulting in source intensity variations (SIVs), negatively impacting trace gas retrievals. I have simulated SIV using synthetic spectra for the Martian atmosphere, and investigated high-pass filters in the wavenumber domain, and smoothing methods in the optical path difference (OPD) domain. The use of a convolution operator in the OPD domain can isolate the SIV and be used to correct for it. Comparing the original synthetic spectra to SIV-corrected spectra, I obtain spectral residuals of less than 0.25% in simulations for both high- and low-dust conditions, and VMR vertical profile differences on the order of 0.5-3% for several trace gases known to be present in the Martian atmosphere. The work presented in this thesis directly addresses some of the problems faced at Mars: detectability and sources of methane, determining the temperature and pressure of the atmosphere, and estimating the impact of dust on high-resolution solar occultation spectra.

Keywords: ACE
atmospheric
ExoMars
FTIR
FTS
Mars
Advisor: Strong, Kimberly
Tunneling Dynamics of a Bose-Einstein Condensate

The simplicity and versatility of ultra-cold atoms make it an ideal system for studying Quantum Mechanical phenomenon like tunneling. This thesis describes progress towards experimentally measuring the time spent by a tunneling particle in the classically forbidden region. A detailed analysis of the experimental requirements to measure the tunneling time is presented along with the experimental tools developed to meet these requirements. These include a thin \SI{1.3}{\micro m} optical tunnel barrier, a smooth atomic waveguide, and a Larmor clock to measure the tunneling time. Delta-kick cooling is used to achieve the extremely low temperatures required for the tunneling time experiments. A 2.4x reduction in the atomic velocity spread is demonstrated, reducing the rms velocity spread to \SI{0.46(5)}{mm/s}. This corresponds to cooling to an effective temperature of \SI{2.0(4)}{nK}. The thin optical barrier opens up the possibility to study the decay of quasi-bound condensates via tunneling. We develop a novel trapping configuration for this purpose, in which the barrier acts as one of the walls of the trap. Inter-atomic interactions strongly dictate the escape dynamics of the condensate out of this trap, giving rise to three distinct regimes--- classical over the barrier spilling, quantum tunneling driven by interactions, and decay dominated by background losses. We show that in the tunneling regime, the decay rate depends exponentially with the chemical potential of the condensate. Experimental results show good agreement with numerical solutions of the 3D Gross-Pitaevskii equation.

Keywords: bose-einstein condensation
laser cooling
tunneling
Advisor: Steinberg, Aephraim M
Molecular Biomarker Discovery in Psoriatic Arthritis

Aim: Psoriatic arthritis (PsA) is an inflammatory arthritis of unknown etiology that develops in approximately 30% of individuals with psoriasis. No objectively measurable biomarker has been identified for PsA, due in part to insufficient knowledge of its etiopathogenesis. This work aims to identify candidate biomarkers of PsA by studying its underlying transcriptomic and epigenomic mechanisms. Methods: Psoriasis (PsC) and PsA patients from a prospective cohort were analyzed. Whole blood, serum, and semen samples were obtained from subsets of patients and unaffected controls for transcriptomic, protein, and epigenomic analyses, respectively. Potential epigenetic mechanisms were also analyzed using self-reported family history data from the entire PsC and PsA cohort to further explore the parent-of-origin effect. Results: Transcriptomic analyses identified several genes involved in innate immunity, particularly toll-like receptor signalling as differentially expressed in whole blood of PsA and PsC patients. Four candidate gene expression biomarkers CXCL10, NOTCH2NL, HAT1, and SETD2 were replicated in an independent cohort of PsC and PsA patients. Soluble CXCL10 was significantly elevated in baseline serum samples of psoriasis patients who later developed PsA compared to patients who did not develop PsA. Excessive paternal transmission was found in PsC and PsA patients, as well as genetic anticipation manifesting as increased disease severity during male transmission. DNA methylation profiling of sperm cells revealed several germ line variations associated with psoriasis and PsA occurring near or within genes involved in inflammatory and immune system processes, including HCG26 within the major histocompatibility complex. Conclusions: Whole blood transcriptomic and serum protein analysis identified the chemokine CXCL10 as a putative predictive biomarker of PsA in PsC patients. Evidence of a parent-of-origin effect, genetic anticipation, and the identification of germ line DNA methylation variations in patients suggest a role for epigenetic mechanisms in psoriatic disease etiopathogenesis, and a potential new avenue of biomarker discovery.

Keywords: Biomarkers
Epigenetics
Genomics
Psoriasis
Psoriatic Arthritis
Rheumatology
Advisor: Gladman, Dafna D