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Cardiac PET Attenuation Correction and Inter-modal Medical Image Translation
No full textPositron Emission Tomography (PET) is a nuclear imaging technique that visualizes metabolic activity in the body by detecting gamma rays emitted from a radiotracer. For accurate quantification of radiotracer uptake, attenuation correction (AC) is essential to compensate for the absorption of photons by different tissues. Traditionally, Computed Tomography (CT) provides ideal attenuation maps for PET correction due to its direct relationship with tissue density. In hybrid PET/Magnetic Resonance Imaging (MRI) systems, however, MRI-based attenuation correction is challenging as MRI cannot directly visualize bone structures critical for proper photon attenuation estimation. This thesis addresses this limitation by developing a novel approach for generating synthetic CT images from MRI data for improved PET AC in cardiac imaging, with applications extending beyond attenuation correction to radiation therapy planning and other inter-modal medical image translation tasks.
This research makes three key contributions: (1) a CT template and multi-modal registration pipeline to establish spatial correspondence between MR and CT images, (2) a Kernel Ridge Regression (KRR) implementation serving as a baseline, and (3) a Dual Contrast cycleGAN (DC-cycleGAN) model incorporating a novel mu-map loss for bidirectional MR-CT translation. The dataset consisted of paired MR and CT images from 10 subjects, with 8 used for training and 2 for testing.
Results demonstrated that the DC-cycleGAN model using in-phase Dixon MR images (GAN-In) achieved superior performance in MR-to-CT translation, with a 39.5% reduction in Mean Absolute Error (MAE) and a 37.1% improvement in Structural Similarity Index compared to the KRR baseline. When applied to PET reconstruction, the synthetic CT-based AC (GAN-AC) achieved substantial improvements: SUVmean bias was reduced by 93% (from 18.85% to 1.27%), SUVmax bias by 89%, Root Mean Square Error by 45%, and MAE by 47% compared to the vendor-provided MR-based AC (MR-AC). The proposed implementation as a web-based application will enable researchers at The Royal's Institute of Mental Health Research to utilize this technology for improved diagnostic precision in PET/MR imaging
LipidCRED: Lipid Computational Reaction and Enzyme Database
No full textMass spectrometry-based lipidomic approaches generate vast datasets of individual lipid species, but translating these compendiums of abundances into meaningful biological insights, particularly regarding enzymatic pathways, remains a significant challenge. Existing bioinformatics tools often struggle with nomenclature heterogeneity, limited reaction coverage, the need for extensive post-hoc validation of enzyme predictions, and/or cumbersome user workflows. To address these limitations, I developed Lipid Computational Reaction and Enzyme Database (LipidCRED), a novel bioinformatics platform designed for comprehensive and validated exploration of lipid metabolism. LipidCRED integrates a robust relational database, amalgamating curated information from SwissLipids, Rhea, UniProtKB, and the HUGO Gene Nomenclature Committee (HGNC), with a sophisticated software engine. Key innovations include advanced nomenclature parsing, a "LipidMatcher" module that intelligently infers specific molecular products from class-level reactions using carbon-chain matching rules, and an emphasis on pre-validated enzyme data. A user-friendly R/Shiny web interface ensures broad accessibility. Benchmarking against leading tools (LipidOne, LINEX, BioPAN) demonstrated LipidCRED's competitive performance in validated lipid-enzyme associations, uniquely providing highly accurate enzyme lists requiring minimal filtering. By streamlining the path from complex lipid lists to reliable enzymatic insights, LipidCRED empowers researchers to more effectively unravel the roles of lipid metabolism in health and disease
Effective Strategies for Providing Post Secondary Education to Refugees in Crisis Situations: A Study of Implementation and Impact
No full textThe global refugee crisis highlights the urgent need for accessible and effective educational opportunities for displaced populations. Education is crucial for refugees, providing stability, empowerment, and pathways to sustainable development amid numerous challenges. Refugees face significant barriers to education, especially at higher levels. This thesis explores the landscape of post-secondary education for refugees, using Niger and Jordan as case studies. It examines existing educational opportunities, such as scholarships, online education, and Technical and Vocational Education and Training (TVET) and suggests strategies to enhance access. Through a comparative case analysis and a mix of primary and secondary data, the study identifies gaps and proposes recommendations for improvement. The findings underscore the importance of higher education in equipping refugees with essential skills and knowledge to rebuild their lives and contribute positively to their host countries
Investigating the Role of AAK1 in Satellite Cell Polarization and Muscle Regeneration
No full textSatellite cells (SCs), or muscle stem cells, divide in two modalities in response to injury. They can divide symmetrically to give rise to two identical daughter cells, or asymmetrically giving rise to a satellite cell and a committed progenitor cell whose role is to aid in muscle regeneration. It is a tightly controlled process that is dysregulated in Duchenne Muscular Dystrophy (DMD). An siRNA screening approach previously identified AAK1 as a gene potentially involved in regulating the asymmetric division of satellite cells. Here, we characterized the role of AAK1 using a full-knockout and conditional knockout mouse models. AAK1 has been shown to be part of the Notch pathway, and it regulates NUMB's localization in the cell. Knowing that NUMB is involved in asymmetric cell division and the activation of the Notch pathway keeps cells quiescence, we hypothesized that ablation of AAK1 has positive effects by promoting asymmetric division and further increasing muscle force. In this study, using PARD3 polarization assay, MYOG staining, proliferation analysis, and senescence evaluation, we observed that ablation of AAK1 in mdx mice led to a rescue of satellite cell polarization, a precursor to asymmetric divisions, and reduced cellular senescence, potentially rescuing the altered division kinetics of mdx SCs. In examining the physiological effects in animals, muscle force did not improve following ablation of AAK1. This outcome may be attributable to potential masking effects from tamoxifen, which is used in our conditional knockout mice, or to kinase-independent functions of AAK1 that require further investigation. Nonetheless, the data suggest that AAK1 is an important factor in satellite cell function, indicating a need for additional research to clarify its mechanisms of action
Investigating the Role of the Dorsal Filament in Weakly Electric Fish
No full textLes humains et les animaux utilisent des récepteurs sensoriels spécialisés pour encoder des informations sur leur environnement. La densité de ces récepteurs peut avoir un impact significatif sur l'acuité sensorielle et la qualité de l'information obtenue. Par exemple, la fovéa de la rétine humaine présente la région de la rétine ayant la densité de photorécepteurs la plus élevée, ce qui améliore l'acuité visuelle.
Le poisson faiblement électrique Apteronotus albifrons habite les eaux néotropicales. Il est réputé pour sa capacité remarquable à naviguer et à capturer des proies dans l'obscurité sans se fier à des repères visuels. Tout comme d'autres poissons faiblement électriques du type ondulatoire, cette espèce génère un champ électrique de faible intensité dans les eaux environnantes. La production de ce champ électrique est continue, et varie dans le temps. Tout objet à proximité du poisson et ayant des propriétés électriques différentes comparativement aux eaux environnantes provoque des perturbations dans ce champ électrique. Ces perturbations sont détectées par des milliers d'électrorécepteurs qui sont situés partout sur la peau du poisson.
Chez l'Apteronotus albifrons, la densité d'électrorécepteurs n'est pas uniforme. Les deux régions ayant la plus haute densité de récepteurs sont la tête et le filament dorsal, une structure située sur la surface dorsale du poisson. La tête contient d'autres systèmes sensoriels tels que la vision, tandis que le filament dorsal ne contient que des électrorécepteurs. Cela suggère qu'il pourrait servir principalement d'organe électrorécepteurs. Bien qu'il y eût des indications d'un biais dorsal lors de la capture de proies, le rôle précis du filament dorsal dans le système électrosensoriel reste incertain.
Dans cette thèse, des mesures quantitatives du comportement des poissons sont utilisées pour analyser la façon dont ceux-ci répondent à des stimuli électrosensoriel positionnés à divers endroits autour de leurs corps. Après l'initiation du stimulus, le poisson se rapproche de l'endroit d'où provient stimulus. Dans certains cas, il y a aussi un léger mouvement de roulis vers le stimulus. De plus, la fréquence de détection des stimuli provenant d'au-dessus du filament dorsal est plus élevée que lorsqu'elle provient d'autres endroits autour de la même région du tronc. Collectivement, ces observations proposent que le filament dorsal produit une image électrique supérieure comparativement au reste du tronc.
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Animals use specialized sensory receptors to encode information about their environment. The density of these receptors can significantly impact sensory acuity and the quality of the information they provide. For instance, the fovea in the human retina has the highest photoreceptor density, which enhances visual acuity.
Apteronotus albifrons, a weakly electric fish that inhabits neotropical waters, is renowned for its remarkable ability to navigate and capture prey in the dark, without relying on visual cues. Like other wave-type weakly electric fishes, this species generates a time-varying electric field in the water surrounding its body. Any nearby object with distinct electrical properties compared to the surrounding waters will cause perturbations in this electric field. These perturbations are detected by thousands of electroreceptors located on the fish's skin.
Electroreceptor density on the fish's skin isn't uniform. The two highest density regions are the head and the dorsal filament, a distinct structure situated on the dorsal edge of the trunk. The head includes other sensory systems like vision, but, the dorsal filament appears to be innervated solely by afferents originating from electroreceptors. This suggests that it primarily serves as an electroreceptive organ. While there is some evidence indicating a dorsal bias during prey capture behavior, the precise role of the dorsal filament in electric sensing is uncertain.
Here, quantitative measurements of fish behavior were used to evaluate sensitivity to electrosensory stimuli positioned at various locations. Upon stimulus onset, fish approached the stimulus location, orienting with small changes in roll angle in some cases. In addition, the fish showed a higher detection frequency for stimuli located over the dorsal filament, compared to the rest of the trunk. These observations collectively suggest that the dorsal filament provides a superior electric image compared to the rest of the trunk
A Case-Control Study to Develop and Test a Predictive Model for Readmissions of Adults with Chronic Heart Failure
No full textÀ la demande de l'auteur, le résumé a été retiré en raison de la nature confidentielle de la thèse. Il sera ajouté une fois la période d'embargo terminée.
At the author’s request, the abstract has been removed due to the confidential nature of the thesis. It will be added once the embargo period has passed
Diving Deep into Human Gut Metaproteomics: Insights from Protein to Peptide Level
No full textThe human gut microbiome has a complex and dynamic relationship with its host and is closely associated with human health and disease states. As an emerging high-throughput omics technique, metaproteomics measures the presence and abundance of proteins in the microbial community and serves as a powerful tool for investigating interactions between the human gut microbiome and the host. However, metaproteomics faces unique challenges due to the complexity of microbial communities. Limited proteome coverage in metaproteomics has recently been highlighted, suggesting it could obscure important biological discoveries. This issue is further compounded by information loss during protein inference. As mass spectrometry-based (meta)proteomics directly measures peptides rather than proteins, information loss occurs due to the difficulty in precisely attributing peptides to their parent proteins. Despite this, most current metaproteomic studies still rely on protein-level analyses, and there are fewer applicable tools for peptide-level analysis. To address these challenges, this thesis enhances traditional protein-level metaproteomics with peptide-level analysis, develops practical tools to reduce information loss.
First, we explored the potential of traditional protein-level metaproteomics analysis by investigating the effects of commonly used sugar substitute sweeteners on ex vivo human gut microbiome. Traditional protein-level metaproteomics analysis revealed that the functional profiles of the microbiomes grouped these sweeteners into two clusters, the noncaloric artificial sweetener (NAS) cluster and the carbohydrate (CHO) cluster. Notably, prebiotics fructooligosaccharide (FOS) and kestose (KES) clustered with the CHO cluster. Protein-level analysis further revealed that the sugar substitute sweeteners in the CHO cluster could modulate the metabolism of Clostridia.
Next, to facilitate peptide-level human gut metaproteomics analysis, we constructed a core peptide database by extracting and reanalyzing data from published human gut metaproteomics studies. Raw files from fifteen publicly available human gut metaproteomics projects were reanalyzed and the identified peptide-spectrum matches (PSMs) were used to construct a core peptide database, MetaPep. The constructed MetaPep database enabled rapid and accurate identification of peptides for human gut metaproteomics. Additionally, annotation and reanalysis of peptides from the MetaPep database revealed the current landscape of human gut metaproteomics research.
Finally, to advance peptide-centric analysis in metaproteomics studies, we explored peptide abundance correlations to enhance taxonomic and functional characterization of the human gut microbiome. Specifically, we analyzed peptide abundance correlations in a metaproteomics dataset derived from six in vitro cultured human gut microbiomes exposed to over one hundred drug treatments. Peptides originating from the same protein or taxon exhibited correlated abundance changes. Peptides from the same taxon were clustered within a peptide correlation map visualized with t-SNE. Leveraging these correlations, we enabled genome-level taxonomic assignments for a larger number of peptides. In addition, by focusing on single-species subsets, we calculated taxon-based normalized peptide abundances (TNPA) and constructed peptide abundance correlation networks, which revealed functional linkages among peptides and provided novel insights into the roles of previously uncharacterized microbial proteins.
Altogether, this thesis demonstrated the utility of protein-level metaproteomics analysis by studying the functional effects of sugar-substitute sweeteners on the human gut microbiome. Furthermore, by constructing a core peptide database, analyzing peptides in this database, and studying peptide abundance correlations in a large metaproteomics dataset, this thesis provided practical tools for peptide-level analysis, which in turn advanced taxonomic and functional analysis in human gut metaproteomics
Economic Expertise in Postcapitalist Democratic Economic Planning
No full textPostcapitalist democratic economic planning (DEP) seeks to democratize economic decision-making. In response to the failures of central planning, DEP is vigilant lest the emergence of some new elite subvert its democratic and egalitarian aspirations. This article considers the possibility that economic expertise intended to support DEP may be means through which new elites are covertly encouraged. DEP advocates seek to safeguard DEP processes from elite control by proposing institutional oversight structures combined with enhanced subjective oversight capacities. In the case of economic expertise, we contend that these responses mitigate the possibility that economists’ analyses will have preferential implications but do not resolve this antidemocratic possibility. Economic expertise poses a problem of democratic accountability because its technical opacity impedes democratic oversight, thus enabling the covert design of economic analysis in ways that favour some groups over others. We conclude by arguing that reconsidering economic expertise in postcapitalism can attenuate this tension
The Impact of Corruption on the Cost of Equity: The Role of ESG
No full textThis study examines whether Environmental, Social, and Governance (ESG) performance mitigates the increase in the cost of equity associated with corporate corruption and whether this effect is further enhanced by board gender diversity. Using a panel dataset of publicly listed firms in the United States and Canada from 2013 to 2022, the analysis reveals that corruption is significantly and positively associated with the cost of equity, while ESG performance - both overall and across its environmental, social, and governance pillars - is negatively associated with it. The interaction terms between ESG and corruption are consistently negative and statistically significant, suggesting that ESG serves as an effective risk-mitigating mechanism in the presence of reputational and operational risk. The moderating role of ESG is more pronounced in firms with greater board gender diversity. These results are robust to various empirical strategies, including instrumental variable regression, theme-level decomposition, and propensity score matching based on anti-corruption policy disclosure. This study contributes to the literature by integrating ESG and corruption into a unified framework, highlighting the financial relevance of ESG practices and inclusive governance. The findings offer practical implications for investors, managers, and policymakers seeking to reduce financing costs and promote long-term value creation in corruption-prone environments
Terahertz Nonlinear Optics of Graphitic Materials: From THz Pulse Manipulation to High-Harmonic Generation
No full textThis thesis investigates the nonlinear optical behavior of graphitic materials in the terahertz (THz) frequency regime, with a focus on enhancing and understanding strong-field light–matter interactions in graphene and its derivatives, including graphene oxide (GO) and its reduced forms. By integrating theoretical modeling, numerical simulations, device fabrication, and experimental investigations of nonlinear THz phenomena, this work explores THz pulse manipulation and establishes a comprehensive platform for scalable and tunable THz nonlinear photonics.
We begin by establishing the theoretical foundations of THz nonlinear optics, including the derivation of the nonlinear wave equation, analysis of second- and third-order polarization responses, and the dynamics of carrier heating and saturable absorption in Dirac materials such as graphene. These concepts are experimentally realized using a high-field table-top THz system based on tilted-pulse-front optical rectification and electro-optic sampling. A key challenge in this regime—the detection of weak nonlinear signals amid broadband excitation in a noisy system—is addressed through the design and fabrication of metamaterial-based THz spectral filters featuring octave-wide bandwidths and high extinction ratios. These custom-built devices are engineered to shape the spectral content of the THz beam, enhance spectral isolation, and significantly improve detection sensitivity. In particular, a configuration of lowpass and highpass filters is developed to selectively transmit generated harmonic signals while suppressing the strong pump background, enabling reliable measurement of weak high-harmonic generation in subwavelength 2D samples.
Using this system, we demonstrate a multi-strategy platform for enhancing third-harmonic generation (THG) in graphene, integrating three complementary approaches: (i) stacking decoupled multilayer graphene sheets to increase the light–matter interaction length, (ii) applying electrical gating to dynamically modulate carrier density and optimize nonlinear conductivity, and (iii) coupling graphene with plasmonic metasurfaces to achieve strong local field enhancement. The synergy of these strategies leads to up to two orders of magnitude enhancement in THG efficiency, underscoring the critical role of both structural and electronic tunability. Despite these gains, further improvement is limited by graphene’s intrinsic linear absorption, which restricts the effective interaction length beyond a few layers. This motivates the use of alternative low-loss, tunable materials such as graphene oxide (GO), which combines reduced THz absorption, chemical flexibility, and access to nonlinear regimes beyond those of pristine graphene.
We next explore GO, a chemically functionalized derivative of graphene that features lower THz absorption and local symmetry breaking due to the presence of oxygen-containing functional groups. These groups can be gradually removed through chemical or thermal reduction, allowing for continuous tuning of GO’s optical properties. Our experiments reveal a distinct nonlinear regime in GO, marked by the coherent generation of both odd and even-like harmonics, as well as a unique saturable transmission behavior under intense THz excitation. To interpret these effects, we develop a phenomenological two-level system model that accurately captures the field-dependent transmission response. This analysis identifies saturable transmission as a new symmetry-defying mechanism for wave mixing in functionalized 2D materials, enabling the generation of even-like harmonics without requiring long-range structural asymmetry.
Together, the results presented in this thesis establish graphitic materials—both pristine and functionalized—as versatile platforms for advancing nonlinear optics in the terahertz regime. By combining material engineering, device fabrication, and nonlinear spectroscopy, this work delivers a unified framework for probing and enhancing THz-driven light–matter interactions in 2D systems. The multi-strategy enhancement approaches for graphene, the discovery of novel nonlinear behavior in graphene oxide, and the implementation of spectral filtering and modeling tools all contribute to a powerful experimental and theoretical platform. This platform not only deepens our understanding of strong-field physics in low-dimensional materials, but also lays the groundwork for next-generation THz photonic technologies, including reconfigurable frequency converters, modulators, and integrated nonlinear devices