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UNDERPINNINGS OF CD8 T CELL ACTIVATION DURING IMMUNOSENESCENCE FOR CANCER IMMUNOTHERAPIES
No full textImmunotherapy has transformed cancer treatment, yet its efficacy remains variable, particularly in the context of aging, where immunosenescence impairs CD8+ T cell function. Aging is a major risk factor for poor responses to infection, therapy, and cancer. Critical gaps remain understanding how early CD8⁺ T cell activation states are regulated during aging. This thesis investigates the interplay between the CD38–NAD⁺ metabolic axis, early CD8⁺ T cell activation, and the ligandome of solid and hematological malignancies, that disproportionately affect older population. We first analyzed patients with pulmonary-only metastatic prostate cancer (PO-mPCa), a rare clinical cohort associated with favorable prognosis. Using an in-house developed pipeline, we defined the human leukocyte antigen (HLA) class I-restricted neoepitope landscape in these patients. This revealed a distinct neoepitope repertoire enriched in immunodominant peptides of optimal length, suggesting that unique HLA-neoepitope interactions may underlie their favorable disease course and providing a rationale for neoantigen-guided interventions. Next, we examined how immunosenescence reprograms early CD8⁺ T cell differentiation. We identified a transient pre-effector (TPE) (P4, CD44lowCD62Llow) that emerges rapidly after activation, functions within an innate-like timeframe, and bridges naïve to effector states. Strikingly, P4 frequencies declined with age, but residual cells were enriched for CD38 expression. Functional assays revealed that type I interferons can restore P4 effector capacity through IFNAR1-dependent bystander activation, rescue NAD⁺ and adenosine-mediated suppression. Finally, we investigated the ligandome of mantle cell lymphoma (MCL), integrating in vitro, in vivo, and patient-derived samples. Immune pressure and oncolytic virus therapy dynamically remodeled the HLA ligandome, dynamically altering predicted neoepitope candidates. Chemotherapy-treated patient samples further revealed reduced mutational and neoepitope burden, consistent with successful immune clearance. Overall, this thesis delineates how aging and therapy reshape the CD8⁺ T cell and tumor antigen landscapes, establishing the CD38–NAD⁺ axis and early P4 differentiation state as key modulators of immune competence. These insights provide both mechanistic underpinnings of immunosenescence and actionable strategies to optimize cancer immunotherapies across solid and hematological malignancies
Framework and Application of a Practical Robustness-Oriented Bridge Upgrade Strategy for Trusses (ROBUST): Supplementary Material
No full textZip files containing supplementary material to accompany the article "Framework and Application of a Practical Robustness-Oriented Bridge Upgrade Strategy for Trusses (ROBUST)" appearing in the Journal of Bridge Engineering
Effects of Pre-Transplant Hemodialysis Timing on Post Kidney Transplant Outcomes
No full textBackground: For kidney transplant patients on hemodialysis there is little evidence examining how timing of individual hemodialysis sessions prior to kidney transplant may affect short and long-term post-transplant outcomes.
Methods: A retrospective cohort study of hemodialysis patients who received a kidney transplantation from 2006-2020, (n=661), was conducted using the Nova Scotia Health Multi-Organ Transplant Program’s Transplant Data Repository, which includes all transplant recipients from the Atlantic Canada provinces. The primary outcome of the study was delayed graft function, with secondary outcomes of transplant graft failure, length of stay, perioperative hypotension, postoperative hypotension. Outcomes were analyzed using either multivariable logistic regression or multivariable Fine and Gray regression.
Results: The primary outcome of delayed graft function had an odds ratio of 0.78 (95% confidence intervals. 0.47-1.28) when comparing hemodialysis ≥1 day before transplant to hemodialysis the same day as transplant. Similarly, no significant relationship was seen between hemodialysis timing and secondary outcomes
Carboniferous Sarcopterygian Fossils and the Marine Paleoenvironment of the Joggins Formation, Nova Scotia, Canada
No full textEarth and Environmental Sciences Undergraduate Honours ThesisJoggins Fossil Cliffs, a UNESCO World Heritage Site in Nova Scotia, Canada, is known for its Late Carboniferous (Pennsylvanian) coal seams and remarkably preserved ecosystems that represent terrestrial tropical Pangea. Of the five formations present, the most significant is the Joggins Formation (Fm) which is divided into approximately 15 sedimentary cycles based on the alternation of flooding plains, coals, and channel bodies. While the site records cyclic terrestrial and marine deposits, the marine influence of the Joggins Fm has rarely been studied. As a result, many fish fossils in the Joggins Fm collection remain unidentified, and there are ongoing debates about the source of the marine influence. I aim to (1) identify five unidentified sarcopterygian fish fossils from the Joggins Fm, and (2) determine their habitat and depositional environment. I have selected seven sarcopterygian fish fossils, most of which are scales, and I identified them to the family level using relevant literature. To learn more about the marine influence at a specific location within the formation, a carbonaceous limestone was chosen as a representative specimen for the marine depositional environment based on its thickness and history of producing determinate fish fossils. Thin sections were made for a vertical representation of the limestone band as well as a sedimentary log for greater marine influence context. Both thin section and microfossil analysis shows extensive bivalve and ostracod fossils layered in organic matter. Phosphate and bone fragments can also be seen in thin sections. The fossil assemblage for this location within the Joggins Fm suggests a paleoenvironment with moderate marine influence, likely a brackish or estuarine environment. Lastly, this work contributes to our complete understanding of both the terrestrial and marine environments of this important site and the animals that lived within it
Reconstructing Global Multi-Person 3D Motions From A Single Moving Camera
No full textTo address 3D human reconstruction in multiple dynamic scenarios, a new optimization-based framework, Opti-Pose3D, is proposed to recover global multi-person motion from a single moving camera by integrating SLAM techniques with a learned human motion prior. To detect and associate individuals across frames, a robust tracking algorithm is employed to handle occlusions effectively. In addition, a learned motion smoothness prior is incorporated into the optimization pipeline to enhance temporal consistency. Using the initial camera parameters estimated by SLAM, human motion trajectories are reconstructed by jointly optimizing the SMPL model and camera parameters to align the projected 3D poses with the detected 2D observations.The reconstruction of 3D human models from in-the-wild videos has emerged as a highly promising research direction, with increasingly practical and widespread applications. To address the challenges of depth ambiguity and human occlusions in monocular videos, an optimization-based framework is proposed that combines SLAM techniques with human motion priors to recover global multi-person motion from a single moving camera. Camera parameters are estimated using SLAM, while a robust tracking algorithm is adopted to mitigate occlusion effects. A learned motion smoothness prior is further integrated into the optimization process. The SMPL model and camera parameters are jointly optimized to align the reconstructed 3D poses with 2D detections. Experimental results on the 3DPW dataset demonstrate that the proposed method outperforms existing approaches in both accuracy and robustness
Sustaining Soil Organic Carbon and Soil Health in Intensively Tilled Short Crop Rotations
No full textSoils in Canada are under degradation due to the intensification of agricultural systems. Intensive field crop rotations are characterized by low crop diversity and crop residues, and high tillage frequency and external nutrient inputs. However, the impact of these intensive short rotations on soil health, earthworm communities, and soil organic carbon (SOC) has been little investigated and is the focus of this thesis. A field survey was conducted over three years on eleven organic grain farms in Québec, Canada, to assess the impact of short crop rotations without forages (corn [Zea mays L.] -soybean [Glycine max (L.) Merr.] – small grain) on the earthworm community and soil health. Earthworm abundance and richness were generally low in both fields and field margins, with earthworm communities in cropped fields primarily dominated by endogeic species. Our findings suggest that long-term manure application, along with frequent use of cover crops, plus inversion tillage favours endogeic species in these systems. In contrast anecic and epigeic species increased under winter cereals. Legacy (prior three years) management practices were characterized using indices for crop diversity (CDI), soil tillage intensity rating (STIR) and organic amendment use (OAI). In-season management indices, in particular CDI (increased by cover crops and winter crops) and STIR, varied across crop fields and had a greater effect on soil health outcomes. A replicated potato (Solanum tuberculum L.) experiment in Prince Edward Island, Canada, compared the impact of contrasting three-year rotations including one full season cover crop on SOC dynamics and distribution. Treatments failed to differ in soil profile (0-45cm) SOC. Our results indicate that, carbon (C) inputs from full season cover crops were insufficient to offset SOC loss due to high tillage intensity in these rotations, affecting both topsoil and subsoil SOC stocks. Overall, this research has shown that reducing tillage intensity by increasing crop diversity was the main driver of earthworm community diversity and soil health. Rotations that enhance C inputs, such as via winter cover crops and cash crops residues, could buffer the earthworm community, and soil health and SOC, against the impacts of greater tillage intensity in short rotation cropping systems
FUNCTIONALIZING GOLD NANOPARTICLES WITH A DNA APTAMER FOR BIOSENSING 25-HYDROXYVITAMIN D3
No full textVitamin D influences over 400 processes in the human body and its deficiency is associated with several diseases such as uterine fibroids. Accessible point-of-need tools are required to detect 25-hydroxyvitamin D3 (25(OH)D3), a Vitamin D biomarker. This thesis investigated conjugation methods for the specific, yet structurally complex 25(OH)D3 aptamer, VDBA14, to gold nanoparticles (AuNPs), common biosensor transducers. Initial approaches using salt-aging, low pH, and freeze conjugation, evaluated with UV-Vis, fluorescence, and salt stability assays, were ineffective due to poor aptamer conjugation and the resulting AuNP aggregation. A promising development was the inclusion of an 18atom hexa-ethyleneglycol spacer between the aptamer and disulphide linker. Freeze conjugation of the modified aptamer improved AuNP stability, with conjugation confirmed by UV-Vis redshift and DNA FT-IR bands. Future experiments are required to demonstrate conjugation without destabilizing AuNPs. This work represents a foundation for functionalizing AuNPs with VDBA14, and the first step towards point-of-need 25(OH)D3 biosensors
THE GENETIC DIVERSITY BETWEEN SUBLINEAGES OF UCYN-A AND THEIR ALGAL HOST PLASTIDS AND THE DYNAMICS OF NITROGEN FIXING MICROBES IN THE BEDFORD BASIN
No full textThe availability of fixed nitrogen, which is imperative to the productivity of the ocean, is largely controlled by microbial diazotrophs. These nitrogen-fixing organisms are diverse and widespread, and studying their ecology and genomics gives us important information on the workings of the marine nitrogen cycle. This thesis focuses on the study of marine diazotrophs in the Northwest Atlantic Ocean. Chapter 2 presents findings from metagenomic analyses of mixed cultures containing the globally important diazotroph UCYN-A, one sublineage of which has recently been presented as a nitrogen fixing organelle, or “nitroplast” within the haptophyte alga Braarudosphaera bigelowii. Results of these analyses produced metagenome assembled genomes of UCYN-A4, and the Braarudosphaera bigelowii host plastid associated with it. Next the pangenome of UCYN-A was examined; the results showed that UCYN-A4 has similar average nucleotide identity to UCYN-A1 and UCYN-A2 as they do to each other, and the genome of UCYN-A4 is missing many of the same genes as the other UCYN-A genomes. The co-occurring microbes within the mixed cultures were also examined and compared to natural co-occurrences and prey of Braarudosphaera bigelowii. Chapter 3 examines the diazotrophic community within the Bedford Basin. Data from the Bedford Basin time series were used as the basis of an analysis of community composition of the nifH amplicon gene sequences and more than doubled the time frame of the data analysed previously. Temporal patterns revealed high cyanobacterial abundances in the summer and fall in the surface waters which contrasted with little seasonal variation in the deeper waters. The environmental drivers of variation in nifH community composition were analysed for the two depths and found temperature driving more variation in the surface and oxygen concentration driving more variation at depth. Using the sequences from Chapter 2, dynamics of UCYN-A and B. bigelowii were studied by sublineage and genotype. Overall, this thesis provides new knowledge on UCYN-A and Braarudosphaera bigelowii and shows the value of high-resolution time series data in monitoring diazotroph community dynamics
Quantifying bias in underwater radiated noise measurement
No full textThe measurement of ship underwater radiated noise (URN) is a foundational element of underwater noise management policies. These measurements are frequently made in shallow water (<50 m). Current methods estimate the power spectrum with a single transmission loss applied for all frequencies. A latent assumption in this is signal stationarity, i.e., propagation loss properties do not change with ship position relative to the hydrophone. A breach of the stationarity assumption leads to bias in calculating the average. Using this work's proposed methodology, the stationarity assumption is shown to be false in the along-track dimension for one ship at one site at two different times of the year, from 30 to 300 Hz. This band covers many noise sources of interest on ships. Linear regression methods demonstrate some violations of stationarity but produce smaller estimates of bias. Single layer neural networks are shown to produce higher levels of estimated bias but only marginally better mean absolute error and root mean squared error statistics for an ideal ship model. When neural networks models are applied back to the original run data, it is found the magnitude of real bias lies between that of the regression models and the ideal ship model
Magnetic properties of ABC-stacked kagome antiferromagnets through the lens of novel Mn3Ge thin films
No full textThis thesis describes the growth and characterization of Mn3Ge thin films. Various classical spin models are introduced and explored in an attempt to explain the complex magnetic behaviour observed.In this thesis, the magnetic properties and transport behaviours of novel, tetragonally
distorted epitaxial thin films of Mn3Ge are explored. Mn3Ge belongs to a class of materials
that exhibit non-collinear antiferromagnetic spin configurations that give rise
to unique electrical transport phenomena, such as the anomalous Hall effect (AHE),
which can be utilized in spintronics applications. The films of this study were deposited
on insulating 4H-SiC(0001) substrates, with successful crystallization leading
to a unique tetragonally distorted L12 phase instead of the expected hexagonal D019
form. Magnetometry and magnetotransport measurements revealed complex magnetic
behaviors including a large saturation magnetization, complicated ferrimagnetic
characteristics, and unusual AHE contributions. These results pointed to the need
for modifications to the phenomenological model used for other L12 structures, such
as Mn3Ir and Mn3Pt. A symmetry analysis of all possible nearest-neighbour and
same-site bilinear magnetic interactions in the L12 system uncovered an anisotropic
exchange term that has been previously overlooked. This term is potentially important
for understanding the canting of the spin structure away from a coplanar configuration.
It was found that a relatively simple modification to the nominal cubic model
that accounts for the tetragonal distortion of the films does a good job of qualitatively
reproducing many of the observed magnetic behaviours. The study concludes with
several potential avenues for future work, including further characterization of the
magnetic configuration, optimization of film growth processes, and investigation of
the material’s electronic band structure, which could deepen the understanding of its
intriguing transport properties. This work advances the field of antiferromagnetic and
ferrimagnetic spintronics and offers insights into the development of robust magnetic
bits with low stray field and potentially high switching speeds