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Inference of ionospheric electron density and electron temperature profiles with regression methods
No full textIn this thesis, the inference of ionospheric electron density profiles and electron temperature profiles is presented and discussed. The analysis is based on the Nearest Neighbor (NNB) and Radial Basis Function (RBF) regression methods. Synthetic data sets used to train and validate the inference models are constructed using the International Reference Ionosphere (IRI 2020) model with randomly chosen years
(1987-2022), months (1-12), days (1-31), latitudes (-60 to 60°), longitudes (0, 360°), times (0-23h), at altitudes distributed uniformly, ranging from 95 to 600 kilometres. For comparison with constructed models with IRI data to infer electron density profiles, I also used a set of actual measurements obtained from an Incoherent Scatter Radar (ISR) provided by Prof. John Bosco Habalurema at Rhodes University and SANSA in South Africa. ISR instruments give full ionospheric electron and temperature profiles but they are complex and expensive to build compared to ionosondes instruments, which give truncated profiles. The NNB and RBF models use the constructed ionosonde-like profiles to infer ISR-like profiles. The results presented show that the inference of ionospheric electron density profiles is better with the NNB model than with the RBF model while the RBF model is better at inferring the electron temperature profiles than the NNB model. Best and worst inference results are plotted, compared and discussed for both models. The NNB model and the RBF model generally overestimate or underestimate the inferred electron density and temperature values, especially at higher altitudes and density values, but tend to produce good matches for the density at lower altitudes. Inferences with ISR data also show
a good match at lower altitudes in general, but they are also found to be less accurate at higher altitudes especially around the maximum height of F2 layer (hmF2). Moreover, the best inference from NNB shows a better agreement of ISR inferred
profiles
Insight into government, September 12, 2025
No full textAlberta's independent newsletter on government & politics
Accessibility of Women in Educational Leadership in K-12 Alberta
Get PDFThis capstone paper investigates the systemic and cultural barriers that limit women’s access to leadership roles within Alberta’s K-12 educational system. Utilizing leadership theory as a conceptual framework, a comprehensive literature review was conducted, with thematic analysis identifying five interrelated themes: implicit gender bias, intersecting barriers of race, class, and gender, insufficient mentorship and sponsorship opportunities, gendered organizational structures, and policy shortcomings. The findings reveal that, despite progressive policy initiatives, entrenched biases and structural impediments persist, hindering women’s progression into senior leadership positions. This research underscores the need for targeted policy reforms,
inclusive leadership training, and enhanced mentorship programs to create equitable leadership pathways. As a capping project for my Master of Education in Studies in Educational Leadership, this work deepens the understanding of gendered leadership dynamics. It provides actionable insights for fostering a more inclusive and supportive educational environment
GrEX-Timelines Section
No full textSample timelines from award-winning IG (Insight Grant) and IDG (Insight Development Grant) applications from 2019-2022
Uncovering Roles For Myristoylation in Cancer, and NMTs as a New Therapeutic Target in Acute Myeloid Leukemia
No full textProtein myristoylation is a form of modification by the attachment of the fatty acid myristate to the N-terminus, helping to regulate protein localization, stability, and function. Myristoylation has been proposed as a therapeutic target in cancer for decades, but only recently have high-quality compounds targeting N-myristoyltransferase 1 and 2 (NMTs, the enzymes catalyzing protein myristoylation) been developed to enable the targeting of this process.
Hematopoietic cancers such as Acute Myeloid Leukemia (AML) have been proposed as vulnerable to NMT inhibitors (NMTi) such as zelenirstat. AML is an aggressive cancer with poor clinical outcomes tied to disease relapse and resistance to therapy. Relapses are believed to be driven by leukemic stem cells (LSCs) which are highly resistant to conventional therapies and expand to re-establish the disease. Patient survival rates upon relapse are extremely low, highlighting a need for new therapies capable of both targeting LSCs, and overcoming common mechanisms of resistance. The primary goal of this study was to conduct a pre-clinical evaluation of zelenirstat as a novel therapeutic for AML, providing proof of concept and the necessary investigation to initiate clinical trials. Zelenirstat inhibits signaling through Src-family kinases necessary for oncogenic signaling through clinically relevant FLT3 and KIT receptors, in addition to inhibiting oxidative phosphorylation and AMPK activity necessary for LSC function. AML cell stress and apoptosis was induced by zelenirstat, and cell killing observed in vitro and in vivo, with an apparently selectivity for LSC-enriched populations of the OCI-AML-22 cell model. Zelenirstat also inhibited glycolysis in AML cells, presenting a potent multi-pathway inhibitor capable of targeting LSCs with high potential for synergy with venetoclax. Analysis of AML patient data revealed NMT2 expression functions as a prognostic marker in AML patients experiencing poor outcomes under current standards of care were associated with both low NMT2 expression and high MISS-54 score, predictive of positive response to zelenirstat.
Following the broad metabolic impacts of zelenirstat in AML, we further explored the impacts upon mitochondria in HeLa cells. We confirmed inhibition of oxidative phosphorylation and glycolysis in this model, and demonstrated induction of cellular calcium leakage and suppression of glutathione metabolism as a consequence of zelenirstat treatment. Additionally, we provide the first evidence of NMTi disrupting mitochondrial structure, with loss of mitochondrial cristae organization and density upon zelenirstat treatment. Additional validation of the impacts of zelenirstat on AMPK show near-complete loss of activation, compromising the ability of the cell to respond to energetic stress.
Next we attempted to contextualize the sensitivity of cancer cells to zelenirstat through pan-cancer analysis of NMT levels, response to zelenirstat, and differential analysis of multi-omics in the context of zelenirstat treatment or genetic NMT ablation. We find that genes related to oxidative phosphorylation are among the most responsive to disruption of protein myristoylation, and present myristoylation inhibition sensitivity signature MISS-54. Developed from differential genomic analysis of more than 1200 cell lines screened for sensitivity against NMTis, MISS-54 allows for prediction of tumor sensitivity to NMTi. MISS-54 is also demonstrated to be lower in cognate healthy tissues than in cancer, supporting the notion of increased sensitivity of cancer to NMTi.
Collectively, this work identifies a critical role for myristoylation in oxidative phosphorylation and mitochondria as a significant, pan-cancer target of NMTi. This represents a key mechanism by which NMTi could target both LSCs and cancer stem cells at large, helping to improve and lengthen patient remissions. The large number of pathways in which myristoylated proteins participate give zelenirstat a pleiotropic function to tackle genetically and functionally diverse cancers, smothering resistance. In AML, zelenirstat is an exciting new therapeutic option starting clinical trials with predicted benefit to patients in desperate need of improved outcomes. This study identifies key mechanisms and provides rationale necessary for clinical trials and beyond
Youth, Care and the Fragile Thread of Hope
Get PDFThis image captures a silhouetted figure reaching toward a heart-shaped balloon at twilight -- a symbol of hope, vulnerability, and change. Taken at the edge of a hill with a vibrant sunset sky above, it portrays the emotional complexity of young people navigating adversity. The image draws from my experience with Youth Empowerment and Support Services (YESS) in Edmonton, Alberta, where I sought to understand the role of YESS in homelessness, trauma, and systemic barriers through community-based engagement. Much like the figure in the photo, these youth are often in an "in-between" phase no longer where they were, not yet where they wish to be, yet still reaching for connection and possibility. The image reflects themes of isolation, aspiration, and resilience central to public health work on trauma-informed youth services and the fragile dichotomy of longing and letting go
Tectonic studies of the lithosphere of Laurentia using magnetotelluric data and the implications for diamond resources
Get PDFCratons are the oldest continental landmasses, have a thick lithosphere, preserve important records on the formation and evolution of the continents, and are key repositories of economic minerals and volatiles. The magnetotelluric (MT) method is a useful tool in studying cratons as it can readily image to the base of the lithosphere. Further, the resistivity measurements are sensitive to a number of conductive phases in the lithosphere that are related to tectonic processes and lithosphere modification. In this thesis, the MT method is used to investigate three regions of the Laurentian craton, a composite craton that makes up much of Canada and the continental United States.
The first study area was the Southern Oklahoma Aulacogen (SOA). Long-period MT data were collected across the SOA, and the resulting resistivity model revealed low resistivity anomalies coincident with the SOA in the crust and upper lithospheric mantle which is underlain by a wider conductive lower lithosphere beneath the region. The crustal and upper lithospheric mantle conductor was interpreted to reflect a combination of olivine grain size reduction, graphite, sulfides, and the enrichment of the water content of nominally anhydrous mantle minerals related to metasomatic processes that occurred when the SOA underwent rifting in the Cambrian. This modification likely caused rheological weakening of the lithosphere, which allowed the SOA to be deformed during the later Pennsylvanian-Permian Ancestral Rocky Mountain (ARM) orogeny. This metasomatic weakening model may provide a plausible mechanism for the isolated and dispersed nature of the enigmatic ARM uplifts. The conductive lower lithosphere was interpreted to reflect a water-rich lithosphere that may be related to accretion of the head of the plume that drove rifting in the Cambrian. The top of this lower lithosphere conductor is coincident with a seismic mid-lithosphere discontinuity and was interpreted to reflect a layer of phlogopite formed along a paleo-lithosphere-asthenosphere boundary during accretion of the plume head.
The next study area was the Trans-Hudson Orogen (THO), located in Saskatchewan, Canada. A grid of long-period MT data were collected over the THO and enigmatic Sask craton to produce the first 3-D resistivity model of the entire lithosphere in the region. The resistivity model showed that a major conductive anomaly was located in the lithospheric mantle beneath the northern Sask craton. This anomaly was interpreted to reflect sulfides formed along the interface between a subducting slab that underwent flat slab subduction and the overriding lithosphere of the northern Sask craton. This implies that much of the lithosphere of the northern Sask craton was added during the THO and that a previously unrecognized episode of west-dipping subduction occurred. A number of conduit-like conductors emanate from this large lithospheric mantle conductor and ascend to the surface, some beneath known mineralization districts. These conductors were interpreted to reflect sulfides that may have formed along pathways for mineralizing fluids. These conductors may then indicate regions of prospective mineralization. Interestingly, kimberlites in the region all erupt along the margin of the main conductor beneath the north Sask craton. This may indicate that kimberlites exploited the terrane boundaries and major trans-lithospheric structures formed during accretion of the flat slab.
The final study area was in northern Alberta over the Birch Mountain and Buffalo Head kimberlite fields. MT stations were collected around the kimberlite fields to provide increased resolution of the provincial resistivity model. The Birch Mountain kimberlite field is underlain by a large conductive anomaly in the lower lithosphere, while the Buffalo Head Hills kimberlite field is among the most resistive lithosphere in the region. Common conductive phases in the lithosphere, including phlogopite, amphibole, water contents, and graphite, cannot explain the low resistivity or slow seismic velocity anomaly observed beneath the Birch Mountains. The nature of this anomaly is currently unknown, but elevated temperature observed in xenoliths from Birch Mountain kimberlites alongside the anomaly connecting with the underlying asthenosphere raises the possibility that it reflects a minor amount of melt and erosion of the diamondiferous lower lithosphere. This erosion may be one of the reasons for the poor diamond contents in the Birch Mountain kimberlites. In comparison, the resistive lithosphere beneath Buffalo Head Hills may indicate an intact diamondiferous lithosphere root, which could explain the good diamond contents in these kimberlites.
