Lakehead University Knowledge Commons

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Preparation, radiolabeling, and conjugation of an Aurora Kinase B Inhibitor to 198Au-activated nanoparticles for cancer imaging and therapy
(2026) Lorentson, Jessica; Campbell, Michael; Hou, Jinqiang; Gottardo, Christine
When targeting cancer, it is often necessary to attack the disease on multiple fronts. This work proposes the development of multifunctional nanoparticles (NPs) to deliver both a therapeutic radiation dose and a cancer-targeting (Aurora Kinase Inhibitor) chemotherapeutic directly to the tumour. Additionally, the incorporation of a diagnostic agent to the NP allows for a theranostic approach. The progression of the therapeutic agent can be subsequently monitored via the NPs as delivery vehicles, with the diagnostic agent allowing assessment of tumour dosage. The presence of leaky vasculature in many tumours facilitates the infiltration and accumulation of NPs in these tissues. The preparation of polyethylene-glycol (PEG)-stabilized gold NPs (AuNPs) has been achieved and enables the targeted delivery of both therapeutic and diagnostic agents directly to the tumour. In a CCK-8 cytotoxicity assay, the AuNPs were found to have an IC50 of 0.06  0.04 (n=10) mg/mL on the SiHa cell line, 0.08  0.07 (n=4) mg/mL on the CaSki cell line, and 0.041  0.002 (n=2) mg/mL on the C33A cell line. The subsequent use of cyclotron-based neutron activation to convert the AuNP into gold-198 NP (198AuNP) can be used to provide a therapeutic radiation dose. This conversion of gold into 198Au has been demonstrated and can facilitate the delivery of beta radiation directly to the tumour. The IC₅₀ of the ¹⁹⁸AuNPs decreased with increasing radioactivity, indicating an increase in cytotoxicity. At lower activity levels (111 and 278 Bq/mL), only a minor increase in toxicity was observed; however, further increases in activity (1,145 and 2,290 Bq/mL) resulted in a continued decrease in IC50, indicating enhanced cytotoxicity. The AuNP has been labelled with an aurora kinase inhibitor (AKI) as a chemotherapeutic and a cancer-targeting moiety. The Aurora Kinase B inhibitor of interest was found to have an IC50 of (1.0  1.2) x 10-3 (n=3) mg/mL on the SiHa cell line, (6.3  1.8) x 10-5 (n=3) mg/mL on the CaSki cell line, and (3.5  2.4) x 10-3 (n=3) mg/mL on the C33A cell line. Conjugating this inhibitor enhances both specific cancer cell targeting in addition to the enhanced permeability and retention (EPR) effect that allows for the AuNPs to enter the tumour tissue, and the killing capacity of the 198AuNP. The PEG chain used for the peptide linkage that connects the inhibitor to the AuNP has been synthesized, as well as the AuNP-AKI conjugate. The IC50 for the AuNP-AKI conjugate was determined to be 0.0298  0.0008 (n=2) mg/mL with a 30:1 ratio of PEG:PEG-AKI on SiHa. This work uniquely employs the use of a medical cyclotron for the simultaneous preparation of [18F]-fluoride for PET labelling and the neutron activation of the prepared AuNPs via the 197Au(n,γ)198Au reaction. A model system for the PET-radiolabelling of the AuNPs has been investigated and a method has been proposed to achieve 18F-labelling.
Exploring climate emotions and coping strategies of Canadian youth in a climate-focused program
(2026) Tait, Maren; Field, Ellen; Galway, Lindsay
Climate change education holds particular significance amid today’s social and ecological realities. Youth specifically are feeling the pressure of our changing climate, manifesting in feelings of anxiety and hopelessness. A climate education which recognizes these complex emotions and provides opportunities for youth to cope with these emotions through action is key. This research explores the role of an interdisciplinary, hope-focused environmental education program in shaping the climate emotions and coping strategies of its students. In this mixed methods case study, grade ten and grade twelve students from Claremont Secondary School’s Institute for Global Solutions participated in surveys and a focus group to gain insights to the relationship between the programming and their climate emotions and coping. The study found that youth in the IGS program are experiencing a breadth of emotions in relation to climate change, and use a variety of coping strategies. It was also identified that programming such as IGS can provide students with a positive orientation to both personal and collective climate action. This demonstrates the importance of educational models which support and acknowledge the emotional dimensions of teaching climate change, and fostering student agency. This research holds implications for educational practice, curriculum development, program development, and student well-being.
Moment stability of strongly nonlinear structural systems under random excitations
(2026) Ghaedi, Maral; Deng, Jian; Wiebe, Richard; Siddiqui, Sultan; Gong, Yanglin
Many structures in civil engineering are subjected to dynamic loadings. Examples include wind-induced vibrations of cables and tall buildings, wave loading on offshore structures, and seismic excitations acting on civil infrastructure. These dynamic excitations can often be described satisfactorily in probabilistic terms. Current research trends in structural dynamics are evolving from deterministic to stochastic analysis, from linear to nonlinear systems, from elastic to viscoelastic behavior, and from external excitation alone to incorporating parametric excitation. This thesis investigates the stochastic stability of strongly nonlinear structural systems subjected to random parametric excitations, with stochastic stability referring to the long-term probabilistic growth or decay of the system response. The principal stability measure employed in this study is the Moment Lyapunov Exponent (MLE), which characterizes the exponential growth or decay rate of the statistical moments of the system response. Knowledge of the MLE gives the almost-sure asymptotic stability of a stochastic dynamical system through the corresponding Lyapunov exponent. The MLE is the ideal avenue and the ultimate characteristic number for the study of the dynamic stability of stochastic dynamical systems. A unified analytical and numerical methodology is developed for the evaluation of MLEs of nonlinear oscillatory systems. The analysis is primarily based on the stochastic averaging method, which allows the original nonlinear stochastic differential equations to be reduced to averaged equations governing the slow evolution of key response variables. Particular emphasis is placed on transformations based on the system Hamiltonian or total mechanical energy, through which the response of strongly nonlinear oscillators can be represented by an energy envelope. This formulation enables the derivation of analytical expressions for the drift and diffusion coefficients governing the stochastic evolution of the system energy and provides a tractable framework for moment stability analysis. In addition to the analytical formulation, a modified Monte Carlo simulation framework is developed for the numerical estimation of MLEs. In contrast with conventional algorithms that rely on the Euclidean norm of the state vector, the proposed approach employs the square root of the system energy as the generalized amplitude used in periodic normalization procedures. This energy-based formulation offers improved numerical robustness and provides a physically meaningful measure for the response of strongly nonlinear systems, allowing reliable estimation of the MLE through long-term stochastic simulations. Using the developed framework, the stochastic stability characteristics of nonlinear systems are investigated under three representative classes of stochastic excitation: Gaussian white noise, real noise modeled by the Ornstein–Uhlenbeck process, and bounded noise with phase modulation generated by a Wiener process. These excitation models represent different spectral and amplitude characteristics and physical realism commonly encountered in engineering applications. For each case, analytical expressions or approximate eigenvalue formulations for the MLE are derived, and the corresponding stability regions are evaluated. The analytical MLE predictions are compared against independent Monte Carlo estimates obtained directly from simulations of the original stochastic equations, demonstrating strong agreement between theoretical and numerical results. Furthermore, the thesis examines the influence of viscoelastic behavior, represented by a Maxwell-type model, on the stochastic stability of nonlinear systems. Viscoelastic effects introduce additional energy dissipation mechanisms and memory-dependent dynamics that may significantly alter the stability characteristics of the system. The results demonstrate that viscoelastic parameters, including relaxation amplitude and decay rate, can modify the effective damping properties of the system and thereby shift the moment stability boundaries under stochastic excitation. Overall, this thesis provides a comprehensive investigation of stochastic stability of strongly nonlinear structural systems and extends the MLE framework to include realistic stochastic excitation models and viscoelastic material behavior. The analytical formulations and numerical methodologies developed herein contribute to a deeper understanding of stochastic parametric instability in nonlinear structures and provide practical tools for assessing the probabilistic stability and reliability of engineering systems subjected to uncertain dynamic environments.
Vitality-centred education for adulthood: exploring alumni perspectives on the influences of Springhouse School on subjective adulthood
(2026) Lyngstad, Michael; Berger, Paul; Greenwood, David; Brown, Hilary
As we enter the second quarter of the 21st century, longstanding markers of adulthood in North American society such as marriage, parenthood, educational attainment, career establishment, financial independence, and home ownership are often delayed or are no longer being reached by many people in their twenties (Cannon, 2024a; Dalessandro, 2019; Hemez & Vespa, 2025; Ho et al., 2022). This is framed as a social problem (Cerullo, 2025) and a contributor to a growing mental health crisis among young people (Ladhani et al., 2019). Education is a factor in propagating these qualifiers of adulthood since schooling is said to contribute to adult identity development (A. Dewey, 2021; Sloan, 2005). However, little research has been done regarding correlates between school experiences and conceptions of adulthood (Erentaitė et al., 2018; Rich & Schachter, 2012). I spoke with seven young adult alumni of an alternative day school designed around holistic educational principles. I asked them about how they felt their school experiences influenced their views of what it means to be an adult. The findings reveal participants emphasised developing healthy relationships with themselves and community through practises such as cultivating emotional intelligence, exploring core values, and personal introspection. These qualities are not significantly represented in adulthood research. The findings point to the participants’ novel view of adulthood being influenced by a school environment grounded in relationships built on mutual trust and vulnerability.
Pathway-based multi-omics survival modeling: evaluating weak-modality contributions and robustness across cancer types
(2026) Guo, Jingfeng; Alkhateeb, Abedalrhman; Alsmadi, Malek; Ahmed, Saad B.
Multi-omics survival prediction must distinguish whether a modality enters a model from whether it improves prediction. This thesis evaluated the contributions of copy number variation (CNV) and somatic mutation (MUT) beyond clinical variables and ribonucleic acid (RNA) expression, together with the effects of pathway-based modeling and missing-modality training. Data from The Cancer Genome Atlas (TCGA) covered liver hepatocellular carcinoma (LIHC), breast invasive carcinoma (BRCA), and lower-grade glioma (LGG). Complete-case cohorts comprised 346 and 345 patients for LIHC progression-free interval (PFI) and overall survival (OS), respectively; 778 patients for each BRCA endpoint; and 503 patients for LGG OS. Gene set variation analysis (GSVA) mapped RNA expression to Hallmark pathways, each combined with seven CNV and four MUT summaries. Pathway-grouped composite minimax concave penalty (cMCP) Cox models were compared with Elastic Net using identical features and five frozen train–test splits. A gated residual model tested additional CNV/MUT information beyond a clinical-plus-RNA baseline. Paired bootstrap and permutation controls supported evaluation. Matched ensembles trained with and without modality dropout were tested under synthetic and natural missingness. Elastic Net assigned zero coefficients to at least one molecular block in every cancer–endpoint combination. Relative to same-feature Elastic Net, cMCP improved the mean concordance index (C-index) by 0.0374 for BRCA PFI and 0.0658 for BRCA OS, with both paired confidence intervals above zero. These discrimination gains did not consistently reduce absolute-risk prediction error. Conditional CNV/MUT increment was supported only for LGG OS, with a paired C-index increase of 0.0164 and a 95% confidence interval of [0.0051, 0.0300]; residual corrections were zero in all LIHC and BRCA splits. Modality dropout improved mean discrimination under synthetic missingness for LIHC and LGG but reduced it for BRCA, while natural-incompleteness results varied by endpoint. Exploratory graph ablations did not support a biological-topology advantage, and mediation analysis yielded 11 indirect statistical associations without establishing causality. The results separate penalization benefit, conditional modality information, and robustness to missing inputs. BRCA supported structured penalization, whereas LGG supported conditional weak-modality increment. These internally validated findings define endpoint-specific benefit boundaries without establishing universal model superiority or clinical utility.