123129 research outputs found
Sort by
Identifying Strategies for Access to Cultural Belongings in Museum Collections: Developing a Professional Toolkit
Full text linkIn the field of museum collections management, establishing tools that can give process to emergent philosophies such as radical access will help collections stewards adapt to the edict of new museology that forefronts meaningful relationships between communities, collections, and museums as cultural and public institutions. This research begins with an overview of the considerations involved in radical access which outline how access to collections, particularly to cultural belongings, is essential to the decolonizing process in the museum. Following this, I explore how radical access manifests in everyday collections work through a case study at the Textile Museum of Canada, utilizing a set of scenarios to observe the workflows, policies, and potential access barriers at a community-focused institution. The research culminates in the development of a toolkit which serves as a guide for collections staff to begin identifying barriers to access and implementing access-oriented emerging practices in their own collections.M.M.St
Examining the role of Accredited Social Health Activists (ASHAs) in improving uptake of essential primary health care services for mothers and children in India.
Full text linkHealth inequalities continue to impede access to essential primary healthcare for mothers and children in low- and middle-income countries (LMICs). Community Health Workers (CHWs), as culturally adept community members, are important in enhancing primary healthcare delivery. However, the effectiveness of CHW programs and the impact of socio-economic attributes of health-seekers on health-seeking behaviors remain underexplored. This dissertation aims to address these gaps, focusing on India, where Accredited Social Health Activists (ASHAs) contribute to improving maternal and child health outcomes. By examining the role of ASHAs and the impact of financial incentives, this research aims to provide insights that can optimize CHW programs and address socio-economic barriers to healthcare access. This dissertation comprises three interconnected studies that examine the role of ASHAs in improving maternal and child health outcomes in India. Utilizing data from the Indian National Family Health Survey (2019-2021), the studies employ robust analytical methods, including multivariable logistic regression, Propensity Score Matching, Generalized Estimating Equations, and inverse probability weighting regression adjustment. The first study investigated the socio-demographic determinants associated with ASHA service utilization and predictors of institution-based births. The second study assessed the association between use of ASHA services on the receipt of benefits from the Janani Suraksha Yojana (JSY). The third study explores the effect of additional state-level financial incentives for ASHAs on maternal service utilization, including institution-based deliveries, complete antenatal care, and full immunization for children aged 12-24 months.
Findings show the use of ASHA services improve maternal and child health outcomes, increasing the likelihood of institution-based deliveries by 1.6 times (95% CI: 1.51-1.65) and receipt of the JSY benefit by 1.3 times (95% CI:1.3-1.4). States offering supplementary incentives to ASHAs report higher utilization of key maternal health services. However, the impact of varying incentive amounts remains inconclusive.
This research highlights the positive role of ASHAs in enhancing maternal and child healthcare access, thereby supporting Sustainable Development Goals 3 (Good Health and Well-being) and 10 (Reduced Inequalities). Further research is needed to optimize financial incentives. This research offers important insights for scaling CHW programs in India and other LMICs to improve maternal and child health outcomes globally.Ph.D
Targeting Mitochondrial Guanine Quadruplexes to Shift Heteroplasmy Therapeutically and Understanding the Downstream Mechanism of Berberine-Induced Heteroplasmy Shift
Full text linkPathogenic mitochondrial DNA (mtDNA) variants are responsible for diverse pathologies and can result in childhood lethality. To date, no effective therapies have been identified (Y. S. Ng & Turnbull, 2016). These mtDNA variants are typically heteroplasmic, where both the wild-type and pathogenic variant coexist within the same cell, which makes shifting heteroplasmy a potential therapeutic strategy as heteroplasmy load directly correlates with disease penetrance and severity (C. V. Pereira & Moraes, 2017). The T>C variant at m.10191 is associated with Leigh syndrome, a pediatric disorder present in around 1:40,000 individuals. We previously found that this change resulted in an increased potential to form a local guanine quadruplex (G4) (Naeem et al., 2019). G4s are non-canonical DNA secondary structures formed by short poly-guanine tracks which can stall polymerase activity (Hurley et al., 2000). Therefore, the G4 structure can be utilized to decrease transcription and replication of the pathogenic C variant, hence increasing the proportion of the wild-type T variant inside the cell and shifting heteroplasmy. The first part of my PhD aimed to identify small molecule compounds with high specificity towards m.10191C which are able to shift heteroplasmy therapeutically. Through a collaboration, I screened over 20,000 small molecule compounds for those with G4 binding propensities based upon interaction with the m.10191C (Felsenstein et al., 2016a); I performed downstream assays to characterize the effect of candidate compounds on patient fibroblasts. The second part of my project aimed to understand the molecular mechanism behind heteroplasmy shift. As our lab has previously identified G4 binding agents (G4BA) capable of shifting heteroplasmy, I wanted to better understand its mechanism to help future drug discovery efforts and to uncover potential synergistic treatment options. A better understanding of small molecule based heteroplasmy shifting may prove worthwhile for not just metabolic disorders, as mitochondrial function has been implicated in more common disorders such as autism spectrum disorder (ASD) (Andreazza & Nierenberg, 2018; Pei & Wallace, 2018). Some recent research has demonstrated a potential link between mtDNA heteroplasmy and manifestation of ASD (Yiqin Wang et al., 2016), the third chapter of my thesis aims to further explore this in the MSSNG patient cohort.
Taken together, my thesis provides a strategy towards mitochondrial heteroplasmy shifting, uncovers the role of fission and autophagy in mitochondrial heteroplasmy, and explores the role of heteroplasmy in ASD patients.Ph.D
Self-supervised Learning for Segmentation in Two-Photon Fluorescence Microscopy
Full text linkDeveloping deep learning models for microscopy analysis is challenging due to the lack of labeled training data. Self-supervised learning (SSL), which leverages unlabeled data to improve downstream performance, may be beneficial to streamline the annotation of two-photon fluorescence microscopy (TPFM) data. We developed a pipeline using SSL to assess whether unlabeled data can improve the segmentation accuracy of neurons and vessels in TPFM. We devised four pretext tasks, including shuffling, rotation, axis rotation, and reconstruction, to train models without supervision using the U-Net architecture. We introduced the neighborhood density metric to assess model performance that is more sensitive to downstream analyses than typical overlap metrics. We examined our pipeline by finetuning pretrained models on noisy data and by removing crosstalk. We applied our framework to multiple datasets, including out-of-distribution data, demonstrating that SSL-trained models outperform fully-supervised models on segmentation tasks and are more robust to noisy distributions.M.Sc
Investigating Mechanisms Dictating Tissue-Specific Alternative Splicing Patterns in C. elegans
Full text linkAlternative splicing contributes to transcriptomic and proteomic diversity. However, the complete repertoire of regulatory features and the dynamics of sequence evolution would benefit from more detailed study. This thesis explores mechanisms that mediate tissue-specific alternative splicing in the model organism C. elegans. In the first part of my thesis, mRNA profiling datasets from three tissue types (muscle, neuron, intestine) were mined to identify tissue-specific splicing patterns in vivo. Multiple sequence alignments of alternative exons and flanking sequences revealed a notable conservation of tissue-regulated exons and their adjacent intronic regions, indicating robust evolutionary constraints. Two-colour splicing reporters were generated to visualize tissue-biased alternative splicing patterns at a single-cell resolution. Mutagenesis experiments pinpointed essential conserved cis-regulatory elements that influence splicing patterns in specific tissue contexts.
The subsequent section of the thesis delves into the role of UNC-75, a conserved CELF RNA binding protein and splicing regulator, particularly focusing on its impact on zoo-1 exon 9 splicing, which undergoes tissue-biased splicing in neurons versus muscle cells. Reverse genetics experiments underscored the critical role of UNC-75 in suppressing neuronal exon 9, with sequence alignments and mutagenesis studies identifying four conserved intronic elements that affect splicing. I further revealed that the unc-75 gene produces two isoforms with distinct functions, influencing exon 9 splicing through different mechanisms. Moreover, UNC-75 consensus sequences at the 5′ splice site of the downstream intron were found to enhance exon repression, suggesting the evolution of a flexible 5′ splice site in a tissue-biased exon that is responsive to CELF proteins.
These significant discoveries shed light on the evolutionary constraints imposed by tissue-regulated alternative splicing patterns, and regulation of neuronal alternative splicing by a conserved family of RNA-binding proteins. Together, my studies lay a solid groundwork for future investigations into the molecular mechanisms and functional implications of these regulatory elements in neurodevelopment and associated disorders.Ph.D
Supportive Care Needs of Patients with Breast Cancer Who Self-Identify as Black: An Integrative Review
Full text linkBlack-identifying patients face many barriers to the receipt of equitable breast cancer care; however, little is currently known about the unique needs of this patient population, particularly in Canada. To address this gap, we identified and thematically grouped constructs from the published literature reporting on the needs of Black-identifying patients with breast cancer and compared these findings to a list generated through a virtual nominal consensus group (NG) attended by Canadian patients with breast cancer who self-identified as Black (n = 3). A scoping review was undertaken, and relevant citations published from database inception until January 2025 were identified from MEDLINE, Embase, and CINAHL. The literature review yielded 34 articles from the United States and identified 15 constructs consistent with the NG, which spanned the cancer continuum from screening to survivorship. The NG identified four additional constructs that were not found in the literature: advocacy and outreach, communication and health literacy, comorbidities and personalized care, and end-of-life care. The final set of constructs was then validated and prioritized by an expert panel consisting of patients with lived experience and relevant community partner organizations (n = 9) to drive future research, advocacy, and policy work. Patient navigation was identified as the top need, with financial support, access to culturally tailored information and resources, culturally relevant care, racialized data for treatment decision-making, and emotional support identified as high-priority needs
Closed-loop geothermal system is a potential source of low-carbon renewable energy
Full text linkDecarbonizing the energy sector requires renewable sources that are economic and responsive to demand. Intermittency and seasonal variability, therefore, limit the potential of wind and solar. Geothermal energy can potentially provide low-carbon renewable power that is dispatchable and responsive to demand. However, conventional geothermal methods require high permeability in high-temperature subsurface zones, which restricts their application. Here, we assess the global potential of the closed-loop geothermal system (CLGS), an emerging technology that does not require high permeability. Using thermodynamic, process, and technoeconomic modeling, we analyze the potential for CLGS in 12,000 candidate regions to estimate global viability. With the base case of water as the working fluid in a Rankine cycle, we estimate the global potential to be 9 TWe, equivalent to 70% of current electricity production. We assess using phase change working fluids to broaden applicability and improve efficiency, and evaluate the remaining technological barriers to closed-loop geothermal energy production
Can a photon spend a negative amount of time in an atom cloud?
Full text linkWhen a pulse of light traverses a material, it incurs a time delay referred to as the group delay. Should the group delay experienced by photons be attributed to the time they spend as atomic excitations? However reasonable this connection may seem, it appears problematic when the frequency of the light is close to the atomic resonance, as the group delay becomes negative in this regime. To address this question, I used the cross-Kerr effect to probe the degree of atomic excitation caused by a resonant transmitted photon by measuring the phase shift on a separate beam that is weak and off-resonant. These results, over a range of pulse durations and optical depths, are consistent with the recent theoretical prediction that the mean atomic excitation time caused by a transmitted photon (as measured via the time integral of the observed phase shift) equals the group delay experienced by the light. Specifically, I measured mean atomic excitation times ranging from for the most narrowband pulse to for the most broadband pulse. I report these times normalized to the non-post-selected excitation time , which is equal to the scattering (absorption) probability multiplied by the atomic lifetime . These results suggest that negative values taken by times such as the group delay have more physical significance than has generally been appreciated.Ph.D
Physiological Responses to Heat Stress in Groundskeepers: An Observational Field Study
Full text linkThe extent to which groundskeepers experience thermal and cardiovascular strain, dehydration, and accompanying declines in kidney function during work in hot-humid conditions is unknown. Demographics, thermal and cardiovascular strain, hydration, and kidney function were assessed in 20 groundskeepers (18 men; mean±SD, age=37.9±8.4 y, body mass index=31.5±7.5 kg·m-2) during work on 2 summer days. Before (AM) and after (PM) the work shift, resting blood pressure (BP) and heart rate (HR) were measured and urine and blood samples were collected. During the work shift, fluid intake was recorded, gastrointestinal temperature (TGI) was recorded, and HR was recorded continuously. In 45% of participants, AM BP >130/80 mm Hg on Day 1 and Day 2. Peak HR and TGI achieved across both days were 143±15 b·min-1 and 37.7±0.3 °C, respectively and average peak wet bulb globe temperature was 39.1±3.5 °C. On both days, urine specific gravity (USG=1.021±01) and urine color (UCOL=6±1) did not change across the work shift (all P>0.28), but most subjects began with concentrated urine (62.5% USG≥1.020 and 95% UCOL≥4). Total fluid intake=2.3±1.6 L during work and consisted of 70% water, 25% sugar-sweetened beverages, 5% other. For 6 subjects, the average estimated glomerular filtration rate (eGFR) at AM was ≤60 mL·min-1·1.73 m-2. Five subjects had SCr increases from AM to PM ≥0.3 mg·dL-1, signifying an acute kidney injury (AKI). While hyperthermia was not prevalent, subjects began and ended the workday with concentrated urine. Hypertension, obesity, and low water intake may have contributed to the overall low kidney function and AKIs observed.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
Synergistic Tri-Metallic Ca/Mg/Sr Crab Shell Catalyst for Transesterification: Probing Active Site Basicity
Full text linkThis study investigates the catalytic potential of crab body powder (CBP) derived from waste crab bodies for the conversion of triglycerides (TG) to fatty acid methyl esters (FAME). CBP is subjected to temperature treatments and characterized using various techniques. Its catalytic activity is compared to that of commercial materials such as CaO and MgO. The results demonstrate that the tri-metallic Ca/Mg/Sr catalyst derived from CBP heated at 900 °C (CBP900) exhibits the highest TG to FAME conversion rate of 96.8%. Interestingly, CaCO3 heated to 900 °C shows comparable activity to CBP900. The enhanced catalytic performance is attributed to the presence of oxygenated surface functional groups, which enhance the basicity of the catalyst, as well as improved crystallinity, facilitated mass transport, and well-defined active sites within the CBP structure. These findings highlight the potential of waste-derived tri-metallic Ca/Mg/Sr crab body powder as a sustainable and efficient catalyst for biodiesel production. Further investigations are warranted to optimize reaction conditions and explore the underlying mechanisms, thereby opening avenues for utilizing waste biomass in renewable energy applications.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author