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Synthesis of a Carbazole Nucleoside for Incorporation into Oligonucleotides to Study Z-DNA structures & Study of Phosphorothioate Structures in Human DNA
Get PDFDNA is known to exist in different forms, such as A-, B-, and Z-DNA duplex, with the
B-form being predominant under biological conditions. While the structure of Z-DNA has been
known for decades, its role is still poorly understood. This project aims to study Z-DNA
structures under biological conditions. Toward this goal a modified nucleoside, 3-
cyanovinylcarbazole nucleoside K (CVNK 1), will be synthesized and incorporated into
oligonucleotides. CVNK 1 is capable of crosslinking with the opposite strand of DNA following
photoirradiation, which will allow DNA to be locked into the B- or Z-form. In previous work, 3-
cyanovinylcarbazole 3 was successfully synthesized in both the cis- and trans-isomers. In this
thesis, various glycosylation methods were explored in order to synthesize CVNK 1. Tin (IV)
chloride was found to be an effective activator in the glycosylation of ribose tetraacetate with
carbazole and 3-cyanovinylcarbazole. While the deoxygenation of the carbazole ribonucleoside
under the Barton-McCombie condition gave the corresponding N-carbazole 2′-deoxyriboside, the
same condition failed to give the corresponding 3-cyanovinylcarbazole 2′-deoxyriboside, likely
due to the reduction of the vinyl group.
Phosphorothioates (PTs) are a modification to the phosphodiester backbone of nucleic
acids where a non-bridging oxygen in replaced with a sulfur. PTs are commonly found in
bacteria, such as Streptomyces lividans, as part of a restriction-modification system encoded by
the DNA degradation (dnd) gene cluster. Comparison of the human reference genome with the
dnd gene cluster using the BLAT tool revealed a sequence homology of over 90%. In order to
explore the possibility of PT modifications in human DNA, PT dinucleotides standards were
synthesized using the modified H-phosphonate chemistry. These standards were compared to
digested human genomic DNA using mass spectrometry. Preliminary analysis of the mass
spectrometric data revealed that a CP(S)C dinucleotide may be present in the human genome
Monte Carlo Validation of Dose, Quality Assurance Protocols and Shielding in Radiation Therapy
Get PDFThis work is a two-fold Monte Carlo study of radiation transport through medical linear accelerator treatment heads and the shielded rooms that house them. Firstly, a Monte Carlo model of the Elekta Agility treatment head in use at the Walker Family Cancer Center was created and validated using experimental data for three different treatment energies (6 MV, 10 MV and 18 MV). This model was used for an in-depth study of incident beam deviations and their impact on dose collected at patient level. Standard quality assurance tests of beam flatness, profile constancy, and TPR20/10 were used to characterize how these deviations presented themselves in the treatment beam. Deviations in the beam energy, position, and direction showed, for the first time, a direct link of the sensitivity of current quality assurance tests to beam parameters. A novel quality assurance metric, known as the Wasserstein distance, was implemented to determine if the two deviations were distinguishable at patient level.
The second study focused on neutron transport throughout the patient treatment room and surrounding areas. While the treatment beam used at the Walker Family Cancer Center is a photon beam, photo-neutrons are an unwanted secondary particle created in the treatment head and must be shielded for in accordance with the Canadian Nuclear Safety Commission. The Walker Family Cancer Center uses a new style of doorless bunker, the design of which was commissioned on theoretical predictions - based solely on empirical data - alone. We use our validated Monte Carlo study of the treatment head to simulate the photo-neutron production at the highest treatment energy. This information was then used in a secondary Monte Carlo simulation of the treatment room to predict the yearly dose at key radiation survey points around the room. On top of these specific points, the dose was also determined for various other locations inside of the treatment room, allowing for a more in-depth study of the theoretical equations that govern radiation transport through the room
Investigating the Importance of Physiological Cell Culture Conditions in Modeling Cancer Metabolism and Metabolic Reprogramming
Get PDFStandard cell culture conditions do not mimic the physiological environment of cancer cells. Traditional culture media contain metabolites at concentrations that far exceed conditions measured in vivo, and oxygen is often unregulated, exposing cells to atmospheric oxygen concentrations (~18%), rather than the 0-3% O2 measured in solid tumours in vivo. Recently, plasma-like media have been developed to address these limitations, aiming to improve culture conditions and maintain biologically relevant cancer phenotypes in vitro. However, these conditions remain unrepresentative of interstitial fluid in solid tumours. The goal of this thesis was to investigate how physiological culture conditions affect cancer cell behaviours, specifically cell metabolism and adaptive metabolic responses. In the first data chapter of this thesis, I explored nutrient exhaustion in physiological plasma-like medium (Plasmax) at 18% and 5% O2, and the adaptive mechanisms by which cancer cells can maintain survival under metabolic stress conditions. Here, I found that glucose and amino acid depletion from Plasmax over 48 hours is associated with several adaptive mechanisms consistent with metabolic reprogramming in vivo. Given these responses, I hypothesized that a media formulation designed using metabolite concentrations from tumour interstitial fluid may modulate metabolic phenotypes in a similar manner, providing a more physiologically relevant culture model for cancerous cells. Data chapter 2 addresses this hypothesis, whereby I formulated a novel cell culture medium using quantitative metabolite data from murine pancreatic ductal adenocarcinoma (PDAC) tumour interstitial fluid, named Tumour Microenvironment Medium (TMEM), and investigated the effects of TMEM and 1.5% O2 on an adapted murine PDAC cell line (KPCY). Importantly, I found that tumour-like conditions elicited a substantial transcriptional and functional response in cultured cells, modulating cell proliferation, migration, glucose utilization, and mitochondrial bioenergetics in ways relevant to in vivo cancer biology. Overall, the results of this thesis highlight the responsiveness of cultured cells to their environment, and the importance of representative culture conditions in the acquisition of biologically accurate experimental data
Self-reported physical activity and sleep quality is associated with working memory function in middle-aged and older adults during the COVID-19 pandemic
Get PDFWhile previous work has consistently shown a positive relationship between cognitive
performance and various lifestyle factors (including sleep quality and physical activity) in younger
adults, evidence for this relationship among middle-aged and older adults has been mixed. The
current study aimed to further test the relationship among self-reported measures of physical
activity, sleep quality, and memory performance in middle-aged and older adults (n = 302; age
range = 45 - 75 years old), and to test whether this relationship holds up during a period of
unprecedented stress and reduced physical activity caused by the COVID-19 pandemic. Our results
showed that self-reported physical activity was associated with better subjective sleep quality and
better working memory performance, and better subjective sleep quality was associated with better
working memory and self-perceptions of everyday memory abilities. Additionally, we found that
the effects of physical activity on working memory were partially mediated by sleep quality,
suggesting that physical activity may contribute to improved cognitive performance via improved
sleep. Participants reported that the pandemic was affecting their sleep quality and mental health,
and pandemic-related stress and sleep disturbances were negatively associated with physical
activity, memory, and mental health. While these effects were small and only correlational in
nature, they lend further support to the notion that sleep quality and physical activity are beneficial
to memory later in life, even (or maybe especially) during a global pandemic that negatively
affected people’s ability to sleep and exerciseTiago Guardia was supported by an Ontario Trillium Scholarship
M. Karl Healey by The National Science Foundation under [Grant 1848972]
Karen L. Campbell by the Natural Sciences and Engineering Research Council of Canada [Grant RGPIN-2017-03804
Global Trends in Generative Artificial Intelligence Adoption
Get PDFThe presentation was presented at the 2024 Digital Pedagogies InstituteThis presentation reports on the research study, which was an empirical investigation of the extent of General Artificial Intelligence (GenAI) usage, particularly technologies like ChatGPT, among postsecondary education (PSE) students at universities and colleges across the globe. Preliminary findings indicate a higher-than-expected adoption rate, challenging prevailing assumptions in the field and differences based on gender. Other connections (across levels of study and English as a primary language) are also presented, and their implications are discussed
Niagara Falls Local Council of Women fonds, 1950-1975
Get PDFThe Niagara Falls Local Council of Women was organized around 1919.The fonds contains three scrapbooks of the Niagara Falls Local Council of Women. The scrapbooks contain news clippings, programs and photographs. There is also a list of donations dated April 13, 1975 that includes a book, pamphlets, articles and newsletters, briefs, and cash books and minutes of the Niagara Falls Local Council of Women. The location of these materials is not known
Provincial Sport Policy in Ontario: Trends, Issues, and Ways Forward
Get PDFIn Canada, the amateur sport sector operates under a multi-level governance system in which authority is shared between the federal and provincial/territorial governments. Sport participation, however, is facilitated by various organizations at the community-level. The Canadian Sport Policy provides direction for ensuring sport's positive impact on individuals and communities. Yet through two iterations of the national policy, goals for increasing participation have not been met. Despite investments and political will, increasing sport participation remains an elusive and poorly understood policy objective. Regional differences and local implementation challenges persist and are shaped by divergent approaches to governing sport across the provinces and territories. Therefore, it is crucial to examine provincial/territorial approaches to sport policy to understand their strategies and outcomes.
Our analysis revealed four overarching findings across the workshop and interview data. Findings consistently underscored challenging experiences with sport policy that hindered their organization’s ability to carry out their mandates and reach their goals and objectives
Letter to Joseph King from Peter West, February 22, 1813
Get PDFA letter addressed to the Honorable Joseph King at Garth from Peter West, February 22, 1813. West is offering to serve in the War of 1812. The following excerpt has been edited for clarity: “Sir you are not unacquainted with my repeated offers to serve my country any way I can do the most good. I am not afraid to take a few of the water of Quebec and the towers but it would be my choice to guard some fort. I believe I can raise a company in a few days. I have been in two wars before this from a soldier to an officer. It is not for want of a liver that I would leave my family but my country calls…I had as [?] fight the enemy abroad as at home…I leave the matter with your honor in whom my country puts confidence. The man that hands this to you is Captain Young my acquaintance and a good man…
Niagara Region 10-year published review, 1980
Get PDFThe Regional Municipality of Niagara was created on January 1, 1970 when Lincoln County and Welland County were amalgamated. With this change 26 cities, towns, townships and villages became part of the Regional Municipality of Niagara. This change was part of a larger political movement from 1965 to 1975 that resulted in the reorganization of many county governments around the Great Lakes.A newspaper-style 10-year published review of the Niagara Region titled Niagara The Regional Municipality of Niagara Ten Years of Service for You. The review was published in October 1980 and contains articles on early municipal history and formation of regional government; municipal government basic relationships; community services; basic organization of regional Niagara; the Regional Planning’s role in community development; amalgamation of essential services for tax savings; a plan to burn garbage to produce electricity; Public Works; Social Services Department; Senior Citizens Department; Niagara Regional Health Unit; Niagara Children’s Services Committee; Family and Children’s Services; Niagara Regional Police Force; Tourism; and the Niagara Peninsula Conservation Authority
The Power of Connection: Enhancing Executive Functioning in Preschoolers at Risk of Attention Difficulties through Mother-Child Synchrony
Get PDFThe intricate dance of mother-child interaction plays a pivotal role in shaping a child's cognitive landscape, particularly in the realm of executive functioning. This study delves into the captivating world of mother-child synchrony, exploring its potential to enhance executive functioning in preschoolers at risk of attention difficulties through the universal language of music. In a novel approach, we coordinated a harmony between scientific rigor and the melodious world of child-directed music. 50 preschoolers, each carrying the subtle weight of potential attention challenges, were randomly assigned to either a music intervention group or a colouring control group. The music group embarked on a 15-minute journey of synchronized singing and movement with their mothers, while the control group engaged in independent colouring activities. Our findings struck a resonant chord: the music intervention group demonstrated significantly improved executive functioning scores compared to the control group. The Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P) revealed a symphony of positive changes across various executive function domains. Moreover, the Dyadic Mutuality Code (DMC) painted a picture of enhanced mother-child synchrony in the music group, suggesting a harmonious interplay between musical engagement and relational attunement. Intriguingly, the Minnesota Executive Function Scale (MEFS) app provided an objective counterpoint, offering insights into immediate cognitive performance changes. This multi-faceted approach allowed us to compose a nuanced understanding of how music-based interventions might orchestrate improvements in both perceived and actual executive functioning. However, our study is not without its complex harmonies. We critically examine whether the observed changes reflect genuine improvements in children's executive functioning or shifts in parental perceptions, acknowledging the limitations of short-term interventions in
altering long-standing behavioural patterns. This research opens new avenues for understanding the intricate relationship between mother-child synchrony, music, and cognitive development. It offers a promising prelude to future investigations and interventions, potentially composing a new symphony in the support of preschoolers facing attention challenges. As we continue to unravel this cognitive melody, we inch closer to harmonizing child development with the rhythms of effective, music-based interventions