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Characterizing the Thin-Film Response of Metal Phthalocyanine-Based OTFT Cannabinoid Sensors
No full textMetal phthalocyanine (MPc)-based organic thin-film transistors (OTFTs) provide a potentially cost-effective solution to cannabis consumers, producers and regulators alike to detect and speciate Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) in both solution and vapor cannabis samples. This sensing response is driven by unique coordinating interactions with MPcs and cannabinoids in solution and thin films which cause a change in the device performance upon exposure. This thesis looked to further characterize and understand these interactions to inform optimization efforts for OTFT sensors using multiple approaches, including optimization of the channel and device architecture, and molecular tuning. Through the integration of device performance data and physical characterization techniques such as atomic force microscopy (AFM), grazing incidence wide-angle X-ray scattering (GIWAXS), and Raman spectroscopy, the interactions between cannabinoids and thin films of MPcs can be characterized and correlated to improved performance. Firstly, I investigated the effect of channel dimension and film thickness on the response of chloro aluminum phthalocyanine (Cl-AlPc) based OTFT sensors, where the film roughness and thickness were found to have the greatest influence on the sensing response. Following, I performed a series of axial phenoxylations to improve the performance of R-AlPc in OTFT cannabinoid sensors. The phenoxy-AlPc compounds were found to adopt different thin film motifs from Cl-AlPc that made them more responsive to THC and/or CBD. Finally, I investigated the sensing response of the air-stable, n-type molecule (F₅PhO)₂-F₁₆-SiPc to expand our library of sensing molecules and further studied its thin film structure. In this case, substitution of the hydrogen atoms with fluorines was detrimental to its sensing response. I conclude this thesis with my additional work on other projects related to thin film characterization, physical vapor deposition, and sensor integration in our group, and detail how my expertise has shaped our lab’s knowledge on structure-property relationships of a variety of materials. As the push for the commercialization of OTFTs and OTFT-based sensors continues, establishing an understanding of the thin film and electronic properties of a range of materials remains essential
Elucidating Key Proteins in the Internalization Pathway of Small Extracellular Vesicles
No full textThe delivery of oligonucleotide therapeutics, such as silencing RNAs (siRNA), into the cytoplasm of cells is the central plight of their use as a therapeutic. Our lab demonstrated that small extracellular vesicles (sEVs) are highly efficient delivery vehicles, capable of delivering 3-30% of the RNAs they contain into cells, and, importantly, traverse the blood–brain barrier, highlighting their promise as RNA carriers and making them a potent candidate for drug delivery in neurodegenerative diseases. The stark therapeutic potential of sEVs is contrasted heavily by the fact that the mechanism surrounding sEV internalization is relatively understudied. Our electron microscopy results reveal that sEVs can enter the cell through direct fusion with the cell membrane through a series of intermediates that deliver the sEV contents directly to the cytoplasm. Typical fusion mechanisms involve recruiting fusion proteins to decrease the free energy needed for a complete fusion event. Using mass spectrometry and gene ontology term analysis, the retromer complex was identified as a significantly enriched complex surrounding our sEVs as they enter into cells. Functional knock-down of core retromer subunits abolishes fusion-dependent lipid mixing and prevents siRNA-mediated gene silencing, implicating retromer as a previously unrecognized facilitator of vesicle fusion and cargo release.. Elucidating the mechanism of sEV internalization will fill the knowledge gap of a foundational pathway in cell biology, facilitating their use as therapeutic vehicles for various drugs and increasing our understanding of their use in neurodegenerative diseases
Investigation of Enzymes for the Depolymerization of Nylon
No full textPlastic waste is ubiquitous in modern society, and a problem that every person interfaces with daily. As well as mismanagement of plastic waste posing a threat to ecosystems, the loss of plastic material to the environment or landfill represents loss of a valuable resource for new materials and other products. While current recycling practices are limited and produce lower-quality materials, biocatalysis offers a promising route to recover the value of plastic waste through generation of new materials through a more environmentally-compatible process. However, while enzymes have been identified and optimized to degrade ester-based polymers efficiently, other types of polymers pose a greater challenge.
Nylon is a useful and ubiquitous plastic, and forms a large component of ocean plastic waste in the form of discarded fishing equipment. Nylon is not easily recycled through traditional means, and is therefore an attractive target for biocatalytic degradation. In this thesis, we explore enzymes with the potential to degrade nylon, via two distinct approaches. First, we investigate Bacillus subtilis transglutaminase (bTG), which belongs to a class of enzymes known to be able to form and break aliphatic amide bonds. We discover that the activity of bTG is highly substrate-selective, and does not demonstrate the desired amide hydrolysis activity for this project. Second, we explore a known class of nylon oligomer hydrolases (NylCs) and develop assays to improve the efficiency of engineering campaigns for this and related enzymes. Our first class of substrate analogues are soluble, chromogenic substrates that can rapidly detect acyltransfer activity in NylC enzymes. Our second class of substrates are insoluble linear amide analogues which more closely resemble nylon, which are readily hydrolyzed by NylCs. We demonstrate the applicability of our assays to high-throughput screens, while exploring the substrate scope and specificity of this class of enzyme
Essays on Monetary Policy Impacts on Wage Inequality
No full textChapter 1 - This paper examines the impact of non-systematic monetary policy on wage inequality in Canada, using two key measures: the wage Gini index, which captures overall wage dispersion, and the wage ratio, which reflects disparities between high- and low-skilled workers. We obtain a non-systematic monetary policy innovations measure from an estimated standard Taylor rule. To estimate cumulative impulse response functions over the short and medium terms, we employ a smooth local projection method. Controlling for lagged oil price returns, employment rate, and fiscal policy variables, we find no significant effects on the wage Gini coefficient. On the other hand, contractionary monetary policy shocks widen the skill-based wage gap (over the two-year horizon), and expansionary monetary policy shocks narrow it (over both the one- and two-year horizons). These findings highlight the nuanced role of monetary policy in shaping wage dynamics and equitable labour market outcomes.
Chapter 2 - This paper proposes a novel approach for comparing impulse response functions across groups of countries, regions, or monetary zones. Our test statistics are Wald-type statistics with a weighting matrix that accounts for cross-sectional dependency. Instead of using HAC correction for the time dependency, we propose a non-overlapping block bootstrap procedure for the test. We assess the properties of the test by simulation. Our main findings are: (1) our proposed test has good size and power properties in finite samples; (2) the χ² approximation does not suffice to control size; and (3) the test performs well for assessing short-, medium-, and long-term impacts, both non-cumulative and cumulative impacts.
Chapter 3 - This paper examines the heterogeneous effects of non-systematic monetary policy on wage inequality across Canadian provinces. Using two measures of wage inequality - the Gini coefficient and the wage ratio between high- and low-skilled workers - and a monetary policy innovation series derived from a Taylor rule framework, our smooth local projection based analysis reveals that the effects of non-systematic monetary policy on wage inequality vary significantly across regions. In particular, regional heterogeneity is more pronounced when we consider the entire wage distribution. Moreover, these effects are asymmetric: expansionary monetary policy shocks lead to more heterogeneous regional responses in wage inequality than contractionary monetary policy shocks
Optical Properties of Nanowire-based Quantum Dots across the Near-Infrared
No full textIdeal single-photon sources are key elements to realizing quantum technologies such as quantum information processing and cryptography, using photons as the smallest unit to carry information. Solid-state two-level emitters are considered promising candidates for generating single photons with high efficiency, high single-photon purity and a high degree of indistinguishability. In particular, quantum dots, made of binary semiconductor (e.g. II-VI, III-V) materials, are artificial atoms that exhibit outstanding optical performance. A well-studied example is the InGaAs/GaAs self-assembled quantum dot system. However, these dots are typically formed through random nucleation on a sample substrate. To overcome this barrier, a position-controlled nanowire-based quantum dot system, made of InAsP/InP will be investigated in this work.
This thesis will first introduce the growth technique of embedding a disk-shaped quantum dot (InAsP) in a nanowire waveguide (InP). The optical properties of three different samples with tunable emission wavelengths are demonstrated. A tuning range from 890 nm to 1530 nm is achieved using two approaches. By varying the size and the As composition of the dot, the emission wavelengths can reach up to ∼1 µm. Furthermore, devices can be made to operate in the telecom C-band by employing a dot-in-a-rod structure. Time-resolved photoluminescence measurements and second-order auto-correlation measurements are conducted under different excitation schemes (above-band, p-shell and resonant excitation) to investigate the optical performance of these samples.
For the first time, strictly resonant excitation was applied to the nanowire quantum dot system. Photoluminescence spectra, coherent control, and auto-correlation measurements demonstrated that the pump laser’s overlap with the quantum dot emission can be effectively suppressed using a polarization-rejection optical setup. Additionally, experimental results suggest that resonant excitation significantly reduces the excitation timing jitter compared to above-band excitation.
Lastly, this work focuses on the coherence properties and two-photon indistinguishability of the photons emitted from different samples. Linewiths were measured using high-resolution photoluminescence spectroscopy with a Fabry-Pérot etalon and the two-photon indistinguishability was investigated with Hong-Ou-Mandel interferometry. Both measurements were performed under above-band and resonant excitation. The linewidths and the visibilities of the two-photon interference consistently demonstrated the impact of excitation methods on the coherence properties and aligned well with findings from other quantum dot systems
Characteristics of malaria vector populations and transmission before a randomised controlled trial assessing the efficacy of next-generation insecticide-treated nets in Côte d’Ivoire
No full textAbstract Background The World Health Organization (WHO) recommends mass distribution of insecticide-treated nets (ITNs) to prevent malaria transmission. Unfortunately, resistance to pyrethroids affects the efficacy of standard ITNs. To overcome this resistance and continue to protect the population, the WHO has recommended new types of ITNs that combine a pyrethroid insecticide with either a synergist (PBO) or a second insecticide, such as chlorfenapyr. This study examines the baseline characteristics of malaria vectors prior to the distribution of three types of insecticide-treated nets as part of a three-arm randomised controlled trial: Interceptor G2 (pyrethroid–chlorfenapyr), VEERALIN (pyrethroid–PBO), and MAGNet (pyrethroid only). Methods The study was carried out in 40 villages (grouped into 33 clusters) of Tiébissou district in central Côte d’Ivoire. To assess biting rate and biting behaviour, human landing catches were conducted hourly indoors and outdoors in six randomly selected houses in each cluster, starting at 18:00 and continuing until 08:00 the next morning. Adult mosquitoes collected were morphologically identified, and a subset of Anopheles gambiae sensu lato (s.l.) and An. funestus s.l. were speciated by quantitative PCR (qPCR). Plasmodium sporozoite infections were detected by qPCR to estimate infection rates. The entomological inoculation rate was calculated as the product of the mosquito biting rate and the sporozoite infection rate. Results Among the 10,698 mosquitoes collected, An. gambiae s.l. was the predominant species, accounting for 62.5% (n = 6683) of the catch, followed by An. funestus s.s., which accounted for 19.8% (n = 2120). Of the sub-sample of An. gambiae s.l. processed by PCR, 79.0% (n = 1291/1635) were An. coluzzii and the remaining were Anopheles gambiae s.s. Malaria vectors were highly aggressive, with an average of 14.8 bites/person/night for An. coluzzii, 2.0 b/p/n for An. gambiae s.s. and 5.4 b/p/n for An. funestus, representing an overall average of 22.2 b/p/n (95% CI 17.2–27.2 b/p/n). No significant difference was found in biting activity between indoor and outdoor environments (Z = −0.25, P = 0.803). Plasmodium sporozoite infection rate was 2.4% (95% CI 1.3–3.6%) for An. coluzzii, 1.5% (95% CI 0.3–2.6%) for An. gambiae s.s. and 2.7% (95% CI 1.2–4.3%) for An. funestus. The estimated overall entomological inoculation rate was 0.4 infected b/p/n (95% CI 0.3–0.6) and varied between 0.0 and 0.2 infective bites/person/night according to species. There was no difference observed in entomological infection rate (EIR) between capture locations (indoors versus outdoors; Z = 1.521, P = 0.128). Conclusions This study shows that An. coluzzii and An. funestus were the main malaria vectors and showed similar biting patterns both indoors and outdoors. Anopheles funestus was found in high density in a limited number of villages. Malaria transmission was high despite universal distribution of pyrethroid-ITN in the district. Graphical Abstrac
Mentors as Allies for Disabled Scientists
No full textClose to twenty-eight percent of the population in the US and Canada is living with disability, yet despite this prevalence, persons with disabilities remain mostly absent in biomedical research. While the role of mentors has been demonstrated to be effective in increasing the number of women and other groups in biomedical research, mentoring disabled scientists remains a gray area. In this short perspective, I share my personal experience as a person with a disability who was mentored by a non-disabled person, who ultimately became an all
Genetic Risk Variants Contributing to Arterial Calcification
No full textBackground: Arterial calcification, characterized by the accumulation of calcium minerals in the arterial wall, is a complex process that is influenced by genetic and molecular factors. This study explores how the 9p21.3 genetic risk variants interact with statherin (STATH), matrix GLA protein (MGP), and the bisphosphonate drug alendronate to affect arterial calcification.
Results: Microarray gene expression profiling of human aortic smooth muscle cells (SMCs) revealed that STATH expression was silenced in carriers homozygous for 9p21.3 risk variants. STATH, like MGP, is a hydroxyapatite-binding protein produced by human SMCs that blocks bone morphogenetic protein 4 (BMP4)-dependent signaling, promotes the chondrogenic/osteogenic differentiation, and prevents SMC calcification. In mice lacking MGP (MgpKO), severe arterial calcification leads to death through aortic rupture. However, the expression of human statherin in the SMCs of Mgp-null mice rescued the arterial calcification phenotype. To further investigate the role of MGP and potential treatments, alendronate was tested in mice lacking Mgp (MgpKO mice). Unexpectedly, although alendronate treatment improved dental malocclusion, it also worsened calcification and decreased the number of CD68-positive macrophages in the arterial wall. A single dose of alendronate increased the aberrant expression of the chondrogenic/osteogenic factor Runx2 in SMCs of the aorta of MgpKO mice and alendronate treatment increased calcium endo/lysosomal accumulation in the cultured macrophages.
In mouse models, warfarin rapidly induces significant arterial calcification by inhibiting the vitamin K cycle, which prevents the γ-carboxylation of MGP, rendering it inactive. Humans with MGP mutations (Keutel syndrome) show a more variable and milder calcification phenotype than do mice. This difference is partially attributed to the expression of statherin, a hydroxyapatite-binding protein absents in mice but present in human SMCs. Statherin compensates for the loss of MGP in humans and prevents severe arterial calcifications. The 9p21.3 genetic risk variants suppress statherin expression through ALU interaction, which blocks bone morphogenic protein 4 (BMP4)-dependent signaling and prevents calcification in human SMCs, contributing to the variability in arterial calcification observed in individuals with these risk alleles. The paradoxical effects of alendronate in worsening arterial calcification in MgpKO mice suggest that functional MGP is necessary to prevent soft tissue calcification. These findings highlight the complex interplay between genetics, protein expression, and pharmacological interventions, offering new targets for reducing calcification in susceptible individuals
Underexposed: Postpartum Depression, Infection, and the Hidden Gaps in Perinatal Mental Health Care in Canada
No full textEnglish
In Canada, nearly one in four individuals who have recently given birth have experienced symptoms consistent with that of postpartum depression (PPD) or an anxiety disorder, showcasing perinatal mental health as a public health concern. This thesis examines the relationship between infection during pregnancy and PPD among Canadian individuals within five years postpartum. While no significant association was found between infection and PPD onset, prior PPD emerged as a strong predictor of recurrence. The study reveals systemic gaps in Canadian perinatal mental health care, including inconsistent screening, limited interdisciplinary collaboration, and inadequate access for at-risk groups. Quantitative and qualitative findings reveal a need for standardized national guidelines with improved provider training and equitable service delivery. The research calls for coordinated efforts across sectors to build a responsive and inclusive perinatal mental health system in Canada.
Français
Au Canada, près d'une personne sur quatre ayant récemment accouché a présenté des symptômes correspondant à ceux de la dépression post-partum (DPP) ou d'un trouble anxieux, ce qui montre que la santé mentale périnatale est un problème de santé publique. Cette thèse examine la relation entre une infection lors la grossesse et la dépression post-partum chez les Canadiennes dans les cinq années suivant l'accouchement. Bien qu'aucune association significative n'ait été trouvée entre l'infection et l'apparition de la DPP, une DPP antérieure s'est révélée être un facteur prédictif important de récurrence. L'étude révèle des lacunes systémiques dans les soins de santé mentale périnatale au Canada, notamment un dépistage inconstant, une collaboration interdisciplinaire limitée et un accès inadéquat aux services pour les groupes à ii risque. Les résultats quantitatifs et qualitatifs révèlent la nécessité d'établir des lignes directrices nationales normalisées, d'améliorer la formation des prestataires et d'assurer une prestation de services équitable. La recherche appelle à des efforts coordonnés entre les secteurs pour mettre en place un système de santé mentale périnatale adapté et inclusif au Canada
Associations between patient characteristics and delayed acute care discharge post-hip fracture surgery: a cohort study using linked health administrative data in Ontario, Canada
No full textAbstract Background Older patients frequently experience delays in discharge post-hip fracture surgery. Our study aimed to describe the sociodemographic and clinical characteristics of patients who had a surgical repair for a hip fracture and to examine the associations between these characteristics and delayed discharge (> 6 days post-surgery) for frail vs. non frail patients. Methods We conducted a retrospective population-based cohort study using routinely collected health administrative data housed at ICES. The study population included all individuals aged 50 to 105 years with a hip fracture who had a surgical repair in Ontario, Canada between January 1, 2015, and December 31, 2021. We used descriptive statistics and multivariable logistic regression models to characterize the association of patient socio-demographics, baseline health, and characteristics of the acute care episode with delayed discharge between non-frail and frail groups. Results We included 74,838 patients, with a mean age of 80.9 (SD 10.7) years, among which 37,234 (49.8%) had a delayed discharge. Some factors increased the odds of delayed discharge in both non-frail and frail groups included prior location in complex continuing care (non-frail OR 1.64, 95% CI 1.14,2.35, P = 0.007; frail OR 2.33, 95% CI 1.70,3.21, P < 0.0001), as well as prior residence in the community with home care (non-frail OR 9.71, 95% CI 8.89,10.6, P < 0.0001; frail OR 13.8, 95% CI 12.0,15.8, P < 0.0001), or without home care (non-frail OR 5.81, 95% CI 5.35,6.32, P < 0.0001; frail OR 4.60, 95% CI 4.14,5.11, P < 0.0001) compared to long-term care as well as residing in a neighbourhood with a higher Racialized and Newcomer Populations Index quintile (non-frail OR 1.45, 95% CI 1.37,1.55, P < 0.0001; frail OR 1.90, 95% CI 1.68,2.16, P < 0.0001). Factors that reduced the odds of delayed discharge in both non-frail and frail groups included individuals living in rural areas (non-frail OR 0.44, 95% CI 0.42,0.47, P < 0.0001; frail OR 0.41, 95% CI 0.36,0.46, P < 0.0001), or having previous fragility fractures (non-frail OR 0.44, 95% CI 0.40,0.49, P < 0.0001; frail OR 0.56, 95% CI 0.51,0.62, P < 0.0001). However, patients in the non-frail group were more likely to be delayed for the presence of comorbidities including mood or mental health conditions (OR 1.22, 95% CI 1.16,1.28, P < 0.0001), stroke (OR 1.46, 95% CI 1.28,1.67, P < 0.0001), chronic obstructive pulmonary disease (OR 1.35, 95% CI 1.24,1.47, P < 0.0001), dementia (OR 1.41, 95% CI 1.34,1.48, P < 0.0001), or diabetes (OR 1.26, 95% CI 1.20,1.32, P < 0.0001). Factors that reduced the odds of delayed discharge in the non-frail group were female sex (OR 0.87, 95% CI 0.83,0.90, P < 0.0001), or having cancer (OR 0.94, 95% CI 0.90,0.98, P = 0.0089). Conclusion Delayed discharge was common after hip fracture surgery in both the non-frail and frail groups. Preoperative residential status, comorbidities and sociodemographic factors are associated with delayed discharge. These data can help to inform strategies to improve timely discharge from acute care and the overall outcomes of the older adult hip fracture population