VictorJuiz/thesis huggingface dataset:
An Exploration into the Molecular Recognition of Signal Transducer and Activator of Transcription 3 Protein Using Rationally Designed Small Molecule Binders
Keywords: Inhibitor design
STAT3
Protein-protein interaction
Molecular recognition
Molecular modelling
Pharmacophore model
Antitumour cell effects
SH2 domain

Signal transducer and activator of transcription 3 (STAT3) is a cancer-driving proto-oncoprotein that represents a novel target for the development of chemotherapeutics. In this study, the functional requirements to furnish a potent STAT3 inhibitor was investigated. First, a series of peptidomimetic inhibitors were rationally designed from lead parent peptides. Prepared peptidomimetics overcame the limitations normally associated with peptide agents and displayed improved activity in biophysical evaluations. Notably, lead peptidomimetic agents possessed micromolar cellular activity which was unobserved in both parent peptides. Peptidomimetic design relied on computational methods that were also employed in the design of purine based STAT3 inhibitory molecules. Docking studies with lead STAT3-SH2 domain inhibitory molecules identified key structural and chemical information required for the construction of a pharmacophore model. 2,6,9-heterotrisubstituted purines adequately fulfilled the pharmacophore model and a library of novel purine-based STAT3 inhibitory molecules was prepared utilizing Mitsunobu chemistry. Several agents from this new library displayed high affinity for the STAT3 protein and effectively disrupted the STAT3:STAT3-DNA complex. Furthermore, these agents displayed cancer-cell specific toxicity through a STAT3 dependant mechanism. While purine agents elicited cellular effects, the dose required for cellular efficacy was much higher than those observed for in vitro STAT3 dimer disruption. The diminished cellular activity could be attributed to the apparent poor cell permeability of the first generation purine library; thus, a second library of purine molecules was constructed to improve cell penetration. Unfortunately, iii 2nd generation purine inhibitors failed to disrupt phosphorylated STAT3 activity and suffered from poor cell permeability. However, a lead sulfamate agent was discovered that showed potent activity against multiple myeloma cancer cells. Investigations revealed potential kinase inhibitory activity as the source of the sulfamate purine’s biological effect. Explorations into the development of a potent STAT3 SH2 domain binder, including the creation of salicylic purine and constrained pyrimidine molecules, are ongoing. Finally, progress towards the creation of a macrocyclic purine combinatorial library has been pursued and is reported herein.
Mindfulness Training for Adolescents with ADHD and their Families: A Time-series Evaluation
Keywords: mindfulness
ADHD
adolescents
parent-adolescent conflict
parenting Stress
meditation

The present study involved an extension and evaluation of a mindfulness-based training program for families of adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). MYmind: Mindfulness training for Youth with ADHD and their parents (Bogels et al., 2008) is an eight-week manualized treatment incorporating elements of mindfulness meditation, ADHD psychoeducation and cognitive behavioural therapy. MYmind focuses on helping families cultivate mindfulness through training in formal meditation practices and integrating this skill into the context of everyday life as a means of managing ADHD symptoms, stress, family relations and difficult emotions. A North American sample of 13 parents and 9 adolescents (ages 13-18) participated in MYmind; during the intervention, parents and adolescents attended separate groups that ran simultaneously. Using a time-series multiple baseline design, constructs of stress, distress from family conflict, ADHD symptomatology and meditation practice were measured via short questionnaires emailed daily to both parents and adolescents throughout baseline, treatment and six months of follow-up. For multiple baseline purposes, intervention was introduced in a time-lagged fashion. Results from parent and adolescent reports indicated reductions in parent and adolescent stress, parent and adolescent distress due to family conflict, and increased frequency and duration of meditation practice. Parent reports suggested a decrease in their adolescents’ inattention, hyperactivity and impulsivity symptoms after participating in MYmind, a reduction that was not confirmed by adolescent reports. Most treatment gains were maintained up to six-months following treatment completion. Meditation practice was significantly correlated with reduced stress levels for both groups. Both parents and adolescents reported high satisfaction with the MYmind program overall. Mindfulness training appears to hold considerable potential for improving the multiple difficulties experienced by adolescents with ADHD and their parents.
The Structural Basis of Prion Disease Susceptibility and the Transmission Barrier
Keywords: prion
prp

When prions are transmitted between species, there can be a delay in pathogenesis due to a phenomenon referred to as the transmission barrier. Some species also show very low susceptibility to prion disease. In this study I hypothesized that the susceptibility of species to prion disease is proportional to the tendency of their endogenous prion protein, PrP, to adopt the β-state, an oligomeric form of misfolded recombinant PrP that is rich in β sheet. Using a novel method of two-wavelength CD analysis, it could be shown that recombinant PrP from prion-susceptible species have a higher propensity to refold to the β-state than resistant species. The crystal structure of rabbit PrPC 121-230 revealed a helix-cap motif at the N-terminus of helix-2 that contributes to the reduced β-state propensity of rabbit PrP. Single amino acid changes in the sequence of PrP can lead to a transmission barrier and/or resistance in species. Mutating single residues in rabbit PrPC to those found in corresponding positions in hamster PrPC, ablated the helix-cap observed in the wild-type and caused an increase in the β-state propensity of rabbit PrP. Conversely, a decrease in β-state propensity was observed when rabbit mutations were introduced into PrP of hamster, a susceptible species. A dimeric association is hypothesized to be involved in the function of PrP and/or the conversion mechanism to infectious prion. In the structures of the wild-type and mutant rabbit PrPCs a dimeric arrangement was observed in the asymmetric unit of the crystals. Using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC), a dimer of rabbit and hamster PrPC was crosslinked in solution. The dimer crosslink was specific and dependent on the tertiary structure of PrPC. Crosslinking of the β-state octamer with EDC showed that similar contacts may be present in this oligomeric form. Together these data provide strong evidence that species susceptibility is linked to β-state propensity.
An Investigation of the Use of Real-time Image Mosaicing for Facilitating Global Spatial Awareness in Visual Search
Keywords: human factors
mosaicing
visual search

Three experiments have been completed to investigate whether and how a software technique called real-time image mosaicing applied to a restricted field of view (FOV) might influence target detection and path integration performance in simulated aerial search scenarios, representing local and global spatial awareness tasks respectively. The mosaiced FOV (mFOV) was compared to single FOV (sFOV) and one with double the single size (dFOV). In addition to advancing our understanding of visual information in mosaicing, the present study examines the advantages and limitations of a number of metrics used to evaluate performance in path integration tasks, with particular attention paid to measuring performance in identifying complex routes. The highlights of the results are summarized as follows, according to Experiments 1 through 3 respectively. 1. A novel response method for evaluating route identification performance was developed. The surmised benefits of the mFOV relative to sFOV and dFOV revealed no significant differences in performance for the relatively simple route shapes tested. Compared to the mFOV and dFOV conditions, target detection performance in the local task was found to be superior in the sFOV condition. 2. In order to appropriately quantify the observed differences in complex route selections made by the participants, a novel analysis method was developed using the Thurstonian Paired Comparisons Method. 3. To investigate the effect of display size and elevation angle (EA) in a complex route environment, a 2x3 experiment was conducted for the two spatial tasks, at a height selected from Experiment 2. Although no significant differences were found in the target detection task, contrasts in the Paired Comparisons Method results revealed that route identification performance were as hypothesised: mFOV > dFOV > sFOV for EA = 90°. Results were similar for EA = 45°, but with mFOV being no different than dFOV. As hypothesised, EA was found to have an effect on route selection performance, with a top down view performing better than an angled view for the mFOV and sFOV conditions.
New Harmonic Generation Microscopy Techniques based on Focal Volume Modelling
Keywords: Nonlinear microscopy
Numerical modelling
Harmonic generation

Nonlinear microscopy has become an indispensable tool in the study of biological systems. It includes many nonlinear contrast mechanisms, each sensitive to different biological structures. However, interpretation of the images generated in nonlinear microscopy is a complex matter due to factors such as the structural complexity of the sample, phase relationships between the excitation beam and the detected signal and the nonlinear interactions in the focal volume of the microscope. This thesis contains a new theoretical and numerical framework that describes the focusing of an excitation beam in a nonlinear microscope, the nonlinear optical interactions with the material in the focal volume, and the resulting nonlinear optical signal in the far field. The framework is the first to include reflection and refraction of the excitation beam and nonlinear signals by an arbitrary number of interfaces in the focal volume, which is especially significant for the interpretation of third harmonic generation (THG). It also uses the chirp-z transform to speed up calculations by orders of magnitude compared to numerical integration techniques. The framework is used to investigate second harmonic generation (SHG) by collagen. Focusing effects alter polarization-dependent SHG measurements of collagen properties compared to the plane wave approximation, and this is verified experimentally. Furthermore, a technique of imaging the far field SHG radiation from collagen fibres is proposed, which can be used to extract the orientation of collagen fibres unambiguously. The framework is then applied to analyze the influence of interfaces on THG. Reflection effects at interfaces significantly affect THG, which leads to the development of a new super-resolution THG imaging technique based on backward-propagating THG. This super-resolution technique is experimentally demonstrated by imaging surface profiles with tens of nanometers resolution, which is the first time that such resolution is obtained in coherent nonlinear microscopy. Therefore, this imaging technique shows promise to become an important tool in high-resolution imaging of (biological) samples. The theoretical and numerical framework provides a foundation for future research on the origin of nonlinear microscopy signals. The new imaging techniques based on this framework have great potential in quantifying fibrillar structures and interfaces in biological samples.
Effects of Aqueous Organic Coatings on the Interfacial Transport of Atmospheric Species
Keywords: aqueous organic coatings
gas transport
sea surface microlayer (SML)
nitrogen dioxide (NO2)
molecular iodine (I2)
carbon dioxide (CO2)
water surfaces
air--water interfaces
gas to solution partitioning
Incoherent Broadband Cavity-Enhanced Absorption Spectroscopy (IBBC-EAS)

Species must interact with air—aqueous interfaces in order to transport between either phase, however organic coated water surfaces are ubiquitous in the environment, and the physical and chemical processes that occur at organic coated aqueous surfaces are often different than those at pure air—water interfaces. Three studies were performed investigating the transport of species across air—aqueous interfaces with organic coatings in an effort to gain further insight into these processes. Gas and solution phase absorption spectroscopy were used to study the effect of octanol coatings on the formation of molecular iodine (I2) by the heterogeneous ozonation of iodide and its partitioning between phases. Compared to uncoated solutions, the presence of octanol monolayers had a minor effect on the total amount of I2 produced, however, it did significantly enhance the gas to solution partitioning of I2. Incoherent broadband cavity-enhanced absorption spectroscopy (IBBC-EAS) was used to measure the gas-phase nitrogen dioxide (NO2) evolved via photolysis of aqueous nitrate solutions either uncoated or containing octanol, octanoic acid and stearic acid monolayers. Both octanol and stearic acid reduced the rate of gaseous NO2 evolution, and octanol also decreased the steady-state amount of gaseous NO2. Alternatively, octanoic acid enhanced the rate of gaseous NO2 evolution. Finally, the loss of aqueous carbon dioxide (CO2) from aqueous solutions saturated with CO2 was measured using a CO2 electrode in the absence and presence of stearic acid monolayers and octanol coatings, and a greenhouse gas analyzer was used to measure the evolution of gaseous CO2 from solutios with octanol monolayers. Enhanced losses of aqueous and evolved gaseous CO2 were observed with organic coated solutions compared to those uncoated. The results of these studies suggest that organic coatings influence the transport of I2, NO2 and CO2 via one, or a combination of: barrier effects, surface tension effects, chemistry effects and aqueous – surface – gas partitioning effects. These results, particularly the enhanced partitioning of these species to octanol coated aqueous surfaces, have important implications for species transport at air—aqueous interfaces, and may provide useful insight for future studies and parameters for atmospheric models of these species.
Biskanewin Ishkode (The Fire that is Beginning to Stand): Exploring Indigenous Health and Healing Concepts and Practices for Addressing Sexual Traumas
Keywords: Indigenous healing
Trauma

Multiple traumas, including sexual vulnerabilities, sexual abuse, and sexualized violence, remain substantially higher among Indigenous peoples in Canada than among non-Indigenous peoples. These trends are rooted in a colonial history that includes systemic racism, a deprivation of lands and culture and other intergenerational traumas. Mental health sequelae following sexual vulnerabilities such as abuse and violence may include mood disorders, low self-worth, posttraumatic stress and a range of issues related to anxiety—yet Western mental health services are typically under-used by Indigenous peoples managing these issues. Indigenous mental health and healing services are explored as a more culturally appropriate and successful alternative for Indigenous clients experiencing multiple traumas.
Exploring The Relationship of Associate Teachers And Teacher Candidates Within The Teaching Practicum
Keywords: Practicum
Teacher Training

There is broad agreement that the practicum is a key part of teacher education. In the context of the classroom, the teacher candidate begins to adopt the role of teacher as outlined by the Ministry of Education in Ontario. One challenge for teacher candidates is to translate to the classroom what they have experienced in their university program. Associate Teachers influence this translation of pedagogy by how they shape what Student Teachers have explored in theory. The broad scope of research literature on the role of the Associate Teacher lacks clarity on the varied perceptions of the supportive roles of Associate Teachers. Research is needed on how Teacher Candidates and Associate Teachers perceive their pre-service practice experience and the impact of the Associate Teacher support. This study is a qualitative one. The research is based on a series of semi-structured interviews conducted with teachers who were participants in the 2007/2008 elementary pre-service consecutive teacher education program at one Ontario University. Findings from the research suggest that the use of participatory dialogue throughout the practicum is essential to support the learning process of Student Teachers concerning teaching in the classroom. Additionally, differentiated mentored support by the Associate Teacher proved essential to the completion of the practicum by the Teacher Candidate.
Genetic Diversity and Phylogeographic Structure of the Parasitic Plant Genus Conopholis (Orobanchaceae): Implications for Systematics and Post-glacial Colonization of North America
Keywords: Phylogeography
Molecular Systematics
Morphometrics
Microsatellite marker development
North America
Parasitic Plant
Holoparasite
Last Glacial Maximum
refugia
Post-glacial colonization

Parasitism in plants is often accompanied by a suite of morphological and physiological changes resulting in a condition known as the ‘parasitic reduction syndrome’. With changes including extreme vegetative reduction, frequently beyond any resemblance to its photosynthetic relatives, accompanied by significant losses of genes linked to photosynthesis, the study of parasitic plants can be challenging. Conopholis (Orobanchaceae) is a small holoparasitic genus distributed across eastern and southwestern North America and Central America. This genus has never been the subject of a molecular phylogenetic or morphometric analyses. In addition, very little is known of the relationships among populations and of their post-glacial history. To investigate the species limits and phylogenetic relationships in Conopholis, we conducted a comprehensive molecular phylogenetic study of the genus as well as a fine-scale morphometric study. Based on plastid and nuclear sequences, Conopholis was found to contain three distinct and well-supported lineages which have varying degrees of overlap with previously proposed taxa. The clustering and ordination analyses of the morphometric study corroborated the molecular data, demonstrating the morphological differentiation between the three lineages detected within Conopholis. A taxonomic re-alignment is proposed for the genus that recognizes three species, C. americana, C. panamensis, and C. alpina. To address genetic diversity and phylogeographic structure of C. americana in eastern North America, microsatellite markers were developed and characterized for the first time in this species. Using these newly generated markers along with sequences from the plastid genome, the persistence of a minimum of two glacial refugia at the last glacial maximum were inferred, one in Florida and southern Alabama and another in the Appalachian Mountains near the southern tip of Blue Ridge Mountains. The diversity seen across the southern Appalachian Mountains supports the hypothesis that populations derived from the southern and northern refugia come together in this area.
The Meaning of Discontent: A Multi-method Qualitative Investigation of Women's Lived Experiences with Body Dissatisfaction
Keywords: body image
body dissatisfaction
qualitative
arts-based
hermeneutic phenomenology
adult
women

This study explored adult women’s lived experiences with body dissatisfaction. Using a multi-methods qualitative approach incorporating in-depth semi-structured interviews and arts-based projects, women between the ages of 20-39 engaged in a critical exploration of their body experiences in order to deepen understanding of the psychological construct of body dissatisfaction and its ongoing influence in their lives. Ten women from diverse social and ethnocultural backgrounds took part in the study, completing 1-2 interviews, an in-session drawing exercise, and a creative project. Interview transcripts, drawings, and creative projects were analyzed for themes using an hermeneutic phenomenological approach. Four core categories emerged from the data. The first category contained the women’s understanding of the experience and meaning of body dissatisfaction. The second category captured the external reinforcement of body dissatisfaction and related body beliefs. The third emergent category delineated the impact of body dissatisfaction on daily life, including body-self relationships and interpersonal relationships. The final category captured the difficulties the women encountered as they attempted to overcome their feelings of body dissatisfaction and their negative body beliefs. This research highlighted the complex and multidimensional meaning of body dissatisfaction in adult women’s lives.
All in Good Time: The Evolving Role of Faculty in Ontario Colleges
Keywords: college
leadership
faculty
research

The purpose of this study was to explore how the role of Ontario college faculty has evolved since the advent of the Post-Secondary Education Choice and Excellence Act of 2000 and the Colleges of Applied Arts and Technology Act of 2002, and to consider whether or not the decision to create a research culture at the colleges included making time available to the professoriate to engage in applied research activities. Web content was analyzed to select four Ontario colleges at various stages of research evolution using D.J. Madder’s typology of college research and innovation. The study compared the current state of the four Ontario colleges focusing on whether the institutions had developed policies or procedures to provide time for faculty-based applied research. Interviews were also conducted with two senior members from the relevant provincial government sector involved in planning the implementation of applied research in the colleges, and with five senior college leaders who were present in the college system when the Acts were introduced. Additional interviews with four senior college leaders examined the current conditions surrounding the development of applied research cultures in Ontario colleges. Findings indicated that regardless of where a college is located on Madder’s typology of research evolution, time for applied research activities is provided to the college faculty in an inconsistent manner. Ontario colleges may want to consider what other jurisdictions have done to develop successful, applied research-focused colleges. The development of a more robust, fully integrated applied research culture in the colleges will require more comprehensive planning by the colleges either by themselves or in concert with agencies of the Ministry of Training, Colleges and Universities, than has been experienced to date. As long as the Collective Agreement governing the allotment of time for faculty activities exists in its current iteration, allocating time for faculty to engage in applied research activities outside the classroom will likely continue on an ad hoc basis. In the near term, having curriculum-based applied research activities could partially solve the problem, accommodate program specific needs, and be of enormous benefit to students and faculty alike.