Long interspersed nuclear elements-1 (Line-1 or L1) accounts for approximately 17% of the human genome. The majority of L1s are inactive, but ~100 remain retrotransposon competent (RC-L1) and retrotranspose through RNA intermediates to different locations of the genome. It is well established that L1 is involved in both disease initiation and progression via retrotransposition dependent and independent mechanisms. Retrotransposed L1 sequences disrupt loci (e.g. gene structure) in ways that lead to human disease, and activities of L1 si/piRNA, ORF1 and ORF2 proteins are implicated in the etiology and progression of human diseases such as in breast and colon cancer (Miki et al., 1992; Ohms et al., 2014). Despite these implications, very little is known about pharmacological molecules that inhibit and reverse L1’s harmful effects. The clinical utility of L1 as a player in tumorigenesis and as a biomarker for disease initiation and progression is not thoroughly understood. In this review, we analyzed the life cycle of L1, its roles in disease initiation and progression, clinical utilities and potential as a pharmacological target and a biomarker for the diagnosis and treatment of human diseases, such as cancer.

Ankyrin-B (Ank-B) is a crucial scaffolding protein regulating expression and localization of contractile machinery in the cardiac muscle. Recent genetic investigations in the First Nations Community, the Gitxsan of Northern BC, identified a mutation in Ank-B (p.S646F c.1937 C>T) associated with a cardiac arrhythmia, Long QT Syndrome Type 4 (LQTS4). Distinct from other LQTS4 subtypes, individuals harbouring the p.S646F variant exhibit development deficits including cardiomyopathies and accessory electrical pathways. How p.S646F interferes with the development of the heart is unknown due to a fundamental lack of understanding regarding Ank-B proteostasis and its role in cardiac differentiation. Initial in silico analyses predicted the p.S646F mutant to be deleterious to the Ank-B protein. Using in vitro techniques, I determined p.S646F mutant reduced levels of Ank-B in H9c2 rat ventricular cardiomyoblasts. Furthermore, haploinsufficiency in mice was previously shown to result in developmental cardiac deficits. I, therefore, hypothesized that p.S646F interferes with Ank-B proteostasis, thereby affecting cardiomyocyte development. I showed that p.S646F destabilized Ank-B in cardiomyoblasts, due to increased degradation via the proteasome. Furthermore, overexpression of p.S646F Ank-B had a significant impact on cellular behaviour including reduced cell viability, and altered expression of cellular differentiation markers. Together these data address critical knowledge gaps with regards to Ank-B protein homeostasis and the role of Ank-B in cardiomyocyte viability and development. These findings inform the diagnosis and treatment of patients with the p.S646F variant, creating potential targeted pathways of intervention, and furthering our understanding of the role of the Ank-B in the development of the heart. / Graduate / 2019-04-26

Recent years have seen a significant increase in the number of ventilator-dependent children being discharged from the hospital. There is a wealth of literature describing the issues surrounding the complex discharge process required for these children however there has been limited exploration of the experiences of parents during their child’s admission to hospital. Interpretive phenomenology based on Heideggerian research philosophy was used to explore the lived experiences of hospital for parents of children commenced on invasive long-term ventilation (I-LTV). Purposive sampling was utilised to select parents of children who had been cared for at one NHS hospital trust. Eight in-depth, unstructured qualitative interviews involving sixteen parents (eight couples) were conducted over a six month period during 2014 to gather data about the parent’s recollections of the time spent with their child in hospital. Most children were cared for on both the paediatric intensive care (PIC) and high dependency units (HDU) with the majority having been discharged from hospital at the time of the interviews. All interviews were transcribed verbatim, and analysed using a modified van Manen (1990) approach. Thematic analysis provided an insight in to the lived world of the parents caring for their technology-dependent child, with two over-arching concepts of uncertainty and transitions characterising the parents’ journeys. The findings revealed multiple transitions in a world of complexity and uncertainty with four main themes emerging from the data; 1) Going in to the Unknown, 2) This wasn’t what we wanted, 3) Safer at Home, and 4) Clawing every little bit back. Parents were required to develop coping strategies to deal with the transitions and uncertainties experienced and establish new roles and identities as they became experts in caring for their technology-dependent child. As a result of the findings a new framework combining the concepts of uncertainty and transitions was derived identifying areas for consideration including: health-illness, psycho-social, situational and developmental transitions together with existential, biographical, environmental, relational and temporal uncertainties. Strategies for facilitating coping and adaptation towards healthier outcomes were identified and a strong argument emerged for the development of more effective management of transitions and uncertainty delivered within an environment more conducive to family-centred care.

This thesis reports the calibration, imaging and analysis of one epoch of VLBI observations of the v (italics) = J (italics) = 1-0 transition of SiO towards VY CMa. Full polarisation information was recorded, allowing high resolution synthesis maps of each of the four Stokes parameters to be produced. A total of 81 maser components were extracted from the total intensity map, each approximately 1 mas in size. The emission spans approximately 100 x 80 mas in right ascension and declination and is concentrated to the east. The maser component positions were fitted to a ring of radius ~ 3.2R₊ (italics), or 7.2 x 1O¹⁴ cm for a stellar distance of 1.5 kpc. If the stellar position is assumed to be the centre of this ring then almost all of the maser components fall within the inner dust shell radius, which is at ~ 5R (italics)ϰ All of the maser components fall between 1.5R (italics)ϰ and 6R (italics)ϰ. A velocity gradient with position angle was observed in the sparsely filled western region of the maser ring. If interpreted as evidence of shell rotation, this gradient implies a rotational velocity of v (italics) rot (subscirpt) sin i (italics) = 18 km.s⁻¹. The fractional circular and linear polarisations of the maser spots were derived from the Stokes parameter maps. The mean fractional circular polarisation of the masers components was ~ 2 percent and the median fractional linear polarisation was ~ 6 percent, with many spots displaying over ~ 30 percent linear polarisation. The mean circular polarisation implies a magnetic field of ~ 4 G in the SiO maser region if the polarisation is due to Zeeman splitting. Two maser components display a rotation of linear polarisation position angle with velocity, possibly implying a connection between the magnetic field and the velocity field variations in the region of these components.

Drop-in centers for individuals with serious and persistent mental illness offer a unique and perhaps under-recognized environment option for adjunct treatment. The current study examines and evaluates components thought to be a part of an enriched drop-in center experience that contribute to positive member outcomes through the effects of empowerment. These components include self-help, peer support, and creative expression. Outcomes were evaluated based on quality of life, self-worth, and symptom reduction. Such data are necessary in promoting the growth and development of drop-in centers and identification of components that contribute to positive member outcomes. Participants (n=101) were administered a series of measures including The Multidimensional Scale of Perceived Social Support, The Empowerment Scale, The Rosenberg Self-Esteem Scale, The World Health Organization Quality of Life-BREF, The BASIS-32™, and a series of questions created for the purposes of the current study regarding creative expression and self-help. The psychometric properties of each measure were evaluated and reviewed. Additionally, mean differences between normative data and participant means were examined and demographic data were analyzed. It was hypothesized from the literature that self-help, peer support, and creative expression would have significant indirect effects on all of the proposed outcome variables through the effects of empowerment. Results revealed significant indirect relationships between peer support and all of the outcome variables through the effects of empowerment and between self-help and all of the outcome variables through the effects of empowerment. No significant relationships were found between creative expression and any of the outcome variables through the effects of empowerment. These findings suggest that peer support and self-help may be instrumental in achieving positive outcomes through the effects of empowerment. Centers that offer experiences to enhance self-help and peer support will subsequently enhance feelings of empowerment in members, which relates to higher levels of self-worth, higher levels of quality of life, and lower levels of psychiatric symptomatology. Further implications of such findings and suggestions for continuation of this research are discussed in detail.

Farmers will supply the raw ingredients for the emerging cellulosic ethanol industry. The long-term relationship between a farmer and a processing firm is expected to be contractual. A processing firm has an incentive to sign long-term contracts to ensure a cost-efficient level of raw ingredient supply. However, farmers generally prefer to operate with either no contract or a short-term contract in order to maintain options for adjustments in future acreage allocations due to changes in relative prices. Of interest in this research is to understand the incentives of farmers and calculating the efficient level of the “inflexibility premium”, which a processing firm must provide to a farmer when a long term contract is signed. A stochastic dynamic programming model is solved and with the help of Microsoft Excel numerically evaluated to illustrate the marginal inflexibility premium is increasing with contract length and the level of price variability, and is decreasing with the size of acreage adjustment costs. / Land and Food Systems, Faculty of / Graduate

Long-term residential care (LTRC) is a complex sociopolitical milieu where people from diverse backgrounds come to live and work together. In recent years health care restructuring has resulted in the closure of facilities; health care policy has narrowed the population that accesses LTRC so that only those who are the most medically and socially complex are admitted; and there has been a transformation of the work force, a workforce that is mainly comprised of Women of Colour and is among the lowest paid in health care. The purpose of this study was to critically examine the organization of care in LTRC within this context. The theoretical perspective guiding the study was informed by postcolonialism, postcolonial feminism, intersectionalities, and Foucaudian epistemology. The method of inquiry for the study was critical ethnography, which allowed for critical analysis of `taken for granted' assumptions in the organization of care. Over a period of ten months, I was immersed in two LTRC facilities in the Lower Mainland of British Columbia. Field work consisted of approximately 218 hours of participant observation. I conducted 51 interviews with administrators, family members, residents, and staff. I reviewed relevant provincial policies and facility-based policies and procedures. I also collected quantitative data related to resident transitions in the health care system (for example, admissions, discharges, and hospital admissions), and staffing levels. Findings from this study were discussed in three key themes. First, a systematic decommissioning of citizenship occurred for residents and staff in this setting. Second, the impact of health care restructuring over the past decade had important consequences for relationships between residents, family, and staff. Third, relational care took place in `stolen' moments that occurred despite heavy workloads. All of these themes were underscored by intra-gender oppression, relations of power, and influenced by discourses of ageism and corporatism, which ultimately played out in day to day interactions between those who live and work there. Recommendations from this study included: addressing the entrenched hierarchies in nursing, further examination of the public-private funding model in LTRC, and the introduction of an independent ombudsperson to ensure consistent, high quality care across the LTRC sector. / Applied Science, Faculty of / Nursing, School of / Graduate

In this thesis, we propose two continuous time stochastic volatility models with long memory that generalize two existing models. More importantly, we provide analytical formulae that allow us to study option prices numerically, rather than by means of simulation. We are not aware about analytical results in continuous time long memory case. In both models, we allow for the non-zero correlation between the stochastic volatility and stock price processes. We numerically study the effects of long memory on the option prices. We show that the fractional integration parameter has the opposite effect to that of volatility of volatility parameter in short memory models. We also find that long memory models have the potential to accommodate the short term options and the decay of volatility skew better than the corresponding short memory stochastic volatility models.

Sport for development programs are becoming increasingly popular to address a variety of social issues such as poverty, lack of education, gender equality, and conflict within marginalized communities. Within Canada, many sport for development programs are created for Aboriginal peoples, as they are considered marginalized communities. However, there is a dearth of research on what the actual impacts of sport for development programs are on the recipients of the program, as well as on those who provide the program. My thesis, which is written in the publishable paper format, is comprised of two papers. Using a case study approach in paper one, I explore the impacts that Alberta’s Future Leaders Program’s (AFL) youth leadership retreat has had on its participants (Aboriginal youth). Similarly, using a case study approach in paper two, I explore if/how working for AFL had lasting impacts on the former employees, known as youth workers and arts mentors. Together, the two papers in this thesis show the need for a deeper look into the actual impacts sport for development programs yield, provide insights into some of the lasting impacts AFL has had on its participants, and address the importance of long-term evaluation for sport for development programs.

The salinity distribution in an inverse estuary (where the sea water is concentrated by the estuary water) possesses its own uniqueness due to excessive net freshwater loss and restricted circulation. The study of long-term balance of salinity can contribute to a better understanding of the mixing and transport properties in such a distinct type of water body (i.e., inverse estuary water), and can provide valuable information for sound water management and environmental assessment. The Persian Gulf is chosen to be the study region, as it is a typical large-scale inverse estuary with severe shortages of freshwater resources and has been of significant research interest during the past several decades. For basin-wide examinations of a large-scale inverse estuary, analytical solutions are typically unavailable and field measurements are expensive, so numerical modeling as well as validation with available data is the main focus in this thesis. Firstly, the salinity distribution in the Persian Gulf is simulated with 8 different schemes, and the obtained results are compared with the World Ocean Atlas 2013 (WOA13) data. The comparisons can validate the utilization of the numerical model in predicting the salinity distribution in a large-scale inverse estuary. Given that results are affected by the choice of the numerical scheme, a performance analysis of candidate schemes is performed. The most appropriate scheme for the Persian Gulf is figured out in this stage. Secondly, the validated scheme is used for the prediction with respect to the long-term salinity response of the Persian Gulf to the climate change and anthropogenic activities. The results show that without mitigation measures taken, the salinity in the Persian Gulf will continually increase with time. The long-term and basin-wide simulations that will be presented in this thesis are expected to be more useful than previous studies (which were generally limited in time from hours to a few months) in terms of inspecting long-term characteristics. The performance of various numerical schemes has been assessed for the first time through a practical case study, which can contribute to a better understanding of the applications and characteristics of these schemes. Besides, the long-term salinity variations in the Persian Gulf are predicted for the next half-century, and this is the first numerical prediction of the long-term salinity response of the Persian Gulf to climate changes and anthropogenic activities.