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The selection of 5' splice sites in pre-mRNA transcripts containing multiple splice sites is poorly understood. RNA flexibility and how it affects splice site selection has not currently been investigated on a molecular level. However, secondary structures in proximity to the splice site and RNA-protein/small molecule binding events has been shown to shift splicing using ensemble fluorescence methods. Evidence suggests that using small molecules which target cancerous mutations caused by incorrectly spliced genes such as induced myeloid leukaemia cell differentiation and β-cell lymphoma proteins may have therapeutic application. Single molecule experiments are not limited by ensemble averaging and so can be used to study the conformational flexibility of individual RNA molecules in functional splicing conditions. Single molecule fluorescence resonance energy transfer was used in this thesis to monitor the conformational flexibility of different nucleic acids including DNA (Holliday junction and molecular beacon) and RNA (adenovirus and β-cell lymphoma sequences) structures. The experiments were performed under different conditions using various methods of surface passivation and surface tethering (direct tethering and encapsulation in lipid vesicles). The experiments outlined here indicate two main things: firstly, that monitoring nucleic acids which are freely diffusing in lipid vesicles (100 nm) is more representative of physiological conditions. Single molecules in lipid vesicles demonstrated more homogeneous conformational dynamics than those samples which had been tethered directly to the imaging surface. Secondly, we have shown that the G-quadruplex putative to the Xs splice site in the β-cell lymphoma gene forms and is stabilised by ellipticine derivative, GQC-05 in HeLa cell nuclear extract. This suggests that the stabilisation of the quadruplex and alteration to mRNA flexibility upon binding likely underlies its ability to shift splicing of β-cell lymphoma, from an anti- to a pro-apoptotic isoform. The single molecule results presented here complement previous literature and combined suggest that GQC-05 is a candidate pro-drug molecule for the therapeutic relief of tumours.

Adults with an autism spectrum condition (ASC) experience a range of socio-economic disadvantages across the life course including; social isolation, low educational attainment, unemployment, and poverty. These outcomes are also risk factors for homelessness. Whilst emerging research in the UK suggests a disproportionate amount of autistic adults experience homelessness, little is known about what predisposes autistic people to homelessness and how best to support them. Additionally, it is likely that many homeless autistic adults are undiagnosed and unable to access suitable support. Therefore, in order to examine the relationship between autism and homelessness, it is first imperative to explore how ASC is defined and diagnostic criteria applied. This thesis presents a multi-causal, social interpretational model of autism which posits that ASC has no singular biological marker and that diagnostic boundaries are historically and socially constructed. From this position, the label of autism still has meaning, as it describes a set of behaviours which sit outside of normative ideals. Using this model as a framework, study recruitment involved identifying adults with a clinical diagnosis of autism, or those who self-identified as autistic, who had experienced homelessness. Ten participants were accessed through homelessness services and consented to take part in the study. Each participant took part in two to three narrative interviews which centred on their life history and experiences of homelessness. Thematic analysis revealed complexity of life experience, with participants reporting abuse in childhood, multiple co-occurring conditions, historic or current substance dependency, or imprisonment. The majority of participants experienced episodic homelessness, sometimes from childhood, which was usually triggered by relationship breakdown coupled with lack of financial and social support. Participants found it difficult to navigate support systems and statutory accommodation provision was insufficient when considering social and sensory needs. In terms of contributors to homelessness, analysis of narratives revealed social rejection across the life course which impeded participants' ability to do well at school, find and maintain employment, access welfare and expand support networks. Participants responded to this exclusion in two distinct ways; by attempting to mask autistic behaviours in order to fit in, or by rejecting social expectations and withdrawing from society. Whilst neither strategy mitigated against homelessness, the majority of participants went on to renegotiate their autistic identities which enabled them to become self-advocates, challenging discriminatory practice and exclusion. This thesis reinterprets study findings using a critical realist framework. Exclusion across the life course is explained through the lens of Critical Disability Studies, wherein disabled persons are rejected for not meeting normative ideals. This thesis goes on to engage with Dis/human Theory, explaining how the labelling of individuals as autistic can be utilised as a position from which to challenge structural inequities. Study findings suggest a need for increased awareness of autism and flexibility of provision in education, employment, welfare, and homelessness services. Whilst some adaptations can be made within existing frameworks, significantly reducing risk of homelessness for autistic adults requires deeper structural changes and the repositioning of accepted forms of personhood and normalcy.

Problem: The purpose of this research was to explore the effects of incorporating computer spreadsheets on the development of algebraic thinking as it pertains to growth patterns of functions. The study also examined students' ability to transfer skills learned on a computer spreadsheet to problems using pencil and paper, as well the effect of incorporating computer spreadsheets on student motivation, engagement, and communication. Specific questions addressed in the study include: How does investigating an algebra problem about growth patterns by entering numbers, creating formulas, and noticing patterns on a computer spreadsheet affect students' ability to learn the concepts of linear and exponential growth functions? In what ways does the use of a computer spreadsheet to introduce and explore function concepts transfer skills to students' performance on working through similar concepts using pencil and paper? How does using a computer spreadsheet affect students' motivation in learning concepts of function growth? Procedure: Students from two Algebra 2 courses participated in this study. The treatment group worked in the computer lab to creating Excel™ spreadsheets, while the control group worked in the classroom using paper, pencil, and calculator. The research study included collection of both quantitative and qualitative data. The quantitative procedure involved a comparison of worksheet and post-instruction assessment scores. The qualitative data consisted of a student engagement survey used to assess attitudes and actions during participation in class activities. Informal teacher researcher observations of classroom activities are also part of the analysis. Findings: This study found no difference between the treatment group and the control groups with respect to their conceptual development of function growth patterns. Students who used computer spreadsheets were able to finish the assigned work more quickly than students using traditional paper and pencil methods. Students using a computer spreadsheet were able to transfer their knowledge of function behavior to paper and pencil when a spreadsheet was not available. Student engagement in both the treatment group and control group was similar.