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Mammalian/mechanistic target of mTOR complex 1 (mTORC1) regulates multiple cellular processes, including de novo protein synthesis, autophagy and apoptosis. mTORC1 overactivation occurs in a range of cancers and benign tumour dispositions as a result of mutations which increase mitogenic stimulus or cause malfunction of the tuberous sclerosis complex, the prime regulator of mTORC1 activity. mTORC1 overactivation results in elevated endoplasmic reticulum (ER) stress which, at low levels, elicits a pro-survival response. However, prolonged or excessive ER stress causes cell death. The present study utilised clinically relevant drug combinations to simultaneously enhance levels of ER stress and inhibit compensatory survival pathways in in vitro models of mTORC1 overactivity in order to cause non-genotoxic cell death. The main drugs used in this study were nelfinavir, an ER stress-inducer, chloroquine, an autophagy inhibitor, and bortezomib, a proteasome inhibitor. The key findings of this study include identification of drug combinations nelfinavir and chloroquine, nelfinavir and mefloquine, or nelfinavir and bortezomib to induce significant and selective cell death in mTORC1-driven cells, as measured by flow cytometry with DRAQ7 staining and western blot analysis for cleavage of apoptotic markers. Cell death is likely mediated through ER stress signalling, as shown by increased ER stress markers at both the level of mRNA and protein. Of interest, this study found cell death as a result of combined treatment with nelfinavir was not dependent on proteasome inhibition by nelfinavir, or autophagy inhibition by chloroquine. Additionally, nelfinavir-chloroquine-mediated cell death was completely rescued by inhibition of the vacuolar ATPase by bafilomycin-A1. In conclusion, mTORC1 overactive cells have higher basal levels of ER stress which can be manipulated with drug treatment beyond a survivable threshold, whereas cells capable of reducing mTORC1 signalling are able to survive. This study ascertained a combination of nelfinavir and chloroquine, nelfinavir and mefloquine, or nelfinavir and bortezomib, to cause effective cytotoxicity in mTORC1-driven cells.

This thesis explores the relationship between people, their things and socio-economic change. Based on Belgraders’ experiences of Serbia’s economic transition, it focuses on the material impacts produced inside homes as objects are revalued, ownership lines are redrawn and domestic space is reconfigured. These material alterations are linked to social changes as they provoke residents to reflect on how their state, neighbourhoods or families should be organised. I focus on five residential buildings built at different points in the city’s development, from 1939 to 2010. I study the buildings’ archives and the activities of today’s residents to trace relationships constructed through infrastructure, drawing attention to three types of systems that permeate domestic space. I follow the consumer credit industry’s IT architecture and find how financial value is created as households manage their day to day living. I explore the municipal heating system’s liberalisation and find it is reshaping ideas about social good and individual autonomy. I study the buildings' communal spaces and find an institutional vacuum in which residents self-organise to maintain their buildings and manage social relations. I argue that these infrastructures - finance, heating and maintenance - are the basis for both continuity and change as they reach into the domestic sphere to shape the relationship between people and things, but are themselves reworked. Supplementing my anthropological approach with literature from STS and economic geography, I find that the regulatory reforms partially rework the fabric of Belgrade homes. This leads me to argue that transition changes the nature of things and can be interpreted as a loss of ontological certainty, but I show that this is an uneven reworking of materials. Visions of the socialist good life, corruption from the 1990s turmoil and aspirations of liberalism can all be found scripted into the contemporary organisation of housing in Belgrade.

Although dreams have fascinated humans for millennia, the function of dreams and nightmares is a matter of ongoing debate in the fields of neurophysiology, evolutionary psychology and cognitive psychology. Some authors argue that nightmares are purely a by-product of neurophysiological processes that occur during sleep, whilst others suggest that they serve some kind of adaptive function. What is widely recognised, however, is the link between nightmares and psychological well-being. Research indicates that clients frequently bring dreams to therapy and that dream work can improve the psychological wellbeing of individuals who are experiencing distressing dreams. Clinicians do not have a great deal of training in dream work, however, and do not always know how to approach working with dreams. Chapter 1. The first chapter offers an overview of the theories proposing that dreams and nightmares play a role in affect regulation. Subsequently the empirical evidence for these theories is critically appraised and synthesised. Some support is offered for the overnight mood regulation theory of dreaming, and there is contrary evidence to suggest that nightmares negatively impact on mood and behaviour. Chapter 2. The second chapter reports on the findings from a mixed methodology design. Initially the prevalence of dream work across three NHS Trusts in the UK was investigated through a questionnaire-based survey. Secondly, the experiences of clinicians who use dream work in therapy in the NHS were explored through indepth semi-structured interviews. Five main themes emerged from the qualitative analysis of the data: benefits of using dream work, barriers to using dream work, dream work in practice, personal experience of dreaming and dream work and dream work in the wider context. Chapter 3. The third chapter explores the lead author’s own dreams over the duration of the research process, specifically examining these in light of dream and dream work theory.

Educational institutions create organizational structures for younger students with limited work experience. New generations of adult students require different organizational structures to improve success. The current phenomenological qualitative study addressed the lack of consensus of what types of organizational structures in higher education influence student learning. The purpose of the current qualitative, phenomenological study was to explore and describe the lived experiences of student leaders' perceptions of what type of organizational structure in higher education meet the needs of students in a diverse private university in the Midwestern, United States. The recognition of systematic oppression of minority students emerged in theme one. Early involvement and access to leadership positions advanced as a key factor in advancing into leadership positions in later academic career surfaced in theme two. Network actively with peers and other leaders came forward in theme three. Student leaders acquired more knowledge about diversity issues on campus through his or her experience on campus emerged in theme four. Finally, finding a career path and developing work experience came forward in theme five. Of significance, the interrelationship of theme one and two was an important finding for leadership. Leadership should actively recruit minority students into leadership roles early in his or her academic career and track the student's progress throughout their academic career. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]