Investigating stress responses in models of Amyotrophic Lateral Sclerosis

The ability of motor neurons and surrounding glia to respond to stressful conditions is crucial for their survival in injury or disease states. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease defined by the loss of both upper and lower motor neurons resulting in muscle paralysis. Several pathomechanisms in both motor neurons and glial cells contribute to motor neuron death in ALS. Among these, dysfunction in stress responsive pathways involved in inflammation, proteostasis and mitochondrial function are known to be important. Since ALS is defined by loss of motor neurons in specific anatomical areas, with spinal motor neurons most affected, regional differences in glial stress responses may contribute towards this specific pattern of damage. In this Thesis, a regional difference in the NO-iNOS-NF-κB inflammatory pathway was observed, with spinal cord glia displaying a stronger response than cortical glia. While this regional difference was observed, no clear differences were found in the inflammatory responses of glia from mutant SOD1 (mSOD1) models of ALS. However, mSOD1 glia were unable to activate the heat shock response (HSR), a cytoprotective response involving the upregulation of heat shock proteins (Hsps), as effectively as wildtype glia. Reduced activation of the HSR increased the inflammatory responses of mSOD1 glia. Therefore, dysregulation of the HSR may further exacerbate an inherent ability of spinal cord glia to promote inflammatory damage in ALS. Mitochondrial dysfunction is also an important pathomechanism in ALS. Several Hsps are specifically localised to mitochondria. mSOD1 spinal cord motor neurons expressed lower levels mitochondrial Hsps TRAP1 and Hsp60. In a cellular ALS model of oxidative stress, overexpression of these proteins was protective to mitochondrial functions in motor neurons, while knockdown was detrimental. Together, these data suggest that manipulating stress responses of motor neurons and glia may be a viable therapeutic target for ALS

The Entrepreneurial Management Process in a Growing Small Business: A Case Study

This research case study focuses on the identification and analysis of the entrepreneurial management process and its applicability as a practical solution to the problems resulting from growth and maturity of an entrepreneurial small business. The entrepreneurial management process is one which focuses on managing on organization to develop and capitalize on its entrepreneurial characteristics. It is examined in the context of the development of an entrepreneurial culture, employee empowerment, entrepreneurial teamwork, strategic planning, new ventures, and compensation. The working hypotheses suggest that the entrepreneurial management process is a practical and effective solution of the identified problems related to small business growth. The hypotheses also suggest that a strategic planning focus is a necessary element of the entrepreneurial management process in order for an organization to continue its pattern of entrepreneurial growth

The Production of Space, Place, and Food: The Ecology of Money and the Emergence of Transformative Circuits of Money Capital

Title from PDF of title page, viewed on August 10, 2015Dissertation advisor: Mathew ForstaterVitaIncludes bibliographic references (pages 182-196)Thesis (Ph.D.)--Department of Economics and Social Science Consortium. University of Missouri--Kansas City, 2015This dissertation argues that Henri Lefebvre’s (1991) The Production of Space expresses a theoretical blueprint for the construction of an interdisciplinary approach to social science that integrates political economy, ecology, and geoscience under common meta-theoretical commitments. From this foundation a comparative analysis of the production, distribution, and consumption of two food systems is undertaken. The orthodox or industrial food system, characterized by intensive agriculture, and the countervailing agriculture of alternative food networks supply contrasting subjects for investigating the role of distance in the production and reproduction of social and environmental externalities. By means of the Marxian circuits of money capital, each of these food systems is modeled to analyze metabolic changes as distance between the stages: purchase, production, and sale are spatially differentiated. The capacity to investigate distances is facilitated by efforts to overcome critiques of Lefebvre’s theory of space as being too abstract for practical application. This is accomplished by mapping the stages of the Marxian circuits of money capital to the physical locations in which they take place using geographic information systems (GIS). From this perspective, social and environmental externalities are interpreted both visually on maps and quantitatively using spatial analysis techniques. Given this interdisciplinary perspective of the contrasting food systems, it is hypothesized that the primary energy sources used in production are fundamental to understanding distance. Although energy is typically discussed in terms of fossil fuel or biological resources, this investigation extends the analysis to include money. Money as a social relation contributes to a spatial understanding of what Marx called the “opposite metamorphosis” or the valorization of commodities taking place between the stages of purchase and sale. The final substantive chapter outlines a policy proposal to reduce the distance of the “opposite metamorphosis” through the issue of a community currency. The issuance of the community currency expands the money ecology and stabilizes sustainable alternative food networks.Introduction -- A contribution to the production of space -- Industrial food and the ideology of growth -- Modeling alternative food networks using the circuit of money capital -- Moving the production of space into a geographic information system-first steps -- A comparative spatial examination of food's circuits of money capital -- Money as social energy -- Reflections and future inquire

The Use of Social Media by Terrorists

With the rise of digital technology, particularly social media, terrorist groups have gained a valuable new tool for furthering their goals. Terrorist propaganda, for the purposes of this brief, is defined as any video, picture, post, or any other form of media posted to the internet to further the cause of the terrorist organization, such as recruitment or communication with followers around the world. The manipulation of technology by non-state actors is not a new phenomenon; however, social media and other new digital technologies have proven a valuable resource for many terrorist organizations. Not only have terrorist groups been adept in using new technologies such as Twitter, Bitcoin, and small drone aircraft, but the use of new technologies has also fundamentally changed their methods of operation [1]. This issue leads us to ask how the interaction between terrorist groups and emerging digital technologies has created challenges in the counter-terrorism landscape of the twenty-first century? In this brief, we specifically address these three questions: (1) how have terrorist groups used social media to further their causes, (2) how has the use of social media changed the operating nature of these groups, and (3) what are governments doing to protect against it? We also suggest policy to counter this emerging threat

Service user experience of the Norfolk youth service

Purpose: There is an international drive to improve mental health services for young people. This study aims to investigate service user experience of a youth mental health service in Norfolk, UK. In addition to suggesting improvements to this service, recommendations are made for the development of youth mental health services in general. Design/methodology/approach: A mixed-methods approach was used. Quantitative data from satisfaction questionnaires were analysed using descriptive statistics and compared between two time points. A semi-structured interview was used to generate qualitative data. Thematic analysis was used to identify themes in the interview transcripts and triangulation was used to synthesise quantitative and qualitative data. Findings: Service users appeared satisfied with the service. Significant improvements in satisfaction were found between two time points. Qualitative analysis identified three main themes that were important to service users, including support, information and personhood. Practical implications: Recommendations for the development of youth mental health services are provided. Although these are based on findings from the Norfolk youth service, they are likely to apply to other mental health services for young people. Originality/value: Mental health care for young people requires significant improvement. The Norfolk youth service is one of the first services of its kind in the UK. The findings from this study might be helpful to consider in the development of youth mental health services across the world

Quantifying triplet formation in conjugated polymer/non-fullerene acceptor blends

Triplet formation is generally regarded as an energy loss process in organic photovoltaics. Understanding charge photogeneration and triplet formation mechanisms in non-fullerene acceptor blends is essential for deepening understanding of photophysics in these important organic photovoltaic materials. Here, we present a comprehensive spectroscopy and morphology study on non-fullerene acceptors ITIC, ITIC-Th, ITIC-2F and Y6, both pristine and blended with reference polymer PffBT4T-C9C13. Atomic force microscopy and grazing-incidence X-ray diffraction provided information regarding the morphology of the films while spectroelectrochemistry combined with microsecond transient absorption spectroscopy allowed triplets and charge carriers to be investigated in detail. Crucially, we used triplet sensitisation to determine molar extinction coefficients of the non-fullerene acceptor triplets (2.7–6.5 × 104 L mol−1 cm−1), allowing triplet populations to be quantified in the blends. Intriguingly, no consistent trends were found in the photophysics of the studied blend systems, with each presenting its own unique mechanism. PffBT4T-C9C13:Y6 showed no triplet formation, only charge carriers that decayed rapidly in a relatively crystalline environment, consistent with the observed highly segregated morphology. In contrast, all blends in the ITIC series produced evidence of considerable triplet formation in addition to charge carriers. PffBT4T-C9C13:ITIC-Th blend produced acceptor triplets irrespective of excitation wavelength, and these were formed via intersystem crossing and/or energy transfer. Conversely, both ITIC and ITIC-2F blends displayed triplet formation via non-geminate recombination of charge carriers, with both NFA and polymer triplets observed. However, PffBT4T-C9C13:ITIC-2F produced a substantially higher charge carrier population than the ITIC blend. Because its triplet formation mechanism relies on the presence of charge carriers, PffBT4T-C9C13:ITIC-2F, with the highest charge carrier population, also had the highest triplet population. These results exemplify the prevalence of triplet states across a range of NFA blend systems, despite the varying formation mechanisms. Furthermore, they showcase that triplet populations can reach very high levels, particularly in cases of concomitantly high charge populations. Since high charge carrier densities correlate with large short circuit currents, this has significant ramifications for organic photovoltaic performance

Post-caldera eruptions and pyroclastic density current hazard in the Main Ethiopian Rift

The eruption of a peralkaline rhyolite magma has never been observed, yet these eruptions are amongst the most common in the Main Ethiopian Rift Valley since 1 Ma and dominate the eruption record of volcanoes that have undergone caldera collapse. The unusual rheological properties of peralkaline rhyolites, in combination with the lack of direct observations of eruptions, means that the style and hazards associated with them is essentially unknown. With 1 million people living within 10 km of a volcano in Ethiopia, and numerous geothermal power stations being built directly on these volcanoes, understanding their eruptive style and hazards is timely, and essential to robustly assess risk. This thesis aims to evaluate the eruptive styles and pyroclastic density current (PDC) hazards of post-caldera peralkaline rhyolite eruptions. I focus on Aluto volcano, a restless caldera system which has seen a multitude of peralkaline rhyolite eruptions over at least the past 16 Ka. By studying the deposits from these eruptions, I attempt to evaluate the styles of eruptive activity these magmas undergo; whether they generate PDCs, how these PDCs are generated, and how mobile they might be. I find that eruptions at Aluto occur across the edifice, akin to a monogenetic field, and that each eruption tends to undergo a very similar eruption sequence, albeit over a range of magnitudes. Eruptions typically begin with the formation of an eruption column, generating tephra fall deposits. Whilst investigating these deposits we have discovered, described and investigated a largely unrecognised type of pyroclast which I term a ‘pumiceous achnelith’. Thermal and ballistic modelling of these pumiceous achneliths indicates that pumice cones are generated by pyroclastic material falling from the sides of these columns, accumulating around the vent. Towards the end of the eruption, the eruption-column becomes unsteady, repeatedly collapsing and re-establishing, generating multiple PDCs. These PDCs usually have a high particle-concentration at their base, and tend to be confined to drainages. In most cases, the final stage of the eruption is marked by the effusion of a silicic lava flow, though it is uncertain how explosive this phase is. Using these insights, I have selected analogue PDC data, combined with modelled collapse heights and a kernel-density vent-susceptibility model, to inform a simple energy-cone model which estimates the inundation footprints of hypothetical PDCs. I employ a Monte-Carlo approach to evaluate a full range of probable eruption scenarios, and I find that the caldera, and its NW, N, and SE flanks, are particularly prone to inundation by PDCs. I combine this with geospatial data of people and infrastructure around Aluto to evaluate the collective risk, and the risk to individuals posed by PDCs. In terms of collective risk, I find that although most PDCs are constrained to within a few kilometers of the edifice, though it is still possible for more distal settlements to be inundated during rarer high-magnitude events. The population of these distal settlements is much denser than in local settlements, meaning that the collective risk is often similar between proximal and distal locations. For the individual, PDC risk is much higher closer to the edifice. I frame this risk amongst ‘everyday’ risks experienced by individuals in Ethiopia, and establish that for residents on the volcano, the time-averaged yearly risk of death by PDC is comparable to that of death by malaria, house-fire, malnutrition or road traffic accident. Using current best-practices, I have produced PDC hazard maps for different stakeholder groups at Aluto. Though there is still great uncertainty surrounding the styles and hazards associated with peralkaline rhyolites globally, this work shows that they’re capable of producing intense eruptions (intensity 7-10); generating moderate to tall eruption columns (3-16 km), which can collapse to form pyroclastic density currents with the potential to devastate local settlements and infrastructure