12,178 research outputs found
Embodying entrepreneurship: everyday practices, processes and routines in a technology incubator
The growing interest in the processes and practices of entrepreneurship has
been dominated by a consideration of temporality. Through a thirty-six-month
ethnography of a technology incubator, this thesis contributes to extant
understanding by exploring the effect of space. The first paper explores how
class structures from the surrounding city have appropriated entrepreneurship
within the incubator. The second paper adopts a more explicitly spatial analysis
to reveal how the use of space influences a common understanding of
entrepreneurship. The final paper looks more closely at the entrepreneurs within
the incubator and how they use visual symbols to develop their identity. Taken
together, the three papers reject the notion of entrepreneurship as a primarily
economic endeavour as articulated through commonly understood language and
propose entrepreneuring as an enigmatic attractor that is accessed through the
ambiguity of the non-verbal to develop the ‘new’. The thesis therefore contributes
to the understanding of entrepreneurship and proposes a distinct role for the non-verbal in that understanding
Unraveling the effect of sex on human genetic architecture
Sex is arguably the most important differentiating characteristic in most mammalian
species, separating populations into different groups, with varying behaviors, morphologies,
and physiologies based on their complement of sex chromosomes, amongst other factors. In
humans, despite males and females sharing nearly identical genomes, there are differences
between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides
the genome with a distinct hormonal milieu, differential gene expression, and environmental
pressures arising from gender societal roles. This thus poses the possibility of observing
gene by sex (GxS) interactions between the sexes that may contribute to some of the
phenotypic differences observed. In recent years, there has been growing evidence of GxS,
with common genetic variation presenting different effects on males and females. These
studies have however been limited in regards to the number of traits studied and/or
statistical power. Understanding sex differences in genetic architecture is of great
importance as this could lead to improved understanding of potential differences in
underlying biological pathways and disease etiology between the sexes and in turn help
inform personalised treatments and precision medicine.
In this thesis we provide insights into both the scope and mechanism of GxS across the
genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK
Biobank. We found small yet widespread differences in genetic architecture across traits
through the calculation of sex-specific heritability, genetic correlations, and sex-stratified
genome-wide association studies (GWAS). We further investigated whether sex-agnostic
(non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we
studied the potential functional role of sex differences in genetic architecture through sex
biased expression quantitative trait loci (eQTL) and gene-level analyses.
Overall, this study marks a broad examination of the genetics of sex differences. Our findings
parallel previous reports, suggesting the presence of sexual genetic heterogeneity across
complex traits of generally modest magnitude. Furthermore, our results suggest the need to
consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms
Probing the Intergalactic medium properties using X-ray absorption from multiple tracers
Based on the Lambda Cold Dark Matter concordance cosmological model (ΛCDM), the majority of baryons exist in the Intergalactic medium (IGM). It is extremely challenging to observationally trace the IGM, especially at higher temperatures and low densities. Post reionisation, the vast majority of hydrogen and helium is ionized in the IGM and therefore, the observation of metals is essential for parametrising the IGM properties.
My hypothesis is that there is significant absorption in the diffuse highly ionisied IGM and that this IGM column density increases with redshift. I use X-ray absorption in multiple tracers which yields information on the total absorbing column density of the matter between the observer and the source. Clear IGM detections require tracer sources that are bright, distant, and common enough to provide a good statistical sample of IGM lines of sight (LOS). To more accurately isolate any IGM contribution to spectral absorption, I examine each tracer host type to realistically model it, in addition to using appropriate intrinsic continuum curvature models. I test the robustness of the result from a number of perspectives. I examine the impact of the key underlying assumptions that affect the column density calculations including metallicity, ionisation and location of absorption. I look for any evidence of evolution in the parameters.
In Chapters 2, 3, 4 and 5, I use gamma-ray bursts (GRBs), blazars and quasars (QSOs) to estimate IGM baryon column densities, metallicity, temperature, ionisation parameters and redshift distributions. My results for each tracer
are presented in each of the respective chapters and collectively in Chapter 5 which includes comparative analysis.
In conclusion, through the work in this thesis I demonstrate a consistent case for strong X-ray absorption in the IGM on the LOS to three different tracer types and that it is related to redshift. The results are consistent with the ΛCDM model for density, temperature and metallicity. Given these results, I would recommend that studies of distant objects should not follow the convention of assuming all X-ray absorption in excess of our Galaxy is attributed to the host galaxy, that the host is neutral and has solar metallicity. Instead, particularly at higher redshift, absorption in the IGM should be accounted for to give more accurate results for the tracer host properties
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Evaluation of a Remote Implementation of the Well-Being Promotion Program with Middle School Students during COVID-19
The COVID-19 pandemic and pivot to emergency remote teaching changed the way in which many students access school-based mental health interventions. Furthermore, the effects of the pandemic heightened distress and decreased life satisfaction amongst many youth, increasing the need for schools to provide targeted mental health supports (Lazarus et al, 2021; Magson et al., 2021). Empirically supported Tier 2 mental health interventions exist (i.e., the Well-Being Promotion Program; Suldo, 2016), but little is known about how these interventions can be adapted and feasibly implemented in remote school contexts. This retrospective case study evaluated the implementation of a remote version of the Well-Being Promotion Program, a targeted positive psychology intervention, with eighth grade students during the COVID-19 pandemic. The study aimed to (1) to describe the co-design process through which a research-practice partnership modified the WBPP for remote delivery and (2) to explore the implementation strategies that influenced the feasibility of implementing the resulting digital version of the WBPP. The study used qualitative data (e.g., meeting notes, interviews and written feedback from providers, students, and caregivers) and quantitative data (e.g., pre-/post-measures, intervention integrity, attendance) to evaluate the co-design process and the feasibility of the adapted WBPP. Through co-design, the intervention was modified to be facilitated via videoconference, to use digital versions of WBPP materials, to use email to share with caregivers the handouts and a recorded version of the information session, to add additional sessions for data collection, and to adapt language to align with school vernacular. Using reflexive thematic analysis (Braun & Clarke, 2006; Braun et al., 2019), themes were constructed from the data to provide insight into the implementation strategies used by the research-practice partnership to influence feasibility. Findings suggest that (a) maintaining the structure of the WBPP, (b) using technology for remote implementation, (c) collaborating through the research-practice partnership, and (d) recognizing the effectiveness of intervention efforts influenced the feasibility of the remote implementation. Lessons learned from this case study suggest that research-practice partnerships can be critical for influencing the feasibility of intervention implementation in local school contexts, especially during novel situations such as the COVID-19 pandemic
Cooking the wild: the role of the Lundayeh of the Ulu Padas, (Sabah, Malaysia) in managing forest foods and shaping the landscape
This thesis provides an account of the Lundayeh subsistence system as found in the villages of Long Pasia and Long Mio, situated in the Ulu Padas, Sabah. The research focuses on Lundayeh food and diet, describing the diversity of resources used and the importance of forest foods. Comparison with studies from elsewhere in Borneo suggests that there are many similarities between Lundayeh practices and those of other highland peoples. These data are used to critically examine the concepts of 'wild' and 'wilderness', considering whether these concepts are meaningful, either analytically or for the Lundayeh. Investigation of the way in which the Lundayeh manipulate and manage their resources suggests that they have had a profound influence on their environment. Consequently, the Ulu Padas cannot be described as a wilderness, nor its resources as wild. The extent to which the Lundayeh themselves construct the categories of 'wild' and 'cultivated' foods is investigated through examining how these resources are owned, and their different roles in the diet. These data suggest that the Lundayeh recognise that there is no simple dichotomy of 'wild' and 'cultivated', but rather, that there is a gradation between these two categories. There is also evidence to suggest that the Lundayeh do not consider any resources as wild, in the sense of being uninfluenced by people. The environmental perceptions of the Lundayeh are also investigated, and how these have been shaped by their particular way of life, history, beliefs and knowledge systems. It is apparent that for the Lundayeh, the Ulu Padas is a cultural landscape. However, this is changing, as a result of recent social and environmental changes. This thesis concludes by examining the impact of changing perceptions on how the Lundayeh are managing their environment, and on their attitudes towards conservation
Balancing the urban stomach: public health, food selling and consumption in London, c. 1558-1640
Until recently, public health histories have been predominantly shaped by medical and scientific perspectives, to the neglect of their wider social, economic and political contexts. These medically-minded studies have tended to present broad, sweeping narratives of health policy's explicit successes or failures, often focusing on extraordinary periods of epidemic disease viewed from a national context. This approach is problematic, particularly in studies of public health practice prior to 1800. Before the rise of modern scientific medicine, public health policies were more often influenced by shared social, cultural, economic and religious values which favoured maintaining hierarchy, stability and concern for 'the common good'. These values have frequently been overlooked by modern researchers. This has yielded pessimistic assessments of contemporary sanitation, implying that local authorities did not care about or prioritise the health of populations. Overly medicalised perspectives have further restricted historians' investigation and use of source material, their interpretation of multifaceted and sometimes contested cultural practices such as fasting, and their examination of habitual - and not just extraordinary - health actions. These perspectives have encouraged a focus on reactive - rather than preventative - measures.
This thesis contributes to a growing body of research that expands our restrictive understandings of pre-modern public health. It focuses on how public health practices were regulated, monitored and expanded in later Tudor and early Stuart London, with a particular focus on consumption and food-selling. Acknowledging the fundamental public health value of maintaining urban foodways, it investigates how contemporaries sought to manage consumption, food production waste, and vending practices in the early modern City's wards and parishes. It delineates the practical and political distinctions between food and medicine, broadly investigates the activities, reputations of and correlations between London's guild and itinerant food vendors and licensed and irregular medical practitioners, traces the directions in which different kinds of public health policy filtered up or down, and explores how policies were enacted at a national and local level. Finally, it compares and contrasts habitual and extraordinary public health regulations, with a particular focus on how perceptions of and actual food shortages, paired with the omnipresent threat of disease, impacted broader aspects of civic life
Uso de las histonas circulantes y sus modificaciones post-traduccionales como biomarcadores en sepsis y shock séptico
La sepsis es una afección potencialmente mortal causada por una respuesta anormal del huésped a una infección, produciendo respuestas fisiológicas alteradas que dañan los propios tejidos del paciente y pueden provocar disfunción orgánica e incluso la muerte. Asimismo, algunos pacientes sépticos progresan a shock séptico, caracterizado por alteraciones circulatorias, celulares y metabólicas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunológico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresión, la alta complejidad de la fisiopatología de la sepsis requiere una mayor investigación para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citotóxicos en la sepsis, ya que actúan como patrones moleculares asociados a daño, que inducen estrés oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activación de la piroptosis, un mecanismo de muerte celular programada que produce inflamación mediante la expresión de IL-18, IL-1β and IL-1α. Sin embargo, a pesar de la evidencia de activación del inflamasoma en las células inmunes durante la sepsis, se desconoce si las histonas extracelulares son capaces de activar los inflamasomas endoteliales y sus consecuencias. En este trabajo destacamos el papel previamente desconocido de las histonas extracelulares, mediando la activación del inflamasoma NLRP3 y la piroptosis en las células endoteliales, contribuyendo a la disfunción endotelial y la desregulación de la respuesta inmune mediada por el endotelio. Asimismo, también demostramos cómo la acetilación de histonas disminuye la activación de la piroptosis. Además, demostramos que la piroptosis se produce en pacientes con shock séptico y los niveles de histonas circulantes se correlacionan con la expresión de citoquinas proinflamatorias y citoquinas piroptóticas, la liberación de factores de adhesión endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones clínicas. De manera similar, hemos analizado las respuestas inmunorelacionadas que ocurren durante las primeras etapas de la sepsis con el objetivo de proporcionar nuevos datos comparando las cantidades de citoquinas, inmunomoduladores y otros mediadores endoteliales en pacientes críticamente enfermos no sépticos, sépticos y de shock séptico. Nuestro enfoque ayudará a caracterizar rápidamente las respuestas inmunes alteradas en pacientes sépticos y de shock séptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilación del ADN en el control del sistema inmune séptico. Nuestros resultados demostraron el papel central de la metilación del ADN modulando la respuesta molecular en los pacientes de shock séptico y contribuyendo a la inmunosupresión, a través de la alteración de los patrones de metilación de los promotores de IL-10 y TREM-2.Sepsis is a life-threatening condition caused by an abnormal host response to an infection that produce altered physiological responses which damages own tissues of the patient and can result in organ dysfunction and in some cases death. Likewise, a subset of septic patients progresses to septic shock, characterized by substantial circulatory, cellular and metabolic abnormalities, which substantially increase the risk of mortality. Sepsis is characterized by a malfunction of the immune system and it can lead to an altered immune response and immunosuppression. Moreover, the high complexity of the pathophysiology of sepsis requires of further investigation to characterize the immune responses in sepsis and septic shock. Likewise, circulating extracellular histones have gained relevance as cytotoxic mediators in sepsis pathophysiology, since they act as damage-associated molecular patterns, which induce oxidative stress and activate NLRP3 inflammasome. Subsequently, inflammasome mediates pyroptosis activation, a programmed cell death mechanism that produces inflammation through the release of IL-18, IL-1β and IL-1α. However, despite inflammasome activation may occur in immune cells during sepsis, it is unknown if this process also takes place in endothelial cells and particularly whether extracellular histones are capable of activating endothelial inflammasomes and their consequences. In this work we highlight a previously unknown role for extracellular histones, that mediates the activation of NLRP3 inflammasome and pyroptosis in endothelial cells by contributing to endothelial dysfunction and the dysregulation of the immune response mediated by endothelium. Likewise, we demonstrated how histone acetylation decreases pyroptosis activation. Furthermore, we show how pyroptosis occurs in septic shock patients and how circulating histone levels correlate with the expression of pro-inflammatory and pyroptotic cytokines, the release of endothelial adhesion factors and septic shock severity. We propose histone-mediated pyroptosis as a new target to develop clinical interventions. Similarly, we have analyzed the immune-related responses occurring during the early stages of sepsis with the aim of providing new data by comparing the amounts of cytokines, immune modulators and other endothelial mediators in critically-ill non-septic patients, septic and septic shock patients. Our approach will help to rapidly characterize the altered immune responses in septic and septic shock patients admitted in the Intensive Care Unit. Finally, we also analyzed the role of DNA methylation in the control of septic immune system. Our results demonstrated the central role of DNA methylation modulating the molecular response in septic shock patients and contributing to immunosuppression, through the alteration of DNA methylation patterns of IL-10 and TREM2 promoters
Reforming the United Nations
The thesis deals with the financial crisis that the United Nations faced starting in 1985 when the US Congress decided to withhold a significant part of the US contribution to the UN regular budget in order to force a greater say for the major contributors on budgetary issues, budgetary restraint and greater efficiency. The UN responded by the adoption of resolution 41/213 of 19 December 1986 that was based on the recommendations of a Group of High-level Intergovernmental Experts ("G-18") set up a year earlier. A new system was introduced regarding the formulation of the regular budget of the United Nations Organisation and a broader process of reform was initiated including a restructuring of the Secretariat and of the intergovernmental machinery in the economic and social fields. After an introductory chapter (Chapter I), the thesis examines the UN problems at the budgetary/financial and administrative/structural levels, the solutions proposed from within and without the United Nations established framework and the actual attempts at reform (Chapters II and ifi). The realisation that the implementation of reforms is rather disjointed and often unsuccessful (e.g. the failure to restructure the intergovernmental machi.neiy) prompts a search for the deeper causes of the UN problems at the political level and the attitudes of the main actors, namely the USA, the USSR, some up-and-coming states, notably Japan, the Third World states and, finally, of the UN Secretary-General and the Secretariat (Chapter 1V). Although the financial crisis may have subsided since 1988 and the USA seem committed to paying up their dues, the deeper UN crisis of identity has not been resolved and is expected to resurface if no bold steps are taken. In that direction, some possible alternative courses for the UN in the future are discussed drawing upon theory and practice (Chapte
Botanical Journeys and China's Colonial Frontiers: 1840-1940
Over recent years, a body of scholarship has emerged on the topic of European and American travel writing in China. This thesis contributes to this growing field by examining four writers who travelled in China and worked as plant collectors and botanists. Largely forgotten today, these writers were influential and successful in their own day. Despite differences in geographical location and historical period, there are a number of common links that make a comparison of these travel writings productive. As travellers seeking botanical rarity and novelty, these writers explored regions of China unknown in the West, which over a period of one hundred years expanded outwards from the fringes of the treaty port areas to more remote regions of China's southwest. These writers, therefore, were on the frontiers of Western knowledge of China, and an examination of their writing provides important insights into the ways in which racial, geographical, and ecological differences were articulated and understood in the context of colonial and scientific exploration. While discussing how such differences have imperial significance, this study will also call attention to the instability of colonialist discourse in the context of China. Rather than focus exclusively on questions of imperialism, this study will show how representations of China's periphery regions also speak to metropolitan literary and cultural concerns, and a close reading of these travel writings shows that China offered powerful imaginary landscapes for home audiences. This project is organised chronologically and the chapters are divided according to the authors, with the exception of the first chapter where I introduce the historical and theoretical framework of the study and the final concluding chapter where I consider the significance of this study in the context of modern China
A Cornish palimpsest : Peter Lanyon and the construction of a new landscape, 1938-1964
The thesis examines the emergence of Peter Lanyon as one of the few truly innovative British landscape painters this century. In the Introduction I discuss the problematic nature of landscape art and consider the significance of Lanyon's discovery that direct description and linear perspective can be replaced with allusive representational elements by fusing the emotional and imaginative life of the artist with the physical activity of painting. Chapter One concentrates on the period 1936-8 when Lanyon was taught by Borlase Smart, a key figure in the St Ives art colony between the wars. Chapter Two examines the influence of Adrian Stokes and the links between Lanyon's painting and the theories developed in books such as Colour and Form and The Quattro Cento. Chapter Three analyses the period 1940-45 when Lanyon was directly influenced by the constructivism of Nicholson, Hepworth and Gabo. I look closely at their approaches to abstraction and assess Lanyon's relative position to them. The importance of Neo-Romanticism and the status of St Ives as a perceived avant-garde community is also addressed. In Chapter Four I discuss how Lanyon resolved to achieve a new orientation in his art on his return from wartime service with the RAF by synthesising constructivism, and traditional landscape. The Generation and Surfacing Series demonstrate his preoccupation with a sense of place, a fascination with the relationships between the human body and landscape and his struggle to find a technique and style that was entirely his own. His sense of existential insideness is discussed in Chapter Five through an examination of the work derived from Portreath, St. Just and Porthleven - key places in Lanyon's psychological attachment to the landscape of West Penwith. In Chapter Six I examine Lanyon's attachment to myths and archetypal forms, tracing the influence of Bergson's vitalist philosophy as well as his use of Celtic and classical motifs. Chapter Seven is a discussion of the malaise evident in Lanyon's work by 1955 and the impact of American Abstract Expressionism at the Tate Gallery a year later. In the summer of 1959 Lanyon joined the Cornish Gliding Club and Chapter Eight looks at how this necessitated a dynamic, expanded conception of the landscape and a re-thinking of relations within the picture field. The ability to dissolve boundaries encouraged him to break down distinctions between painting and construction so that abstract sculptural elements were now assembled into independent works of art. Finally, Chapter Nine assesses Lanyon's overall position in relation to his early influences and to St Ives art as a whole, his response to new directions in art coming out of London and NewYork in the early 1960s and the importance of travel as a stimulus for further realignment in his artistic and topographical horizons. His pictorial inventiveness and vitality remained unabated at the time of his death and would undoubtedly have continued to be enriched by travel abroad and contact with new movements in modem art on both sides of the Atlanti
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