44 research outputs found
Loss of SOX10 function contributes to the phenotype of human Merlin-null schwannoma cells
No full textLoss of the Merlin tumour suppressor causes abnormal de-differentiation and proliferation of Schwann cells and formation of schwannoma tumours in patients with neurofibromatosis type 2. Within the mature peripheral nerve the normal development, differentiation and maintenance of myelinating and non-myelinating Schwann cells is regulated by a network of transcription factors that include SOX10, OCT6 (now known as POU3F1), NFATC4 and KROX20 (also known as Egr2). We have examined for the first time how their regulation of Schwann cell development is disrupted in primary human schwannoma cells. We find that induction of both KROX20 and OCT6 is impaired, whereas enforced expression of KROX20 drives both myelin gene expression and cell cycle arrest in Merlin-null cells. Importantly, we show that human schwannoma cells have reduced expression of SOX10 protein and messenger RNA. Analysis of mouse SOX10-null Schwann cells shows they display many of the characteristics of human schwannoma cells, including increased expression of platelet derived growth factor receptor beta (PDGFRB) messenger RNA and protein, enhanced proliferation, increased focal adhesions and schwannoma-like morphology. Correspondingly, reintroduction of SOX10 into human Merlin-null cells restores the ability of these cells to induce KROX20 and myelin protein zero (MPZ), localizes NFATC4 to the nucleus, reduces cell proliferation and suppresses PDGFRB expression. Thus, we propose that loss of the SOX10 protein, which is vital for normal Schwann cell development, is also key to the pathology of Merlin-null schwannoma tumours
Based on a true history?: The impact of popular "Medieval Film" on the public understanding of the Middle Ages
No full textThis thesis examines the understanding of the Middle Ages among the UK public and the impact that popular big-budget films which depict the period have on that understanding. Three films released between 2000 and 2009 are chosen for detailed study, their selection being determined by success at the UK box office as a measure of popularity: Lord of the Rings, Return of the King (Jackson, 2003), Kingdom of Heaven (Scott, 2005) and Beowulf (Zemeckis, 2007).
Ten focus group interviews were conducted with nineteen participants, all between eighteen and twenty-six years of age, none of whom had studied the Middle Ages at GCSE level (age 14-16) or higher. In these groups, participants discussed their knowledge of the Middle Ages, were shown a film, and then discussed what they had seen. Participants were asked open-ended interview questions to encourage them to respond in their own terms and define what was important to them. As a result, topics ranged widely. In preliminary discussions, participants discussed how they understood the period, their academic, experiential and pop-culture sources of knowledge, their definitions of the similar terms ‘medieval’ and ‘Middle Ages’ and also their ideas about medieval culture, religion, warfare and crusade. After the films, participants discussed what they had seen usually in the context of what they already knew, sometimes constructing false memories of what they had seen which fit with their previous knowledge. Often they used the language of historical veracity to criticise the film for other related reasons (like poor filmmaking or inappropriate accents). They found support for many of their historical misconceptions in the films, but, rather than accepting all they saw as historical truth, they engaged in a complex critical discourse with what they were shown.
The findings of this thesis have implications for medieval (and medievalism) studies, public history, and for the delivery of history in primary, secondary and higher education
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Culture après le déluge: heritage ecology after disaster
No full textThis PhD dissertation examines the relationships between cultural heritage and the environment, focusing specifically on the devastation and rebuilding of New Orleans, Louisiana after Hurricane Katrina in 2005. Departing from conventional approaches to the natural world (such as documentation- and conservation-based approaches), this thesis adopts a developmental-systems based approach to cultural heritage in order to construct a new way of interpreting it, within the specific context of natural disaster. This new approach, termed ‘heritage ecology’, reinterprets cultural heritage in two ways: first, as a physical assemblage of sites, materials, traditions, beliefs, and practices that are constructed in significant ways by their natural environments; and second, as a metaphorical ecosystem which impacts back on the assessment and construction of that natural environment in turn.
In order to construct this approach, the thesis poses three interrelated questions: how is cultural heritage transformed as a result of disaster, how do societies rebuild their heritage after disaster, and how does heritage contribute to the rebuilding process? Examining a rebuilding process in real-time provides a unique window on these processes; events and developments in New Orleans taken from the first four years of recovery (2005-2009) suggest that prior understandings of how societies rebuild themselves after disaster have neglected crucial aspects of cultural heritage that are integral to that process. The examination of data from the case study -- data of diverse forms, such as historiography, the culinary arts, music, the built environment, and memorial sites and landscapes -- reveals the limitations of traditional approaches to heritage and prompts a reassessment of a range of issues central to heritage research, issues such as materiality, authenticity, and commodification. This study moreover incorporates into heritage research concepts previously unconsidered, such as infrastructure and policy. In the coming century of global climate change and increased environmental hazards, this last theme will become increasingly central to heritage policy and research; the dissertation concludes accordingly, with a reflection on contingency and future disaster
Designing 21st Century Standard Ware: The Cultural Heritage of Leach and the Potential Applications of Digital Technologies
No full textThis practice-based research investigates the potential applications of digital manufacturing technologies in the design and production of hand-made tableware at the Leach Pottery. The methodology for the research establishes an approach grounded in my previous experience as a maker that is informed by an open, experimental, emergent, and responsive framework based on Naturalistic Inquiry.
A critical contextual review describes the cultural heritage of Leach which, for the purposes of the research, is developed through the Leach Pottery as a significant site, the historical production of the iconic Leach Standard Ware and the contemporary production of Leach Tableware. This is followed by an examination of Potter’s Tools in the Leach production environment, and a review of makers’ digital ceramic practice.
The contextual review is followed by an explication of ‘standards’ presented through visual lineages of Standard Ware and Leach Tableware to define ‘standard’ at a design (macro) level, followed by an examination of how ‘standard’ operates at a making (micro level) level. This chapter presents new knowledge in relation to defining the visual field of Leach Pottery tableware production and its standards of design.
A chapter focussed on practice presents the outcomes and analysis of my engagement with digital manufacturing technologies which resulted in the development of new tools to support Leach Tableware production and the interrogation of Leach forms, in different mediums, which led to the creation of Digital-Analogue Leach forms. The practice culminated in the design and development of new 21st century Standard Ware: a range of 9 forms, called Echo of Leach, that were developed by myself using digital and analogue methods: the designs were realised by myself, the Leach Studio, and a further four makers. The outcomes of the research were presented in a three month exhibition at the Leach Pottery in 2013.
The conclusions of the research draw on the key points raised in the analysis of the practice and relate these to the approaches to making pottery that are highlighted in the cultural heritage of Leach in the contextual review. These are also discussed in relation to ways in which these findings could be taken forward into development of knowledge about Standard Ware, especially in a broader studio pottery context
Loss of SOX10 function contributes to the phenotype of human Merlin-null schwannoma cells.
No full textLoss of the Merlin tumour suppressor causes abnormal de-differentiation and proliferation of Schwann cells and formation of schwannoma tumours in patients with neurofibromatosis type 2. Within the mature peripheral nerve the normal development, differentiation and maintenance of myelinating and non-myelinating Schwann cells is regulated by a network of transcription factors that include SOX10, OCT6 (now known as POU3F1), NFATC4 and KROX20 (also known as Egr2). We have examined for the first time how their regulation of Schwann cell development is disrupted in primary human schwannoma cells. We find that induction of both KROX20 and OCT6 is impaired, whereas enforced expression of KROX20 drives both myelin gene expression and cell cycle arrest in Merlin-null cells. Importantly, we show that human schwannoma cells have reduced expression of SOX10 protein and messenger RNA. Analysis of mouse SOX10-null Schwann cells shows they display many of the characteristics of human schwannoma cells, including increased expression of platelet derived growth factor receptor beta (PDGFRB) messenger RNA and protein, enhanced proliferation, increased focal adhesions and schwannoma-like morphology. Correspondingly, reintroduction of SOX10 into human Merlin-null cells restores the ability of these cells to induce KROX20 and myelin protein zero (MPZ), localizes NFATC4 to the nucleus, reduces cell proliferation and suppresses PDGFRB expression. Thus, we propose that loss of the SOX10 protein, which is vital for normal Schwann cell development, is also key to the pathology of Merlin-null schwannoma tumours
The role of the international patent system in the transfer of technology to West Africa : case studies : Ghana and Nigeria
No full textThe principal aim of this thesis is to undertake a critical
examination of the role of the international patent system in the
transfer of technology to West Africa, particularly Ghana and Nigeria.
It focuses mainly on the patent systans and technology regulatory
regimes of the two countries. The study is intended to identify and
evaluate the impact of the international patent system on the transfer
and development of technology in this area.
The first chapter provides a theoretical foundation to some of
the more practical issues to be discussed in the subsequent chapters.
The Paris Convention and the diplomatic revision exercise thereof, as
well as other efforts and policies regarding patents and technology
transfer at various levels are discussed in Chapter Two. Chapters
Three to Eight consider the two case-studies undertaken in this
thesis. Chapter Three begins with the historical development of the
patent system in both Ghana and Nigeria, and the remaining chapters
continue with a discussion of the present patent and technology
regulatory regimes of both countries. Based on facts and figures the
two case-studies examine critically the patent law and systems and
technology transfer laws of these two countries including other
related institutional measures highlighting their strengths and
weaknesses.
The study argues that if the patent systems of both countries
are to play a meaningful role in the transfer and developnent of
technology they nust be utilized as a tool of economic policy and also
be related to the technology transfer regimes which nust necessarily
be integrated into the national technology policy which should, in
turn, be made an integral part of the entire national developnent
plan. It is concluded that it is only in this way that the patent
system can effectively contribute to the transfer of technology and
the development of indigenous technological capabilities in the two countries
EphB Signaling Directs Peripheral Nerve Regeneration through Sox2-Dependent Schwann Cell Sorting
No full textSummaryThe peripheral nervous system has astonishing regenerative capabilities in that cut nerves are able to reconnect and re-establish their function. Schwann cells are important players in this process, during which they dedifferentiate to a progenitor/stem cell and promote axonal regrowth. Here, we report that fibroblasts also play a key role. Upon nerve cut, ephrin-B/EphB2 signaling between fibroblasts and Schwann cells results in cell sorting, followed by directional collective cell migration of Schwann cells out of the nerve stumps to guide regrowing axons across the wound. Mechanistically, we find that cell-sorting downstream of EphB2 is mediated by the stemness factor Sox2 through N-cadherin relocalization to Schwann cell-cell contacts. In vivo, loss of EphB2 signaling impaired organized migration of Schwann cells, resulting in misdirected axonal regrowth. Our results identify a link between Ephs and Sox proteins, providing a mechanism by which progenitor cells can translate environmental cues to orchestrate the formation of new tissue.PaperFlic
Questioning modern time with Hannah Arendt and Walter Benjamin
No full textFour texts from Arendt and Benjamin are the scene of our thinking. We enact the question of time as a refusal to abide by the modern conception of time, where the present is the only ground of the real. We argue for a notion of time, in which all that-has-been is considered a site of real experience.
Firstly we discuss Arendt's book On Revolution. Through issues such as history, the eventful and revolt we show the usefulness of the question of time to further our understanding. Secondly in Arendt's 'What is Freedom', freedom is discussed beyond the private individual, as a matter of plurality, of living together. The question of time shows freedom grounded beyond the individual's present, in the historical time of plurality.
With Benjamin's essay 'On some motifs in Baudelaire' we show poetry as a challenge to the symbolic environment of the commodity world. Poetry appears as a keeper of our relation to the time of memory and language that precedes us. In Benjamin's 'The Work of Art in the Age of Its Technological Reproducibility', we distinguish art from technology through the question of time. Art's experience
involves an active relation with what-has-been, with past generations; it challenges the technological way of relating to the world that destroys the depth of human expenence.
Finally, Arendt and Benjamin are presented together, stressing their use of history and tradition to address the problems of modernity. Their effort to think the eventful is related to their negation of historical progression. From the question of time, their thinking teaches us a form of critique that denies the preconception of presence as being the totality of the real. Under their gaze presence is revealed as a changing surface under the sway of history, of time
Fiction and film : the influence of cinema on writers from Trinidad and Jamaica 1950-1985
No full textThis thesis considers the relationship between film and novels that were published by writers from Trinidad and Jamaica between the years 1950 - 1985. Through close textual analysis and by utilising a combination of cinematic and literary theories, the thesis examines the extent to which filmic references have been absorbed into
fictional writing and reflects upon the implications for such cultural transformations. The thesis also provides a detailed, historical background to the development of cinema in both islands, with a further analysis of the specific role played by the Hindi film in Trinidad. The interdisciplinary nature of the literary analysis and the detailed historical data contained herein should be considered an original contribution to knowledge within the field of Caribbean studies
Author Correction: A detailed map of Higgs boson interactions by the ATLAS experiment ten years after the discovery
No full textIn the version of this article initially published, the ATLAS Collaboration
author names, affiliations and acknowledgements were omitted and
have now been included in the HTML and PDF versions of the article
