1,442 research outputs found

    DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire

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    The majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire

    George MacLeod’s open-air preaching: performance and counter-performance

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    Stuart Blythe uses the methodology of performance to analyse George MacLeod’s open-air preaching. He points out that MacLeod’s preaching was derived from a theology of the incarnation, and an understanding of the paradoxes and dichotomies of common human life. This preaching, Blythe suggests, was also a counter-performance in the context of outlooks and ideologies inimical to the gospel. The paper raises interesting issues related to preaching as performance, and the further question as to whether or not the life and work of the Church as a whole might now be better understood as a counter-performance.Publisher PD

    Redemption in the work of Francis Stuart

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    The idea of redemption is central to an understanding of the work of Francis Stuart. Through an examination of its development and expression, it is possible to demonstrate the integrity of his work and its distinctive qualities. Such a demonstration is necessary because Stuart's writing has been subjected to comparatively little scholarly inquiry, although reviews of his work, especially that produced since 1949, suggest that it is impressive and important. First, a general background to Stuart's work, a discussion of the special problems associated with reading it, and a summary of his corpus is provided. This indicates that the idea of redemption is important to his earliest writing. The state of redemption is shown to be a necessary apotheosis for Stuart's outcast heroes; it involves spiritual suffering through which may be found a sense of reintegration and a higher reality. This is expressed through interrelated themes such as those of gambler, artist and ordinary man; mystic and criminal; sacred and profane love; and spirituality and the mundane. The nature of the redemptive experience is further elaborated by distinctive, complex motifs, especially the hare, the ark and the woman-Christ. Their recurrence provides an important element in the unity of Stuart's work. Because Stuart's idea of the outcast raises important biographical questions, an examination of the relationship between Stuart's life and his work is made. Finally, the way in which the idea of redemption exists in the language structures of Stuart's novels is examined, with especial reference to his most recent work, The High Consistory. The thesis shows that the development of the these of redemption demonstrates the integrity of Stuart's work

    John Stuart Mill’s projected science of society: 1827-1848

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    The purpose of the thesis is to examine John Stuart Mill’s political thought from about 1827 to 1848 as an exercise in intellectual history. It focuses, first, on Mill’s view, formulated by the late 1830s, that contemporary society was ‘civilized’, and second, on his project of a science of society, which he aspired to develop in the late 1830s and early 1840s. By the late 1830s, Mill came to the view that his contemporary society was a ‘commercial society or civilization’, dominated by the middle, commercial class. The first part of my thesis, constituted by Chapters 2-4, discusses the way in which Mill formed his notion of civilization, and what he meant by the term ‘civilization’. Mill paid attention to the implications of the rise of the middle class, and regarded such phenomena of contemporary society as the corruption of the commercial spirit and excessive social conformity as an inevitable consequence of the rise of the middle class. The second part of the thesis, constituted by Chapters 5-9, examines Mill’s projected science of society. In the late 1830s and early 1840s, Mill attempted to develop a new science of society whose subject-matter was the nature and prospects of commercial, civilized society. This aspiration culminated in A System of Logic, published in 1843. In examining Mill’s projected science, I pay particular attention to the fact that he conceived new sciences of history and of the formation of character, both of which were indispensable in his project, although he failed to give a complete account of these sciences. My thesis shows that the implications of his interest both in history and in the formation of character are more significant than Mill scholars have assumed

    Corrigendum: Pneumococcal vaccine impacts on the population genomics of non-typeable haemophilus influenzae: (Microbial Genomics 2021; 9, 10.1099/mgen.0.000209)

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    There was a change in the author names in the published article. The new list should read: David W. Cleary1,2, Vanessa T. Devine3, Denise E. Morris1, Karen L. Osman1, Rebecca A. Gladstone4, Stephen D. Bentley4, Saul N. Faust1,5, Stuart C. Clarke1,2,6 1Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK. 2NIHR Southampton Biomedical Research Centre, University Hospital Southampton Foundation NHS Trust, Southampton, UK. 3Northern Ireland Centre for Stratified Medicine and Clinical Translational Research Innovation Centre, Londonderry, UK. 4Pathogen Genomics, Wellcome Trust Sanger Institute, UK. 5NIHR Southampton Clinical Research Facility, University Hospital Southampton Foundation NHS Trust, Southampton, UK. 6Global Health Research Institute, University of Southampton, Southampton, UK.</p

    A systematic analysis of user experience dimensions for interactive digital narratives

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    Providing intelligent feedback to aid authoring has been proposed as a way to speed up authoring, give the author more control, and to enable the authoring of more complex interactive narratives. However, there is little research investigating what concrete feedback items would be useful for interactive digital narrative (IDN) creators. In this paper, we discuss potentially useful feedback items in relation to authoring goals and concerns. We perform a systematic literature review to make a list of concrete feedback items of interest related to the most emphasised concern of authoring - the effect of the interactive narrative on the user. We identify 47 User Experience (UX) dimensions in the IDN literature that could serve as useful feedback items, covering 8 categories - Agency, Cognition, Immersion, Affect, Drama, Rewards, Motivation and Dissonance. This list combines and untangles how different IDN researchers have interpreted and expressed interest in the complex idea of UX in the past decade and gives us insight into what concrete aspects of UX might be useful to estimate via automated feedback

    Educational philosophy: what's relevant to contemporary pedagogy??

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    During traditional pedagogy training, new teachers must learn a myriad of educational philosophies from different philosophers and psychologists.How do children learn and how must educators teach them is the question that is answered by each philosophy. Is a child's aptitude determined by genetics (nature) or by environmental influences (nurture)? This paper will examine different educational philosophies of great thinkers; some who believe that children are genetically predisposed to intelligence and others who posit that all intelligence is experiential. It will also discuss which philosophies are relevant to teachers in contemporary times.M.A.Includes abstractIncludes bibliographical referencesby Corissa T. Swinto

    Stuart T. Haines, PharmD, BCPS, BCACP, BC-ADM

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    Stigma Unraveled: Addiction Unmasked

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    Poster Presenter: Becky Hall Research Team: Becky Hall, Stuart T. Haines, Jefferson Parker, Brynn Knox, Carolanne Wartman, Charles Richardson, Kim Adcock, Brenda Foster, & Sophie Durham Abstract: Stigma Unraveled: Addiction Unmasked is a one-day workshop with an online community of practice for health professionals. It aims to reduce stigma, encourage screening for SUD, foster open conversations about substance use, and improve referrals to local resources

    Beauty for the Present: Mill, Arnold, Ruskin and Aesthetic Education

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    The present thesis examines the idea of aesthetic education of three eminent Victorians: John Stuart Mill, Matthew Arnold and John Ruskin. By focusing on the essence of what they meant with ‘the cultivation of the beautiful’ and, more importantly, the way their ideas of beauty informed their criticism of society, my study aims to contribute to our understanding of the idea of aesthetic education in the Victorian context and, further, to participate in a recent debate about the nature of beauty and aesthetic education. Chapter One focuses on John Stuart Mill’s concept of ‘feeling’ in a series of essays. I will demonstrate how Mill’s idea of ‘aesthetic education’ was an ‘education of feelings,’ and moreover, how this idea was integrated into his literary criticism, his later critique of democratisation, his description of an ideal liberal society and even his own style of writing. Chapter Two contains a comparative study of Matthew Arnold and Friedrich Schiller. Through a rereading of Arnold, I will argue that his idea of aesthetic education is essentially Schillerian and that their resemblance consists primarily in their stress on the importance of aesthetic unity for modern life, which was becoming increasingly fragmentary and multitudinous. Chapter Three examines John Ruskin’s idea of aesthetic education and concentrates particularly on the cultivation of perception. Perception, as I shall show, was pivotal in Ruskin’s idea of aesthetic education. Just as what happened in Mill and Arnold, the emphasis on the education of seeing continued from his early writings well into his art and social criticisms. It not only differentiated him from his fellow art critics; the conviction that people should perceive with a pure heart also enabled him to link observation of artistic details with moral criticism of contemporary society and, thereby, to turn the cultivation of the beautiful into a moral-aesthetic experience
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