1,119 research outputs found
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
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
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
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
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)
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
“NATURE NEVER FORMED SUCH AN ADVANTAGEOUS PLACE:” MOUNTAIN LOGISTICS AND WARFARE IN THE TRANS-APPALACHIAN SOUTH, 1756-1776
This thesis will examine two significant periods of conflict in between the Cherokee and Euro-American military forces in the trans-Appalachian South. The first period is a series of three punitive campaigns launched by the British against the Cherokee from 1759 to 1761. The second period concerns near-simultaneous punitive campaigns launched by the newly independent colonies of Georgia, South Carolina, North Carolina, and Virginia against the Cherokee in 1776. It examines several aspects of these conflicts. First, the impact of the mountain environment, an unrestrained culture of war, and the objectives on the nature of the battles. Second, it analyzes the adaptation of logistics to the trans-Appalachian environment. Lastly, it examines the tactical adaptations of the Cherokee, British, and South Carolinians in three battles
A systematic analysis of user experience dimensions for interactive digital narratives
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??
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
Beauty for the Present: Mill, Arnold, Ruskin and Aesthetic Education
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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