224 research outputs found
Text as process : creative composition in Wordsworth, Tennyson and Emily Dickinson
No full textBushell’s aim in Text as Process is to develop a research method for the study of compositional material. Although she draws on an international context – mainly French and German traditions – for current approaches to textual criticism, hers is the first book to apply a new form of critical analysis to authors in the Anglo-American tradition. Bushell revisits issues of intention within process and makes this the center of her new approach, employing “case studies” of the work of three major nineteenth-century poets: Wordsworth, Tennyson and Dickinson. She applies her methodology to each writer in different ways, allowing for cross-comparison as well as the recognition of individual distinctiveness in creativity. In doing so, Bushell demonstrates the need for a unique hermeneutics in relation to the making of the literary work of art. The author concludes with a philosophical account of the status and meaning of the literary work as it comes into being
Assessing the impact of immunosuppressive drugs on regulatory T cell therapy
No full textImmunosuppressive drugs have facilitated the progression of solid organ transplantation from experimental therapy to routine practice, however transplant recipients are still susceptible to chronic rejection and co-morbidities. The emergence of regulatory T cells (Treg) as a key regulator of the immune system, together with an abundance of evidence from experimental transplant models, has led to clinical trials asking whether Treg can improve transplant outcomes. However, given that Treg cellular therapy will only be acceptable if introduced into current immunosuppressive regimens, a critical question is how Treg will respond in the presence of concomitant immunosuppression. Whilst in vitro data are available, very few credible experiments have been done asking whether individual immunosuppressive drugs have a positive, a neutral or a detrimental impact on the Treg function in vivo. Thus the aims of this thesis were firstly to generate sufficient numbers of adaptive Treg for extensive experimental use and secondly to evaluate their ability to control transplant rejection in vivo in the presence of biologically valid doses of individual, clinically relevant immunosuppressive drugs. Importantly, the model chosen was the heterotopic heart transplant model in lymphoreplete mice to avoid possible artefacts that can occur in cell reconstituted lympho-depleted mice. The model also has the added advantage that by dealing with an intact immune system, it perhaps represents a small step closer to the clinical situation.
Generating sufficient numbers of stable Treg was necessary for planned in vivo experiments. Incubating CD4+ T cells with anti-CD44 antibody, prior to driving them with bone-marrow derived dendritic cells, enriched for a stable population of Treg and importantly yielded sufficient numbers of cells for in vivo experiments. It is frequently stated that alloantigen-driven Treg are more efficacious than activated autologous nTreg, however there was no difference in rejection kinetics in either a skin or heart allograft model when comparing alloantigen-driven Treg with nTreg. As generating alloantigen-driven Treg is less efficient than nTreg, pursuing the former as a potential therapy might therefore be unnecessary. This could have a considerable impact on the logistics and the practicality of clinical Treg cellular therapeutics.
The timing of Treg administration is an important consideration to maximise efficacy. Pre-transplant administration led to the longest graft survival times, suggesting that this is the most effective time for cell delivery.
Preclinical models provide a useful tool to ask how immunosuppressive drugs will affect adoptively transferred Treg. The data presented in this thesis suggest that combining Treg with Rapamycin, Mycophenolate Mofetil (MMF) or Tacrolimus did not completely prevent Treg function. However, Methylprednisolone (MP) did prevent Treg function, suggesting it cannot be used with adoptively transferred Treg. Overall, these results provide important data for the design of immunosuppressive regimens for future clinical trials assessing the efficacy of Treg in transplant recipients.</p
Does receptor activation initiate the NF kappa B pathway in hippocampal neurones?
No full textTrevor Bushell et al reviews receptor activation and initiation of the NF kappa B pathway in hippocampal neurone
Mystery Author Stan Jones and Sepculative Fiction Authors Sterling Emmal and L. S. Goulet
No full textSterling Emmal is author of the sci-fi fantasy The Executioner of Rawule and L. S. Goulet is author of the fantasy book Sword of Dragonblood. Tundra Kill is Stan Jones' latest Nathan Active mystery. His other books include White Sky, Black Ice; Shaman Pass, Frozen Sun; Village of the Ghost Bears, and the nonfiction classic, The Spill: Personal Stories from the Exxon Valdez Disaster, coauthored with Sharon Bushell
Detailed profile of Northeast Harbor author Marguerite Yourcenar, who is better
No full textDetailed profile of Northeast Harbor author Marguerite Yourcenar, who is better known in other nations than in the United States
The Effectiveness of the Size Matters Handwriting Program
No full textAbstract
Date Presented 3/31/2017
With school-based occupational therapists reporting up to 75% of their caseload related to handwriting, the urgency to identify a proven and efficient instructional program is paramount. Effective, embeddable, measurable, easy, and fast, the Size Matters Handwriting Program promotes collaboration in the natural environment and the Workload model.
Primary Author and Speaker: Beverly Moskowitz
Additional Authors and Speakers: Beth Carswell, Jennifer Kitzmiller, Moira Bushell, Laura Neikrug, Chaya Gottesman
Contributing Authors: Beth Pfeiffer, Gillian Rai, Tammy Murray</jats:p
Regulatory immune cells in transplantation.
No full textImmune regulation is fundamental to any immune response to ensure that it is appropriate for the perceived threat to the host. Following cell and organ transplantation, it is essential to control both the innate immune response triggered by the injured tissue and the adaptive immune response stimulated by mismatched donor and recipient histocompatibility antigens to enable the transplant to survive and function. Here, we discuss the leukocyte populations that can promote immune tolerance after cell or solid-organ transplantation. Such populations include regulatory T cells, B cells and macrophages, as well as myeloid-derived suppressor cells, dendritic cells and mesenchymal stromal cells. We consider the potential of these regulatory immune cells to develop and function in transplant recipients and their potential use as cellular therapies to promote long-term graft function
The role of CD4+CD25+ regulatory T cells in a mouse transplantation tolerance model
No full textClinical transplantation continues to rely on the use of non-specific immunosuppressive therapy, which reduces the incidence of graft rejection but also carries with it undesirable side effects such as infection and malignancy. A preferable option would be to induce operational graft tolerance without the need for such non-specific therapy, for example by harnessing natural mechanisms. In recent years there has been much progress in the characterisation of CD4+ cells that possess suppressive or regulatory properties in experimental systems; particular attention has been focussed upon CD4+ cells expressing CD25, the α subunit of the IL-2 receptor, which have been shown to possess regulatory capacity both in vitro and in vivo in autoimmune disease and transplantation models. The aim of this study was to examine the potential role of CD4+CD25+ regulatory T cells (Treg) in the induction phase of tolerance in a transplantation model. Pre-treatment of mice with fully allogeneic blood administered under the cover of anti-CD4 antibody is shown to lead to the generation of CD4+CD25+ cells capable of preventing the rejection of donor type, but not third party, skin allografts mediated by CD4+CD45RBhigh cells in secondary recipients. In addition to their suppressive properties in vivo, these CD4+CD25+ cells also display the ability to regulate the proliferation of target T cell populations in vitro. Generation of CD4+CD25+ Treg by the pre-treatment protocol is not reliant upon an intrathymic selection process nor upon the expansion of a pre-existing CD4+CD25+ Treg population, but can occur through the conversion of peripheral CD4+CD25- cells to a regulatory phenotype. Although the regulatory function of the CD4+CD25+ cells generated by pre-treatment is donor strain-specific in vivo, this specificity can be overcome by activating the cells before their regulatory capacity is tested. Moreover, CD4+CD25+ cells generated by pre-treatment with a non-cellular protein antigen completely unrelated to the graft can also regulate skin allograft rejection provided that these Treg are first activated. It is hoped that the principles defined by these findings identify a strategy that may be applicable in clinical transplantation and in the therapy of autoimmune disease
- …
