I Cannot Tell: Edward Thomas's Uncertainties

Poster, Jeremy, 'I Cannot Tell: Edward Thomas's Uncertainties', In: 'Branch-Lines: Edward Thomas and Contemporary Poetry', Guy Cuthbertson & Lucy Newlyn (eds), (London: Enitharmon Press), pp.264, 2007 RAE2008

Impact of Leukocyte Function-Associated Antigen-1 Blockade on Endogenous Allospecific T Cells to Multiple Minor Histocompatibility Antigen Mismatched Cardiac Allograft.

BACKGROUND: Blocking leukocyte function-associated antigen (LFA)-1 in organ transplant recipients prolongs allograft survival. However, the precise mechanisms underlying the therapeutic potential of LFA-1 blockade in preventing chronic rejection are not fully elucidated. Cardiac allograft vasculopathy (CAV) is the preeminent cause of late cardiac allograft failure characterized histologically by concentric intimal hyperplasia. METHODS: Anti-LFA-1 monoclonal antibody was used in a multiple minor antigen-mismatched, BALB.B (H-2B) to C57BL/6 (H-2B), cardiac allograft model. Endogenous donor-specific CD8 T cells were tracked down using major histocompatibility complex multimers against the immunodominant H4, H7, H13, H28, and H60 minor Ags. RESULTS: The LFA-1 blockade prevented acute rejection and preserved palpable beating quality with reduced CD8 T-cell graft infiltration. Interestingly, less CD8 T cell infiltration was secondary to reduction of T-cell expansion rather than less trafficking. The LFA-1 blockade significantly suppressed the clonal expansion of minor histocompatibility antigen-specific CD8 T cells during the expansion and contraction phase. The CAV development was evaluated with morphometric analysis at postoperation day 100. The LFA-1 blockade profoundly attenuated neointimal hyperplasia (61.6 vs 23.8%; P < 0.05), CAV-affected vessel number (55.3 vs 15.9%; P < 0.05), and myocardial fibrosis (grade 3.29 vs 1.8; P < 0.05). Finally, short-term LFA-1 blockade promoted long-term donor-specific regulation, which resulted in attenuated transplant arteriosclerosis. CONCLUSIONS: Taken together, LFA-1 blockade inhibits initial endogenous alloreactive T-cell expansion and induces more regulation. Such a mechanism supports a pulse tolerance induction strategy with anti-LFA-1 rather than long-term treatment.

The Role of Direct Presentation by Donor Dendritic Cells in Rejection of Minor Histocompatibility Antigen-Mismatched Skin and Hematopoietic Cell Grafts

Background. The success of transplantation is hampered by rejection of the graft by alloreactive T cells. Donor dendritic cells (DC) have been shown to be required for direct priming of immune responses to antigens from major histocompatibility complex-mismatched grafts. However, for immune responses to major histocompatibility complex-matched, minor histocompatibility (H) antigen mismatched grafts, the magnitude of the T-cell response to directly presented antigens is reduced, and the indirect pathway is more important. Therefore, we aimed to investigate the requirement for donor DC to directly present antigen from minor H antigen mismatched skin and hematopoietic grafts.

Dynamic pricing for used products in remanufacturing with back orders(ABS 3* Journal, Accepted with Revision on 2nd December 2011).

In remanufacturing, the supply of used products and the demand for remanufactured products are usually mismatched because of the great uncertainties on both sides. In this paper, we propose a dynamic pricing policy to balance this uncertain supply and demand. Specifically, we study a remanufacturer’s problem of pricing a single class of cores with random price-dependent returns and random demand for the remanufactured products with backlogs. We model this pricing task as a continuous-time Markov decision process, which addresses both the finite and infinite horizon problems, and provide managerial insights by analyzing the structural properties of the optimal policy. We then use several computational examples to illustrate the impacts of particular system parameters on pricing policy.

Evidencing reflective practice in social work education: Theoretical uncertainties and practical challenges

Reflective practice has become an increasingly influential idea in social work education and, in the UK context, it has recently been acknowledged as key to ensuring that social workers are better equipped to engage in complex decision making and effective practice. However, there remains a lack of clarity about how this concept is defined and operationalised in teaching and learning and there has been little systematic empirical examination of its utility in facilitating professional development. Drawing on research with undergraduates at Queen's University Belfast, this paper aims to develop understanding of students' experience of reflective practice. The results suggest that agency systems that have become over-reliant on rules and procedures present formidable obstacles to learning both at an individual and at an organisational level. The paper argues that the relationship between how reflective practice is taught and how it is enacted in practice needs to be better understood if such obstacles are to be overcome. The paper concludes by considering the implications of the findings for developing reflective practice in social work education and practice and highlights the challenges that need to be addressed if reflection and critical thinking are to become more firmly embedded within agency systems and practice cultures.

Examining the uncertainties in a 'tuned and stacked' peatland water table reconstruction

Tuning and stacking approaches have been used to compile non-annually resolved peatland palaeo-water table records in several studies. This approach has been proposed as a potential way forward to overcome the chronological problems that beset the correlation of records and may help in the upscaling of palaeoclimate records for climate model-data comparisons. This paper investigates the uncertainties in this approach using a published water table compilation from Northern Ireland. Firstly, three plausible combinations of chronological match points are used to assess the variability of the reconstructions. It is apparent that even with markedly different match point combinations, the compilations are highly similar, especially when a 100-year running mean line is used for interpretation. Secondly, sample-specific reconstruction errors are scaled in relation to the standardised water table units and illustrated on the compiled reconstruction. Thirdly, the total chronological errors for each reconstruction are calculated using Bayesian age-modelling software. Although tuning and stacking approaches may be suitable for compiling peat-based palaeoclimate records, it is important that the reconstruction and chronological errors are acknowledged and clearly illustrated in future studies. The tuning of peat-based proxy climate records is based on a potentially flawed assumption that events are synchronous between sites. © 2011 Elsevier Ltd and INQUA.

Signal and variability within a Holocene peat bog - Chronological uncertainties of pollen, macrofossil and fungal proxies

A single raised bog from the eastern Netherlands has been repeatedly analysed and ¹⁴C dated over the past few decades. Here we assess the within-site variability of fossil proxy data through comparing the regional
pollen, macrofossils and non-pollen palynomorphs of four of these profiles. High-resolution chronologies were obtained using ¹⁴C dating and Bayesian age-depth modelling. Where chronologies of profiles overlap, proxy curves are compared between the profiles using greyscale graphs that visualise chronological uncertainties. Even at this small spatial scale, there is considerable variability of the fossil proxy curves. Implications regarding signal (climate) and noise (internal dynamics) of the different types of fossil proxies are discussed. Single cores are of limited value for reconstructing centennial-scale climate change, and only by combining multiple cores and proxies can we obtain a reliable understanding of past environmental change and possible forcing factors (e.g., solar variability).

Gold-based optical biosensor for single-mismatched DNA detection using salt-induced hybridization

In this study, a gold nanoparticle (Au-NP)-based detection method for sensitive and specific DNA-based diagnostic applications is described. A sandwich format consisting of Au-NPs/DNA/PMP (Streptavidin-coated MagnetSphere Para-Magnetic Particles) was fabricated. PMPs captured and separated target DNA while Au-NPs modified with oligonucleotide detection sequences played a role in recognition and signal production. Due to the much lower stability of mismatched DNA strands caused by unstable duplex structures in solutions of relatively low salt concentration, hybridization efficiency in the presence of different buffers was well investigated, and thus, the optimized salt concentration allowed for discrimination of single-mismatched DNA (MMT) from perfectly matched DNA (PMT). Therefore, quantitative information concerning the target analyte was translated into a colorimetric signal, which could easily and quantitatively measured by low-cost UV–vis spectrophotometric analysis. The results indicated this to be a very simple and economic strategy for detection of single-mismatched DNA strands.