Shaping Spirits, or, Imagination and "Abstruse Research": the perils of metaphysics and Coleridge's loss of form in the years of his philosophical accomplishment

Includes bibliographical references (leaves 78-81).The mystical nature of Samuel Taylor Coleridge's poems, 'The Rime of the Ancient Mariner', 'Christabel' and 'Kubla Khan' has intrigued readers for over two centuries. Of these full poems only the "Rime" is complete and yet they all still enjoy the scrutiny of a wide audience. This thesis examines the circumstances surrounding Coleridge's inability to continue writing such poems of imaginative force

Retrovirus Mediated Gene Expression in Haematopoietic Cells

The expression of retroviral vectors in cell lines and primary cells was investigated, with emphasis on autocrine stimulation of haematopoietic cells by GM-CSF. In this study, two distinct retroviral vectors were used which allowed a dual approach to the investigation of expression of exogenous sequences in haematopoietic cells. Retroviral expression of GM-CSF in the growth factor dependent FDCP1 cell line resulted in factor independent colony growth, the frequency of which was related to the vector used. The characterisation of cell lines derived from viral infection of FDCP1 cells revealed that these cells required the concentration of self produced growth factor to attain a critical level before colony development occured. As a result of virus infection, FDCP1 cells which express the retrovirally encoded GM-CSF have a proliferative advantage over the parental cell line. Finally, a number of variables which might influence the success of retroviral infection of primary murine bone marrow cells were investigated. Initial results suggest that bone marrow cells can be infected with retroviral constructs containing the neomycin gene, the efficiency of which may be related to the origin of the vector. Thus, this study demonstrates the feasability of using retrovirus vectors to express exogenous sequences in haematopoietic cells. It also provides a system which can be used to evaluate the efficiency with which new vectors will express genes in primary haematopoietic cells

Learning alters theta-nested gamma oscillations in inferotemporal cortex

How coupled brain rhythms influence cortical information processing to support learning is unresolved. Local field potential and neuronal activity recordings from 64- electrode arrays in sheep inferotemporal cortex showed that visual discrimination learning increased the amplitude of theta oscillations during stimulus presentation. Coupling between theta and gamma oscillations, the theta/gamma ratio and the regularity of theta phase were also increased, but not neuronal firing rates. A neural network model with fast and slow inhibitory interneurons was developed which generated theta nested gamma. By increasing N-methyl-D-aspartate receptor sensitivity similar learning-evoked changes could be produced. The model revealed that altered theta nested gamma could potentiate downstream neuron responses by temporal desynchronization of excitatory neuron output independent of changes in overall firing frequency. This learning-associated desynchronization was also exhibited by inferotemporal cortex neurons. Changes in theta nested gamma may therefore facilitate learning-associated potentiation by temporal modulation of neuronal firing

Behaviour of fibre composite walkways and grating

Throughout modern engineering, there has been a push to research, develop and implement new and innovative building materials as a substitution for the materials currently being used which have showed various forms of deterioration and faulting. This project specifically focuses on the field of construction of boardwalks and walkways. The aim of this research project was to investigate how fibre reinforced polymer (FRP) grating behaves mechanically while being subject to various types of static loading. A numerical simulation using 3D modelling software was also undertaken to compare simulation results with results found during the physical testing. A series of full scale and sample sized tests were undertaken to help in determining the mechanical properties and behaviour of the FRP grating. The full scale testing included static line loading, and two different concentrated loadings; central to the panel as well as off centre loading. 3 different sample sized tests were also undertaken to help gain an understanding of the material properties. These sample sized tests included, flexural, compressive, as well as a burn out test. The failure of the full scale line loading test was observed as major cracking and slight delamination of the grating directly underneath the loading bar. The two concentrated loading cases showed very similar failure modes to each other which consisted of the loading block sinking into the grid immediately surrounding the loading area while the rest of the panel remained intact. The line loading cases reached a maximum of approximately 56.16kN of force which resulted in 64.85mm of deflection. The centred concentrated load was tested to 33.37kN for a maximum deflection of 49.14mm, whereas the off centre loading reached 57.24mm for a maximum load of 34.93kN. As part of the sample sized testing system, a burn out test was undertaken to estimate firstly the density of the provided FRP grating as well as the glass to resin ratio. The density of this material was calculated to be 1544kg/m3 with a glass to resin ratio of 54% glass fibre to 46% resin. As part of the sample sized tests, other material properties were determined including a flexural modulus of 9.89GPa and a compressive strength of approximately 69.84GPa. These results aided in assigning a material property to a model as part of the FE analysis using the software PTC Creo for simulation. The results from the various FEA simulations gave very closely comparable results to those in the physical testing

Diversity of institutional support for research impact implementation

No abstract available

MDM2 negatively regulates the human telomerase RNA gene promoter

BACKGROUND: We have previously demonstrated that NF-Y and Sp1 interact with the human telomerase RNA (hTR) promoter and play a central role in its regulation. We have also shown that pRB activates the hTR promoter, but the mechanism of pRb directed activation is unknown. It has recently been reported that pRB induces Sp1 activity by relieving inhibition mediated by mdm2. The aim was to investigate possible roles for mdm2 in hTR promoter regulation. METHODS: Chromatin immunoprecipitation was used to determine binding of mdm2 to the hTR promoter. Transfection and luciferase assays were used to investigate mdm2 repression of the promoter activity and interaction with known transcriptional modulators. RESULTS: Here we show using chromatin immunoprecipitation that mdm2 specifically binds the hTR promoter in vivo. Transient co-transfection experiments using an hTR promoter luciferase reporter construct show that hTR promoter activity is inhibited by over-expression of mdm2 in 5637 bladder carcinoma cells (p53 and pRB negative, low mdm2). Titration of mdm2 was able to antagonise activation of hTR promoter activity mediated by pRB or Sp1 over-expression, although in the presence of pRB, mdm2 could not repress promoter activity below basal levels. Using an Sp1 binding site mutation construct we showed that mdm2 repression did not absolutely require Sp1 binding sites in the hTR promoter, suggesting the possibility of pRB/Sp1 independent mechanisms of repression. Finally, we show that NF-Y mediated transactivation of the hTR promoter was also suppressed by mdm2 in a dose-dependent manner. CONCLUSIONS: These studies suggest that mdm2 may inhibit the hTR promoter by multiple mechanisms. Mdm2 may directly repress activation by both pRB and Sp1, or activation by NF-Y. Furthermore, the ability of mdm2 to interact and interfere with components of the general transcription machinery might partly explain the general repressive effect seen here. Elucidation of new regulators affecting hTR basal promoter activity in cancer cells provides a basis for future studies aimed at improving our understanding of the differential hTR expression between normal and cancer cells

A design methodology for portable software on parallel computers

This final report for research that was supported by grant number NAG-1-995 documents our progress in addressing two difficulties in parallel programming. The first difficulty is developing software that will execute quickly on a parallel computer. The second difficulty is transporting software between dissimilar parallel computers. In general, we expect that more hardware-specific information will be included in software designs for parallel computers than in designs for sequential computers. This inclusion is an instance of portability being sacrificed for high performance. New parallel computers are being introduced frequently. Trying to keep one's software on the current high performance hardware, a software developer almost continually faces yet another expensive software transportation. The problem of the proposed research is to create a design methodology that helps designers to more precisely control both portability and hardware-specific programming details. The proposed research emphasizes programming for scientific applications. We completed our study of the parallelizability of a subsystem of the NASA Earth Radiation Budget Experiment (ERBE) data processing system. This work is summarized in section two. A more detailed description is provided in Appendix A ('Programming Practices to Support Eventual Parallelism'). Mr. Chrisman, a graduate student, wrote and successfully defended a Ph.D. dissertation proposal which describes our research associated with the issues of software portability and high performance. The list of research tasks are specified in the proposal. The proposal 'A Design Methodology for Portable Software on Parallel Computers' is summarized in section three and is provided in its entirety in Appendix B. We are currently studying a proposed subsystem of the NASA Clouds and the Earth's Radiant Energy System (CERES) data processing system. This software is the proof-of-concept for the Ph.D. dissertation. We have implemented and measured the performance of a portion of this subsystem on the Intel iPSC/2 parallel computer. These results are provided in section four. Our future work is summarized in section five, our acknowledgements are stated in section six, and references for published papers associated with NAG-1-995 are provided in section seven

Attitudes Toward Using Social Networking Sites in Educational Settings with Underperforming Latino Youth: A Mixed Methods Study

The researchers examined the online social networking attitudes of underperforming Latino high school students in an alternative education program that uses technology as the prime venue for learning. A sequential explanatory mixed methods study was used to cross-check multiple sources of data explaining students’ levels of comfort with utilizing a social networking site platform as a supplemental communication tool in connection with their schoolwork. Students were found to be significantly less comfortable using social networking sites than other online communication tools in connection with their schoolwork, and females were significantly more uncomfortable than males using such sites in school

Cardiovascular computed tomography imaging for coronary artery disease risk: plaque, flow and fat

Cardiac imaging is central to the diagnosis and risk stratification of coronary artery disease, beyond symptoms and clinical risk factors, by providing objective evidence of myocardial ischaemia and characterisation of coronary artery plaque. CT coronary angiography can detect coronary plaque with high resolution, estimate the degree of functional stenosis and characterise plaque features. However, coronary artery disease risk is also driven by biological processes, such as inflammation, that are not fully reflected by severity of stenosis, myocardial ischaemia or by coronary plaque features. New cardiac CT techniques can assess coronary artery inflammation by imaging perivascular fat, and this may represent an important step forward in identifying the ‘residual risk’ that is not detected by plaque or ischaemia imaging. Coronary artery disease risk assessment that incorporates clinical factors, plaque characteristics and perivascular inflammation offers a more comprehensive individualised approach to quantify and stratify coronary artery disease risk, with potential healthcare benefits for prevention, diagnosis and treatment recommendations. Furthermore, identifying new biomarkers of cardiovascular risk has the potential to refine early-life prevention strategies, before atherosclerosis becomes established