Genetic mapping and mechanism of action of rat mammary carcinoma susceptibility quantitative trait locus Mcs1b.

Breast cancer is a complex disease that involves genetic, epigenetic, and environmental components. High and moderate penetrant genes have been identified that affect risk to developing breast cancer; however, these risk alleles are present in a small percentage of breast cancer cases. Low penetrant modifier genes have risk-associated alleles that are common in the population. Although these genes have lower penetrance, it is expected that the majority of genetic risk to developing breast cancer is controlled by common genetic variation. Studying mechanisms of common genetic variants on breast cancer risk is difficult due to their small individual effects and overlapping contribution of other risk factors; thus, animal models are commonly used. The rat mammary carcinoma susceptibility quantitative trait locus (QTL) Mcs1b was identified between mammary carcinoma-resistant Copenhagen (COP) and susceptible Wistar Furth (WF) rats on chromosome 2. This rat QTL is an ortholog of a human breast cancer-associated locus identified on human chromosome 5q; therefore, the rat Mcs1b model can be used to identify mechanisms and causative factors contributing to breast cancer risk associated with human breast cancer-associated locus 5q. The goal of the work presented in this dissertation is to identify quality candidate breast cancer risk genetic elements associated with the rat Mcs1b locus. This project utilized a well-defined rat mammary carcinogenesis system and congenic rat model to fine map and characterize the rat Mcs1b locus. My studies reduced the number of candidate genes by narrowing the rat Mcs1b locus from a 13 megabase (Mb) to a 1 Mb containing nine annotated transcripts. I determined that Mcs1b-conferred mammary carcinoma resistance is being controlled by a cell type within the mammary gland. This is an important finding because mammary carcinogenesis is dependent on both mammary gland-extrinsic and -intrinsic factors. I also found that the transcript Mier3 is differentially expressed between resistant and susceptible rat mammary glands with or without carcinogen exposure providing genetic evidence that Mier3 is a strong mammary carcinoma susceptibility gene. Taken together, these results provide insight into the mechanism by which Mier3 controls mammary carcinogenesis and implicate human MIER3 as a potential target for breast cancer prevention

The Commercialization of Digital Information: Implications for the Public Role of Museums

In recent decades, Canadian, British and American museums have faced a number of significant challenges to their traditional role. One of the major challenges has been the reduction of government funding and the incipient pressure to find new sources of revenue. A second has been the introduction of digital technologies that provide new opportunities for museums to communicate with their public, but that require significant investments of both time and money. This thesis explores the impact of both on the public role of museums. Drawing on the work of Jurgen Habermas and, in particular, his belief in the importance of cultural institutions and democratic communication in maintaining a healthy public sphere, this thesis argues that universality remains an important objective for museums. The commitment to serving a universal public, although imperfectly realized, was gradually recognized as an important principle in nineteenth-century Britain. Under the financial pressures of recent decades, however, notions of equality and access have been overshadowed as Anglo American museums have increasingly looked to a paying public to generate revenue. This trend can also be seen in museums’ approach to digital information, where early expectations of financial returns through the licensing of museum content, coupled with the high costs of creating and maintaining digital resources, have resulted in a tendency to view information as a commodity rather than as a public good. By means of two case studies, this thesis argues that digital information does not represent an important new source of revenue for museums. The first case study examines the commercialization of information at the Canadian Museum of Civilization, long a proponent of new technologies, while the second looks more broadly at the experience of stock agencies, museums and consortia in licensing digital content. Together, they throw into doubt the belief that the Internet and other forms of technology will unleash pent-up public demand for museum images and result in significant new revenues flowing into institutional coffers. Given the centrality of the dissemination of information to institutional missions, this thesis argues on behalf of open and equitable access. Museums would be better served by a more critical view of technology that balances benefits with costs, experimentation with evaluation, and short-term goals with strategic, long term institution-wide planning. Renewed government support for education would allow museums to re-establish a balance between market and mission both in the physical and virtual environments

Efficacy of Conventional and Organic Insecticides against Scaphoideus titanus: Field and Semi-Field Trials

Scaphoideus titanus is the main vector of phytoplasmas associated with Flavescence dorée (FD), one of the most serious threats to viticulture in many European countries. To minimize the spread of this disease, mandatory control measures against S. titanus were decided in Europe. In the 1990s, the repeated application of insecticides (mainly organophosphates) proved to be an effective measure to control the vector and the related disease in north-eastern Italy. These insecticides and most of the neonicotinoids were recently banned from European viticulture. Serious FD issues detected in the recent years in northern Italy could be related to the use of less effective insecticides. Trials aimed at evaluating the efficacy of the most used conventional and organic insecticides in the control of S. titanus have been performed in semi-field and field conditions to test this hypothesis. In efficacy trials, carried out in four vineyards, etofenprox and deltamethrin proved to be the best conventional insecticides, while pyrethrins were the most impactful among organic insecticides. Insecticide residual activity was evaluated in semi-field and field conditions. Acrinathrin showed the most significant residual effects in both conditions. In semi-field trials, most of the pyrethroids were associated with good results in terms of residual activity. However, these effects declined in field conditions, probably due to high temperatures. Organic insecticides showed poor results in terms of residual efficacy. Implications of these results in the context of Integrated Pest Management in conventional and organic viticulture are discussed

Marine Aggregate Dredging: A New Regional Approach to Environmental Monitoring

The subject of this thesis is the marine aggregate dredging industry, and specifically the approach taken to the monitoring of environmental effects on the seabed. The thesis forms the evidence required to allow the author to be examined for a PhD by Publication, and comprises of a list of the author’s publications, a confirmation of the author’s contribution to the multi-authored papers, and a critical analysis of the published work. The critical analysis takes the form of an essay, in which a case for switching to a new system of environmental monitoring is outlined. The essay presents a logical development of ideas, starting with a description of the aggregates dredging industry. This is followed by a critical analysis of the author’s past research, with a particular emphasis on how the findings from this work are relevant to the issue of monitoring. This earlier work has addressed themes of: Impact (Cumulative Effects), The Relationship between Sediments and Benthos, Recovery, Restoration, Habitat Mapping and Natural Variability. The essay then describes the current approach to monitoring, together with its limitations. This is followed by a description of the new monitoring approach, with an explanation of why it is considered more suitable for meeting the needs of both the industry and the industry regulators. The essay considers what steps would need to be taken to implement the approach in the major dredging regions of the UK

Using the Question-Answer Relationship Strategy to Improve Listening Comprehension in Young Children with Autism Spectrum Disorder

A well-established research base indicates that many children diagnosed with autism spectrum disorder (ASD) experience deficits in reading comprehension skills. There is currently limited research which examines the relation between the communication and language impairments in ASD and emergent literacy skills in early childhood. Listening comprehension has been identified as one emergent literacy skill closely linked to reading comprehension development. The purpose of the study is to examine the effects of the question-answer relationship strategy (QAR) and QAR cue cards as a shared book reading intervention package on the listening comprehension skills of children with ASD. A single-subject concurrent multiple-baseline design across participants with continuous acquisition probes was used to evaluate the effect of the QAR strategy on the correct answers to four levels of comprehension questions: Fact, Search, Inference, and Connection. Visual analysis and Tau-U statistical analysis were used to determine the treatment effects on each participant. Results showed that all or some aspects of the intervention were effective for each of the five participants in the study. Practitioners and participants reported positive social validity of the intervention. An examination of the results, along with implications for future research and educational practices are discussed

Habitat dynamics in response to constructional impacts (JadeWeserPort) a biological approach

During the construction of a deep-water port (JadeWeserPort), bathymetry, sediment distribution, and macrofauna community structure were studied in the Inner Jade, a tidal channel located in the southern North Sea. The relationships between macrofauna community structure and natural as well as anthropogenic environmental variables were investigated in this very heterogeneous study area. The manual expert hydroacoustic classification of the backscatter image derived by side scan sonar was successful to detect the different dredging activities and the natural bedforms in the undisturbed areas. The sediment distribution was very patchy and no significant congruence with the hydroacoustic classification could be identified. In contrast, low, but significant relationships between the hydroacoustic classification and the macrofauna community structure as well as the sediment distribution and the macrofauna communities were found. The most important impact on the spatial community structure was the number of days after the last dredging/dumping activity for the JadeWeserPort (JWP), followed by the sediment characteristics explained by grey values of the backscatter image. This study stresses the problems of benthic habitat mapping in such a heterogeneous area. In order to assess the effects of physical disturbance by dredging activities, macrofaunal community compositions between 2002 (before the construction work had begun) and 2010 (during the final construction phase) were compared. The sand extraction for land reclamation and the redirection of the navigation channel changed the bathymetry markedly. While the old navigation channel in the centre of the study area remained mud dominated, a general increase in coarse sediments was detected in 2010. The dynamic nature of the study area in combination with the direct and indirect effects of dredging increased the bathymetric heterogeneity (measured by singlebeam (2002) and multibeam (2010) echo-sounder). In 2010, the macrofauna community structure roughly resembled the different categories of dredging activities. A general increase in macrofaunal abundance and taxa number was observed in 2010, with the exception of the recently dredged area. The structure of the macrofauna community during the port construction phase seemed to be determined by secondary dispersal of the dominant taxa and recolonisation by highly mobile and opportunistic species. The effects of the presence of two adult bivalve species with different feeding modes on the post-settlement dispersal of their juveniles were examined in a flume experiment