“THE GEOGRAPHICALL COMPASS”: HISTORY, AUTHORITY AND UTILITY IN THE ENGLISH VOYAGE ACCOUNT, 1660-1730

The late-seventeenth and early-eighteenth centuries saw a dramatic increase in the publication of accounts of voyages on the London book market. These publications ranged from brief extracts of romantic narratives involving shipwrecks in the East Indies to multi-volume compilations of voyages to all parts of the world, printed in folio and containing numerous maps and engravings. Existing scholarship often views such accounts as entertainment destined for a popular audience. This dissertation shows how the voyage account was used in multiple genres and multiple intellectual contexts, finding its way into debates about natural philosophy, religion, and history, and playing as important a role in the work of the Royal Society as it did in the literary practices of the period. By investigating these books as key texts in a changing intellectual and cultural climate, and understanding their relationships with other genres, “The Geographicall Compass” offers a reader’s view of empire and the world in England between 1660 and 1730. This project analyses the interaction between the narrative and paratextual elements of accounts of long-range voyages of discovery in the early-modern era, in order to investigate how ideas about the New World found their way into political, scientific and cultural spheres in seventeenth-century Europe. I argue that we can understand how the commercial market shaped knowledge of the New World by considering these books as books – written, published, bought and sold for a reading public, subject to commercial pressures and prone to failure. Focussing mainly but not exclusively on voyages to the New World, this dissertation uses Samuel Purchas’ metaphor – the voyage account as a compass – to discuss these texts in their scientific, religious, literary and political contexts. As the cartographers of the seventeenth and eighteenth centuries used the geometrical compass to shape their maps, and seamen used the magnetic compass to find their direction in the expanse of the sea, so I use the compass as a way of understanding texts that are composite, multi-layered, and were produced in multiple, overlapping contexts

Mining and Manipulation of Antibiotic Biosynthesis in Streptomyces

New small-molecule drugs are needed, both to address existing disease and to combat the rise of antibiotic resistance in pathogenic microbes. A major source of antibiotics and other valuable therapeutic agents remains the natural products produced by Streptomyces and allied bacteria. The advent of genome-level sequencing has changed how such bioactive products are identified in two ways: first, by enabling new approaches to engineering of known clusters to obtain new analogues; and secondly by enabling mining of their large (8-12 Mbp) genomes to make rapid links between valuable compounds and the gene clusters responsible for their biosynthesis; as well as a complete inventory of orphan clusters for decryption. In this work, both of these aspects were explored. Accelerated Evolution (AE) is a new method of induced recombination in Streptomyces that produces libraries of analogues of a parent compound in a single experiment. It has been previously applied to a typical assembly-line biosynthetic pathway involving a multimodular polyketide synthase, that for the immunosuppressant rapamycin. Here, the utility of AE was initially explored with several polyketide antibiotics, before focussing on the polyene filipin. Unfortunately, this system proved refractory to the AE method, since only recombinants which had either lost filipin production, or which maintained some level of filipin production, were recovered. These results suggested that deeper understanding of the fundamental processes of recombination in Streptomyces are now needed to allow the AE approach to flourish. A genome mining approach was taken to identify and analyse the gene cluster in Streptomyces albus DMS40763 for pseudouridimycin (PUM), a rare C-nucleoside antibiotic and a newly-recognised selective inhibitor of bacterial RNA polymerase. The fully-sequenced genome (8.01 Mbp) of S. albus was analysed and 27 biosynthetic gene clusters were found, including those for 11 novel assembly-line systems. A strong candidate for the PUM gene cluster was identified through BLAST searches with a gene probe (truD) found in the gene cluster for a different C-nucleoside in other Streptomyces spp., hinting at a common mechanism for formation of the C-nucleoside moiety. Identification of the enzymes predicted to be encoded by the gene cluster allowed a detailed biosynthetic pathway to be proposed. Several genes from the PUM cluster were expressed and purified as recombinant proteins in Escherichia coli, and the proposed enzymatic roles of two of them were verified. One of these, a pseudouridine oxidase, also showed activity against uridine. Consistent with this finding, feeding of uracil to a mutant S. albus lacking the pseudouridine synthase-like gene truD gave production of the novel N-linked analogue of PUM, suggesting that the biosynthetic enzymes may be sufficiently flexible to incorporate other, non-natural nucleosides into PUM analogues for testing

Wetland Connectivity and Macroinvertebrate Diversity

Wetlands are important in filtering pollutants from aquatic ecosystems and also serve as habitats for a diverse array of organisms. However, wetland-river networks are often subject to human disturbances such as dyke construction. These decreases in connectivity have the potential to impede movement of organisms and nutrients between habitats. This study examined how the food web structure and diversity of macroinvertebrate communities differ between wetland sites connected and disconnected to nearby rivers. According to macroinvertebrate surveys in wetlands connected to nearby rivers and dyked wetlands (not connected to nearby rivers), there is an increase in average species richness and diversity (Shannon index) in connected sites. This may be because wetland-river connections provide opportunities for species to enter adjacent ecosystems. I used stable isotope analyses to examine the impact of species diversity and connectivity on the nutrient source and trophic position of odonates (dragonflies and damselflies)- top predators in many wetlands. Because stable nitrogen isotope values (δ15N) increase by 3-5 ‰ with each trophic transfer, the offset in δ15N between odonates and amphipods (primary consumers in wetland food webs) served as a proxy for food chain length. Although there was not evidence to conclude that the offset in δ15 N is greater in connected wetlands, average Odonate δ15N values in sites connected to a river were higher than in dyked sites. This observed shift in δ15N may be an indication of different nitrogen inputs to connected and disconnected wetlands, specifically, the relative input of terrestrial (allochthonous) nutrients. Notably, amphipods are often assumed to be primary consumers in wetlands. However, amphipods in this study had variable δ15N values, providing evidence for the claim that they can function as both primary consumers and secondary-tertiary consumers. While managers increasingly promote the restoration of natural connectivity between wetlands and rivers, there are few studies showing the likely impacts to wetland food web structure. My research will help to fill this gap and provide a more solid foundation for management decisions aimed at preserving wetland biodiversity

Active music

We are a group of eleven young people with intellectual disability and three music therapists. We did action research at a university. We wanted to find out how a music group might be helpful for young people with intellectual disabilities. We wanted to tell our own story and use our own words because we have a lot to say. We wanted people to read our story and to use our ideas to help young people with intellectual disabilities to have good lives. We went to twenty sessions of music research, and five more sessions of research analysis. We also did a lot of research work in between sessions. We found out that music groups can be fun. They can also be hard work. They help us develop skills like listening and waiting. They are places where we can be independent. But music groups are also good places to practice working as a team. They can be safe places for people to express emotions. Music helps us to know people. It brings us together. Playing musical instruments can also help physical development. A good life for us would include having the chance to play music with others or to have music lessons. But it is not always easy for us to go to ordinary lessons or music groups. It might be important for young people with intellectual disability to have support from people who understand them at first. We want to be independent but we need help to develop our dreams in practical ways. We found that doing research is fun and interesting. We were all researchers but we had different things to do. The adults had to be the organisers, setting up the research. We knew from the start the research would be about what young people think about music. The adults had done their reading and had written the literature review. The young people decided on other questions, and gathered data in lots of different ways. They also did some of the analysis, and decided on the findings of each cycle. The findings of each cycle, with more of the young people’s words, are in the appendices. Later, the adults wrote the main findings, the discussion and conclusion. We all discussed the things we wrote along the way and at the end of the research. The adults have tried to help the young people understand what has been written. The research took a lot of time and it was hard work for everybody. To be a good researcher you need to learn research skills. It is important that young people with intellectual disabilities are not exhausted by research. They need to be able to enjoy the things they are doing. We all liked being involved in research even though it was hard work. We think that research is important and helpful. Young people should be involved in research that is about them. We learnt that young people with intellectual disabilities can go to university. Going to university was scary at first but we got used to it and we started to enjoy it. We need to do more research to make sure universities are ready to welcome students with intellectual disabilities. We can use our research to show universities that it can be a good idea to support people with intellectual disabilities to go to university. We can also use our research show people what we can do; what we like to do; and what we want to do in the future. Most of us would like to do more music and research in future

Validity of Borg Ratings of Perceived Exertion During Active Video Game Play

International Journal of Exercise Science 6(2) : 164-170, 2013. During physically interactive video game play (e.g., Nintendo Wii), users are exposed to potential distracters (e.g., video, music), which may decrease their ratings of perceived exertion (RPE) throughout game play. The purpose of this investigation was to determine the association between RPE scores and heart rate while playing the Nintendo Wii. Healthy adults (N = 13, 53.5 ± 5.4 years old) participated in two exercise sessions using the Nintendo Wii Fit Plus. During each session participants played a five-minute warm-up game (Basic Run), two separate Wii Fit Plus games (Yoga, Strength Training, Aerobics or Balance Training) for fifteen minutes each, and then a five-minute cool down game (Basic Run). Borg RPE and heart rate were assessed during the final 30 seconds of the warm up and cool down, as well during the final 30 seconds of play for each Wii Fit Plus game. Correlation analysis combining data from both exercise sessions indicated a moderate positive relationship between heart rate and RPE (r = 0.32). Mixed-effects model regression analyses demonstrated that RPE scores were significantly associated with heart rate (p \u3c 0.001). The average percentage of age-predicted heart rate maximum achieved (58 ± 6%) was significantly greater (p = 0.001) than the percentage of maximum RPE indicated (43 ± 11%). Borg RPE scores were positively associated with heart rate in adults during exercise sessions using the Wii Fit Plus. However, this relationship was lower than observed in past research assessing RPE validity during different modes of exercise (e.g. walking, running) without distracters

Transcriptome sequencing of black grouse (Tetrao tetrix) for immune gene discovery and microsatellite development

The black grouse (Tetrao tetrix) is a galliform bird species that is important for both ecological studies and conservation genetics. Here, we report the sequencing of the spleen transcriptome of black grouse using 454 GS FLX Titanium sequencing. We performed a large-scale gene discovery analysis with a focus on genes that might be related to fitness in this species and also identified a large set of microsatellites. In total, we obtained 182 179 quality-filtered sequencing reads that we assembled into 9035 contigs. Using these contigs and 15 794 length-filtered (greater than 200 bp) singletons, we identified 7762 transcripts that appear to be homologues of chicken genes. A specific BLAST search with an emphasis on immune genes found 308 homologous chicken genes that have immune function, including ten major histocompatibility complex-related genes located on chicken chromosome 16. We also identified 1300 expressed sequence tag microsatellites and were able to design suitable flanking primers for 526 of these. A preliminary test of the polymorphism of the microsatellites found 10 polymorphic microsatellites of the 102 tested. Genomic resources generated in this study should greatly benefit future ecological, evolutionary and conservation genetic studies on this species

Temporal Gene Expression Profiling during Rat Femoral Marrow Ablation-Induced Intramembranous Bone Regeneration

Enhanced understanding of differential gene expression and biological pathways associated with distinct phases of intramembranous bone regeneration following femoral marrow ablation surgery will improve future advancements regarding osseointegration of joint replacement implants, biomaterials design, and bone tissue engineering. A rat femoral marrow ablation model was performed and genome-wide microarray data were obtained from samples at 1, 3, 5, 7, 10, 14, 28, and 56 days post-ablation, with intact bones serving as controls at Day 0. Bayesian model-based clustering produced eight distinct groups amongst 9,062 significant gene probe sets based on similar temporal expression profiles, which were further categorized into three major temporal classes of increased, variable, and decreased expression. Osteoblastic- and osteoclastic-associated genes were found to be significantly expressed within the increased expression groups. Chondrogenesis was not detected histologically. Adipogenic marker genes were found within variable/decreased expression groups, emphasizing that adipogenesis was inhibited during osteogenesis. Differential biological processes and pathways associated with each major temporal group were identified, and significantly expressed genes involved were visually represented by heat maps. It was determined that the increased expression group exclusively contains genes involved in pathways for matrix metalloproteinases (MMPs), Wnt signaling, TGF-β signaling, and inflammatory pathways. Only the variable expression group contains genes associated with glycolysis and gluconeogenesis, the notch signaling pathway, natural killer cell mediated cytotoxicity, and the B cell receptor signaling pathway. The decreased group exclusively consists of genes involved in heme biosynthesis, the p53 signaling pathway, and the hematopoietic cell lineage. Significant biological pathways and transcription factors expressed at each time point post-ablation were also identified. These data present the first temporal gene expression profiling analysis of the rat genome during intramembranous bone regeneration induced by femoral marrow ablation

Reason, conscience and equity: bishops as the king's judges in later Medieval England

It has long been recognized that many late medieval bishops were heavily involved in secular government. Scholars have tended to characterize these activities in fairly general terms, labelling those who chose to serve the crown as ‘administrators’, ‘bureaucrats’ or ‘civil servants’. In fact, they are better described as king’s judges, for a large part of what bishops did in government was dispensing justice in the king’s name. The first part of this article explores the contexts of this judicial activity, showing that bishops were especially active in institutions such as parliament, chancery and the council which offered justice to the king’s subjects on a discretionary basis. Discretionary justice was closely informed by the precepts of natural law, which in turn derived authority from the abstract notion of the divine will. The second half of the article suggests that the strong theological underpinning of discretionary justice meant that bishops’ involvement in secular government did not stand in opposition to their spiritual vocation or their role as leaders of the church. I argue that the sweeping and rather disparaging contemporary and modern characterizations of ‘civil-servant’ bishops as self-serving careerists ought to be replaced by a more nuanced understanding of the rationale and motivation of those senior clergymen who involved themselves in secular governance