919 research outputs found

    Race, politics and the frontier in American literature, 1783-1837

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    Divided chronologically into two sections, this thesis examines how ways of conceptualising and writing about the American frontier, and the Native Americans who inhabit that frontier, reflect and participate in the emergent political and regional divisions of the early republic. Although 'the West' and 'the Indian' are pervasive images in early American literature, their meanings are indeterminate. During the Revolution, the frontier functions as a patriotic locus, the settlement of the wilderness providing a metaphor for the project of independence and nation-building. However, in the early republic, as conceptions of national destiny splinter along regional and political lines, the West and its inhabitants, white or native, take on conflicting meanings: independence and limitless potential on the one hand, savagery and degeneration on the other. Part I spans the period from the end of the Revolution to the end of the War of 1812, beginning with a survey of the contemporaneous attitudes towards the West and the Indians, represented by influential public figures of the early republic, such as Jefferson and Washington. I then consider the literary representation of the frontier by John Filson, Ann Eliza Bleecker, the pseudonymous 'Abraham Panther', Hugh Henry Brackenridge, and Charles Brockden Brown, demonstrating the ways in which their generically diverse work reflects and responds to the ideological debates about the frontier which characterise the period. Part II focuses on the literature of Jacksonian America. Race and expansionism were still at the root of ideological divisions within the nation, the frontier was still perceived to be the most appropriate subject for national literature, and the historical romance had become the dominant literary form in America. I examine the work of three writers - James Kirke Paulding, William Gilmore Simms and Robert Montgomery Bird - each of whom historicizes the frontier, legitimising the contemporary ideologies articulated in their fiction by association with an earlier 'golden age' of American history

    Extending the GERG-2008 equation of state: Improved departure function and interaction parameters for (methane+butane)

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    The Groupe Européen de Recherches Gazières (GERG) 2008 multi-parameter equation of state (EOS) is considered the reference model for the prediction of natural gas mixture properties. However, the limited quality of thermodynamic property data available for many key binary mixtures at the time of its development constrained both its range of validity and achievable uncertainty. The data situation for the binary system (CH4 + C4H10) in particular was identified previously as limiting the ability of the GERG-EOS to describe rich natural gases at low temperatures. Recently, new vapour-liquid equilibrium (VLE) and liquid mixture heat capacity data measured at low temperatures and high pressures have been published that significantly improve the data situation for this crucial binary, allowing erroneous literature data to be identified and the predictive behaviour of the GERG-EOS when extrapolated to be tested. The 10 basis functions in the generalised departure function used by the GERG-EOS for several binaries including (CH4 + C4H10) were examined to eliminate the term causing a divergence between measured and predicted liquid mixture isobaric heat capacities at T < 150 K. With a simplified nine-term departure function, the maximum relative deviation between the measured and predicted heat capacities was reduced from nearly (110 to 7) %. The interaction parameters in the GERG equation were also re-determined by including, for the first time for this binary, reliable low temperature VLE data together with most of the other high temperature data used in the original development of the model. The new interaction parameters for (CH4 + C4H10) reduced the relative deviation of bubble point pressures measured and calculated at T = 244 K from (9 to 1.4) %, without affecting the accuracy of property predictions at higher temperature

    Regulatory mutations in Sin recombinase support a structure-based model of the synaptosome

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    The resolvase Sin regulates DNA strand exchange by assembling an elaborate interwound synaptosome containing catalytic and regulatory Sin tetramers, and an architectural DNA-bending protein. The crystal structure of the regulatory tetramer was recently solved, providing new insights into the structural basis for regulation. Here we describe the selection and characterization of two classes of Sin mutations that, respectively, bypass or disrupt the functions of the regulatory tetramer. Activating mutations, which allow the catalytic tetramer to assemble and function independently at site I (the crossover site), were found at ∼20% of residues in the N-terminal domain. The most strongly activating mutation (Q115R) stabilized a catalytically active synaptic tetramer in vitro. The positions of these mutations suggest that they act by destabilizing the conformation of the ground-state site I-bound dimers, or by stabilizing the altered conformation of the active catalytic tetramer. Mutations that block activation by the regulatory tetramer mapped to just two residues, F52 and R54, supporting a functional role for a previously reported crystallographic dimer–dimer interface. We suggest how F52/R54 contacts between regulatory and catalytic subunits might promote assembly of the active catalytic tetramer within the synaptosome

    A Generalized Training Approach for Multiagent Learning

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    This paper investigates a population-based training regime based on game-theoretic principles called Policy-Spaced Response Oracles (PSRO). PSRO is general in the sense that it (1) encompasses well-known algorithms such as fictitious play and double oracle as special cases, and (2) in principle applies to general-sum, many-player games. Despite this, prior studies of PSRO have been focused on two-player zero-sum games, a regime wherein Nash equilibria are tractably computable. In moving from two-player zero-sum games to more general settings, computation of Nash equilibria quickly becomes infeasible. Here, we extend the theoretical underpinnings of PSRO by considering an alternative solution concept, α\alpha-Rank, which is unique (thus faces no equilibrium selection issues, unlike Nash) and applies readily to general-sum, many-player settings. We establish convergence guarantees in several games classes, and identify links between Nash equilibria and α\alpha-Rank. We demonstrate the competitive performance of α\alpha-Rank-based PSRO against an exact Nash solver-based PSRO in 2-player Kuhn and Leduc Poker. We then go beyond the reach of prior PSRO applications by considering 3- to 5-player poker games, yielding instances where α\alpha-Rank achieves faster convergence than approximate Nash solvers, thus establishing it as a favorable general games solver. We also carry out an initial empirical validation in MuJoCo soccer, illustrating the feasibility of the proposed approach in another complex domain

    Prebiotic effects: metabolic and health benefits

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    The different compartments of the gastrointestinal tract are inhabited by populations of micro-organisms. By far the most important predominant populations are in the colon where a true symbiosis with the host exists that is a key for well-being and health. For such a microbiota, 'normobiosis' characterises a composition of the gut 'ecosystem' in which micro-organisms with potential health benefits predominate in number over potentially harmful ones, in contrast to 'dysbiosis', in which one or a few potentially harmful micro-organisms are dominant, thus creating a disease-prone situation. The present document has been written by a group of both academic and industry experts (in the ILSI Europe Prebiotic Expert Group and Prebiotic Task Force, respectively). It does not aim to propose a new definition of a prebiotic nor to identify which food products are classified as prebiotic but rather to validate and expand the original idea of the prebiotic concept (that can be translated in 'prebiotic effects'), defined as: 'The selective stimulation of growth and/or activity(ies) of one or a limited number of microbial genus(era)/species in the gut microbiota that confer(s) health benefits to the host.' Thanks to the methodological and fundamental research of microbiologists, immense progress has very recently been made in our understanding of the gut microbiota. A large number of human intervention studies have been performed that have demonstrated that dietary consumption of certain food products can result in statistically significant changes in the composition of the gut microbiota in line with the prebiotic concept. Thus the prebiotic effect is now a well-established scientific fact. The more data are accumulating, the more it will be recognised that such changes in the microbiota's composition, especially increase in bifidobacteria, can be regarded as a marker of intestinal health. The review is divided in chapters that cover the major areas of nutrition research where a prebiotic effect has tentatively been investigated for potential health benefits. The prebiotic effect has been shown to associate with modulation of biomarkers and activity(ies) of the immune system. Confirming the studies in adults, it has been demonstrated that, in infant nutrition, the prebiotic effect includes a significant change of gut microbiota composition, especially an increase of faecal concentrations of bifidobacteria. This concomitantly improves stool quality (pH, SCFA, frequency and consistency), reduces the risk of gastroenteritis and infections, improves general well-being and reduces the incidence of allergic symptoms such as atopic eczema. Changes in the gut microbiota composition are classically considered as one of the many factors involved in the pathogenesis of either inflammatory bowel disease or irritable bowel syndrome. The use of particular food products with a prebiotic effect has thus been tested in clinical trials with the objective to improve the clinical activity and well-being of patients with such disorders. Promising beneficial effects have been demonstrated in some preliminary studies, including changes in gut microbiota composition (especially increase in bifidobacteria concentration). Often associated with toxic load and/or miscellaneous risk factors, colon cancer is another pathology for which a possible role of gut microbiota composition has been hypothesised. Numerous experimental studies have reported reduction in incidence of tumours and cancers after feeding specific food products with a prebiotic effect. Some of these studies (including one human trial) have also reported that, in such conditions, gut microbiota composition was modified (especially due to increased concentration of bifidobacteria). Dietary intake of particular food products with a prebiotic effect has been shown, especially in adolescents, but also tentatively in postmenopausal women, to increase Ca absorption as well as bone Ca accretion and bone mineral density. Recent data, both from experimental models and from human studies, support the beneficial effects of particular food products with prebiotic properties on energy homaeostasis, satiety regulation and body weight gain. Together, with data in obese animals and patients, these studies support the hypothesis that gut microbiota composition (especially the number of bifidobacteria) may contribute to modulate metabolic processes associated with syndrome X, especially obesity and diabetes type 2. It is plausible, even though not exclusive, that these effects are linked to the microbiota-induced changes and it is feasible to conclude that their mechanisms fit into the prebiotic effect. However, the role of such changes in these health benefits remains to be definitively proven. As a result of the research activity that followed the publication of the prebiotic concept 15 years ago, it has become clear that products that cause a selective modification in the gut microbiota's composition and/or activity(ies) and thus strengthens normobiosis could either induce beneficial physiological effects in the colon and also in extra-intestinal compartments or contribute towards reducing the risk of dysbiosis and associated intestinal and systemic pathologies

    Effect of processed and red meat on endogenous nitrosation and DNA damage

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    Haem in red meat (RM) stimulates the endogenous production of mutagenic nitroso compounds (NOC). Processed (nitrite-preserved red) meat additionally contains high concentrations of preformed NOC. In two studies, of a fresh RM versus a vegetarian (VEG) diet (six males and six females) and of a nitrite-preserved red meat (PM) versus a VEG diet (5 males and 11 females), we investigated whether processing of meat might increase colorectal cancer risk by stimulating nitrosation and DNA damage. Meat diets contained 420 g (males) or 366 g (females) meat/per day. Faecal homogenates from day 10 onwards were analysed for haem and NOC and associated supernatants for genotoxicity. Means are adjusted for differences in male to female ratios between studies. Faecal NOC concentrations on VEG diets were low (2.6 and 3.5 mmol/g) but significantly higher on meat diets (PM 175 ± 19 nmol/g versus RM 185 ± 22 nmol/g; P = 0.75). The RM diet resulted in a larger proportion of nitrosyl iron (RM 78% versus PM 54%; P < 0.0001) and less nitrosothiols (RM 12% versus PM 19%; P < 0.01) and other NOC (RM 10% versus PM 27%; P < 0.0001). There was no statistically significant difference in DNA breaks induced by faecal water (FW) following PM and RM diets (P = 0.80). However, PM resulted in higher levels of oxidized pyrimidines (P < 0.05). Surprisingly, VEG diets resulted in significantly more FW-induced DNA strand breaks than the meat diets (P < 0.05), which needs to be clarified in further studies. Meats cured with nitrite have the same effect as fresh RM on endogenous nitrosation but show increased FW-induced oxidative DNA damage

    Social, environmental and psychological factors associated with objective physical activity levels in the over 65s

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    Objective: To assess physical activity levels objectively using accelerometers in community dwelling over 65 s and to examine associations with health, social, environmental and psychological factors. Design: Cross sectional survey. Setting: 17 general practices in Scotland, United Kingdom. Participants: Random sampling of over 65 s registered with the practices in four strata young-old (65–80 years), old-old (over 80 years), more affluent and less affluent groups. Main Outcome Measures: Accelerometry counts of activity per day. Associations between activity and Theory of Planned Behaviour variables, the physical environment, health, wellbeing and demographic variables were examined with multiple regression analysis and multilevel modelling. Results: 547 older people (mean (SD) age 79(8) years, 54% female) were analysed representing 94% of those surveyed. Accelerometry counts were highest in the affluent younger group, followed by the deprived younger group, with lowest levels in the deprived over 80 s group. Multiple regression analysis showed that lower age, higher perceived behavioural control, the physical function subscale of SF-36, and having someone nearby to turn to were all independently associated with higher physical activity levels (R2 = 0.32). In addition, hours of sunshine were independently significantly associated with greater physical activity in a multilevel model. Conclusions: Other than age and hours of sunlight, the variables identified are modifiable, and provide a strong basis for the future development of novel multidimensional interventions aimed at increasing activity participation in later life.Publisher PDFPeer reviewe
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