130 resultados para Nicholas of Cusa


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This paper investigates the challenge of representing structural differences in river channel cross-section geometry for regional to global scale river hydraulic models and the effect this can have on simulations of wave dynamics. Classically, channel geometry is defined using data, yet at larger scales the necessary information and model structures do not exist to take this approach. We therefore propose a fundamentally different approach where the structural uncertainty in channel geometry is represented using a simple parameterization, which could then be estimated through calibration or data assimilation. This paper first outlines the development of a computationally efficient numerical scheme to represent generalised channel shapes using a single parameter, which is then validated using a simple straight channel test case and shown to predict wetted perimeter to within 2% for the channels tested. An application to the River Severn, UK is also presented, along with an analysis of model sensitivity to channel shape, depth and friction. The channel shape parameter was shown to improve model simulations of river level, particularly for more physically plausible channel roughness and depth parameter ranges. Calibrating channel Manning’s coefficient in a rectangular channel provided similar water level simulation accuracy in terms of Nash-Sutcliffe efficiency to a model where friction and shape or depth were calibrated. However, the calibrated Manning coefficient in the rectangular channel model was ~2/3 greater than the likely physically realistic value for this reach and this erroneously slowed wave propagation times through the reach by several hours. Therefore, for large scale models applied in data sparse areas, calibrating channel depth and/or shape may be preferable to assuming a rectangular geometry and calibrating friction alone.

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The paper begins by considering the importance of springs as a focus for votive deposits in Bronze Age Britain. This is not a new idea, but nowhere has this association been examined through the excavation of one of these features. The point is illustrated by excavation at the findspot of a famous group of Late Bronze Age weapons, the Broadward hoard, discovered in 1867. Little was known about the site, where it was found or the character of the original deposit, but a study of contemporary accounts of the hoard, combined with geophysical and topographical surveys, led to small-scale excavation in 2010, which showed that the deposit had most probably been buried in a pit on the edge of a spring. Other finds associated with the spring included an Early Bronze Age macehead, a Roman pot and various Saxon and medieval animal bones. The latest deposit, with a post-medieval carbon date, included a wooden knife or dagger. An adjacent palaeochannel provided an important environmental sequence for this part of the English–Welsh borderland and suggests that the Late Bronze Age hoard had been deposited not far from a settlement. A nearby earthwork enclosure was associated with a clay weight, which may be of similar date. Despite the limited scale of the fieldwork, it illustrates the potential for treating springs associated with artefact finds on the same terms as other archaeological deposits.

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Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway.

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The role of the local atmospheric forcing on the ocean mixed layer depth (MLD) over the global oceans is studied using ocean reanalysis data products and a single-column ocean model coupled to an atmospheric general circulation model. The focus of this study is on how the annual mean and the seasonal cycle of the MLD relate to various forcing characteristics in different parts of the world's ocean, and how anomalous variations in the monthly mean MLD relate to anomalous atmospheric forcings. By analysing both ocean reanalysis data and the single-column ocean model, regions with different dominant forcings and different mean and variability characteristics of the MLD can be identified. Many of the global oceans' MLD characteristics appear to be directly linked to different atmospheric forcing characteristics at different locations. Here, heating and wind-stress are identified as the main drivers; in some, mostly coastal, regions the atmospheric salinity forcing also contributes. The annual mean MLD is more closely related to the annual mean wind-stress and the MLD seasonality is more closely to the seasonality in heating. The single-column ocean model, however, also points out that the MLD characteristics over most global ocean regions, and in particular the tropics and subtropics, cannot be maintained by local atmospheric forcings only, but are also a result of ocean dynamics that are not simulated in a single-column ocean model. Thus, lateral ocean dynamics are essentially in correctly simulating observed MLD.

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BACKGROUND: Although the peroxisome proliferator-activated receptor γ (PPARγ) pathway is central in adipogenesis, it remains unknown whether it influences change in body weight (BW) and whether dietary fat has a modifying effect on the association. OBJECTIVES: We examined whether 27 single nucleotide polymorphisms (SNPs) within 4 genes in the PPARγ pathway are associated with the OR of being a BW gainer or with annual changes in anthropometry and whether intake of total fat, monounsaturated fat, polyunsaturated fat, or saturated fat has a modifying effect on these associations. METHODS: A case-noncase study included 11,048 men and women from cohorts in the European Diet, Obesity and Genes study; 5552 were cases, defined as individuals with the greatest BW gain during follow-up, and 6548 were randomly selected, including 5496 noncases. We selected 4 genes [CCAAT/enhancer binding protein β (CEBPB), phosphoenolpyruvate carboxykinase 2, PPARγ gene (PPARG), and sterol regulatory element binding transcription factor 1] according to evidence about biologic plausibility for interactions with dietary fat in weight regulation. Diet was assessed at baseline, and anthropometry was followed for 7 y. RESULTS: The ORs for being a BW gainer for the 27 genetic variants ranged from 0.87 (95% CI: 0.79, 1.03) to 1.12 (95% CI: 0.96, 1.22) per additional minor allele. Uncorrected, CEBPB rs4253449 had a significant interaction with the intake of total fat and subgroups of fat. The OR for being a BW gainer for each additional rs4253449 minor allele per 100 kcal higher total fat intake was 1.07 (95% CI: 1.02, 1.12; P = 0.008), and similar associations were found for subgroups of fat. CONCLUSIONS: Among European men and women, the influence of dietary fat on associations between SNPs in the PPARγ pathway and anthropometry is likely to be absent or marginal. The observed interaction between rs4253449 and dietary fat needs confirmation.

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Arnold v Britton marks the final stage of the longstanding dispute as to the correct interpretation of a number of 99-year leases of chalets on a leisure park at Oxwich, in the Gower peninsula, near Swansea. The aspect of the case which has attracted most discussion has, understandably, been its main ratio: the proper way to construe a provision of a lease which arguably has an absurd result. This will be considered in this case-note. The judgment of the Supreme Court – particularly the judgment of Lord Neuberger PSC – does, however contain some observations on the possible reform of the law on service charges which are of interest to those engaged in this field. It also contains some obiter comments on ‘letting schemes’ which are – in the view of the present author – highly unorthodox. These three rather disparate issues which are raised by this case will be considered in turn. As they have little in common with each other, they will be considered as separate sections.

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This paper contributes to the growing multidisciplinary body of literature on subjective well-being by investigating the longitudinal stability and impact of societal cultural values (SCVs) – as opposed to the more common organizational values – on job satisfaction. It is assumed that SCVs evolve slowly; hence, their impact on job satisfaction is likely to remain stable over time. False adherence to this assumption could cause misalignment between organizational policies/practices and expectations formed by societal culture, decreasing job satisfaction and adversely affecting productivity, competiveness and prosperity. Four waves of the European Values Study are used to examine whether SCVs have evolved and their impacts on job satisfaction over a relatively short time: 1981–2008. SCVs are parameterized through reference to traditional vs secular-rational, and survival vs self-expression value continuums. Results indicate that the strength of many SCVs has declined, the impacts of traditional societal values on job satisfaction have remained fairly constant, and the impacts of survival societal values on job satisfaction have declined substantially over this sample period. These reductions in SCVs amplify the importance of accounting for such changes when designing new or adjusting existing policies/practices to enhance job satisfaction and stimulate improvements in productivity, competitiveness and prosperity.

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The first agricultural societies were established around 10 ka BP and had spread across much of Europe and southern Asia by 5.5 ka BP with resultant anthropogenic deforestation for crop and pasture land. Various studies (e.g. Joos et al., 2004; Kaplan et al., 2011; Mitchell et al., 2013) have attempted to assess the biogeochemical implications for Holocene climate in terms of increased carbon dioxide and methane emissions. However, less work has been done to examine the biogeophysical impacts of this early land use change. In this study, global climate model simulations with Hadley Centre Coupled Model version 3 (HadCM3) were used to examine the biogeophysical effects of Holocene land cover change on climate, both globally and regionally, from the early Holocene (8 ka BP) to the early industrial era (1850 CE). Two experiments were performed with alternative descriptions of past vegetation: (i) one in which potential natural vegetation was simulated by Top-down Representation of Interactive Foliage and Flora Including Dynamics (TRIFFID) but without land use changes and (ii) one where the anthropogenic land use model Kaplan and Krumhardt 2010 (KK10; Kaplan et al., 2009, 2011) was used to set the HadCM3 crop regions. Snapshot simulations were run at 1000-year intervals to examine when the first signature of anthropogenic climate change can be detected both regionally, in the areas of land use change, and globally. Results from our model simulations indicate that in regions of early land disturbance such as Europe and south-east Asia detectable temperature changes, outside the normal range of variability, are encountered in the model as early as 7 ka BP in the June–July–August (JJA) season and throughout the entire annual cycle by 2–3 ka BP. Areas outside the regions of land disturbance are also affected, with virtually the whole globe experiencing significant temperature changes (predominantly cooling) by the early industrial period. The global annual mean temperature anomalies found in our single model simulations were −0.22 at 1850 CE, −0.11 at 2 ka BP, and −0.03 °C at 7 ka BP. Regionally, the largest temperature changes were in Europe with anomalies of −0.83 at 1850 CE, −0.58 at 2 ka BP, and −0.24 °C at 7 ka BP. Large-scale precipitation features such as the Indian monsoon, the Intertropical Convergence Zone (ITCZ), and the North Atlantic storm track are also impacted by local land use and remote teleconnections. We investigated how advection by surface winds, mean sea level pressure (MSLP) anomalies, and tropospheric stationary wave train disturbances in the mid- to high latitudes led to remote teleconnections.

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The fifteenth century saw a striking upturn in the number of texts from foreign vernaculars that were translated into Irish. Indeed, one might go so far as to speak in terms of a ‘translation trend’ in Ireland during the mid to late fifteenth century. A notable feature of this trend is that a particularly high number of these Irish translations are of romances; contextual and textual evidence suggests that the original exemplars for many of these translated texts appear to have come from England, though not all of them were necessarily in English. Irish translations of eight romances have survived to the present day: Guy of Warwick; Bevis of Hampton; La Queste de Saint Graal; Fierabras; Caxton’s Recuyell of the Histories of Troie; William of Palerne; the Seven Sages of Rome; and Octavian. This paper addresses two aspects of these texts of particular relevance to romance scholars who do not work within the sphere of Celtic studies. Firstly, it argues that certain aspects of the dissemination and reception of romance in Ireland are quite distinctive. Manuscript and textual evidence suggests that the religious orders, particularly the Franciscans, seem to have played a role in the importation and translation of these narratives. Secondly, examination of the Irish versions of romance tends to bear out an observation made by Flower many years ago, but not pursued by subsequent scholars: ‘texts of an unusual kind were current in Ireland, and it may be that interesting discoveries are to be made here’. Certain narrative features of several of these Irish translations diverge from all the surviving versions of the relevant romance in other languages and may witness to a variant exemplar that has since been lost from its own linguistic corpus.

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The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease- causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next generation sequencing was carried out revealing variants in a number of other known complex spastic paraplegia genes, including five in SPG7 (5/97), four in FA2H (also known as SPG35) (4/97) and two in ZFYVE26/SPG15. Variants were identified in genes usually associated with pure spastic paraplegia and also in the Parkinson’s disease-associated gene ATP13A2, neuronal ceroid lipofuscinosis gene TPP1 and the hereditary motor and sensory neuropathy DNMT1 gene, highlighting the genetic heterogeneity of spastic paraplegia. No plausible genetic cause was identified in 51% of probands, likely indicating the existence of as yet unidentified genes.