269 research outputs found

    The Asperian Design

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    Reality is two-fold, composed of the lighted world as revealed in Genesis, and the darker primordiality which preceded it. The illuminated represents that which the human mind can comprehend, manipulate and re-order to its will: a “designed” and mechanical universe of parts. But behind it, in the backspace of reality, remains the darkness. A formless state of pre-creation, the darkness exists as an endless series of intertwining “signatures” – single possibilities waiting to be created in the illuminated forefront of reality. Permitting each and every part of the lighted world to be connected to the rest, it possesses a “design” all of its own. The question is, if we are blind in the dark, how could we ever come to know it

    The Field

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    Life is a battlefield onto which we are thrown at birth, with only fate and fortune settling upon where we land. Wherever we land, whether it's on the front lines or surrounded by a network of defenses, we are all asking the same question: why are we here? The problem with this question, however, is that we tend to answer it from our own relative positions, and so we all arrive at different conclusions. The many answers we've created have filled the field. They have become banners that are raised high so that we can see and follow them. These banners are always at risk of being toppled though; always at risk of losing their capacity for belief. But then, what if belief is more than a mere by-product of our universal search? What if belief can change the very fabric of this field? That is, what if truth is actually irrelevant, and the only real thing that makes up this battlefield is the belief, and consequently the collective will, which we invest in our answers

    Sequence-based prediction for vaccine strain selection and identification of antigenic variability in foot-and-mouth disease virus

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    Identifying when past exposure to an infectious disease will protect against newly emerging strains is central to understanding the spread and the severity of epidemics, but the prediction of viral cross-protection remains an important unsolved problem. For foot-and-mouth disease virus (FMDV) research in particular, improved methods for predicting this cross-protection are critical for predicting the severity of outbreaks within endemic settings where multiple serotypes and subtypes commonly co-circulate, as well as for deciding whether appropriate vaccine(s) exist and how much they could mitigate the effects of any outbreak. To identify antigenic relationships and their predictors, we used linear mixed effects models to account for variation in pairwise cross-neutralization titres using only viral sequences and structural data. We identified those substitutions in surface-exposed structural proteins that are correlates of loss of cross-reactivity. These allowed prediction of both the best vaccine match for any single virus and the breadth of coverage of new vaccine candidates from their capsid sequences as effectively as or better than serology. Sub-sequences chosen by the model-building process all contained sites that are known epitopes on other serotypes. Furthermore, for the SAT1 serotype, for which epitopes have never previously been identified, we provide strong evidence - by controlling for phylogenetic structure - for the presence of three epitopes across a panel of viruses and quantify the relative significance of some individual residues in determining cross-neutralization. Identifying and quantifying the importance of sites that predict viral strain cross-reactivity not just for single viruses but across entire serotypes can help in the design of vaccines with better targeting and broader coverage. These techniques can be generalized to any infectious agents where cross-reactivity assays have been carried out. As the parameterization uses pre-existing datasets, this approach quickly and cheaply increases both our understanding of antigenic relationships and our power to control disease

    No Plan B: the Achilles heel of high performance sport management

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    Research question: The severity and immediacy of funding cuts to UK National Governing Bodies of Sport (NGBs), driven by the ‘No Compromise’ policy framework for Olympic funding, triggers a cyclical need for turnaround management. Adept strategies during times of considerable challenge is stark, yet literature investigating turnaround management within NGBs remains limited. Consequently, this paper examines two questions: how do NGBs respond to UK Sport funding cuts and how are their responses enabled or restricted by their organisational context? Research methods: A case study methodology was used to develop in-depth insights into how three NGBs responded over a twelve-month period of turnaround management. This was informed by 21 semi-structured interviews with chief executives/presidents, performance managers/head coaches and elite athletes. The actions of the NGBs were analysed through a thematic analysis that made use of Boyne’s (2004) 3 Rs of turnaround strategy. Results and findings: The results highlight that NGBs’ turnaround strategies were constrained by extreme funding dependency and a prohibitive institutional environment that led to states of flux and a focus on short-term operational survival. As a result, the measures taken undermined future success. Implications: An embedded feature of the ‘No Compromise’ framework is severe funding cuts. This should be a significant theme in NGB strategy development. The evidence of this study is that NGBs do not prepare, nor react strategically, when faced with the prospect (or fact of) severe cuts. Consequently, the cases of turnaround management in this study signal the urgent need for further research into the impact of the ‘No Compromise’ framework on the management of NGBs

    Frontiers in soil ecology—Insights from the World Biodiversity Forum 2022

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    Global change is affecting soil biodiversity and functioning across all terrestrial ecosystems. Still, much is unknown about how soil biodiversity and function will change in the future in response to simultaneous alterations in climate and land use, as well as other environmental drivers. It is crucial to understand the direct, indirect and interactive effects of global change drivers on soil communities and ecosystems across environmental contexts, not only today but also in the near future. This is particularly relevant for international efforts to tackle climate change like the Paris Agreement, and considering the failure to achieve the 2020 biodiversity targets, especially the target of halting soil degradation. Here, we outline the main frontiers related to soil ecology that were presented and discussed at the thematic sessions of the World Biodiversity Forum 2022 in Davos, Switzerland. We highlight multiple frontiers of knowledge associated with data integration, causal inference, soil biodiversity and function scenarios, critical soil biodiversity facets, underrepresented drivers, global collaboration, knowledge application and transdisciplinarity, as well as policy and public communication. These identified research priorities are not only of immediate interest to the scientific community but may also be considered in research priority programmes and calls for funding

    Native diversity buffers against severity of non-native tree invasions

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    Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2^{1,2}. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4^{3,4}. Here, leveraging global tree databases57^{5–7}, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions

    The global biogeography of tree leaf form and habit

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    Understanding what controls global leaf type variation in trees is crucial for comprehending their role in terrestrial ecosystems, including carbon, water and nutrient dynamics. Yet our understanding of the factors influencing forest leaf types remains incomplete, leaving us uncertain about the global proportions of needle-leaved, broadleaved, evergreen and deciduous trees. To address these gaps, we conducted a global, ground-sourced assessment of forest leaf-type variation by integrating forest inventory data with comprehensive leaf form (broadleaf vs needle-leaf) and habit (evergreen vs deciduous) records. We found that global variation in leaf habit is primarily driven by isothermality and soil characteristics, while leaf form is predominantly driven by temperature. Given these relationships, we estimate that 38% of global tree individuals are needle-leaved evergreen, 29% are broadleaved evergreen, 27% are broadleaved deciduous and 5% are needle-leaved deciduous. The aboveground biomass distribution among these tree types is approximately 21% (126.4 Gt), 54% (335.7 Gt), 22% (136.2 Gt) and 3% (18.7 Gt), respectively. We further project that, depending on future emissions pathways, 17–34% of forested areas will experience climate conditions by the end of the century that currently support a different forest type, highlighting the intensification of climatic stress on existing forests. By quantifying the distribution of tree leaf types and their corresponding biomass, and identifying regions where climate change will exert greatest pressure on current leaf types, our results can help improve predictions of future terrestrial ecosystem functioning and carbon cycling

    Cultural distance, mindfulness and passive xenophobia: Using Integrated Threat Theory to explore home higher education students' perspectives on 'internationalisation at home'

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    This paper addresses the question of interaction between home and international students using qualitative data from 100 home students at two 'teaching intensive' universities in the southwest of England. Stephan and Stephan's Integrated Threat Theory is used to analyse the data, finding evidence for all four types of threat that they predict when outgroups interact. It is found that home students perceive threats to their academic success and group identity from the presence of international students on the campus and in the classroom. These are linked to anxieties around 'mindful' forms of interaction and a taboo around the discussion of difference, leading to a 'passive xenophobia' for the majority. The paper concludes that Integrated Threat Theory is a useful tool in critiquing the 'internationalisation at home' agenda, making suggestions for policies and practices that may alleviate perceived threats, thereby improving the quality and outcomes of intercultural interaction. © 2010 British Educational Research Association

    TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

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    <p>Abstract</p> <p>Background</p> <p>Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM) on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta) signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited.</p> <p>Methods</p> <p>Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4) in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2) vs. high-grade (i.e. grade 3 and 4)), lymph node metastasis, distant metastasis, 5 year cancer related survival) using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed.</p> <p>Results</p> <p>High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and shorter survival. Stromal TGF-beta receptor 2 expression was an independent prognostic factor for cancer related survival.</p> <p>Conclusion</p> <p>Histological phenotype and clinical behaviour of colon cancer is not only influenced by mutational incidents in tumour cells but also affected by interaction of tumour tissue with inflammatory cells like macrophages and associated stroma and TGF-beta signalling is one important part of this crosstalk. Further studies are needed to elucidate the exact mechanisms.</p

    Native diversity buffers against severity of non-native tree invasions

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    Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies. Here, leveraging global tree databases, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions
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