572 research outputs found

    Critical and umbilical points of a non-Gaussian random field.

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    Theoretical Physic

    Separation of breast cancer and organ microenvironment transcriptomes in metastases

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    Background: The seed and soil hypothesis was proposed over a century ago to describe why cancer cells (seeds) grow in certain organs (soil). Since then, the genetic properties that define the cancer cells have been heavily investigated; however, genomic mediators within the organ microenvironment that mediate successful metastatic growth are less understood. These studies sought to identify cancer- and organ-specific genomic programs that mediate metastasis. Methods: In these studies, a set of 14 human breast cancer patient-derived xenograft (PDX) metastasis models was developed and then tested for metastatic tropism with two approaches: spontaneous metastases from mammary tumors and intravenous injection of PDX cells. The transcriptomes of the cancer cells when growing as tumors or metastases were separated from the transcriptomes of the microenvironment via species-specific separation of the genomes. Drug treatment of PDX spheroids was performed to determine if genes activated in metastases may identify targetable mediators of viability. Results: The experimental approaches that generated metastases in PDX models were identified. RNA sequencing of 134 tumors, metastases, and normal non-metastatic organs identified cancer- and organ-specific genomic properties that mediated metastasis. A common genomic response of the liver microenvironment was found to occur in reaction to the invading PDX cells. Genes within the cancer cells were found to be either transiently regulated by the microenvironment or permanently altered due to clonal selection of metastatic sublines. Gene Set Enrichment Analyses identified more than 400 gene signatures that were commonly activated in metastases across basal-like PDXs. A Src signaling signature was found to be extensively upregulated in metastases, and Src inhibitors were found to be cytotoxic to PDX spheroids. Conclusions: These studies identified that during the growth of breast cancer metastases, there were genomic changes that occurred within both the cancer cells and the organ microenvironment. We hypothesize that pathways upregulated in metastases are mediators of viability and that simultaneously targeting changes within different cancer cell pathways and/or different tissue compartments may be needed for inhibition of disease progression

    Personal identity (de)formation among lifestyle travellers: A double-edged sword?

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    This article explores the personal identity work of lifestyle travellers – individuals for whom extended leisure travel is a preferred lifestyle that they return to repeatedly. Qualitative findings from in-depth semi-structured interviews with lifestyle travellers in northern India and southern Thailand are interpreted in light of theories on identity formation in late modernity that position identity as problematic. It is suggested that extended leisure travel can provide exposure to varied cultural praxes that may contribute to a sense of social saturation. Whilst a minority of the respondents embraced a saturation of personal identity in the subjective formation of a cosmopolitan cultural identity, several of the respondents were paradoxically left with more identity questions than answers as the result of their travels

    Review debate: we need human rights not nationalism 'lite': globalization and British solidarity

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    The article explores the relationship of multiculturalism to social solidarity. The multicultural nature of Britain is accepted as a welcome reality but certain problems in relation to the development of multiculturalism in Britain are acknowledged. Various approaches to buttress or replace multiculturalism are reviewed. These are: a strengthened and/or reconstituted nationalism (`Britishness'); human rights; and social equality. The issue of citizenship recurs throughout. It is argued that a combined emphasis on human rights and greater social equality offer a better basis than nationalism for strengthening solidarity in Britain, especially in the longer term. Sociological theory offers a fruitful if strangely neglected starting point for understanding social solidarity. I draw critically on Durkheim and Marx to obtain some objective perspective on this controversial matter. Copyright 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution

    Gradient models of the axion-photon coupling

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    We establish an extended version of the Einstein - Maxwell - axion model by introducing into the Lagrangian cross-terms, which contain the gradient four-vector of the pseudoscalar (axion) field in convolution with the Maxwell tensor. The gradient model of the axion-photon coupling is applied to cosmology: we analyze the Bianchi-I type Universe with an initial magnetic field, electric field induced by the axion-photon interaction, cosmological constant and dark matter, which is described in terms of the pseudoscalar (axion) field. Analytical, qualitative and numerical results are presented in detail for two distinguished epochs: first, for the early Universe with magnetic field domination; second, for the stage of late-time accelerated expansion.Comment: 26 pages, 5 figures, accepted for publication in The European Physical Journal

    Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

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    Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes

    Cosmic-ray positron fraction measurement from 1 to 30 GeV with AMS-01

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    A measurement of the cosmic ray positron fraction e+/(e+ + e-) in the energy range of 1-30 GeV is presented. The measurement is based on data taken by the AMS-01 experiment during its 10 day Space Shuttle flight in June 1998. A proton background suppression on the order of 10^6 is reached by identifying converted bremsstrahlung photons emitted from positrons
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