572 research outputs found
Separation of breast cancer and organ microenvironment transcriptomes in metastases
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?
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
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Accounting for information: Information and knowledge in the annual reports of FTSE 100 companies
The purpose of this study was to assess the ways in which a sample group of companies discuss information and knowledge.
Quantitative and qualitative content analyses were used to survey the way that companies present and value information and knowledge, based on the annual reports of the FTSE 100, the United Kingdom's largest publicly-listed companies. A novel content analysis approach is used, based on a set of categories proposed by Oppenheim, Stenson and Wilson.
Many of the companies analysed made explicit the importance of information and knowledge, through either discussion in the text of the annual report or through an attempt to assign a monetary value to information assets. Where the importance of information and knowledge was not made explicit, the study revealed links between successful performance and effective use of information assets. Different categories of information assets were identified within the annual reports.
Conclusions drawn from the analysis include that information and knowledge are demonstrably important to FTSE 100 companies, although the specific term “knowledge” does not appear to have a special significance in the companies’ lexicon; and that certain sectors, such as General Financial, General Retail, Travel & Leisure, Mining, Aerospace & Defence and Software & Computer Services, mention information and knowledge more than others
Review debate: we need human rights not nationalism 'lite': globalization and British solidarity
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
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
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
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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