325 resultados para Parke, Davis


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Background The microenvironment plays a pivotal role in tumor cell proliferation, survival and migration. Invasive cancer cells face a new set of environmental challenges as they breach the basement membrane and colonize distant organs during the process of metastasis. Phenotypic switching, such as that which occurs during epithelial-mesenchymal transition (EMT), may be associated with a remodeling of cell surface receptors and thus altered responses to signals from the tumor microenvironment. Methodology/Principal Findings We assessed changes in intracellular Ca 2+ in cells loaded with Fluo-4 AM using a fluorometric imaging plate reader (FLIPR TETRA) and observed significant changes in the potency of ATP (EC 50 0.175 μM (-EGF) versus 1.731 μM (+EGF), P<0.05), and the nature of the ATP-induced Ca 2+ transient, corresponding with a 10-fold increase in the mesenchymal marker vimentin (P<0.05). We observed no change in the sensitivity to PAR2-mediated Ca 2+ signaling, indicating that these alterations are not simply a consequence of changes in global Ca 2+ homeostasis. To determine whether changes in ATP-mediated Ca 2+ signaling are preceded by alterations in the transcriptional profile of purinergic receptors, we analyzed the expression of a panel of P2X ionotropic and P2Y metabotropic purinergic receptors using real-time RT-PCR and found significant and specific alterations in the suite of ATP-activated purinergic receptors during EGF-induced EMT in breast cancer cells. Our studies are the first to show that P2X 5 ionotropic receptors are enriched in the mesenchymal phenotype and that silencing of P2X 5 leads to a significant reduction (25%, P<0.05) in EGF-induced vimentin protein expression. Conclusions The acquisition of a new suite of cell surface purinergic receptors is a feature of EGF-mediated EMT in MDA-MB-468 breast cancer cells. Such changes may impart advantageous phenotypic traits and represent a novel mechanism for the targeting of cancer metastasis.

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The purpose of this study was to examine the effect of prolonged exercise oil plasma lipid and lipoprotein concentrations and to identify caloric time-points where changes occurred. Eleven active male Subjects ran oil a treadmill at 70%,, of maximal fitness (VO2max) and expended 6 278.7 kilojoules (Kj) energy (1500 kcal). Blood samples were obtained at the 4185.8 Kj (1000 kcal) time-point during exercise and at each additional 418.6 Kj (100 kcal) expenditure until 6278.7 Kj was expended. After correcting for plasma volume changes, decreases in low-density lipoprotein cholesterol (LDL-C) were observed during exercise at time-points corresponding to 4604.4 and 5441.5 Kj (1100 and 1300 kcal) of energy expenditure, and immediately after exercise. Total cholesterol concentrations decreased significantly at exercise kilojoule expenditures of 4604.4, 5441.5 and 5860.1 (1100, 1300 and 1400 kcal). There were also exercise induced increases in high-density lipoprotein cholesterol (HDL-C) and HDL2-C concentrations immediately after exercise. Although acute lipid and lipoprotein changes are typically reported in the days following exercise, the Current data indicate that some lipoprotein concentrations change during acute exercise. Our data suggest that a threshold of exercise may be necessary to change lipoproteins during exercise. Future work Should identify potential mechanisms (lipoprotein lipase, cholesterol ester transport protein, LDL uptake) that alter lipoprotein concentrations during prolonged exercise.

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Public libraries are increasingly using social media in an attempt to meet users in their own spaces. Social media can be useful when used to create a participatory library service â to engage with users. However, there has been little empirical investigation into the success of social media use by public libraries. This article reports on the findings of a research project that explored the use of social media by Australian public libraries. Two organisations participated in case studies that involved interviews, document analysis, and social media observation. To contextualise the use of social media in the case study organisations, a sub study was undertaking involving observation of an additional 24 public libraries across Australia. This article focuses on the findings from the observation sub study. It presents and applies a methodology for classifying social media content to determine whether the sample librariesâ social media use is indicative of a participatory approach to service delivery. This article explores how a range of social media platforms are used by the sample libraries and considers what â˜best practiceâ in participatory library service looks like. The two case study organisationsâ use of social media is highlighted as exemplary practice.

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In this Letter a hydrodynamic theory of liquid slippage on a solid substrate near a moving contact line is proposed. A family of spatially varying slip lengths in the Navier slip law recovers the results of past formulations for slip in continuum theories and molecular dynamics simulations and is consistent with well-established experimental observations of complete wetting. This formulation gives a general approach for continuum hydrodynamic theories. New fluid flow behaviors are also predicted yet to be seen in experiment. © 2013 American Physical Society.

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Wastewater containing human sewage is often discharged with little or no treatment into the Antarctic marine environment. Faecal sterols (primarily coprostanol) in sediments have been used for assessment of human sewage contamination in this environment, but in situ production and indigenous faunal inputs can confound such determinations. Using gas chromatography with mass spectral detection profiles of both C27 and C29 sterols, potential sources of faecal sterols were examined in nearshore marine sediments, encompassing sites proximal and distal to the wastewater outfall at Davis Station. Faeces from indigenous seals and penguins were also examined. Faeces from several indigenous species contained significant quantities of coprostanol but not 24-ethylcoprostanol, which is present in human faeces. In situ coprostanol and 24-ethylcoprostanol production was identified by co-production of their respective epi isomers at sites remote from the wastewat er source and in high total organic matter sediments. A C 29 sterols-based polyphasic likelihood assessment matrix for human sewage contamination is presented, which distinguishes human from local fauna faecal inputs and in situ production in the Antarctic environment. Sewage contamination was detected up to 1.5 km from Davis Station.

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Perspective taking involves mentally putting yourself in another's shoes and has been shown to offer interpersonal benefits, however, despite its use in campaigns targeting adolescents, it has been relatively neglected in marketing. This paper examines the moderating effect of entitlement in young adolescent consumers, focusing on perspective taking encouraging a prosocial behavior. This research extends existing marketing literature which to date has examined perspective taking in relation to adult behavior (Davis et al., 2004; Galinsky et al., 2008; Dietvorst et al., 2009), contributing to the study and understanding of adolescent consumers' consumer behavior. Three experiments were conducted which demonstrate that perspective taking benefits occur for nonentitled adolescents but not for entitled adolescents. Effects for perspective taking and entitlement are driven by evaluative concern for nonentitled adolescents and a perceived lack of relational closeness for entitled adolescents.

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"The German word for experience - Erlebnis - the experience of the life, to live through something - underpins this book: making visible scholarly opportunities for richer and deeper contextualizations and examinations of the lived-world experiences of people in everyday contexts as they be, do and become." (Ross Todd, Preface). Information experience is a burgeoning area of research and still unfolding as an explicit research and practice theme. This book is therefore very timely as it distils the reflections of researchers and practitioners from various disciplines, with interests ranging across information, knowledge, user experience, design and education. They cast a fresh analytical eye on information experience, whilst approaching the idea from diverse perspectives. Information Experience brings together current thinking about the idea of information experience to help form discourse around it and establish a conceptual foundation for taking the idea forward. It therefore "provides a number of theoretical lenses for examining people's information worlds in more holistic and dynamic ways." (Todd, Preface)

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In this paper we contribute to the growing body of research into the use and design of technology in the kitchen. This research aims to identify opportunities for designing technologies that may augment existing cooking traditions and in particular familial recipe sharing practices. Using ethnographic techniques, we identify the homemade cookbook as a significant material and cultural artifact in the family kitchen. We report on findings from our study by providing descriptive accounts of various homemade cookbooks, and offer design considerations for digitally augmenting homemade cookbooks.

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Four new acylated pteridine alkaloids, duramidines A-D, two new acylated thymidine alkaloids, leptoclinidines A and B, two new 1-acylglyceryl-3-(O- carboxyhydroxymethylcholine) alkaloids, durabetaines A and B, three new 1,3-dimethyl-5-methylsulfanylimidazole alkaloids, leptoclinidamines D-F, and the known alkaloids leptoclinidamines B and C and 6-bromo-1H-indolo-3-yl-oxoacetic acid methyl ester were isolated from the Australian ascidian Leptoclinides durus. The duramidines are the first pteridine alkaloids, possessing a three carbon side chain esterified at C-1â² with a 4-hydroxy-2â²- methoxycinnamic acid, and are either hydroxylated or sulfated at C-2â². The leptoclinidines are the first 3â²-indole-3-carboxylic acid ester derivatives of thymidine to be reported in the literature. The durabetaines are the first glyceryl-3-(O-carboxyhydroxymethylcholine) alkaloids to be reported from an animal source and are also the only known derivatives from this class to be acylated with aromatic carboxylic acids. MS and NMR data analysis established the structures of the new compounds. All compounds were shown to be inactive when tested for cytotoxic activity against prostate (LNCaP) and breast (MDA-MB-231) cancer cell lines and antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus.

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Chemical investigation of the CH2Cl2/MeOH extract from the Australian ascidian Leptoclinides kingi led to the isolation of a new brominated indole alkaloid, kingamide A (1). The planar structure of kingamide A was elucidated following the interpretation of 1D/2D NMR and MS data, and the absolute configuration was determined using Marfey's method. This is the first report of a natural product from L. kingi.

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Sustainability is a global issue that urgently needs addressing, the most serious consequences of which concern children and future generations. This insightful research text tackles one of the most significant contemporary issues of our times â the nexus between society and environment â and how early childhood education can contribute to sustainable living. By offering international and multidisciplinary research perspectives on Early Childhood Education for Sustainability, each chapter explores and investigates the complex topic of sustainability and its relationship to early childhood education. A particular emphasis that runs through this text is young children as empowered citizens, capable of both contributing to and creating change for sustainability. The chapter authors work from, or are aligned with, a transformative education paradigm that suggests the socio-constructivist frameworks currently underpinning Early Childhood Education require reframing in light of the social transformations necessary to address humanityâs unsustainable, unjust and unhealthy living patterns. This research text is designed to be provocative and challenging; in so doing it seeks to encourage exploration of current understandings about Early Childhood Education for Sustainability, offers new dimensions for more deeply informed practice, and proposes avenues for further research in this field.

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In this closing chapter the editors review key themes that have emerged through the book. We recognize the varied and dynamic nature of information experience across multiple contexts, and present our own conceptualization of information experience. Finally, we consider possible future directions for information experience research.

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This publication arose from the interests of the chapter authors, â˜a small group of thoughtful peopleâ almost all of whom participated in one or both Transnational Dialogues in Research in Early Childhood Education for Sustainability, held in Stavanger, Norway in 2010 and Brisbane, Australia in 2011 (Refer Appendix 1 for list of participants). These meetings were the first time that a critical mass of researchers from vastly different parts of the globe - Norway, Sweden, Australia and New Zealand at the inaugural meeting, with additional participants from Korea, Japan and Singapore attending the second - had come together to debate, discuss and share ideas about research and theory in the emerging field of Early Childhood Education for Sustainability (ECEfS. Some of the researchers who joined these Transnational Dialogues, had met serendipitously at earlier conferences and meetings, or corresponded via email, but many had never met face-to-face. Now a significant number are contributing authors in this text. It is a testament to these researchersâ interest in this agenda that they mostly self-funded their travel and other costs to attend the Transnational Dialogues research meetings. While most chapter authors come from the field of early childhood education, a few are more aligned with education for sustainability/environmental education, while a much smaller number are already working at the intersection of early childhood education and education for sustainability. What we share as a group is a range of perspectives and orientations to research and to the research focus at the heart of this book - young children and their actual and potential capabilities as agents of change for sustainability. As researchers, regardless of experience and perspectives, participants knew they had something extra to offer - their expertise as researchers - providing scholarly insights into the work of practitioners, applying critically reflective lenses to curricula, pedagogies and assumptions, testing of ideas and theories, and presenting a sense for where ECEfS might fit or, indeed, go beyond norms and orthodoxies. This is a text, then, for both researchers and those whose primary interests lie in daily interactions with children, families and communities.

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This chapter calls for rethinking about the rights base of early childhood education. The United Nations Convention on the Rights of the Child (UNCRC) (UNICEF1989) has been seen as an important foundation internationally for early childhood education practise. In this paper, I argue that whilst the UNCRC (1989) still serves its aspirational purpose, it is an inadequate vehicle for enacting early childhood education in the twenty-first century given the pressing challenges of sustainability. The UNCRC emerged from an individual rights perspective, and despite attempts to broaden the rights agenda towards greater child participation and engagement, these approaches offer an inadequate response to global sustainability concerns. In this chapter, I propose a five dimensional approach to rights that acknowledges the fundamental rights of children as espoused in the UNCRC and the call for agentic rights as advocated more recently by early childhood academics and practitioners. Additionally, however, discussion of collective rights, intergenerational rights and bio/ecocentic rights are forwarded, offering a expanded way to think about rights with implications for how early childhood education is practised and researched.

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Seemingly straightforward tasks often have a way of becoming complex. This was the case for our guest editorial team charged with creating Early Childhood Australiaâs Best of Sustainability publication drawn from the the Australasian Journal of Early Childhood and Every Child. The complexities we encountered ranged from the varied terminologies and understandings of constructs such as education for sustainable development, environmental education and education for sustainability, through to the fundamental lack of published research on which to draw as the basis for a special issue. It is timely to explore these complexities as we face the global challenges of The Critical Decade (DCCEE, 2011) including rising sea levels, extreme weather events and food security. At a local level, the early childhood field in Australia is seeking to interpret sustainability with systemic support from the National Quality Standards(NQS) (ACECQA, 2011), while elsewhere environmental/sustainability education is encouraged through national curricula documents (for example, Singapore Ministry of Education, 2008; Swedish National Agency for Education,2010; Ministry of Education of Korea, 2011). Both The Critical Decade and the NQS provide imperatives to drive early childhood educationâs engagement with sustainability. In other words, sustainability in early childhood education is no longer optional, but essential (Elliott, 2010). While some twenty years of advocacy has led to this somewhat subdued celebratory position, in this publication we do recognise the historical contexts that have led to early childhood education for sustainability (ECEfS), as we (Elliott & Davis) phrase it, becoming almost â˜mainstream not marginalâ (Davis, 1999)â a stitching together of the isolated â˜patches of greenâ, first identified a decade ago by Elliott (NSW EPA, 2003). Here we weave together, through these articles, a story of the evolving history of ECEfS from our particular perspective. In so doing, we also acknowledge that there are other perspectives or â˜pathsâ for this field as identified by Edwards and Cutter-McKenzie in their concluding paper to this compilation.