397 resultados para Transition Out
Resumo:
In this paper, the authors combine Pierre Bourdieu’s concept of hysteresis (the ‘fish out of water’ experience) with the discourse historical approach to critical discourse analysis (CDA) as a theoretical and analytical framework through which they examine specific moments in the schooling experiences of one refugee student and one international student, both enrolled in post-compulsory education in Australian mainstream secondary schools. We examine specific moments – as narrated by these students during interviews – in which these students can be described as ‘fish out of water’. As such, this paper takes up the concerns of researchers who call for an examination of the lived geographies and the everyday lives of individual students in mainstream schools. We find that our students’ habitus, conditioned by their previous schooling experiences in their home countries, did not match their new Australian schools, resulting in frustration with, and alienation from, their mainstream schools. However, we also note that schools, too, need to adapt and adjust their habitus to the new multicultural world, in which there are international and refugee students among their usual cohort of mainstream students.
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Resistance to chemotherapy and metastases are the major causes of breast cancer-related mortality. Moreover, cancer stem cells (CSC) play critical roles in cancer progression and treatment resistance. Previously, it was found that CSC-like cells can be generated by aberrant activation of epithelial–mesenchymal transition (EMT), thereby making anti-EMT strategies a novel therapeutic option for treatment of aggressive breast cancers. Here, we report that the transcription factor FOXC2 induced in response to multiple EMT signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT- and CSC-enriched breast cancer cell lines. More specifically, attenuation of FOXC2 expression using lentiviral short hairpin RNA led to inhibition of the mesenchymal phenotype and associated invasive and stem cell properties, which included reduced mammosphere-forming ability and tumor initiation. Whereas, overexpression of FOXC2 was sufficient to induce CSC properties and spontaneous metastasis in transformed human mammary epithelial cells. Furthermore, a FOXC2-induced gene expression signature was enriched in the claudin-low/basal B breast tumor subtype that contains EMT and CSC features. Having identified PDGFR-β to be regulated by FOXC2, we show that the U.S. Food and Drug Administration-approved PDGFR inhibitor, sunitinib, targets FOXC2-expressing tumor cells leading to reduced CSC and metastatic properties. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies for the treatment of claudin-low/basal B breast tumors or other EMT-/CSC-enriched tumors.
Resumo:
Transition between epithelial and mesenchymal states is a feature of both normal development and tumor progression. We report that expression of chloride channel accessory protein hCLCA2 is a characteristic of epithelial differentiation in the immortalized MCF10A and HMLE models, while induction of epithelial-to-mesenchymal transition by cell dilution, TGFβ or mesenchymal transcription factors sharply reduces hCLCA2 levels. Attenuation of hCLCA2 expression by lentiviral small hairpin RNA caused cell overgrowth and focus formation, enhanced migration and invasion, and increased mammosphere formation in methylcellulose. These changes were accompanied by downregulation of E-cadherin and upregulation of mesenchymal markers such as vimentin and fibronectin. Moreover, hCLCA2 expression is greatly downregulated in breast cancer cells with a mesenchymal or claudin-low profile. These observations suggest that loss of hCLCA2 may promote metastasis. We find that higher-than-median expression of hCLCA2 is associated with a one-third lower rate of metastasis over an 18-year period among breast cancer patients compared with lower-than-median (n=344, unfiltered for subtype). Thus, hCLCA2 is required for epithelial differentiation, and its loss during tumor progression contributes to metastasis. Overexpression of hCLCA2 has been reported to inhibit cell proliferation and is accompanied by increases in chloride current at the plasma membrane and reduced intracellular pH (pHi). We found that knockdown cells have sharply reduced chloride current and higher pHi, both characteristics of tumor cells. These results suggest a mechanism for the effects on differentiation. Loss of hCLCA2 may allow escape from pHi homeostatic mechanisms, permitting the higher intracellular and lower extracellular pH that are characteristic of aggressive tumor cells.
Resumo:
Ethnography is now a well-established research methodology for virtual environments, and the vast majority of accounts have one aspect in common, whether textual or graphic environments – that of the embodied avatar. In this article, I first discuss the applicability of such a methodology to non-avatar environments such as Eve Online, considering where the methodology works and the issues that arise in its implementation – particularly for the consideration of sub-communities within the virtual environment. Second, I consider what alternative means exist for getting at the information that is obtained through an ethnographic study of the virtual environment. To that end, I consider the practical and ethical implications of utilizing existing accounts, the importance of the meta-game discourse, including those sources outside of the control of the environment developer, and finally the utility in combining personal observations with accounts of other ethnographers, both within and between environments.
Resumo:
The resection of DNA double-strand breaks (DSBs) to generate ssDNA tails is a pivotal event in the cellular response to these breaks. In the two-step model of resection, primarily elucidated in yeast, initial resection by Mre11-CtIP is followed by extensive resection by two distinct pathways involving Exo1 or BLM/WRN-Dna2. However, resection pathways and their exact contributions in humans in vivo are not as clearly worked out as in yeast. Here, we examined the contribution of Exo1 to DNA end resection in humans in vivo in response to ionizing radiation (IR) and its relationship with other resection pathways (Mre11-CtIP or BLM/WRN). We find that Exo1 plays a predominant role in resection in human cells along with an alternate pathway dependent on WRN. While Mre11 and CtIP stimulate resection in human cells, they are not absolutely required for this process and Exo1 can function in resection even in the absence of Mre11-CtIP. Interestingly, the recruitment of Exo1 to DNA breaks appears to be inhibited by the NHEJ protein Ku80, and the higher level of resection that occurs upon siRNA-mediated depletion of Ku80 is dependent on Exo1. In addition, Exo1 may be regulated by 53BP1 and Brca1, and the restoration of resection in BRCA1-deficient cells upon depletion of 53BP1 is dependent on Exo1. Finally, we find that Exo1-mediated resection facilitates a transition from ATM- to ATR-mediated cell cycle checkpoint signaling. Our results identify Exo1 as a key mediator of DNA end resection and DSB repair and damage signaling decisions in human cells.
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MediaClub is an after-school digital literacy activity for Year 4-7 students at Waterford West State School. Since it began in 2010, as part of the URL project, the club has provided approximately 18 students from the school each term with a structured program of media production opportunities. Here we describe the aims and organisation of the club and student experiences and outcomes.
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Prompted by the continuing transition to community care, mental health nurses are considering the role of social support in community adaptation. This article demonstrates the importance of distinguishing between kinds of social support and presents findings from the first round data of a longitudinal study of community adaptation in 156 people with schizophrenia conducted in Brisbane, Australia. All clients were interviewed using the relevant subscales of the Diagnostic Interview Schedule to confirm a primary diagnosis of schizophrenia. The study set out to investigate the relationship between community adaptation and social support. Community adaptation was measured with the Brief Psychiatric Rating Scale (BPRS), the Life Skills Profile (LSP) and measures of dissatisfaction with life and problems in daily living developed by the authors. Social support was measured with the Arizona Social Support Interview Schedule (ASSIS). The BPRS and ASSIS were incorporated into a client interview conducted by trained interviewers. The LSP was completed on each client by an informal carer (parent, relative or friend) or a professional carer (case manager or other health professional) nominated by the client. Hierarchical regression analysis was used to examine the relationship between community adaptation and four sets of social support variables. Given the order in which variables were entered in regression equations, a set of perceived social support variables was found to account for the largest unique variance of four measures of community adaptation in 96 people with schizophrenia for whom complete data are available from the first round of the three-wave longitudinal study. A set of the subjective experiences of the clients accounted for the largest unique variance in measures of symptomatology, life skills, dissatisfaction with life, and problems in daily living. Sets of community support, household support and functional variables accounted for less variance. Implications for mental health nursing practice are considered.
Resumo:
The preparedness theory of classical conditioning proposed by Seligman (1970, 1971) has been applied extensively over the past 40 years to explain the nature and "source" of human fear and phobias. In this review we examine the formative studies that tested the four defining characteristics of prepared learning with animal fear-relevant stimuli (typically snakes and spiders) and consider claims that fear of social stimuli, such as angry faces, or faces of racial out-group members, may also be acquired utilising the same preferential learning mechanism. Exposition of critical differences between fear learning to animal and social stimuli suggests that a single account cannot adequately explain fear learning with animal and social stimuli. We demonstrate that fear conditioned to social stimuli is less robust than fear conditioned to animal stimuli as it is susceptible to cognitive influence and propose that it may instead reflect on negative stereotypes and social norms. Thus, a theoretical model that can accommodate the influence of both biological and cultural factors is likely to have broader utility in the explanation of fear and avoidance responses than accounts based on a single mechanism.
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The last few decades have witnessed a broad international movement towards the development of inclusive schools through targeted special education funding and resourcing policies. Student placement statistics are often used as a barometer of policy success but they may also be an indication of system change. In this paper, trends in student enrolments from the Australian state of New South Wales are considered in an effort to understand what effect inclusive education has had in this particular region of the world.
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Attention Deficit Hyperactivity Disorder is a diagnostic term now indelibly scored on the public psyche. In some quarters, a diagnosis of “ADHD” is regarded with derision. In others it is welcomed with relief. Despite intense multi-disciplinary research, the jury is still out with regards to the “truth” of ADHD. Not surprisingly, the rapid increase in diagnosis over the past fifteen years, coupled with an exponential rise in the prescription of restricted class psychopharmaceuticals has stirred virulent debate. Provoking the most interest, it seems, are questions regarding causality. Typically, these revolve around possible antecedents for “disorderly” behaviour – bad food, bad tv and bad parents. Very seldom is the institution of schooling ever in the line of sight. To investigate this gap, I draw on Foucault to question what might be happening in schools and how this may be contributing to the definition, recognition and classification of particular children as a particular kind of “disorderly”.
Resumo:
Can China improve the competitiveness of its culture in world markets? Should it focus less on quantity and more on quality? How should Chinese cultural producers and distributors target audiences overseas? These are important questions facing policy makers today. In this paper I investigate how China might best deploy its soft power capabilities: for instance, should it try to demonstrate that it is a creative, innovative nation, capable of original ideas? Or should it put the emphasis on validating its credentials as an enduring culture and civilisation? In order to investigate these questions I introduce the cultural innovation timeline, a model that explains how China is adding value. There are six stages in the timeline but I will focus in particular on how the timeline facilitates cultural trade. In the second part of the paper I look at some of the challenges facing China, particularly the reception of its cultural products in international markets.