997 resultados para Diverse Als Inhibitors


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This thesis investigates the place of online moderation in supporting teachers to work in a system of standards-based assessment. The participants of the study were fifty middle school teachers who met online with the aim of developing consistency in their judgement decisions. Data were gathered through observation of the online meetings, interviews, surveys and the collection of artefacts. The data were viewed and analysed through sociocultural theories of learning and sociocultural theories of technology, and demonstrates how utilising these theories can add depth to understanding the added complexity of developing shared meaning of standards in an online context. The findings contribute to current understanding of standards-based assessment by examining the social moderation process as it acts to increase the reliability of judgements that are made within a standards framework. Specifically, the study investigates the opportunities afforded by conducting social moderation practices in a synchronous online context. The study explicates how the technology affects the negotiation of judgements and the development of shared meanings of assessment standards, while demonstrating how involvement in online moderation discussions can support teachers to become and belong within a practice of standards-based assessment. This research responds to a growing international interest in standards-based assessment and the use of social moderation to develop consistency in judgement decisions. Online moderation is a new practice to address these concerns on a systemic basis.

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The adoption of IT Governance (ITG) continues to be an important topic for research. Many researchers have focused their attention on how these practices are currently being implemented in the many diverse areas and industries. Literature shows that a majority of these studies have only been based on industries and organizations in developed countries. There exist very few researches that look specifically within the context of a developing country. Furthermore, there seems to be a lack of research on identifying the barriers or inhibitors to IT Governance adoption within the context of an emerging yet still developing Asian country. This research sets out to justify, substantiate and improve on a priori model developed to study the barriers to the adoption of ITG practice using qualitative data obtained through a series of semi-structured interviews conducted on organizations in Malaysia.

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Patients with metastatic melanoma or multiple myeloma have a dismal prognosis because these aggressive malignancies resist conventional treatment. A promising new oncologic approach uses molecularly targeted therapeutics that overcomes apoptotic resistance and, at the same time, achieves tumor selectivity. The unexpected selectivity of proteasome inhibition for inducing apoptosis in cancer cells, but not in normal cells, prompted us to define the mechanism of action for this class of drugs, including Food and Drug Administration-approved bortezomib. In this report, five melanoma cell lines and a myeloma cell line are treated with three different proteasome inhibitors (MG-132, lactacystin, and bortezomib), and the mechanism underlying the apoptotic pathway is defined. Following exposure to proteasome inhibitors, effective killing of human melanoma and myeloma cells, but not of normal proliferating melanocytes, was shown to involve p53-independent induction of the BH3-only protein NOXA. Induction of NOXA at the protein level was preceded by enhanced transcription of NOXA mRNA. Engagement of mitochondrial-based apoptotic pathway involved release of cytochrome c, second mitochondria-derived activator of caspases, and apoptosis-inducing factor, accompanied by a proteolytic cascade with processing of caspases 9, 3, and 8 and poly(ADP)-ribose polymerase. Blocking NOXA induction using an antisense (but not control) oligonucleotide reduced the apoptotic response by 30% to 50%, indicating a NOXA-dependent component in the overall killing of melanoma cells. These results provide a novel mechanism for overcoming the apoptotic resistance of tumor cells, and validate agents triggering NOXA induction as potential selective cancer therapeutics for life-threatening malignancies such as melanoma and multiple myeloma.

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Fibroblast growth factor receptors (FGFRs) play diverse roles in the control of cell proliferation, cell differentiation, angiogenesis and development. Activating the mutations of FGFRs in the germline has long been known to cause a variety of skeletal developmental disorders, but it is only recently that a similar spectrum of somatic FGFR mutations has been associated with human cancers. Many of these somatic mutations are gain-of-function and oncogenic and create dependencies in tumor cell lines harboring such mutations. A combination of knockdown studies and pharmaceutical inhibition in preclinical models has further substantiated genomically altered FGFR as a therapeutic target in cancer, and the oncology community is responding with clinical trials evaluating multikinase inhibitors with anti-FGFR activity and a new generation of specific pan-FGFR inhibitors.

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Women are substantially under-represented in the professoriate in Australia with a ratio of one female professor to every three male professors. This gender imbalance has been an ongoing concern with various affirmative action programs implemented in universities but to limited effect. Hence, there is a need to investigate the catalysts for and inhibitors to women’s ascent to the professoriate. This investigation focussed on women appointed to the professoriate between 2005, when a research quality assessment was first proposed, and 2008. Henceforth, these women are referred to as “New Women Professors”. The catalysts and inhibitors in these women’s careers were investigated through an electronic survey and focus group interviews. The survey was administered to new women professors (n=255) and new men professors (n=240) to enable a comparison of responses. However, only women participated in focus group discussions (n=21). An analysis of the survey and interview data revealed that the most critical catalysts for women’s advancement to the professoriate were equal employment opportunities and mentoring. Equal opportunity initiatives provided women with access to traditionally male-dominated forums. Mentoring gave women an insider perspective on the complexity of academia and the politics of the academy. The key inhibitors to women’s career advancement were negative discrimination, the culture of the boys’ club, the tension between personal and professional life, and isolation. Negative discrimination and the boys’ club are problematic because they favour men and marginalise women. The tension between personal and professional life is a particular concern for women who bear children and typically assume the major role in a family for child rearing. Isolation was a concern for both women and men with isolation appearing to increase after ascent to the professoriate. Knowledge of the significant catalysts and inhibitors provides a pragmatic way to orient universities towards redressing the gender balance in the professoriate.

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Bio-diverse-city was a group exhibition curated by Barry Fitzpatrick, showcasing different approaches to designing for resilient and sustainable futures. Elastic urbanism was exhibited within the framework of artworks exploring the different solutions to designing for the future. A design proposition for new models of sustainable and ecological urban growth structured around natural water and infrastructure. The project integrates four different modelling techniques and is developing an alternative system for predicting the impact of urban growth in the future. The design proposition and exhibition is part of an ongoing research project.

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For millennia humans have sought, organized, and used information as they learned and evolved patterns of human information behaviors to resolve their human problems and survive. However, despite the current focus on living in an "information age," we have a limited evolutionary understanding of human information behavior. In this article the authors examine the current three interdisciplinary approaches to conceptualizing how humans have sought information including (a) the everyday life information seeking-sense-making approach, (b) the information foraging approach, and (c) the problem-solution perspective on information seeking approach. In addition, due to the lack of clarity regarding the role of information use in information behavior, a fourth information approach is provided based on a theory of information use. The use theory proposed starts from an evolutionary psychology notion that humans are able to adapt to their environment and survive because of our modular cognitive architecture. Finally, the authors begin the process of conceptualizing these diverse approaches, and the various aspects or elements of these approaches, within an integrated model with consideration of information use. An initial integrated model of these different approaches with information use is proposed.