998 resultados para Critical doses


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Can learning quality be maintained in the face of increasing class size by the use of Computer Supported Co-operative Learning (CSCL) technologies? In particular, can Computer-Mediated Communication promote critical thinking in addition to surface information transfer? We compared face-to-face seminars with asynchronous computer conferencing in the same Information Management class. From Garrison's theory of critical thinking and Henri's critical reasoning skills, we developed two ways of evaluating critical thinking: a student questionnaire and a content analysis technique. We found evidence for critical thinking in both situations, with some subtle differences in learning style. This paper provides an overview of this work.

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This paper gives a detailed account of the content analysis method developed at Queen's University Belfast to measure critical thinking during group learning, as used in our controlled comparisons between learning in face-to-face and computer conference seminars. From Garrison's 5 stages of critical thinking, and Henri's cognitive skills needed in CMC, we have developed two research instruments: a student questionnaire and this content analysis method. The content analysis relies on identifying, within transcripts, examples of indicators of obviously critical and obviously uncritical thinking, from which several critical thinking ratios can be calculated.

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Interferons (IFNs) are essential for host defense. Although the antiviral effects of the type 1 IFNs IFN- and IFN- (IFN-/) have been established, their immunoregulatory functions, especially their ability to regulate IFN- production, are poorly understood. Here we show that IFN-/ activate STAT4 directly (STAT, signal transducers and activators of transcription) and that this is required for IFN- production during viral infections of mice, in concert with T cell receptor-derived signals. In contrast, STAT1 appears to negatively regulate IFN-/ induction of IFN-. Thus, type 1 IFNs, in addition to interleukin-12, provide pathways for innate regulation of adaptive immunity, and their immunoregulatory functions are controlled by modulating the activity of individual STATs.

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Thymidylate synthase (TS) is a critical target for chemotherapeutic agents such as 5-fluorouracil (5-FU) and antifolates such as tomudex (TDX),multitargeted antifolate, and ZD9331. Using the MCF-7 breast cancer line, we have developed p53 wild-type (M7TS90) and null (M7TS90-E6) isogenic lines with inducible TS expression (approximately 6-fold induction compared with control after 48 h). In the M7TS90 line, inducible TS expression resulted in a moderate approximately 3-fold increase in 5-FU IC-50(72 h) dose and a dramatic >20-fold increase in the IC-50(72 h) doses of TDX, multitargeted antifolate, and ZD9331. S-phase cell cycle arrest and apoptosis induced by the antifolates were abrogated by TS induction. In contrast, cell cycle arrest and apoptosis induced by 5-FU was unaffected by TS expression levels. Inactivation of p53 significantly increased resistance to 5-FU and the antifolates with IC-50(72 h) doses for 5-FU and TDX of >100 and >10 microM, respectively, in the M7TS90-E6 cell line. Furthermore, p53 inactivation completely abrogated the cell cycle arrest and apoptosis induced by 5-FU. The antifolates induced S-phase arrest in the p53 null cell line; however, the induction of apoptosis by these agents was significantly reduced compared with p53 wild-type cells. Both inducible TS expression and the addition of exogenous thymidine (10 microM) blocked p53 and p21 induction by the antifolates but not by 5-FU in the M7TS90 cell line. Similarly, inducible TS expression and exogenous thymidine abrogated antifolate but not 5-FU-mediated up-regulation of Fas/CD95 in M7TS90 cells. Our results indicate that in M7TS90 cells, inducible TS expression modulates p53 and p53 target gene expression in response to TS-targeted antifolate therapies but not to 5-FU.

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Purpose – The aim of this paper is to analyse how critical incidents or organisational crises can be used to check and legitimise quality management change efforts in relation to the fundamental principles of quality. Design/methodology/approach – Multiple case studies analyse critical incidents that demonstrate the importance of legitimisation, normative evaluation and conflict constructs in this process. A theoretical framework composed of these constructs is used to guide the analysis. Findings – The cases show that the critical incidents leading to the legitimisation of continuous improvement (CI) were diverse. However all resulted in the need for significant ongoing cost reduction to achieve or retain competitiveness. In addition, attempts at legitimising CI were coupled with attempts at destabilising the existing normative practice. This destabilisation process, in some cases, advocated supplementing the existing approaches and in others replacing them. In all cases, significant conflict arose in these legitimising and normative evaluation processes. Research limitations/implications – It is suggested that further research could involve a critical analysis of existing quality models, tools and techniques in relation to how they incorporate, and are built upon, fundamental quality management principles. Furthermore, such studies could probe the dangers of quality curriculum becoming divorced from business and market reality and thus creating a parallel existence. Practical implications – As demonstrated by the case studies, models, tools and techniques are not valued for their intrinsic value but rather for what they will contribute to addressing the business needs. Thus, in addition to being an opportunity for quality management, critical incidents present a challenge to the field. Quality management must be shown to make a contribution in these circumstances. Originality/value – This paper is of value to both academics and practitioners.