558 research outputs found

    The place of values in the aims of school science education

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    Debates about the aims of school science education are perennial (e.g., Reiss & White, 2014; see also Kidman & Fensham, Chapter “ Intended, Achieved and Unachieved Values of Science Education” this volume), particularly in Western cultures. In this chapter we review some of these arguments about the aims of school science education, and look at what has changed in the last decade since one of us (Michael) considered a similar debate (see Reiss, 2007). We have situated this review of arguments in current global circumstances including rapid technological advances, a continuing demand for workers with STEM (Science, Technology, Engineering and Mathematics) qualifications and the increasing acknowledgement of the deeply worrying effects that humans have on the Earth’s ecology, and indeed its future. Part of our argument is that decisions about the aims of school science education are inevitably decisions about values in education in general and values in school science education more specifically. This means that for a country, a group of schools, an individual school or a classroom teacher to come to a view about the aims of science education in the classroom is to have made a judgement, implicitly or explicitly, about values

    DNA damage induced by cis- and carboplatin as indicator for in vitro sensitivity of ovarian carcinoma cells

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    <p>Abstract</p> <p>Background</p> <p>The DNA damage by platinum cytostatics is thought to be the main cause of their cytotoxicity. Therefore the measurement of the DNA damage induced by cis- and carboplatin should reflect the sensitivity of cancer cells toward the platinum chemotherapeutics.</p> <p>Methods</p> <p>DNA damage induced by cis- and carboplatin in primary cells of ovarian carcinomas was determined by the alkaline comet assay. In parallel, the reduction of cell viability was measured by the fluorescein diacetate (FDA) hydrolysis assay.</p> <p>Results</p> <p>While in the comet assay the isolated cells showed a high degree of DNA damage after a 24 h treatment, cell viability revealed no cytotoxicity after that incubation time. The individual sensitivities to DNA damage of 12 tumour biopsies differed up to a factor of about 3. DNA damage after a one day treatment with cis- or carboplatin correlated well with the cytotoxic effects after a 7 day treatment (r = 0,942 for cisplatin r = 0.971 for carboplatin). In contrast to the platinum compounds the correlation of DNA damage and cytotoxicity induced by adriamycin was low (r = 0,692), or did not exist for gemcitabine.</p> <p>Conclusion</p> <p>The measurement of DNA damage induced by cis- and carboplatin is an accurate method to determine the in vitro chemosensitivity of ovarian cancer cells towards these cytostatics, because of its quickness, sensitivity, and low cell number needed.</p

    Luminal-Applied Flagellin Is Internalized by Polarized Intestinal Epithelial Cells and Elicits Immune Responses via the TLR5 Dependent Mechanism

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    Bacteria release flagellin that elicits innate responses via Toll-like receptor 5 (TLR5). Here, we investigated the fate of apically administrated full length flagellin from virulent and avirulent bacteria, along with truncated recombinant flagellin proteins in intestinal epithelial cells and cellular responses. Flagellin was internalized by intestinal epithelial cell (IEC) monolayers of IEC-18. Additionally, apically applied flagellin was internalized by polarized human Caco-2BBe and T-84 cells in a TLR5 dependent mechanism. More, flagellin exposure did not affect the integrity of intestinal monolayers. With immunofluorescent staining, internalized flagellin was detected in both early endosomes as well as lysosomes. We found that apical exposure of polarized Caco-2BBe and T-84 to flagellin from purified Salmonella, Escherichia coli O83:H1 (isolate from Crohn’s lesion) or avirulent E. coli K12 induced comparable levels of basolateral IL-8 secretion. A recombinant protein representing the conserved amino (N) and carboxyl (C) domains (D) of the flagellin protein (ND1/2ECHCD2/1) induced IL-8 secretion from IEC similar to levels elicited by full-length flagellins. However, a recombinant flagellin protein containing only the D3 hypervariable region elicited no IL-8 secretion in both cell lines compared to un-stimulated controls. Silencing or blocking TLR5 in Caco-2BBe cells resulted in a lack of flagellin internalization and decreased IL-8 secretion. Furthermore, apical exposure to flagellin stimulated transepithelial migration of neutrophils and dendritic cells. The novel findings in this study show that luminal-applied flagellin is internalized by normal IEC via TLR5 and co-localizes to endosomal and lysosomal compartments where it is likely degraded as flagellin was not detected on the basolateral side of IEC cultures

    Reculturing schools in England: how ‘cult’ values in education policy discourse influence the construction of practitioner identities and work orientations

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    The imperative of continuous improvement has now become normative in education policy discourse, typically framed as setting ‘aspirational’ targets for pupil performance as a prerequisite for gaining competitive advantage in the global economy. In this context, teachers, leaders, teacher assistants and other practitioners working in schools across England have been under increasing pressure to raise standards. This article focuses on how values are deployed in reculturing and regulating practitioners to develop identities and work orientations which are congruent with the policymakers’ agendas. G.H. Mead’s concept of ‘cult’ values illuminates the process of fostering homogeneity with the dominant policy discourse through an inclusion/exclusion dynamic. Interview data collected in two primary schools revealed a significant convergence of practitioner discourse with policy objectives. Delivering improvement affects how practitioners talk about their work and see themselves as educators. The ‘cult’ of continuous improvement appears to inhibit a critical approach to the implementation of education policies by school practitioners in their everyday work

    Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy

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    Radiotherapy is a well-established treatment for cancer. However, the existence of radioresistant cells is one of the major obstacles in radiotherapy. In order to understand the mechanism of cellular radioresistance and develop more effective radiotherapy, we have established clinically relevant radioresistant (CRR) cell lines, which continue to proliferate under daily exposure to 2 Gray (Gy) of X-rays for >30 days. X-ray irradiation significantly induced autophagic cells in parental cells, which was exiguous in CRR cells, suggesting that autophagic cell death is involved in cellular radiosensitivity. An autophagy inducer, rapamycin sensitized CRR cells to the level of parental cells and suppressed cell growth. An autophagy inhibitor, 3-methyladenine induced radioresistance of parental cells. Furthermore, inhibition of autophagy by knockdown of Beclin-1 made parental cells radioresistant to acute radiation. These suggest that the suppression of autophagic cell death but not apoptosis is mainly involved in cellular radioresistance. Therefore, the enhancement of autophagy may have a considerable impact on the treatment of radioresistant tumor

    Induction of Premature Senescence by Hsp90 Inhibition in Small Cell Lung Cancer

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    BACKGROUND: The molecular chaperone Hsp90 is a promising new target in cancer therapy and selective Hsp90 inhibitors are currently in clinical trials. Previously these inhibitors have been reported to induce either cell cycle arrest or cell death in cancer cells. Whether the cell cycle arrest is reversible or irreversible has not generally been assessed. Here we have examined in detail the cell cycle arrest and cell death responses of human small cell lung cancer cell lines to Hsp90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: In MTT assays, small cell lung cancer cells showed a biphasic response to the Hsp90 inhibitors geldanamycin and radicicol, with low concentrations causing proliferation arrest and high concentrations causing cell death. Assessment of Hsp90 intracellular activity using loss of client protein expression showed that geldanamycin concentrations that inhibited Hsp90 correlated closely with those causing proliferation arrest but not cell death. The proliferation arrest induced by low concentrations of geldanamycin was not reversed for a period of over thirty days following drug removal and showed features of senescence. Rare populations of variant small cell lung cancer cells could be isolated that had additional genetic alterations and no longer underwent irreversible proliferation arrest in response to Hsp90 inhibitors. CONCLUSIONS/SIGNIFICANCE: We conclude that: (1) Hsp90 inhibition primarily induces premature senescence, rather than cell death, in small cell lung cancer cells; (2) small cell lung cancer cells can bypass this senescence through further genetic alterations; (3) Hsp90 inhibitor-induced cell death in small cell lung cancer cells is due to inhibition of a target other than cytosolic Hsp90. These results have implications with regard to how these inhibitors will behave in clinical trials and for the design of future inhibitors in this class

    Relationship between PPI and baseline startle response

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    Prepulse inhibition (PPI) of the startle response to a sudden noise is the reduction in startle observed when the noise is preceded shortly by a mild sensory event, which is often a tone. A part of the literature is based on the assumption that PPI is independent of the baseline startle. A simple model is presented and experimental validation provided. The model is based on the commonly accepted observation that the neuronal circuit of PPI differs from that of startle. But, by using a common output, the measures of both phenomena become linked to each other. But, how can we interpret the numerous experimental data showing PPI to be independent of the startle level? It is suggested that in a number of such cases the baseline startle would have been stabilized by a ceiling effect in the startle/PPI neuronal networks. Reducing the startle level, for example in a PPI evaluation procedure, may disclose properties of startle masked by this ceiling effect. Disclosure of habituation to the startle eliciting noise produced an increase of PPI along its initial measurements. Taken together, even if the neuronal process that sustains startle and PPI are distinct, separating them experimentally requires careful parametric methods and caution in the interpretation of the corresponding observations

    International education and the employability of UK students

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    A common theme within the literature on higher education is the congested nature of the graduate labour market. Researchers have highlighted the lengths to which many students now go, in response to this congestion, to ‘distinguish themselves’ from other graduates: paying increased attention to university status; engaging in a range of extra-curricular activities; and pursuing postgraduate qualifications. Studies that have focused on the strategies of Asian students, specifically, have pointed to the important place of studying abroad as a further strategy in this pursuit of distinction. Given that there is now some evidence that the number of UK students enrolling on a degree programme overseas is increasing, this article explores the extent to which an overseas education can be seen as part of a broader strategy on the part of British students to seek distinction within the labour market and whether such an education does indeed offer tangible employment benefits
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