198 research outputs found

    Introducing a New Grade 8 Curriculum in Children's Rights

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    Existing research indicates that the effective implementation of new curricula depends on several variables including teachers' agreement with the goals of a new program, its impact on workload, and opportunities for professional development. The purpose of this research was to assess how far 31 grade 8 teachers implemented a new children s rights curriculum, whether the implementation of the curriculum changed their and their students' attitudes about children's rights, and to identify factors that encouraged implementation. Major findings were as follows: Workload, defined in terms of years of experience and class size, was predictive of curriculum use. The more teachers used the curriculum, the higher they rated it and the more they expressed attitudes supportive of children's rights. Students' support for the rights of adults, including ethnocultural minorities and those with disabilities, was positively related to their teachers' support for children's rights.La recherche indique que la mise en œuvre réussie d'un nouveau curriculum dépend de plusieurs variables dont l'accord de renseignant quant aux buts du nouveau programme, son impact sur la charge de travail et les occasions de développement professionnel que l'on présente. Cette recherche avait trois buts : évaluer dans quelle mesure 31 enseignants de la 8e année ont mis en application un nouveau curriculum sur les droits des enfants, déterminer si la mise en vigueur a changé l'attitude des enseignants et des élèves face aux droits des enfants, et identifier les facteurs qui facilitent la mise en application. Les résultats indiquent que la charge de travail, définie en fonction des années d'expérience et de la taille de la classe, constituait une valeur prédictive quant à l'emploi que ferait un enseignant du nouveau curriculum. Plus les enseignants utilisaient le curriculum, plus ils l'appréciaient et plus leur attitude face aux droits des enfants était positive. Une corrélation positive a également été établie entre l'appui que manifestaient les élèves face aux droits des adultes, y compris ceux des minorités ethnoculturelles et des personnes ayant une déficience, et l'appui des enseignants pour les droits des enfants

    Understanding OA Ebook Usage: Toward a Common Framework

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    Redacted version of narrative for a proposal to the Andrew W. Mellon Foundation to support the development of international standards and practices for measuring and reporting usage of open-access ebooksSubmitted to the Andrew W. Mellon Foundation on April 27, 2018https://deepblue.lib.umich.edu/bitstream/2027.42/143840/1/Redacted Grant Narrative - OA Ebook Usage_FINAL SUBMISSION_042718.pdfDescription of Redacted Grant Narrative - OA Ebook Usage_FINAL SUBMISSION_042718.pdf : Grant Narrativ

    Establishment of the effectiveness of early versus late stem cell gene therapy in Mucopolysaccharidosis II for treating central versus peripheral disease

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    Mucopolysaccharidosis type II (MPSII) is a rare paediatric X-linked lysosomal storage disease, caused by heterogeneous mutations in the IDS gene, which result in accumulation of heparan sulphate and dermatan sulphate within cells. This leads to severe skeletal abnormalities, hepatosplenomegaly and cognitive deterioration. The progressive nature of the disease is a huge obstacle to achieve full neurological correction. Although current therapies can only treat somatic symptoms, a lentivirus-based hematopoietic stem cell gene therapy (HSCGT) approach has recently achieved improved central nervous system neuropathology in the MPSII mouse model following transplant at 2-months of age. Here we evaluate neuropathology progression in 2-month, 4-month and 9-month-old MPSII mice and using the same HSCGT strategy we investigated somatic and neurological disease attenuation following treatment at 4-months of age. Our results showed gradual accumulation of heparan sulphate between 2 and 4 months of age, but full manifestation of microgliosis/astrogliosis as early as 2 months. Late HSCGT fully reversed the somatic symptoms, thus achieving the same degree of peripheral correction as early therapy. However, late treatment resulted in slightly decreased efficacy in the CNS, with poorer brain enzymatic activity, together with reduced normalisation of heparan sulphate over-sulphation. Overall, our findings confirm significant lysosomal burden and neuropathology in 2-month-old MPSII mice. Peripheral disease is readily reversible by LV.IDS-HSCGT regardless of age of transplant, suggesting a viable treatment for somatic disease. However, in the brain, higher IDS enzyme levels are achievable with early HSCGT treatment, and later transplant seems to be less effective, supporting the view that the earlier patients are diagnosed and treated, the better the therapy outcome

    Exploring Open Access Ebook Usage

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    This white paper was prepared by the Book Industry Study Group (BISG) as part of the Andrew W. Mellon Foundation funded project, Understanding OA Ebook Usage: Toward a Common Framework. Primary authors are: Brian O’Leary (BISG) and Kevin Hawkins (University of North Texas). The project team, who contributed editing and improvements, include Charles Watkinson (University of Michigan), Lucy Montgomery (Curtin University/KU Research), Cameron Neylon (Curtin University/KU Research), and Katherine Skinner (Educopia Institute). Copyright for this white paper is held by BISG and licensed to the general public under a Creative Commons Attribution 4.0 International license

    Fusion of RVG or gh625 to Iduronate-2-Sulfatase for the Treatment of Mucopolysaccharidosis Type II

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    Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disease caused by a mutation in the IDS gene, resulting in deficiency of the enzyme iduronate-2-sulfatase (IDS) causing heparan sulfate (HS) and dermatan sulfate (DS) accumulation in all cells. This leads to skeletal and cardiorespiratory disease with severe neurodegeneration in two thirds of sufferers. Enzyme replacement therapy is ineffective at treating neurological disease, as intravenously-delivered IDS is unable to cross the blood-brain barrier (BBB). Haematopoietic stem cell transplant is also unsuccessful, presumably due to insufficient IDS enzyme production from transplanted cells engrafting in the brain. We used two different peptide sequences (RVG and gh625), both previously published as BBB-crossing peptides, fused to IDS and delivered via haematopoietic stem cell gene therapy (HSCGT). HSCGT with LV.IDS.RVG and LV.IDS.gh625 was compared to LV.IDS.ApoEII and LV.IDS in MPSII mice at 6-months post-transplant. Levels of IDS enzyme activity in the brain and peripheral tissues were lower in LV.IDS.RVG and LV.IDS.gh625 treated mice than in LV.IDS.ApoEII and LV.IDS treated mice, despite comparable vector copy numbers. Microgliosis, astrocytosis and lysosomal swelling were partially normalised in MPSII mice treated with LV.IDS.RVG and LV.IDS.gh625. Skeletal thickening was normalised by both treatments to wild-type levels. Although reductions in skeletal abnormalities and neuropathology are encouraging, given the low levels of enzyme activity compared to control tissue from LV.IDS and LV.IDS.ApoEII transplanted mice, the RVG and gh625 peptides are unlikely to be ideal candidates for HSCGT in MPSII, and are inferior to the ApoEII peptide that we have previously demonstrated to be more effective at correcting MPSII disease than IDS alone

    Preliminary imaging results from the second Mercury encounter

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    The second Mercury encounter has resulted in the acquisition of about 360 pictures of the south polar regions which provide a reliable cartographic and geologic tie between the two sides of the planet photographed on the first encounter. Stereoscopic coverage of large areas of the southern hemisphere was obtained by combining Mercury 1 and 2 pictures taken at different viewing angles. The south polar regions consist of heavily cratered terrain and intercrater plains interspersed with patches of smooth plains. No large areas of smooth plains similar to those surrounding Caloris occur in the south polar regions. No new types of terrain have been recognized, but lobate scarps are common. The second largest basin seen by Mariner 10 (∼600-km diameter) has been confirmed on the new photography. At high solar elevations the surface displays an abundance of rays and rayed craters

    D'Annunzio sulla scena lirica: libretto o "Poema"?

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    Australia Direct Action climate change policy relies on purchasing greenhouse gas abatement from projects undertaking approved abatement activities. Management of soil organic carbon (SOC) in agricultural soils is an approved activity, based on the expectation that land use change can deliver significant changes in SOC. However, there are concerns that climate, topography and soil texture will limit changes in SOC stocks. This work analyses data from 1482 sites surveyed across the major agricultural regions of Eastern Australia to determine the relative importance of land use vs. other drivers of SOC. Variation in land use explained only 1.4% of the total variation in SOC, with aridity and soil texture the main regulators of SOC stock under different land uses. Results suggest the greatest potential for increasing SOC stocks in Eastern Australian agricultural regions lies in converting from cropping to pasture on heavy textured soils in the humid regions

    The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

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    The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

    High-throughput gene discovery in the rat

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    The rat is an important animal model for human diseases and is widely used in physiology. In this article we present a new strategy for gene discovery based on the production of ESTs from serially subtracted and normalized cDNA libraries, and we describe its application for the development of a comprehensive nonredundant collection of rat ESTs. Our new strategy appears to yield substantially more EST clusters per ESTs sequenced than do previous approaches that did not use serial subtraction. However, multiple rounds of library subtraction resulted in high frequencies of otherwise rare internally primed cDNAs, defining the limits of this powerful approach. To date, we have generated >200,000 3′ ESTs from >100 cDNA libraries representing a wide range of tissues and developmental stages of the laboratory rat. Most importantly, we have contributed to ∼50,000 rat UniGene clusters. We have identified, arrayed, and derived 5′ ESTs from >30,000 unique rat cDNA clones. Complete information, including radiation hybrid mapping data, is also maintained locally at http://genome.uiowa.edu/clcg.html. All of the sequences described in this article have been submitted to the dbEST division of the NCBI
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