791 research outputs found

    Implementing an eleven year through-train model to complete Primary and Secondary Education , is it possible? Why Not? : some challenges and principles

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    As learning and teaching is moving away from imparting student with mere "knowledge", the simple one-size-fits-all solution of a prescribed years of schooling with some rigid and prescriptive subject syllabuses designated for different year-levels in primary and secondary schools will no longer meet the developmental needs of students. Logos Academy of Hong Kong has started an "Eleven-year Through-train Program in September 2002, to re-define the different key stages in primary, junior and senior secondary levels to provide a broad and balanced curriculum which maintains seamless continuity. The eleven-year program consists of three stages, each with its particular characteristics: Foundation Stage: (FS1- FS3); Developmental Stage: (DS1 - DS5) and Mastery Stage (MS1 - MS3). We have achieved some pleasing outcome so far and we believe that this re-definition of Key Learning Stages is forward looking and keeping abreast of global trends. If this "Eleven-year Through-Train Schooling System" model is proved to be successful, it will throw some light on a new schooling structure - which will have significant implications on the government's funding and planning policie

    Implementing an eleven year through-train model to complete Primary and Secondary Education: creating a platform for accommodating the newest pedagogical practices and technologies in school

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    In educational transformation, Logos Academy of Hong Kong has started to create space in two aspects: to accommodate for new learning areas, and to use the most updated technologies for learning. In different Learning Stages, new learning areas like "Family Life Education", "Analytical study of Current Issues", Mind-mapping, MegaSkills and Media Education are introduced. The teachers will design different level- and age-appropriate activities and assignments that encourage the mastery of basic concepts and development of aesthetic appreciation, family life education, character formation, physique building and inquiry/research skills. Moreover, integrated tasks and projects intertwining with different study skills are mounted to enable the children to experiment creative designs and try out increasingly complex investigations. To facilitate learning and teaching, Logos Academy also creates new platforms to use the newest technologies for pre-lesson use, for lesson use, and for post-lesson use. It is reviewed that with the aid of some updated technologies, our teachers are committed to facilitate change, reflect on current practices, explore further improvements in new learning areas and to use the new technologies effectively - which will in turn enhance the effectiveness of integrated study skills, self-directed learning, team work and social interaction of the students

    Implementing an eleven year through-train model to complete Primary and Secondary Education: an innovative curriculum design, and optimizing the roles of subject specialists in the early learning stages

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    In an eleven year "through-train" model, to construct a new road map for learning, Logos Academy of Hong Kong has delineated clearly the roles of "Homeroom Teachers" and "Subject Specialists". In the Foundation Stage (The first three years in Primary Schooling), the "Homeroom Teachers" will no longer teach most of the academic subjects for their respective Homeroom classes. They will undertake mainly pastoral care functions whilst different subject specialists are deployed to teach different subject areas accordingly. Each Subject teacher will teach ALL the classes within a year-band. In some Subjects like English Studies, two or three teachers will share the teaching load according to their specialties. After putting in practice for two years, evidence has shown that with this "Subject specialist across the year band" approach, the curriculum rigor has been strengthened and children have made much more remarkable progress in specific learning areas. Moreover, it has created space and opportunities for co-teaching and joint projects. This has in turn facilitated communication, collaboration and professional development of teachers in their subject specialty. Within the same subject area, the inter-teacher difference between classes of the same year level has been diminished, and the effectiveness of teaching and learning across the whole year-band may be better monitored and evaluated. The subject specialist is also in a better position to design and organize necessary follow-up actions (including enrichment or remedial work) more efficientl

    Radiation-induced Assembly of Rad51 and Rad52 Recombination Complex Requires ATM and c-Abl

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    Cells from individuals with the recessive cancer-prone disorder ataxia telangiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutated in A-T) is a protein kinase whose activity is stimulated by I-R. c-Abl, a nonreceptor tyrosine kinase, interacts with ATM and is activated by ATM following I-R. Rad51 is a homologue of bacterial RecA protein required for DNA recombination and repair. Here we demonstrate that there is an I-R-induced Rad51 tyrosine phosphorylation, and this induction is dependent on both ATM and c-Abl. ATM, c-Abl, and Rad51 can be co-immunoprecipitated from cell extracts. Consistent with the physical interaction, c-Abl phosphorylates Rad51 in vitro and in vivo. In assays using purified components, phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I-R, an increase in association between Rad51 and Rad52 occurs in wild-type cells but not in cells with mutations that compromise ATM or c-Abl. Our data suggest signaling mediated through ATM, and c-Abl is required for the correct post-translational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R

    Antitumor Agents. 289. Design, Synthesis, and Anti-Breast Cancer Activity in Vivo of 4-Amino-2 H -benzo[ h ]chromen-2-one and 4-Amino-7,8,9,10-tetrahydro-2 H -benzo[ h ]chromen-2-one Analogues with Improved Water Solubility

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    Previously, we reported that 4-amino-2H-benzo[h]chromen-2-one (ABO) and 4-amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (ATBO) analogues, which were developed from the lead natural produce neo-tanshinlactone, are potent cytotoxic agents. In order to improve on their water solubility, the diamino analogues and related salts were designed. All synthesized compounds were assayed for cytotoxicity, and selected compounds were evaluated for in vivo anti-mammary epithelial proliferation activity in wild-type mice and mice predisposed for mammary tumors due to Brca1/p53 mutations. The new derivatives 10, 16 (ABO), 22, and 27 (ATBO) were the most active analogues with IC50 values of 0.038–0.085 μM in the cytotoxicity assay. Analogue 10 showed around 50-fold improved water solubility compared with the prior lead ABO compound 4-[(4'-methoxyphenyl)amino]-2H-benzo[h]chromen-2-one (3). Compounds 3, 4, 10, and 22 significantly reduced overall numbers of mammary cells as indicated by the reduction of mammary gland branching in mutant mice. A one-week treatment with 10 resulted in 80% reduction in BrdU-positive cells in the cancer prone mammary gland. These four compounds had differential effects on cellular proliferation and apoptosis in wild-type mouse and mouse model of human breast cancers. Compound 10 merits further development as a promising anticancer clinical trial candidate

    Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers

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    Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vitro soft agar colony formation assay and the ability to form tumors in NOD/SCID mice. We found that the expression of stem cell markers varied greatly among breast cancer cell lines. In MDA-MB-231 cells, PROCR and ESA, instead of the widely used breast cancer stem cell markers CD44+/CD24-/low and ALDH, could be used to highly enrich cancer stem/progenitor cell populations which exhibited the ability to self renew and divide asymmetrically. Furthermore, the PROCR+/ESA+ cells expressed epithelial-mesenchymal transition markers. PROCR could also be used to enrich cells with colony forming ability from MB-361 cells. Moreover, consistent with the marker profiling using cell lines, the expression of stem cell markers differed greatly among primary tumors. There was an association between metastasis status and a high prevalence of certain markers including CD44+/CD24−/low, ESA+, CD133+, CXCR4+ and PROCR+ in primary tumor cells. Taken together, these results suggest that similar to leukemia, several stem/progenitor cell-like subpopulations can exist in breast cancer

    Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

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    Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

    Cold Nuclear Matter Effects on J/psi Yields as a Function of Rapidity and Nuclear Geometry in Deuteron-Gold Collisions at sqrt(s_NN) = 200 GeV

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    We present measurements of J/psi yields in d+Au collisions at sqrt(s_NN) = 200 GeV recorded by the PHENIX experiment and compare with yields in p+p collisions at the same energy per nucleon-nucleon collision. The measurements cover a large kinematic range in J/psi rapidity (-2.2 < y < 2.4) with high statistical precision and are compared with two theoretical models: one with nuclear shadowing combined with final state breakup and one with coherent gluon saturation effects. To remove model dependent systematic uncertainties we also compare the data to a simple geometric model. We find that calculations where the nuclear modification is linear or exponential in the density weighted longitudinal thickness are difficult to reconcile with the forward rapidity data.Comment: 449 authors from 66 institutions, 6 pages, 3 figures. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

    Transverse-Momentum Dependence of the J/psi Nuclear Modification in d+Au Collisions at sqrt(s_NN)=200 GeV

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    We present measured J/psi production rates in d+Au collisions at sqrt(s_NN) = 200 GeV over a broad range of transverse momentum (p_T=0-14 GeV/c) and rapidity (-2.2<y<2.2). We construct the nuclear-modification factor R_dAu for these kinematics and as a function of collision centrality (related to impact parameter for the R_dAu collision). We find that the modification is largest for collisions with small impact parameters, and observe a suppression (R_dAu<1) for p_T<4 GeV/c at positive rapidities. At negative rapidity we observe a suppression for p_T1) for p_T>2 GeV/c. The observed enhancement at negative rapidity has implications for the observed modification in heavy-ion collisions at high p_T.Comment: 384 authors, 24 pages, 19 figures, 13 tables. Submitted to Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are publicly available at http://www.phenix.bnl.gov/phenix/WWW/info/data/ppg123_data.htm

    Breast Cancer Cells Induce Cancer-Associated Fibroblasts to Secrete Hepatocyte Growth Factor to Enhance Breast Tumorigenesis

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    It has been well documented that microenvironment consisting of stroma affects breast cancer progression. However, the mechanisms by which cancer cells and fibroblasts, the major cell type in stroma, interact with each other during tumor development remains to be elucidated. Here, we show that the human cancer-associated fibroblasts (CAFs) had higher activity in enhancing breast tumorigenecity compared to the normal tissue-associated fibroblasts (NAFs) isolated from the same patients. The expression level of hepatocyte growth factor (HGF) in these fibroblasts was positively correlated with their ability to enhance breast tumorigenesis in mice. Deprivation of HGF using a neutralizing antibody reduced CAF-mediated colony formation of human breast cancer cells, indicating that CAFs enhanced cancer cell colony formation mainly through HGF secretion. Co-culture with human breast cancer MDA-MB-468 cells in a transwell system enhanced NAFs to secret HGF as well as promote tumorigenecity. The newly gained ability of these “educated” NAFs became irreversible after continuing this process till fourth passage. These results suggested that breast cancer cells could alter the nature of its surrounding fibroblasts to secrete HGF to support its own progression through paracrine signaling
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