94 research outputs found

    “When the water flows, a channel is formed”: professional learning and practice innovation through district research lesson study in the context of China’s new curriculum reform

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    This thesis investigates the systemic and contextualised nature of professional learning and practice development through district research lesson study (DRLS), a widespread LS practice in China. Through close examination of a DRLS case carried out in the context of curriculum reform in the subject area of EFL, the study focuses on understanding the conditions, processes, and outcomes of learning at three levels of analysis: individual teachers, subject teams, and the district EFL teaching community as a whole. The study focuses particular attention to the role and processes of language mediation in the professional learning and practice development of teachers, given the discursive nature of DRLS activities. The study shows that the DRLS provided a collaborative and continuous structure for supporting EFL teachers across a district to collectively make sense of the new curriculum framework, and to innovate, validate, and share practices in contexts of specific curriculum implementation. Over time, the district as a whole developed a shared public repertoire of practices and pedagogic ideas which permeated the thinking and practices of members of the district through the development of a common language for talking about practice. In the collaborative context of DRLS, different kinds of individual teacher’s learning were at play due to differences in their prior knowledge, understandings and approaches to participating in the DRLS. The different ways teachers used language to formulate their conceptions of practice also influenced their learning and practice development. At the team level, teams engaged in two distinct patterns of talk, each of which was reflected in different modes of collaboration and learning. The study proposes a new framework of talk and proposes explicit emphasis in future DRLS practices for developing teachers’ language practices as important ways of supporting their individual and collective learning in contexts of professional collaboration and curriculum development

    Mapping MKP-3/FOXO1 Interaction and Evaluating the Effect on Gluconeogenesis

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    <div><h3>Background</h3><p>MAP kinase phosphatase 3 (MKP-3) is known to attenuate the ERK signaling pathway. It has been recently demonstrated that MKP-3 is also a player in promoting hepatic glucose output in obese state by interacting and activating FOXO1. Reduction of hepatic MKP-3 expression is sufficient to reduce blood glucose levels in both diet-induced and genetically obese mice.</p> <h3>Methodology/Principal Findings</h3><p>In current study, the mechanism of MKP-3/FOXO1 interaction and the effects on transcription of gluconeogenic gene and glucose output was investigated in Fao hepatoma cells by using mutated MKP-3 and FOXO1 adenoviral constructs. The results indicate that MKP-3 phosphatase activity is not required for MKP-3/FOXO1 interaction but is essential for FOXO1 nuclear translocation and MKP-3 promoted gluconeogenesis. Compared to GFP control (1±0.38), MKP-3 increased G6Pase gene expression by 242% (3.42±0.62) while inactive MKP-3 does not change G6Pase expression (0.98±0.17). The residues 200–260 of MKP-3 and the residues 360–456 of FOXO1 are essential for mediating MKP-3/FOXO1 interaction. Interestingly, ERK phosphorylation deficient but not Akt phosphorylation deficient FOXO1 mutant lost interaction with MKP-3. Furthermore, in vivo experiments showed that Akt phosphorylation resistant FOXO1 3A mutant is sufficient to rescue the hypoglycemia caused by MKP-3 knock down in the liver of lean mice (from 141±6.78 to 209±14.64 mg/dL).</p> <h3>Conclusions/Significance</h3><p>1) Critical residues mediating MKP-3/FOXO1 interaction have been identified; 2) ERK phosphorylation deficient FOXO1 mutant is as potent as Akt phosphorylation deficient FOXO1 mutant in activating transcription of gluconeogenic genes; 3) Constitutively active FOXO1 can rescue the hypoglycemic effect caused by reduced hepatic MKP-3 expression in vivo.</p> </div

    Mapping the functional domains of FOXO1 essential for mediating the interaction between MKP-3 and FOXO1.

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    <p><b>A.</b> Co-immunoprecipitaion of FOXO1 WT or mutants truncated from C terminus and MKP-3 WT from Fao cells. FOXO1 WT or mutants and MKP-3 WT were co-expressed in Fao cells via adenovirus-mediated gene transfer. GFP was used as a control. <b>B.</b> Co-immunoprecipitaion of FOXO1 WT or mutants deficient in Akt or ERK phosphorylation sites and MKP-3 WT.</p

    Effect of MKP-3 ERK binding domain and phosphatase activity on expression of endogenous G6Pase gene and glucose output in Fao cells.

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    <p><b>A.</b> Over-expression of MKP-3 WT or mutants in Fao cells and the effect on expression of endogenous G6Pase gene. <b>B.</b> Overexpression of MKP-3 WT or mutants in Fao cells and the effect on glucose output. *, P<0.05, MKP-3 wild type or mutant expressing cells versus control cells expressing GFP.</p

    The Akt phosphorylation resistant FOXO1 mutant (FOXO1 3A) rescues the hypoglycemic effect caused by reduced MKP-3 expression in the liver of lean mice.

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    <p><b>A.</b> Body weight and glucose levels in mice injected with adenovirus expressing shGFP, shMKP-3, GFP or FOXO1 3A (n = 8 for each froup). <b>B.</b> Protein expression of MKP-3 and FOXO1 in mice as described in A (n = 4 for each group). <b>C.</b> Quantitative graphs for B. <b>D.</b> Expression of gluconeogenic genes in mice as described in A (n = 8 for each group). *, P<0.05, between groups as indicated on graphs.</p

    Effect of ERK binding domain and phosphatase activity on MKP-3 promoted transcription of gluconeogenic genes and FOXO1 nuclear translocation.

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    <p><b>A.</b> Overexpression of MKP-3 WT or mutants deficient in ERK binding domain, deficient in phosphatase activity or deficient in ERK phosphorylation sites in Fao cells and the effect on phosphorylation of ERK and FOXO1. MKP-3 WT or mutants were over-expressed in Fao cells via adenovirus-mediated gene transfer. <b>B.</b> Effect of MKP-3 wild type (WT) or mutants on transcription of PEPCK and G6Pase promoters in Fao cells. Results were presented as ratios of firefly luciferase activities (FF) versus renilla luciferase activities (RL). <b>C.</b> Effect of MKP-3 WT or mutants on nuclear translocation of FOXO1-GFP in Fao cells. Vec, vector; Luc, luciferase; veh, vehicle; Dex, dexamethasone. *, P<0.05, MKP-3 wild type or mutant expressing cells versus control cells expressing an empty vector (B) or an inactive kinase (C).</p

    Mapping the functional domains of MKP-3 essential for mediating the interaction between MKP-3 and FOXO1.

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    <p><b>A.</b> Co-immunoprecipitation of FOXO1 WT and MKP-3 WT or mutants deficient in ERK binding domain, deficient in phosphatase activity or deficient in ERK phosphorylation sites from Fao cells. <b>B.</b> Co-immunoprecipitaion of FOXO1 WT and MKP-3 WT or mutants truncated from C terminus.</p

    Table1_Temporal characteristics and associated factors of discontinuation and outcomes after percutaneous coronary intervention.docx

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    Background: Medication adherence in patients after percutaneous coronary intervention (PCI) is suboptimal, and discontinuation is common. Information on the temporal characteristics and associated factors of discontinuation and outcomes after PCI is insufficient to improve medication adherence interventions.Methods: We conducted a single-center retrospective study of post-PCI patients by telephone survey and medical record extraction. Temporal characteristics and associated factors of discontinuation and outcomes were examined by survival curve analysis, Cox regression, or time-dependent Cox regression.Results: Discontinuation and major adverse cardiovascular events (MACE) after PCI had similar temporal characteristics, with the highest incidence in the first year, followed by a decline. Temporary discontinuation was associated with pre-PCI medication nonadherence (HR 1.63; 95% CI: 1.09–2.43), lack of medication necessity (HR 2.33; 95% CI: 1.44–3.78), economic difficulties (HR 2.09; 95% CI: 1.26–3.47), routine disruption (HR 2.09; 95% CI: 1.10–3.99), and emotional distress (HR 2.76; 95% CI: 1.50–5.09). Permanent discontinuation was associated with residence in rural areas (HR 4.18; 95% CI: 1.84–9.46) or small to medium-sized cities (HR 4.21; 95% CI: 1.82–9.73), lack of medication necessity (HR 10.60; 95% CI: 6.45–17.41), and side effects (HR 3.30; 95% CI: 1.94–5.62). The MACE after PCI was associated with pre-PCI hypertension (HR 1.42; 95% CI: 1.04–1.96), two coronary stents (HR 1.42; 95% CI: 1.01–1.99) or three coronary stents (HR 1.66; 95% CI: 1.11–2.49) compared to one coronary stent up to this PCI, and temporary discontinuation (≤60 months HR 2.18; 95% CI: 1.47–3.25; >60 months HR 8.82; 95% CI: 3.65–21.28).Conclusion: Discontinuation and MACE after PCI have similar temporal characteristics, temporary discontinuation and permanent discontinuation have different associated factors, and the former is associated with MACE. These findings may provide guidance for medication adherence interventions.</p

    Functionalized carbon black nanoparticles used for separation of emulsified oil from oily wastewater

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    <p>Functionalized carbon black (F-CB) nanoparticles were synthesized by covalently grafting the polyvinyl alcohol on carbon black (CB) surfaces and used as demulsifier to separate the oil from the emulsified oily wastewater. The bottle test showed that the residual oil content in the separated water was as low as ∼50 mg/L corresponding to a demulsification efficiency of about 99.90% at an optimal condition within a few minutes. It was believed that the surface wettability of the carbon black could be tuned by modifying with the PVA molecules, which enables the F-CB nanoparticles to be readily migrated to the oil/water interface and have the opportunity to interact with and/or displace the stabilizers of the emulsion. As a result, the demulsification process was accomplished with the coalescence of the oil droplets promoted by the F-CB nanoparticles. The interaction behavior between F-CB nanoparticles and asphaltenes was investigated by quantum chemical calculations. The results showed that the F-CB nanoparticles have strong interaction with the asphaltene molecules in form of π−π and θ−π forces. The findings in present study are significant for understanding the demulsification mechanism and also provide a novel demulsifier for the demulsification of emulsified oily wastewater.</p

    Trafficking of Gold Nanorods in Breast Cancer Cells: Uptake, Lysosome Maturation, and Elimination

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    Gold nanorods (AuNRs) have been largely investigated driven by their promising potentials in drug delivery, imaging, and photodynamic therapy because of their distinctive physicochemical properties. It is widely known that AuNRs can be taken up by different cells, however, the trafficking of the nanorods in cells are less known. In this work, the behaviors and fate of AuNRs in the human breast cancer cell line MDA-MB-231 were intensively probed by transmission electron microscopy (TEM) with detailed time resolution, together with induced couple plasmon mass spectroscopy (ICP-MS), confocal microscopy, Western blot, and cell viability assay. We reveal that AuNRs enter the classic lysosome maturation through endocytosis and are sequestered in the vesicular system even during cell division. AuNRs can escape from the lysosomes occasionally and the escaped AuNRs are recycled back into the lysosomal system through cytoprotective autophagy. The dilution of AuNRs in cells is mainly attributed to the cell division rather than exocytosis, because expelled AuNRs can be re-endocytosed by the cells. The feature of vesicular restriction guarantees other organelles such as mitochondria and nucleus are exempted from the direct exposure to AuNRs
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