2,048 research outputs found

    When cloud computing meets with semantic web: A new design for e-portfolio systems in the social media era

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    Abstract The need, use, benefit and potential of e-portfolios have been analysed and discussed by a substantial body of researchers in the education community. However, the development and implementation approaches of e-portfolios to date have faced with various challenges and limitations. This paper presents a new approach of an e-portfolio system design based on Private-Public (PrPl) data index system, which integrates cloud computing applications and storages with Semantic Web architecture, making semantic web-based visualisation and advanced intelligent search possible. It also discusses how the distinctive attributes of the PrPl-based digital asset management system can serve as a large-scale robust e-portfolio system that can address issues with scalability, sustainability, adoptability and interoperability. With such a new distinctive design, a large-scale deployment at a state or national level becomes possible at a very cost-effective manner and also such large-scale deployment with intelligent digital asset management and search features create numerous opportunities in education

    Changing POU dimerization preferences converts Oct6 into a pluripotency inducer

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    � 2016 The Authors. Published under the terms of the CC BY 4.0 license The transcription factor Oct4 is a core component of molecular cocktails inducing pluripotent stem cells (iPSCs), while other members of the POU family cannot replace Oct4 with comparable efficiency. Rather, group III POU factors such as Oct6 induce neural lineages. Here, we sought to identify molecular features determining the differential DNA-binding and reprogramming activity of Oct4 and Oct6. In enhancers of pluripotency genes, Oct4 cooperates with Sox2 on heterodimeric SoxOct elements. By re-analyzing ChIP-Seq data and performing dimerization assays, we found that Oct6 homodimerizes on palindromic OctOct more cooperatively and more stably than Oct4. Using structural and biochemical analyses, we identified a single amino acid directing binding to the respective DNA elements. A change in this amino acid decreases the ability of Oct4 to generate iPSCs, while the reverse mutation in Oct6 does not augment its reprogramming activity. Yet, with two additional amino acid exchanges, Oct6 acquires the ability to generate iPSCs and maintain pluripotency. Together, we demonstrate that cell type-specific POU factor function is determined by select residues that affect DNA-dependent dimerization.Link_to_subscribed_fulltex

    Fractionalization patterns in strongly correlated electron systems: Spin-charge separation and beyond

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    We discuss possible patterns of electron fractionalization in strongly interacting electron systems. A popular possibility is one in which the charge of the electron has been liberated from its Fermi statistics. Such a fractionalized phase contains in it the seed of superconductivity. Another possibility occurs when the spin of the electron, rather than its charge, is liberated from its Fermi statistics. Such a phase contains in it the seed of magnetism, rather than superconductivity. We consider models in which both of these phases occur and study possible phase transitions between them. We describe other fractionalized phases, distinct from these, in which fractions of the electron themselves fractionalize, and discuss the topological characterization of such phases. These ideas are illustrated with specific models of p-wave superconductors, Kondo lattices, and coexistence between d-wave superconductivity and antiferromagnetism.Comment: 28 pages, 11 fig

    Nonvirally Modified Autologous Primary Hepatocytes Correct Diabetes and Prevent Target Organ Injury in a Large Preclinical Model

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    BACKGROUND: Current gene- and cell-based therapies have significant limitations which impede widespread clinical application. Taking diabetes mellitus as a paradigm, we have sought to overcome these limitations by ex vivo electrotransfer of a nonviral insulin expression vector into primary hepatocytes followed by immediate autologous reimplantation in a preclinical model of diabetes. METHODS AND RESULTS: In a single 3-hour procedure, hepatocytes were isolated from a surgically resected liver wedge, electroporated with an insulin expression plasmid ex vivo and reimplanted intraparenchymally under ultrasonic guidance into the liver in each of 10 streptozotocin-induced diabetic Yorkshire pigs. The vector was comprised of a bifunctional, glucose-responsive promoter linked to human insulin cDNA. Ambient glucose concentrations appropriately altered human insulin mRNA expression and C-peptide secretion within minutes in vitro and in vivo. Treated swine showed correction of hyperglycemia, glucose intolerance, dyslipidemia and other metabolic abnormalities for > or = 47 weeks. Metabolic correction correlated significantly with the number of hepatocytes implanted. Importantly, we observed no hypoglycemia even under fasting conditions. Direct intrahepatic implantation of hepatocytes did not alter biochemical indices of liver function or induce abnormal hepatic lobular architecture. About 70% of implanted hepatocytes functionally engrafted, appeared histologically normal, retained vector DNA and expressed human insulin for > or = 47 weeks. Based on structural tissue analyses and transcriptome data, we showed that early correction of diabetes attenuated and even prevented pathological changes in the eye, kidney, liver and aorta. CONCLUSIONS: We demonstrate that autologous hepatocytes can be efficiently, simply and safely modified by electroporation of a nonviral vector to express, process and secrete insulin durably. This strategy, which achieved significant and sustained therapeutic efficacy in a large preclinical model without adverse effects, warrants consideration for clinical development especially as it could have broader future applications for the treatment of other acquired and inherited diseases for which systemic reconstitution of a specific protein deficiency is critical
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