312 research outputs found

    Towards Economic Models for MOOC Pricing Strategy Design

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    MOOCs have brought unprecedented opportunities of making high-quality courses accessible to everybody. However, from the business point of view, MOOCs are often challenged for lacking of sustainable business models, and academic research for marketing strategies of MOOCs is also a blind spot currently. In this work, we try to formulate the business models and pricing strategies in a structured and scientific way. Based on both theoretical research and real marketing data analysis from a MOOC platform, we present the insights of the pricing strategies for existing MOOC markets. We focus on the pricing strategies for verified certificates in the B2C markets, and also give ideas of modeling the course sub-licensing services in B2B markets

    Self-Assessments by U.S. Army Officers: Effects of Skill Level and Item Ambiguity on Accuracy

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    Organizations benefit from the use of training and performance assessments. Self-assessment is a way for trainees to monitor their progress throughout training and on the job. The literature indicates that ambiguity and skill level are factors that impact the accuracy of self-assessments. Previously, the effect of the interaction of ambiguity and skill level on self-assessment accuracy had not been investigated. The present study assessed the effect of skill level and item ambiguity on the accuracy of self-assessments made by Lieutenants and Captains in the U. S. Army. The results indicated that increased skill level resulted in increased accuracy of self-assessments while ambiguity had no effect. Counter to the hypothesis, as items became more ambiguous, both Captains and Lieutenants self-assessed more accurately. Implications and limitations are discussed, along with recommendations for future research

    Trafficking pathways of Cx49-GFP in living mammalian cells

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    In the present study we examined the trafficking pathways of connexin49 (Cx49) fused to green fluorescent protein (GFP) in polar and non-polar cell lines. The Cx49 gene was isolated from ovine lens by RT-PCR. Cx49 cDNA was fused to GFP and the hybrid cDNA was transfected into several cell lines. After transfection of Cx49-GFP cDNA into HeLa cells, it was shown using the double whole-cell patch-clamp technique that the expressed fusion protein was still able to form conducting gap junction channels. Synthesis, assembly, and turnover of the Cx49-GFP hybrid protein were investigated using a pulse-chase protocol. A major 78-kDa protein band corresponding to Cx49-GFP could be detected with a turnover of 16-20 h and a half-life time of 10 h. The trafficking pathways of Cx49-GFP were monitored by confocal laser microscopy. Fusion proteins were localized in subcellular compartments, including the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment, the Golgi apparatus, and the trans-Golgi network, as well as vesicles traveling towards the plasma membrane. Time-dependent sequential localization of Cx49-GFP in the ER and then the Golgi apparatus supports the notion of a slow turnover of Cx49-GFP compared to other connexins analyzed so far. Gap junction plaques resembling the usual punctuate distribution pattern could be demonstrated for COS-1 and MDCK cells. Basolateral distribution of Cx49-GFP was observed in polar MDCK cells, indicating specific sorting behavior of Cx49 in polarized cells. Together, this report describes the first characterization of biosynthesis and trafficking of lens Cx49.Fritz Thyssen-Stiftun

    Anti-melanocortin-4 receptor autoantibodies in obesity

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    Background: The melanocortin-4 receptor (MC4R) is part of an important pathway regulating energy balance. Here we report the existence of autoantibodies (autoAbs) against the MC4R in sera of obese patients. Methods: The autoAbs were detected after screening of 216 patients' sera by using direct and inhibition ELISA with an N-terminal sequence of the MC4R. Binding to the native MC4R was evaluated by flow cytometry and pharmacological effects by measuring adenylyl cyclase activity. Results: Positive results in all tests were obtained in patients with overweight or obesity (prevalence: 3.6%) but not in normal weight patients. The selective binding properties of anti-MC4R autoAbs were confirmed by surface plasmon resonance and by immunoprecipitation with the native MC4R. Finally it was demonstrated that these autoAbs increased food intake in rats after passive transfer via intracerebroventricular injection. Conclusion: These observations suggest that inhibitory anti-MC4R autoAbs might contribute to the development of obesity in a small subpopulation of patients

    Effect of anti-inflammatory agents on transforming growth factor beta over-expressing mouse brains: a model revised.

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    BACKGROUND: The over-expression of transforming growth factor beta-1(TGF-beta1) has been reported to cause hydrocephalus, glia activation, and vascular amyloidbeta (Abeta) deposition in mouse brains. Since these phenomena partially mimic the cerebral amyloid angiopathy (CAA) concomitant to Alzheimer's disease, the findings in TGF-beta1 over-expressing mice prompted the hypothesis that CAA could be caused or enhanced by the abnormal production of TGF-beta1. This idea was in accordance with the view that chronic inflammation contributes to Alzheimer's disease, and drew attention to the therapeutic potential of anti-inflammatory drugs for the treatment of Abeta-elicited CAA. We thus studied the effect of anti-inflammatory drug administration in TGF-beta1-induced pathology. METHODS: Two-month-old TGF-beta1 mice and littermate controls were orally administered pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, or ibuprofen, a non steroidal anti-inflammatory agent, for two months. Glia activation was assessed by immunohistochemistry and western blot analysis; Abeta precursor protein (APP) by western blot analysis; Abeta deposition by immunohistochemistry, thioflavin-S staining and ELISA; and hydrocephalus by measurements of ventricle size on autoradiographies of brain sections. Results are expressed as means +/- SD. Data comparisons were carried with the Student's T test when two groups were compared, or ANOVA analysis when more than three groups were analyzed. RESULTS: Animals displayed glia activation, hydrocephalus and a robust thioflavin-S-positive vascular deposition. Unexpectedly, these deposits contained no Abeta or serum amyloid P component, a common constituent of amyloid deposits. The thioflavin-S-positive material thus remains to be identified. Pioglitazone decreased glia activation and basal levels of Abeta42- with no change in APP contents - while it increased hydrocephalus, and had no effect on the thioflavin-S deposits. Ibuprofen mimicked the reduction of glia activation caused by pioglitazone and the lack of effect on the thioflavin-S-labeled deposits. CONCLUSIONS: i) TGF-beta1 over-expressing mice may not be an appropriate model of Abeta-elicited CAA; and ii) pioglitazone has paradoxical effects on TGF-beta1-induced pathology suggesting that anti-inflammatory therapy may reduce the damage resulting from active glia, but not from vascular alterations or hydrocephalus. Identification of the thioflavin-S-positive material will facilitate the full appraisal of the clinical implication of the effects of anti-inflammatory drugs, and provide a more thorough understanding of TGF-beta1 actions in brain

    Economic evaluation strategies in telehealth: obtaining a more holistic valuation of telehealth interventions

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    Telehealth is an emerging area of medical research. Its translation from conception, to research and into practice requires tailored research and economic evaluation methods. Due to their nature telehealth interventions exhibit a number of extra-clinical benefits that are relevant when valuing their costs and outcomes. By incorporating methods to measure societal values such as patient preference and willingness-to-pay, a more holistic value can be placed on the extra-clinical outcomes associated with telehealth and evaluations can represent new interventions more effectively. Cost-benefit analysis is a method by which relevant costs and outcomes in telehealth can be succinctly valued and compared. When health economic methods are conducted using holistic approaches such as cost-benefit analysis they can facilitate the translation of telehealth research into policy and practice

    Impact of tax reduction policies on consumer purchase of new automobiles : an analytical investigation with real data-based experiments

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    We investigate and compare the impact of the tax reduction policies implemented in the United States and China to stimulate consumer purchase of new automobiles and improve manufacturers\u27 profits. The U.S. policy provides each qualifying consumer with a federal income tax deduction on state and local sales and excise taxes paid on the purchase price (up to a cutoff level), whereas the Chinese policy reduces the vehicle sales tax rate for consumers. We observe that these policy designs are consistent with the tax management system and the economic environment in the respective country. We analytically determine the effects of the two tax reduction policies on the automobile sales and the manufacturer\u27s and the retailer\u27s profits. Numerical examples are then used to provide insights on the importance of certain factors that influence the effects of the two policies. Finally, a numerical experiment with sensitivity analysis based on real data is conducted to compare the merits and characteristics of the two policies under comparable conditions. We find that the U.S. policy is better than the Chinese policy in stimulating the sales of high-end automobiles, whereas the Chinese policy is better than the U.S. policy in improving the sales of low-end automobiles. The U.S. policy is slightly more effective in increasing the profitability of the automobile supply chain; but, in general, the Chinese policy is more cost effective. The methodology developed herein can be used to evaluate other tax reduction policies such as those related to the purchase of energy-saving vehicles and to serve as a decision model to guide the choice of alternative tax reduction policies

    Physiological Intermolecular Modification Spectroscopy for the Prediction of Response to Anti-Tumor Necrosis Factor Therapy in Patients with Inflammatory Bowel Diseases

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    Background/Aims: Anti-tumor necrosis factor (TNF) antibodies have clinical efficiency only in a subgroup of patients with inflammatory bowel diseases (IBD). Prediction of clinical response is a critical clinical problem. Physiological intermolecular modification spectroscopy (PIMS) is a label-free technology performed in physiological conditions. PIMS enables real-time monitoring of dynamic molecular resonance of entire proteins and macromolecules of an individual. The aim of this study was to explore the capacity of PIMS to discriminate IBD patients regarding response to anti-TNF treatment. Methods: Protein extracts of peripheral blood mononuclear cells (PBMC) from 30 outpatients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and treated with infliximab were subjected to PIMS analysis in a blinded transversal study. Total protein from each patient's PBMCs was challenged with infliximab. Dynamic changes in macromolecular interaction were registered while the temperature rose from -37 to 37°C. Individual macromolecular volume and molecular elasticity were determined for each patient. Results: Clinical data revealed that 67% of UC and 79% of CD patients responded to infliximab therapy during the 3-month study period based on their respective clinical activity score. These results confirm that PIMS data predicted response to anti-TNF therapy with an accuracy of 96%. Conclusion: PIMS stratified IBD patients into two groups, responders and nonresponders, which correlated with the clinical efficacy of anti-TNF therapy. PIMS seems to be a powerful technology to adapt IBD treatment to the individual patient. Further studies with PIMS might enable to predict clinical response to biological treatment in IBD patients before the therapy is initiated
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