79 research outputs found

    Shaping a Sustainable Old Worthington

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    Course Code: ENR/AEDE 4567This project is a collaboration between the Old Worthington Partnership, Old Worthington merchants, American Electric Power (AEP), and the Sustainable Worthington Capstone Group from The Ohio State University’s Environment, Economy, Development, and Sustainability (EEDS) major. Old Worthington is located in the historic downtown of Worthington, Ohio. The Old Worthington Partnership is a volunteer group that aims to enhance the Old Worthington experience by pursuing collaboration, engagement, and sustainability. The Old Worthington Partnership reached out to this capstone group for assistance in implementing AEP’s Small Business Express Program among their eligible merchants.Academic Major: Environment, Economy, Development, and Sustainabilit

    <i>Streptococcus thermophilus</i> NCIMB 41856 ameliorates signs of colitis in an animal model of inflammatory bowel disease

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    Treatment of inflammatory bowel disease (IBD) is mainly based on suppression of symptoms, often with numerous side effects. Trials of probiotics in IBD have frequently produced disappointing results. The majority of probiotics are unusual, since they do not require iron for growth, unlike many bacteria resident in the intestine. The IBD intestine is iron-rich due to bleeding and use of oral iron supplements; conventional probiotics would be rapidly outcompeted. We have evaluated an iron-responsive Streptococcus thermophilus strain for its potential to reduce signs of colitis. Efficacy of S. thermophilus was evaluated in the dextran sodium sulphate mouse model of colitis. Treated animals were given 1×108 cfu S. thermophilus per day and clinical observations were taken daily. At termination, gross and histopathological signs of disease, cellular infiltration, location of bacteria, and cytokine expression in the intestine were determined. S. thermophilus delayed onset of colitis and reduced clinical signs of disease, including bodyweight loss and gastrointestinal bleeding. It reduced bacterial translocation into the colonic tissue. Increased numbers of CD8+ intraepithelial lymphocytes were seen in control animals treated with S. thermophilus. S. thermophilus had no effect on gross pathology, histopathology or cytokine production in either colitic or control animals. We propose that S. thermophilus promotes maintenance of mucosal barrier function which reduces bacterial translocation, thereby reducing immune stimulation and associated inflammation. This allows mucosal healing, reducing gastrointestinal bleeding and weight loss. This could be studied as a locally-acting adjunct or alternative to current IBD treatments. </jats:p

    Epithelial-to-mesenchymal transition supports ovarian carcinosarcoma tumorigenesis and confers sensitivity to microtubule-targeting with eribulin

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    Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analysed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumours. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts (PDX). Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a down-regulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8+ T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate EMT plays a key role in OCS tumourigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes

    Improving risk-adjusted performance in high frequency trading using interval type-2 fuzzy logic

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    In this paper, we investigate the ability of higher order fuzzy systems to handle increased uncertainty, mostly induced by the market microstructure noise inherent in a high frequency trading (HFT) scenario. Whilst many former studies comparing type-1 and type-2 Fuzzy Logic Systems (FLSs) focus on error reduction or market direction accuracy, our interest is predominantly risk-adjusted performance and more in line with both trading practitioners and upcoming regulatory regimes. We propose an innovative approach to design an interval type-2 model which is based on a generalisation of the popular type-1 ANFIS model. The significance of this work stems from the contributions as a result of introducing type-2 fuzzy sets in intelligent trading algorithms, with the objective to improve the risk-adjusted performance with minimal increase in the design and computational complexity. Overall, the proposed ANFIS/T2 model scores significant performance improvements when compared to both standard ANFIS and Buy-and-Hold methods. As a further step, we identify a relationship between the increased trading performance benefits of the proposed type-2 model and higher levels of microstructure noise. The results resolve a desirable need for practitioners, researchers and regulators in the design of expert and intelligent systems for better management of risk in the field of HFT

    Epithelial-to-mesenchymal transition supports ovarian carcinosarcoma tumorigenesis and confers sensitivity to microtubule-targeting with eribulin

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    Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analysed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumours. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts (PDX). Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a down-regulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8+ T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate EMT plays a key role in OCS tumourigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes

    The association between treatment adherence to nicotine patches and smoking cessation in pregnancy: a secondary analysis of a randomised controlled trial

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    IntroductionIn non-pregnant ‘quitters’, adherence to nicotine replacement therapy (NRT) increases smoking cessation. We investigated relationships between adherence to placebo or NRT patches and cessation in pregnancy, including an assessment of reverse causation and whether any adherence: cessation relationship is moderated when using nicotine or placebo patches. MethodsUsing data from 1050 pregnant trial participants, regression models investigated associations between maternal characteristics, adherence and smoking cessation. ResultsAdherence during the first month was associated with lower baseline cotinine concentrations (beta -0.08, 95%CI -0.15 to -0.01) and randomisation to NRT (beta 2.59, 95%CI 1.50 to 3.68). Adherence during both treatment months was associated with being randomised to NRT (beta 0.51, 95%CI 0.29 to 0.72) and inversely associated with higher nicotine dependence. Adherence with either NRT or placebo was associated with cessation at one month (OR 1.11, 95%CI 1.08 to 1.13) and delivery (OR 1.06, 95%CI 1.03 to 1.09), but no such association was observed in the subgroup where reverse causation was not possible. Amongst all women, greater adherence to nicotine patches was associated with increased cessation (OR 2.47, 95%CI 1.32 to 4.63) but greater adherence to placebo was not (OR 0.98, 95%CI: 0.44 to 2.18). ConclusionWomen who were more adherent to NRT were more likely to achieve abstinence; more nicotine dependent women probably showed lower adherence to NRT because they relapsed to smoking more quickly. The interaction between nicotine-containing patches and adherence for cessation suggests that the association between adherence with nicotine patches and cessation may be partly causal

    How Californias Local Education Agencies Evaluate Teachers and Principals

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    Teachers and principals alike play key roles in improving education. That's why it's crucial for school districts to have in place effective systems for evaluating their performance.This brief, produced by Regional Educational Laboratory West (REL West), analyzes data from California's Teacher and Principal Evaluation Survey, taken by more than 90 percent of the state's local education agencies (LEAs).The California Department of Education and the Integrated Leadership Development Initiative, a California cross-agency collaboration focused on improving school and district leadership, requested this report to inform their work, assist policymakers interested in teacher and principal evaluation reform, and illustrate how the evaluations of districts and direct-funded charter schools may differ.Some key findings:Sixty-one percent of the LEAs indicated that their teacher evaluation systems are based on the California Standards for the Teaching ProfessionForty-three percent of the LEAs do not use student achievement data as a criterion in teacher evaluation, and 21 percent indicated that these data are not used in principal evaluationsDirect-funded charter schools reported greater reliance on student achievement results than did districts please visit the REL West website for more information on REL West. Information about the Regional Educational Laboratory (REL) system and other REL publications can be found at the national Regional Educational Laboratory Program website

    Streptococcus thermophilus

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