307 research outputs found

    An Assessment of Students’ Satisfaction in Higher Education

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    Student’s Satisfaction (SS) with a particular subject may impact the learning process, being the figure of attentiveness of the utmost importance over time, and also a very difficult undertaking to accomplish. To go forward with such exercise, a workable methodology for problem solving had to be built and tested. It is based on a thermodynamic approach to Knowledge Representation and Reasoning, which is the ultimate goal of SS assessment when working on a particular topic

    Antisense inhibition of methylenetetrahydrofolate reductase reduces survival of methionine-dependent tumour lines

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    Transformed cells have been documented to be methionine-dependent, suggesting that inhibition of methionine synthesis might be useful for cancer therapy. Methylenetetrahydrofolate reductase synthesises 5-methyltetrahydrofolate, the methyl donor utilised in methionine synthesis from homocysteine by vitamin B12-dependent methionine synthase. We hypothesised that methylenetetrahydrofolate reductase inhibition would affect cell viability through decreased methionine synthesis. Using medium lacking methionine, but containing homocysteine and vitamin B12 (M-H+), we found that nontransformed human fibroblasts could maintain growth. In contrast, four transformed cell lines (one colon carcinoma, two neuroblastoma and one breast carcinoma) increased proliferation only slightly in the M-H+ medium. To downregulate methylenetetrahydrofolate reductase expression, two phosphorothioate antisense oligonucleotides, EX5 and 677T, were used to target methylenetetrahydrofolate reductase in the colon carcinoma line SW620; 400 nM of each antisense oligonucleotide decreased cell survival by approximately 80% (P<0.01) and 70% (P<0.0001), respectively, compared to cell survival after the respective control mismatched oligonucleotide. Western blotting and enzyme assays confirmed that methylenetetrahydrofolate reductase expression was decreased. Two neuroblastoma and two breast carcinoma lines also demonstrated decreased survival following EX5 treatment whereas nontransformed human fibroblasts were not affected. This study suggests that methylenetetrahydrofolate reductase may be required for tumour cell survival and that methylenetetrahydrofolate reductase inhibition should be considered for anti-tumour therapy

    MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

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    Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

    Business opportunities analysis using GIS: the retail distribution sector

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    [EN] The retail distribution sector is facing a difficult time as the current landscape is characterized by ever-increasing competition. In these conditions, the search for an appropriate location strategy has the potential to become a differentiating and competitive factor. Although, in theory, an increasing level of importance is placed on geography because of its key role in understanding the success of a business, this is not the case in practice. For this reason, the process outlined in this paper has been specifically developed to detect new business locations. The methodology consists of a range of analyzes with Geographical Information Systems (GISs) from a marketing point of view. This new approach is called geomarketing. First, geodemand and geocompetition are located on two separate digital maps using spatial and non-spatial databases. Second, a third map is obtained by matching this information with the demand not dealt with properly by the current commercial offer. Third, the Kernel density allows users to visualize results, thus facilitating decision-making by managers, regardless of their professional background. The advantage of this methodology is the capacity of GIS to handle large amounts of information, both spatial and non-spatial. A practical application is performed in Murcia (Spain) with 100 supermarkets and data at a city block level, which is the highest possible level of detail. This detection process can be used in any commercial distribution company, so it can be generalized and considered a global solution for retailers.Roig Tierno, H.; Baviera-Puig, A.; Buitrago Vera, JM. (2013). Business opportunities analysis using GIS: the retail distribution sector. Global Business Perspectives. 1(3):226-238. doi:10.1007/s40196-013-0015-6S22623813Alarcón, S. (2011). The trade credit in the Spanish agrofood industry. Mediterranean Journal of Economics, Agriculture and Environment (New Medit), 10(2), 51–57.Alcaide, J. 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Changing methods of location planning for retail companies. GeoJournal, 45, 289–298.Clarkson, R. M., Clarke-Hill, C. M., & Robinson, T. (1996). UK supermarket location assessment. International Journal of Retail and Distribution Management, 24(6), 22–33.Davis, P. (2006). Spatial competition in retail markets: Movie theaters. The RAND Journal of Economics, 37(4), 964–982.Ghosh, A., & McLafferty, S. L. (1982). Locating stores in uncertain environments: A scenario planning approach. Journal of Retailing, 58(4), 5–22.Härdle, W. (1991). Smoothing techniques with implementation in S. Nueva York, NY: Springer.Harris, B., & Batty, M. (1993). Locational models, geographical information, and planning support systems. Journal of Planning Education and Research, 12, 184–198.Hernandez, T. (2007). Enhancing retail location decision support: The development and application of geovisualization. Journal of Retailing and Consumer Services, 14, 249–258.Hernandez, T., & Bennison, D. (2000). 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    Exenatide Improves Glucose Homeostasis and Prolongs Survival in a Murine Model of Dilated Cardiomyopathy

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    There is growing awareness of secondary insulin resistance and alterations in myocardial glucose utilization in congestive heart failure. Whether therapies that directly target these changes would be beneficial is unclear. We previously demonstrated that acute blockade of the insulin responsive facilitative glucose transporter GLUT4 precipitates acute decompensated heart failure in mice with advanced dilated cardiomyopathy. Our current objective was to determine whether pharmacologic enhancement of insulin sensitivity and myocardial glucose uptake preserves cardiac function and survival in the setting of primary heart failure.The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life. TG9 mice develop congestive heart failure and secondary insulin resistance in a highly predictable manner with death by 12 weeks of age. Glucose homeostasis was assessed by measuring glucose tolerance at 8 and 10 weeks and tissue 2-deoxyglucose uptake at 75 days. Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice. Phosphorylation of AMP kinase and AKT was also increased in exenatide-treated animals. Total myocardial GLUT1 levels were not different between groups. Exenatide also abrogated the detrimental effect of the GLUT4 antagonist ritonavir on survival in TG9 mice.In heart failure secondary insulin resistance is maladaptive and myocardial glucose uptake is suboptimal. An incretin-based therapy, which addresses these changes, appears beneficial

    A new research agenda for managing socio-cultural integration

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    Post-acquisition socio-cultural integration has received increasing attention from both scholars and practitioners since the early 1990s. During the past decade, research has increasingly focused on emotions and identity in mergers and acquisitions. This chapter introduces the reader to the vibrant research field and its relevance. This section sets the scene for the book, which provides a deeper understanding of how emotions—both positive and negative—as well as values and identity enable a deeper socio-cultural integration after a merger or acquisition, and how leadership plays a crucial role in making it all happen. This chapter also highlights how the Nordic approach to post-acquisition socio-cultural integration refers to a large community of Nordic academics focusing on the softer social and human side of acquisition, often relying on a huge variety of qualitative methods, and to Nordic companies that are not afraid of adopting a more collaborative approach to post-acquisition integration

    CD8+ T-Cell Interleukin-7 Receptor Alpha Expression as a Potential Indicator of Disease Status in HIV-Infected Children

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    Background: Initiation and modification of antiretroviral therapy in HIV-infected children depend on viral load and CD4+ T-cell count. However, these surrogates have limitations, and complementary immunological markers to assess therapeutic response are needed. Our aim was to evaluate CD8+ T-cell expression of CD127 as a marker of disease status in HIV-infected children, based on adult data suggesting its usefulness. We hypothesized that CD127 expression on CD8+ T-cells is lower in children with more advanced disease. Methods: In a cross-sectional evaluation, we used flow cytometry to measure CD127+ expression on CD8+ T-cells in whole blood from HIV-infected children with varying disease status. This was compared with expression of CD38 on this subset, currently used in clinical practice as a marker of disease status. Results: 51 HIV-infected children were enrolled. There was a strong positive correlation between CD127 expression on CD8+ T-cells and CD4+ T-cell count, and height and weight z-scores, and a strong negative correlation between CD127 expression and viral load. In contrast, we found no association between CD38 expression and these disease status markers. Conclusions: CD8+ T-cell CD127 expression is significantly higher in children with better HIV disease control, and may have a role as an immunologic indicator of disease status. Longitudinal studies are needed to determine the utility of this marker as a potential indicator of HIV disease progression

    Enhanced presentation of MHC class Ia, Ib and class II-restricted peptides encapsulated in biodegradable nanoparticles: a promising strategy for tumor immunotherapy

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    <p>Abstract</p> <p>Background</p> <p>Many peptide-based cancer vaccines have been tested in clinical trials with a limited success, mostly due to difficulties associated with peptide stability and delivery, resulting in inefficient antigen presentation. Therefore, the development of suitable and efficient vaccine carrier systems remains a major challenge.</p> <p>Methods</p> <p>To address this issue, we have engineered polylactic-co-glycolic acid (PLGA) nanoparticles incorporating: (i) two MHC class I-restricted clinically-relevant peptides, (ii) a MHC class II-binding peptide, and (iii) a non-classical MHC class I-binding peptide. We formulated the nanoparticles utilizing a double emulsion-solvent evaporation technique and characterized their surface morphology, size, zeta potential and peptide content. We also loaded human and murine dendritic cells (DC) with the peptide-containing nanoparticles and determined their ability to present the encapsulated peptide antigens and to induce tumor-specific cytotoxic T lymphocytes (CTL) <it>in vitro</it>.</p> <p>Results</p> <p>We confirmed that the nanoparticles are not toxic to either mouse or human dendritic cells, and do not have any effect on the DC maturation. We also demonstrated a significantly enhanced presentation of the encapsulated peptides upon internalization of the nanoparticles by DC, and confirmed that the improved peptide presentation is actually associated with more efficient generation of peptide-specific CTL and T helper cell responses.</p> <p>Conclusion</p> <p>Encapsulating antigens in PLGA nanoparticles offers unique advantages such as higher efficiency of antigen loading, prolonged presentation of the antigens, prevention of peptide degradation, specific targeting of antigens to antigen presenting cells, improved shelf life of the antigens, and easy scale up for pharmaceutical production. Therefore, these findings are highly significant to the development of synthetic vaccines, and the induction of CTL for adoptive immunotherapy.</p
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