1,097 research outputs found

    Commentary:The safety of early enteral feeding in children with acute pancreatitis

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    α2β1 integrin affects metastatic potential of ovarian carcinoma spheroids by supporting disaggregation and proteolysis

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    Background: Ovarian cancer is characterized by a wide-spread intra-abdominal metastases which represents a major clinical hurdle in the prognosis and management of the disease. A significant proportion of ovarian cancer cells in peritoneal ascites exist as multicellular aggregates or spheroids. We hypothesize that these cellular aggregates or spheroids are invasive with the capacity to survive and implant on the peritoneal surface. This study was designed to elucidate early inherent mechanism(s) of spheroid survival, growth and disaggregation required for peritoneal metastases.Methods: In this study, we determined the growth pattern and adhesive capacity of ovarian cancer cell lines (HEY and OVHS1) grown as spheroids, using the well established liquid overlay technique, and compared them to a normal ovarian cell line (IOSE29) and cancer cells grown as a monolayer. The proteolytic capacity of these spheroids was compared with cells grown as a monolayer using a gelatin zymography assay to analyze secreted MMP-2/9 in conditioned serum-free medium. The disaggregation of cancer cell line spheroids was determined on extracellular matrices (ECM) such as laminin (LM), fibronectin (FN) and collagen (CI) and the expression of &alpha;2, &alpha;3, &alpha;v, &alpha;6 and &beta;1 interin was determined by flow cytometric analysis. Neutralizing antibodies against &alpha;2, &beta;1 subunits and &alpha;2&beta;1 integrin was used to inhibit disaggregation as well as activation of MMPs in spheroids.Results: We demonstrate that ovarian cancer cell lines grown as spheroids can sustain growth for 10 days while the normal ovarian cell line failed to grow beyond 2 days. Compared to cells grown as a monolayer, cancer cells grown as spheroids demonstrated no change in adhesion for up to 4 days, while IOSE29 cells had a 2&ndash;4-fold loss of adhesion within 2 days. Cancer cell spheroids disaggregated on extracellular matrices (ECM) and demonstrated enhanced expression of secreted pro-MMP2 as well as activated MMP2/MMP9 with no such activation of MMP\u27s observed in monolayer cells. Flow cytometric analysis demonstrated enhanced expression of &alpha;2 and diminution of &alpha;6 integrin subunits in spheroidsversus monolayer cells. No change in the expression of &alpha;3, &alpha;v and &beta;1 subunits was evident. Conversely, except for &alpha;v integrin, a 1.5&ndash;7.5-fold decrease in &alpha;2, &alpha;3, &alpha;6 and &beta;1 integrin subunit expression was observed in IOSE29 cells within 2 days. Neutralizing antibodies against &alpha;2, &beta;1 subunits and &alpha;2&beta;1 integrin inhibited disaggregation as well as activation ofMMPs in spheroids.Conclusion: Our results suggest that enhanced expression of &alpha;2&beta;1 integrin may influence spheroid disaggregation andproteolysis responsible for the peritoneal dissemination of ovarian carcinoma. This may indicate a new therapeutic targetfor the suppression of the peritoneal metastasis associated with advanced ovarian carcinomas.<br /

    External and internal noise surveys of London primary schools

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    Internal and external noise surveys have been carried out around schools in London, UK, to provide information on typical levels and sources to which children are exposed while at school. Noise levels were measured outside 142 schools, in areas away from flightpaths into major airports. 86% of the schools surveyed were exposed to noise from road traffic, the average external noise level outside a school being 57 dB LAeq. Detailed internal noise surveys have been carried out in 140 classrooms in 16 schools, together with classroom observations. It was found that noise levels inside classrooms depend upon the activities in which the children are engaged, with a difference of 20 dB LAeq between the 'quietest' and 'noisiest' activities. The average background noise level in classrooms exceeds the level recommended in current standards. The number of children in the classroom was found to affect noise levels. External noise influenced internal noise levels only when children were engaged in the quietest classroom activities. The effects of the age of the school buildings and types of window upon internal noise were examined but results were inconclusive

    Effect of Strain on Ferroelectric Field Effect in Strongly Correlated Oxide Sm0.5Nd0.5NiO3

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    We report the effect of epitaxial strain on the magnitude and retention of the ferroelectric field effect in high quality PbZr0.3Ti0.7O3 (PZT)/3.8-4.3 nm Sm0.5Nd0.5NiO3 (SNNO) heterostructures grown on (001) LaAlO3 (LAO) and SrTiO3 (STO) substrates. For SNNO on LAO, which exhibits a first-order metal-insulator transition (MIT), switching the polarization of PZT induces a 10 K shift in the transition temperature TMI, with a maximum resistance change between the on and off states of Δ/on ~75%. In sharp contrast, only up to 5% resistance change has been induced in SNNO on STO, where the MIT is second-order, with the modulation of TMI negligibly small. We also observe thermally activated retention of the off state resistance Roff in both systems, with the activation energy of 22 meV (28 meV) for devices on LAO (STO). The time dynamics and thermal response of the field effect instability points to phonon-assisted interfacial trapping of charged mobile defects, which are attributed to strain induced oxygen vacancies. At room temperature, Roff stabilizes at ~55% and ~19% of the initial switching levels for SNNO on LAO and STO, respectively, reflecting the significantly different oxygen vacancy densities in these two systems. Our results reveal the critical role of strain in engineering and modeling the complex oxide composite structures for nanoelectronic and spintronic applications

    Using a Crop Model to Benchmark Miscanthus and Switchgrass

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    Crop yields are important items in the economic performance and the environmental impacts of second-generation biofuels. Since they strongly depend on crop management and pedoclimatic conditions, it is important to compare candidate feedstocks to select the most appropriate crops in a given context. Agro-ecosystem models offer a prime route to benchmark crops, but have been little tested from this perspective thus far. Here, we tested whether an agro-ecosystem model (CERES-EGC) was specific enough to capture the differences between miscanthus and switchgrass in northern Europe. The model was compared to field observations obtained in seven long-term trials in France and the UK, involving different fertilizer input rates and harvesting dates. At the calibration site (Estrées-Mons), the mean deviations between simulated and observed crop biomass yields for miscanthus varied between −0.3 t DM ha−1 and 4.2 t DM ha−1. For switchgrass, simulated yields were within 1.0 t DM ha−1 of the experimental data. Observed miscanthus yields were higher than switchgrass yields in most sites and for all treatments, with one exception. Overall, the model captured the differences between both crops adequately, with a mean deviation of 0.46 t DM ha−1, and could be used to guide feedstock selections over larger biomass supply areas

    The high costs of getting ethical and site-specific approvals for multi-centre research.

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    BACKGROUND: Multi-centre studies generally cost more than single-centre studies because of larger sample sizes and the need for multiple ethical approvals. Multi-centre studies include clinical trials, clinical quality registries, observational studies and implementation studies. We examined the costs of two large Australian multi-centre studies in obtaining ethical and site-specific approvals. METHODS: We collected data on staff time spent on approvals and expressed the overall cost as a percent of the total budget. RESULTS: The total costs of gaining approval were 38 % of the budget for a study of 50 centres (mean cost AUD 6960persite)and26960 per site) and 2 % for a study of 11 centres (mean cost AUD 2300 per site). Seventy-five and 90 % of time was spent on repeated tasks, respectively, and many time-consuming tasks, such as reformatting documents, did nothing to improve the study design or participant safety. CONCLUSIONS: Improvements have been made to the ethical approval application system, but more gains could be made without increasing risks of harm to research participants. We propose that ethical review bodies and individual sites publish statistics on how long they take to process approvals which could then be nationally benchmarked

    Monoclonal antibodies reacting with the MUC2 mucin core protein.

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    This study sought to produce monoclonal antibodies (MAbs) which reacted with the MUC2 core protein. Two MAbs [3A2 (IgG1) and 4F1 (IgM)] were produced by immunising female BALB/c mice with gel-formed mucin from the LS174T colon cancer cell line followed by a KLH conjugate of a 29 amino acid synthetic peptide whose sequence was derived from the variable number of tandem repeats (VNTR) region of a MUC2 cDNA clone. The MAbs reacted with synthetic MUC2 VNTR peptides but not synthetic MUC1 or MUC3 VNTR peptides, and showed specific reactivity in Western blotting with a high molecular weight protein produced by the LS174T colon carcinoma cell line. The use of shorter peptides indicated that the minimum peptide epitopes for these MAbs were different. Mab 3A2 reacted with amino acids 5-19 of the MUC2 VNTR by inhibition ELISA but not by direct ELISA, while 4F1 reacted with this peptide in both assays. Furthermore, 4F1 reacted in direct ELISA when a larger (29 amino acid) MUC2-derived peptide was coated onto the assay plate by incubating in carbonate buffer or by drying the peptide onto the assay plate, while 3A2 only reacted when this peptide was coated in carbonate buffer. The different specificity of the MAbs was also illustrated by the reactivity of 4F1 but not 3A2 with partially deglycosylated cystic fibrosis mucin. Immunohistochemical analysis with these MAbs revealed a strong reactivity with lung, gastric and colon tumours relative to normal tissue, with some breast and ovarian tumours also reacting. Both MAbs stained some normal goblet cells in the perinuclear region but not the mucin droplet or secreted mucin, indicating a reaction with immature (poorly glycosylated) mucin in the endoplasmic reticulum and/or golgi, but not with mature (fully glycosylated) mucin. In contrast, tumours showed strong diffuse cytoplasmic staining. 4F1 also showed weak apical cytoplasmic staining in some goblet cells and stained some tumours which showed no reactivity with 3A2. These antibodies should prove useful in the study of MUC2 structure and function, and in the diagnosis of some tumours
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