117 research outputs found

    Asymmetric Silver to Oxide Adhesion in Multilayers Deposited on Glass by Sputtering

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    We have developed a wedge-loaded double-cantilever beam adhesion measurement set-up for thin films deposited on glass by sputtering. The test is described in details. Results on the Glass/sublayer/Ag/ZnO multilayer provide evidence that \SnOd or \TiOd perform better than ZnO as a sublayer. Then however, rupture within the multilayer shifts to the upper Ag/ZnO interface. The latter is shown to be tougher than the lower ZnO/Ag interface, an asymmetry due to non-equilibrium interfacial structures

    High-temperature oxidation of nickel-based alloys and estimation of the adhesion strength of resulting oxide layers

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    The kinetics of isothermal oxidation (1100°C) of commercial nickel-based alloys with different content of sulfur (0.22–3.2 wt ppm) is studied. The adhesion strength in a metal/oxide system is estimated as a function of sulfur content and duration of high-temperature exposure. The scratch-test technique is proposed to quantitatively estimate the work of adhesion of resulting oxide films. It is found that the film microstructure is composed of an inner α-Al2O3 layer and an outer NiAl2O4 spinel layer, which are separated by discrete inclusions of TiO2. Residual stresses in the oxide film are experimentally determined by X-ray diffraction. spinel layer, which are separated by discrete inclusions of TiO2. Residual stresses in the oxide film are experimentally determined by X-ray diffractio

    Dynamic Measurements of Membrane Insertion Potential of Synthetic Cell Penetrating Peptides

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/la403370p.Cell penetrating peptides (CPPs) have been established as excellent candidates for mediating drug delivery into cells. When designing synthetic CPPs for drug delivery applications, it is important to understand their ability to penetrate the cell membrane. In this paper, anionic or zwitterionic phospholipid monolayers at the air-water interface are used as model cell membranes to monitor the membrane insertion potential of synthetic CPPs. The insertion potential of CPPs having different cationic and hydrophobic amino acids were recorded using a Langmuir monolayer approach that records peptide adsorption to model membranes. Fluorescence microscopy was used to visualize alterations in phospholipid packing due to peptide insertion. All CPPs had the highest penetration potential in the presence of anionic phospholipids. In addition, two of three amphiphilic CPPs inserted into zwitterionic phospholipids, but none of the hydrophilic CPPs did. All the CPPs studied induced disruptions in phospholipid packing and domain morphology, which were most pronounced for amphiphilic CPPs. Overall, small changes to amino acids and peptide sequences resulted in dramatically different insertion potentials and membrane reorganization. Designers of synthetic CPPs for efficient intracellular drug delivery should consider small nuances in CPP electrostatic and hydrophobic properties

    Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker

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    BACKGROUND: To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies. METHODS: The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up. RESULTS: Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor. CONCLUSION: Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention

    Baseline Predictors of Sputum Culture Conversion in Pulmonary Tuberculosis: Importance of Cavities, Smoking, Time to Detection and W-Beijing Genotype

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    Background: Time to detection (TTD) on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. The M. tuberculosis W-Beijing genotype is spreading globally, indicating a selective advantage. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes. Aim: To assess baseline predictors of failure of sputum culture conversion, within the first 2 months of antitubercular therapy, in participants with pulmonary tuberculosis. Design: Between May 2005 and August 2008 we conducted a prospective cohort study of time to sputum culture conversion in ambulatory participants with first episodes of smear and culture positive pulmonary tuberculosis attending two primary care clinics in Cape Town, South Africa. Rifampicin resistance (diagnosed on phenotypic susceptibility testing) was an exclusion criterion. Sputum was collected weekly for 8 weeks for mycobacterial culture on liquid media (BACTEC MGIT 960). Due to missing data, multiple imputation was performed. Time to sputum culture conversion was analysed using a Cox-proportional hazards model. Bayesian model averaging determined the posterior effect probability for each variable. Results: 113 participants were enrolled (30.1% female, 10.5% HIV-infected, 44.2% W-Beijing genotype, and 89% cavities). On Kaplan Meier analysis 50.4% of participants underwent sputum culture conversion by 8 weeks. The following baseline factors were associated with slower sputum culture conversion: TTD (adjusted hazard ratio (aHR) = 1.11, 95% CI 1.02; 1.2), lung cavities (aHR = 0.13, 95% CI 0.02; 0.95), ever smoking (aHR = 0.32, 95% CI 0.1; 1.02) and the W-Beijing genotype (aHR = 0.51, 95% CI 0.25; 1.07). On Bayesian model averaging, posterior probability effects were strong for TTD, lung cavitation and smoking and moderate for W-Beijing genotype. Conclusion: We found that baseline TTD, smoking, cavities and W-Beijing genotype were associated with delayed 2 month sputum culture. Larger studies are needed to confirm the relationship between the W-Beijing genotype and sputum culture conversion.Publisher's versio

    Bayesian Information Criterion for Censored Survival Models

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    We investigate the Bayesian Information Criterion (BIC) for variable selection in models for censored survival data. Kass and Wasserman (1995) showed that BIC provides a close approximation to the Bayes factor when a unit-information prior on the parameter space is used. We propose a revision of the penalty term in BIC so that it is defined in terms of the number of uncensored events instead of the number of observations. For a simple censored data model, this revision results in a better approximation to the exact Bayes factor based on a conjugate unit-information prior. In the Cox proportional hazards regression model, we propose defining BIC in terms of the maximized partial likelihood. Using the number of deaths rather than the number of individuals in the BIC penalty term corresponds to a more realistic prior on the parameter space, and is shown to improve predictive performance for assessing stroke risk in the Cardiovascular Health Study. Key words: Bayes factor; Cox ..
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