7 research outputs found

    Advanced fitting algorithms for analysing positron annihilation lifetime spectra

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    Abstract 2 The most common way to analyse PALS spectra involves fitting a parameter-dependent model to the experimental data. Traditionally, this fit involves local nonlinear optimisation routines that depend on a reasonable initial guess for the searched parameters. This, together with the fact that very different sets of parameters may yield indistinguishably good fits for a given experimental spectrum, gives rise to ambiguities in the data analysis in most but the simplest cases. In order to alleviate these difficulties, a computer program named PAScual was developed that incorporates two advanced algorithms to provide a robust fitting tool: on the one hand, it incorporates a global nonlinear optimisation routine based on the Simulated Annealing algorithm and, on the other hand, it yields information on the reliability of the results by means of a Markov Chain Monte-Carlo Bayesian Inference method. In this work the methods used in PAScual are described and tested against both simulated and experimental spectra, comparing the results with those from the well established program LTv9. The examples focus on the type of complex data that results from the study of self-assembled amphiphile materials containing co-existing aqueous and hydrocarbon regions

    High class I HDAC activity and expression are associated with RelA/p65 activation in pancreatic cancer in vitro and in vivo

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    BACKGROUND: The strong association between aberrant HDAC activity and the occurrence of cancer has led to the development of a variety of HDAC inhibitors (HDIs), which emerge as promising new targeted anticancer therapeutics. METHODS: Due to the pivotal role of RelA/p65 in the tumorigenesis of pancreatic neoplasia we examined the expression of class I HDACs 1, 2 and 3 in a large cohort of human pancreatic carcinomas and correlated our findings with RelA/p65 expression status. Furthermore, we investigated the impact of the HDIs SAHA and VPA on RelA/p65 activity in pancreatic cancer cell culture models. RESULTS: Class I HDACs were strongly expressed in a subset of pancreatic adenocarcinomas and high expression was significantly correlated with increased nuclear translocation of RelA/p65 (p = 0.024). The link of HDAC activity and RelA/p65 in this tumor entity was confirmed in vitro, where RelA/p65 nuclear translocation as well as RelA/p65 DNA binding activity could be markedly diminished by HDI treatment. CONCLUSION: The RelA/p65 inhibitory effects of SAHA and VPA in vitro and the close relationship of class I HDACs and RelA/p65 in vivo suggest that treatment with HDIs could serve as a promising approach to suppress NF-kappaB activity which in turn may lead to enhanced apoptosis and chemosensitization of pancreatic cancers

    Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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    Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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