41 research outputs found

    Machining of ceramics and ecological steels using a mill-turn centre equipped with an ultrasonic assisted tooling system

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    Abstract Today, there is a large demand for the machining of simple and/or complex shaped components made of difficult to cut materials such as ceramics. Recently, there is also a demand to machine new type of steels, having restrictions in chemical composition (e.g. lead and sulphur free) in order to comply with recent governmental EU regulations. This paper first describes on-going and planned research activities on the machining (turning) of these advanced materials. For the machining of various ceramic materials, an ultrasonic assisted tooling system has been designed, manufactured and integrated within the available Mori Seiki NL2000Y/500 mill-turn centre. The developed system has been tested through initial machining experiments on aluminium and ZrO 2 . Second, this paper also briefly describes other on-going and planned research and education activities in which the Mori Seiki NL2000Y/500 is involved. It includes advanced NCprogramming of multi-axis machine tools, energy efficient machining of ecological steels and the development of training programs for 3 rd years mechanical engineering students

    Validation of the correct start codon of norX/nxrX and universality of the norAXB/nxrAXB gene cluster in Nitrobacter species

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    The complete norX/nxrX sequence of five Nitrobacter strains was determined showing that the norAXB/nxrAXB gene cluster is present in all hitherto described Nitrobacter species. Evidence is provided that the previously published sequence of norX in N. hamburgensis X14T contains an invalid base “insertion,” which resulted in a frameshift and a misidentified start codon.

    A novel genotoxin-specific qPCR array based on the metabolically competent human HepaRG™ cell line as a rapid and reliable tool for improved in vitro hazard assessment

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    &lt;p&gt;Although the value of the regulatory accepted batteries for in vitro genotoxicity testing is recognized, they result in a high&lt;/p&gt; &lt;p&gt;number of false positives. This has a major impact on society and industries developing novel compounds for pharmaceutical,&lt;/p&gt; &lt;p&gt;chemical, and consumer products, as afflicted compounds have to be (prematurely) abandoned or further tested on&lt;/p&gt; &lt;p&gt;animals. Using the metabolically competent human HepaRG&lt;/p&gt; &lt;p&gt;™ cell line and toxicogenomics approaches, we have developed&lt;/p&gt; &lt;p&gt;an upgraded, innovative, and proprietary gene classifier. This gene classifier is based on transcriptomic changes induced by&lt;/p&gt; &lt;p&gt;12 genotoxic and 12 non-genotoxic reference compounds tested at sub-cytotoxic concentrations, i.e., IC10 concentrations&lt;/p&gt; &lt;p&gt;as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The resulting gene classifier&lt;/p&gt; &lt;p&gt;was translated into an easy-to-handle qPCR array that, as shown by pathway analysis, covers several different cellular&lt;/p&gt; &lt;p&gt;processes related to genotoxicity. To further assess the predictivity of the tool, a set of 5 known positive and 5 known negative&lt;/p&gt; &lt;p&gt;test compounds for genotoxicity was evaluated. In addition, 2 compounds with debatable genotoxicity data were tested&lt;/p&gt; &lt;p&gt;to explore how the qPCR array would classify these. With an accuracy of 100%, when equivocal results were considered&lt;/p&gt; &lt;p&gt;positive, the results showed that combining HepaRG&lt;/p&gt; &lt;p&gt;™ cells with a genotoxin-specific qPCR array can improve (geno)toxicological&lt;/p&gt; &lt;p&gt;hazard assessment. In addition, the developed qPCR array was able to provide additional information on compounds&lt;/p&gt; &lt;p&gt;for which so far debatable genotoxicity data are available. The results indicate that the new in vitro tool can improve human&lt;/p&gt; &lt;p&gt;safety assessment of chemicals in general by basing predictions on mechanistic toxicogenomics information.&lt;/p&gt;</p

    In silico tools and transcriptomics analyses in the mutagenicity assessment of cosmetic ingredients: a proof-of-principle on how to add weight to the evidence.

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    &lt;p&gt;Prior to the downstream development of chemical substances, including pharmaceuticals and cosmetics, their influence on the genetic apparatus has to be tested. Several in vitro and in vivo assays have been developed to test for genotoxicity. In a first tier, a battery of two to three in vitro tests is recommended to cover mutagenicity, clastogenicity and aneugenicity as main endpoints. This regulatory in vitro test battery is known to have a high sensitivity, which is at the expense of the specificity. The high number of false positive in vitro results leads to excessive in vivo follow-up studies. In the case of cosmetics it may even induce the ban of the particular compound since in Europe the use of experimental animals is no longer allowed for cosmetics. In this article, an alternative approach to derisk a misleading positive Ames test is explored. Hereto we first tested the performance of five existing computational tools to predict the potential mutagenicity of a data set of 132 cosmetic compounds with a known genotoxicity profile. Furthermore, we present, as a proof-of-principle, a strategy in which a combination of computational tools and mechanistic information derived from in vitro transcriptomics analyses is used to derisk a misleading positive Ames test result. Our data shows that this strategy may represent a valuable tool in a weight-of-evidence approach to further evaluate a positive outcome in an Ames test.&lt;/p&gt;</p
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