367 research outputs found

    Systematic analysis of the binding behaviour of UHRF1 towards different methyl- and carboxylcytosine modification patterns at CpG dyads

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    The multi-domain protein UHRF1 is essential for DNA methylation maintenance and binds DNA via a base-flipping mechanism with a preference for hemi-methylated CpG sites. We investigated its binding to hemi- and symmetrically modified DNA containing either 5-methylcytosine (mC), 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), or 5-carboxylcytosine (caC). Our experimental results indicate that UHRF1 binds symmetrically carboxylated and hybrid methylated/carboxylated CpG dyads in addition to its previously reported substrates. Complementary molecular dynamics simulations provide a possible mechanistic explanation of how the protein could differentiate between modification patterns. First, we observe different local binding modes in the nucleotide binding pocket as well as the protein's NKR finger. Second, both DNA modification sites are coupled through key residues within the NKR finger, suggesting a communication pathway affecting protein-DNA binding for carboxylcytosine modifications. Our results suggest a possible additional function of the hemi-methylation reader UHRF1 through binding of carboxylated CpG sites. This opens the possibility of new biological roles of UHRF1 beyond DNA methylation maintenance and of oxidised methylcytosine derivates in epigenetic regulation

    Nan-O-Style – experiments and arts

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    In this project, high school students (aged 16-17) tested various protocols of experiments in nanotechnology and evaluated them whether such experiments could also be performed by middle school students (aged 11-15) or even elementary school students (aged 6-10). Protocols pre-selected and provided by the instructing team consisting of Sciencetainment and the Department of Biosciences, University of Salzburg were applied. Laboratory techniques such as thin-layer chromatography, measuring the contact angle by high-resolution 3D microscopy and analyzing and constructing surface layers represented some of the experiments performed. Moreover, students produced short video clips and images and designed photo-collages out of microscopic and electron microscopic pictures. Hence, the school students acquired a number of soft skills during this special science day

    Studying the transfer mechanisms of water based top-of-rail products in a wheel/rail interaction

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    The railway industry uses top-of-rail products to control and manage the friction in the wheel/rail interface to help ensure efficient train operations and reduce wheel and rail damage. A product is typically applied from a wayside applicator that pumps a puddle onto the rail head where a passing wheel will pick it up and then transfer it down the track. The aim of this study was to study the transfer mechanisms of water-based top-of-rail friction modifiers (TOR-FMs) and how they are linked to the friction conditions in the wheel/rail interface. The transfer mechanisms were split into three parts: pick-up, carry-on and consumption. Pick-up looks at how the product transfers from the puddle on the rail to a wheel tread, whereas the carry-on mechanism relates to the product transfer back to the wheel. Consumption focuses on the removal rate of the product layer from the wheel or rail. A full-scale rig and twin disc machine were chosen to perform the tests because each rig could give different insights into understanding the product transfer mechanisms. Two products were tested of similar formulation. Results show that there are differences in the transfer and friction between the two products despite them being relatively similar. The test methods developed can clearly resolve differences between varying product types, which could be useful for product development studies or approvals work. The outcomes could also be used to develop a model of transfer/consumption

    Segmentation-based regularization of dynamic SPECT reconstructions

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    Abstract-Dynamic SPECT reconstruction using a single slow camera rotation is a highly underdetermined problem, which requires the use of regularization techniques to obtain useful results. The dSPECT algorithm We test this approach with a digital phantom simulating the kinetics of Tc99m-DTPA in the renal system, including healthy and unhealthy behaviour. Summed TACs for each kidney and the bladder were calculated for the spatially regularized and nonregularized reconstructions, and compared to the true values. The TACs for the two kidneys were noticeably improved in every case, while TACs for the smaller bladder region were unchanged. Furthermore, in two cases where the segmentation was intentionally done incorrectly, the spatially regularized reconstructions were still as good as the non-regularized ones. In general, the segmentation-based regularization improves TAC quality within ROIs, as well as image contrast

    Virgo calibration and reconstruction of the gravitational wave strain during VSR1

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    Virgo is a kilometer-length interferometer for gravitational waves detection located near Pisa. Its first science run, VSR1, occured from May to October 2007. The aims of the calibration are to measure the detector sensitivity and to reconstruct the time series of the gravitational wave strain h(t). The absolute length calibration is based on an original non-linear reconstruction of the differential arm length variations in free swinging Michelson configurations. It uses the laser wavelength as length standard. This method is used to calibrate the frequency dependent response of the Virgo mirror actuators and derive the detector in-loop response and sensitivity within ~5%. The principle of the strain reconstruction is highlighted and the h(t) systematic errors are estimated. A photon calibrator is used to check the sign of h(t). The reconstructed h(t) during VSR1 is valid from 10 Hz up to 10 kHz with systematic errors estimated to 6% in amplitude. The phase error is estimated to be 70 mrad below 1.9 kHz and 6 micro-seconds above.Comment: 8 pages, 8 figures, proceedings of Amaldi 8 conference, to be published in Journal of Physics Conference Series (JPCS). Second release: correct typo

    Mental health care for irregular migrants in Europe: Barriers and how they are overcome

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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