130 research outputs found

    Confined hydration in nanometer-graded plasma polymer films: Insights from surface-enhanced infrared absorption spectroscopy

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    To shed light on recently explored long-range surface forces generated by subsurface-confined water, the structural characteristics of water molecules penetrating into nanoporous homogeneous and nanograded siloxane plasma polymer films (PPFs) over the time scale of 24 hours are studied by surface-enhanced IR spectroscopy (SEIRAS). Chemically graded PPFs, with embedded hydrophobic-to-hydrophilic gradient, are found to significantly change the average interfacial water orientation due to a unique nanoporous morphology and silanol group coordination. Diffusion of water through the hydrophobic SiO:CH matrix creates an evolution of the coordination of matrix silanol groups, which are eventually deprotonated as soon as the hydration network connects to the aqueous environment. This occurs after -6 hours of water immersion and coincides with the change of average interfacial water orientation. Both effects are present on hydrophobic samples, but are significantly amplified by the presence of the subsurface vertical amphiphilic gradient (Vgrad), whereas enhanced water uptake in oxygen-plasma modified graded PPFs is covering such effects

    Establishment of a patient-derived orthotopic osteosarcoma mouse model

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    Background: Osteosarcoma (OS) is the most common pediatric primary malignant bone tumor. As the prognosis for patients following standard treatment did not improve for almost three decades, functional preclinical models that closely reflect important clinical cancer characteristics are urgently needed to develop and evaluate new treatment strategies. The objective of this study was to establish an orthotopic xenotransplanted mouse model using patient-derived tumor tissue. Methods: Fresh tumor tissue from an adolescent female patient with osteosarcoma after relapse was surgically xenografted into the right tibia of 6 immunodeficient BALB/c Nu/Nu mice as well as cultured into medium. Tumor growth was serially assessed by palpation and with magnetic resonance imaging (MRI). In parallel, a primary cell line of the same tumor was established. Histology and high-resolution array-based comparative genomic hybridization (aCGH) were used to investigate both phenotypic and genotypic characteristics of different passages of human xenografts and the cell line compared to the tissue of origin. Results: A primary OS cell line and a primary patient-derived orthotopic xenotranplanted mouse model were established. MRI analyses and histopathology demonstrated an identical architecture in the primary tumor and in the xenografts. Array-CGH analyses of the cell line and all xenografts showed highly comparable patterns of genomic progression. So far, three further primary patient-derived orthotopic xenotranplanted mouse models could be established. Conclusion: We report the first orthotopic OS mouse model generated by transplantation of tumor fragments directly harvested from the patient. This model represents the morphologic and genomic identity of the primary tumor and provides a preclinical platform to evaluate new treatment strategies in OS

    An element through the looking glass: Exploring the Au-C, Au-H and Au-O energy landscape

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    Gold, the archetypal “noble metal”, used to be considered of little interest in catalysis. It is now clear that this was a misconception, and a multitude of gold-catalysed transformations has been reported. However, one consequence of the long-held view of gold as inert metal is that its organometallic chemistry contains many “unknowns”, and catalytic cycles devised to explain gold's reactivity draw largely on analogies with other transition metals. How realistic are such mechanistic assumptions? In the last few years a number of key compound classes have been discovered that can provide some answers. This Perspective attempts to summarise these developments, with particular emphasis on recently discovered gold(III) complexes with bonds to hydrogen, oxygen, alkenes and CO ligands

    Redirecting T Cells to Ewing's Sarcoma Family of Tumors by a Chimeric NKG2D Receptor Expressed by Lentiviral Transduction or mRNA Transfection

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    We explored the possibility to target Ewing's sarcoma family of tumors (ESFT) by redirecting T cells. To this aim, we considered NKG2D-ligands (NKG2D-Ls) as possible target antigens. Detailed analysis of the expression of MICA, MICB, ULBP-1, -2, and -3 in fourteen ESFT cell lines revealed consistent expression of at least one NKG2D-L. Thus, for redirecting T cells, we fused a CD3ζ/CD28-derived signaling domain to the ectodomain of NKG2D, however, opposite transmembrane orientation of this signaling domain and NKG2D required inverse orientation fusion of either of them. We hypothesized that the particularly located C-terminus of the NKG2D ectodomain should allow reengineering of the membrane anchoring from a native N-terminal to an artificial C-terminal linkage. Indeed, the resulting chimeric NKG2D receptor (chNKG2D) was functional and efficiently mediated ESFT cell death triggered by activated T cells. Notably, ESFT cells with even low NKG2D-L expression were killed by CD8pos and also CD4pos cells. Both, mRNA transfection and lentiviral transduction resulted in high level surface expression of chNKG2D. However, upon target-cell recognition receptor surface levels were maintained by tranfected RNA only during the first couple of hours after transfection. Later, target-cell contact resulted in strong and irreversible receptor down-modulation, whereas lentivirally mediated expression of chNKG2D remained constant under these conditions. Together, our study defines NKG2D-Ls as targets for a CAR-mediated T cell based immunotherapy of ESFT. A comparison of two different methods of gene transfer reveals strong differences in the susceptibility to ligand-induced receptor down-modulation with possible implications for the applicability of RNA transfection

    Sarcoma classification by DNA methylation profiling

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    Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications

    Stereo Evaluation of Cartosat-1 Data for French and Catalonian Test Sites

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    DLR's Remote Sensing Technology Institute has more than 20 years of experience in developing spaceborne stereo scanners (MEOSS, MOMS) and the corresponding stereo evaluation software systems. It takes part in the CARTOSAT-1 Scientific Assessment Program (C-SAP) as a principal investigator for a Catalonian test site (TS-10) and as Co-Investigator for a French test site (TS-5, Mausanne-les-Alpilles). Rational polynomial coefficients (RPC) are provided by the distributing Indian agency as a universal sensor model for each scene of the CARTOSAT-1 stereo pairs. These RPC have to be corrected via ground control points (GCP) as they are derived from orbit and attitude information with an accuracy far worse than the pixel size of 2.5 m (normally, post facto pointing accuracy is in the range of a few hundred meters). GCP of sufficient (sub-pixel) accuracy are derived from high-resolution orthoimages of the Catalonian Survey Institute (ICC) and from JRC DGPS campaigns, respectively. The GCP are identified in the aft images of the stereo pairs because of their superior radiometric quality and then transferred to the fore images via local least squares matching. From these GCP an affine correction to the delivered RPC is estimated. The residual vectors at the GCP are reduced to sub-pixel values. Because of zero denominator problems with the original RPC in small regions of the stereo pairs new RPC are estimated Using the corrected RPC and mass tie points from automatic image matching the digital surface models (DSM) are derived from the CARTOSAT-1 stereo pairs via forward intersection and subsequent interpolation. These DSM are compared to the available sufficiently accurate DEM/DSM provided by ICC and JRC. For the comparison a 3D shift between the individual DSM is estimated via least squares adjustment. Height accuracies (in terms of 1 σ) of 2.5-4 m are achieved. The shifts between the orthoimages of the two looking directions computed on the basis of the reference DEM and the computed DSM are assessed via image matching and are found to be in sub-pixel range

    Comparison of DSM generation methods of urban areas from IKONOS images

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    In this paper two methods, an area based matching and a so called dynamic line warping, for generating digital surface models (DSMs) from IKONOS image pairs are compared and their limitations and usability for the rapid generation of good DSMs are discussed. The new dynamic line warping method is based on techniques used in speech recognition for warping corresponding epipolar lines of the stereo images onto each other in order to extract so parallaxes and object heights. One critical parameter for the derivation of DSMs is the convergence angle of the two stereo images. A small convergence angle gives similar images with smaller parallaxes and is better for area based matching techniques but is said to result in larger height errors and lacks of views from vertical features like walls. A large convergence angle - as used in the standard stereo products of most satellite image providers - on the other hand leads in urban areas to many features hidden in one or the other image and very different viewing conditions leading to more problems for intensity based matching. Therefore three IKONOS scenes with different convergence angles are used and the results are compared qualitatively

    Stereo Evaluation of CARTOSAT-1 Data Summary of DLR Results During CARTOSAT-1 Scientific Assessment Program

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    The Remote Sensing Technology Institute (IMF) of the German Aerospace Center (DLR) has more than 20 years of history in developing spaceborne stereo scanners and the corresponding stereo evaluation software systems. It takes part in the CARTOSAT-1 Scientific Assessment Program (C-SAP) as a principal investigator for German (Southeast Bavaria) and Spanish (Catalonia) test sites and as a Co-I for a French test site (Mausanne-les-Alpilles). A rich variety of landscapes is present in these three test sites. In all cases ground truth in form of GCP (or orthoimages of high resolution) and DTM/DSM (digital terrain or surface models) of sufficient accuracy have been delivered by the principal investigators.Rational polynomial functions (RPC) are provided by the distributing Indian agency (Space Applications Centre (SAC) of ISRO, Ahmedabad) as a universal sensor model for each scene. The inherent absolute orientation accuracy of the RPC models in the CARTOSAT-1 stereo imagery used here turned out to be around 100 m (normally). Thus, to exploit the high resolution of 2.5 m, RPC have to be corrected via the available ground truth. It is shown that the correction by an affine transformation is necessary in order to achieve sub-pixel accuracy in the stereo evaluation of full scenes. The remaining standard deviations of the residuals in image space during RPC correction are about 0.5-1 pixel in ground control points (GCP). Stereo evaluation is done by DLR processing software. Hierarchical intensity based matching and subsequent region growing are used to automatically derive a dense set of stereo tie points. An effective blunder reduction is based upon bi-directional LSM, quasi-epipolar reprojection of the tie points, and control of residuals in stereo forward intersection. Shifts between aft/fore orthoimages are found to be in sub-pixel range. DSM accuracy assessment is done via the statistics of height differences compiled by the forward intersection software. This is sufficient if accurate GCP for RPC correction are available. For direct comparison of the generated DSM with the reference DTM/DSM a 3D shift is estimated via least squares adjustment and mean and standard deviations of the DTM/DSM differences after shifting are provided. In summary, standard deviations of 2-4 m are achieved
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