1,631 research outputs found

    TGF-beta signaling in onset and progression of hepatocellular carcinoma

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    Transforming growth factor (TGF)-beta is a central regulator in chronic liver disease, contributing to all stages of disease progression from initial liver injury through inflammation and fibrosis to cirrhosis and hepatocellular carcinoma. Liver damage-induced levels of active TGF-beta enhance hepatocyte destruction and mediate hepatic stellate cell and fibroblast activation resulting in a wound-healing response, including myofibroblast generation and extracellular matrix deposition. Further evidence points to a decisive role of cytostatic and apoptotic functions mediated on hepatocytes, which is critical for the control of liver mass, with loss of TGF-beta activities resulting in hyperproliferative disorders and cancer. This concept is based on studies that describe a bipartite role of TGF-beta with tumor suppressor functions at early stages of liver damage and regeneration, whereas during cancer progression TGF-beta may turn from a tumor suppressor into a tumor promoter that exacerbates invasive and metastatic behavior. We have delineated this molecular switch of the pathway from cytostatic to tumor promoting in further detail and identify activation of survival signaling pathways in hepatocytes as a most critical requirement. Targeting the TGF-beta signaling pathway has been explored to inhibit liver disease progression. While interfering with TGF-beta signaling in various short-term animal models has demonstrated promising results, liver disease progression in humans is a process of decades with different phases in which TGF-beta or its targeting may have both beneficial and adverse outcomes. We emphasize that, in order to achieve therapeutic effects, targeting TGF-beta signaling in the right cell type at the right time is required. Copyright © 2012 S. Karger AG, Base

    Double ring-closing approach for the synthesis of 2,3,6,7-substituted anthracene derivatives.

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    A method for the synthesis of 2,3,6,7-substituted anthracene derivatives, one of the most challenging anthracene substitution patterns to obtain, is presented. The method is exemplified by the preparation of 2,3,6,7-anthracenetetracarbonitrile and employs a newly developed, stable, protected 1,2,4,5-benzenetetracarbaldehyde as the precursor. The precursor can be obtained in two scalable synthetic steps from 2,5-dibromoterephthalaldehyde and is converted into the anthracene derivative by a double intermolecular Wittig reaction under very mild conditions, followed by a deprotection and intramolecular double ring-closing condensation reaction

    Finite-temperature magnetism of Fex_xPd1−x_{1-x} and Cox_xPt1−x_{1-x} alloys

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    The finite-temperature magnetic properties of Fex_xPd1−x_{1-x} and Cox_xPt1−x_{1-x} alloys have been investigated. It is shown that the temperature-dependent magnetic behaviour of alloys, composed of originally magnetic and non-magnetic elements, cannot be described properly unless the coupling between magnetic moments at magnetic atoms (Fe,Co) mediated through the interactions with induced magnetic moments of non-magnetic atoms (Pd,Pt) is included. A scheme for the calculation of the Curie temperature (TCT_C) for this type of systems is presented which is based on the extended Heisenberg Hamiltonian with the appropriate exchange parameters JijJ_{ij} obtained from {\em ab-initio} electronic structure calculations. Within the present study the KKR Green's function method has been used to calculate the JijJ_{ij} parameters. A comparison of the obtained Curie temperatures for Fex_xPd1−x_{1-x} and Cox_xPt1−x_{1-x} alloys with experimental data shows rather good agreement.Comment: 10 pages, 12 figure

    Optical Scattering Lengths in Large Liquid-Scintillator Neutrino Detectors

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    For liquid-scintillator neutrino detectors of kiloton scale, the transparency of the organic solvent is of central importance. The present paper reports on laboratory measurements of the optical scattering lengths of the organic solvents PXE, LAB, and Dodecane which are under discussion for next-generation experiments like SNO+, Hanohano, or LENA. Results comprise the wavelength range from 415 to 440nm. The contributions from Rayleigh and Mie scattering as well as from absorption/re-emission processes are discussed. Based on the present results, LAB seems to be the preferred solvent for a large-volume detector.Comment: 9 pages, 3 figures, accepted for publication by Rev. Scient. Instr

    An assessment of sub-snow GPS for quantification of snow water equivalent

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    Global Navigation Satellite Systems (GNSS) contribute to various Earth observation applications. The present study investigates the potential and limitations of the Global Positioning System (GPS) to estimate in situ water equivalents of the snow cover (snow water equivalent, SWE) by using buried GPS antennas. GPS-derived SWE is estimated over three seasons (2015/16–2017/18) at a high Alpine test site in Switzerland. Results are validated against state-of-the-art reference sensors: snow scale, snow pillow, and manual observations. SWE is estimated with a high correspondence to the reference sensors for all three seasons. Results agree with a median relative bias below 10&thinsp;% and are highly correlated to the mean of the three reference sensors. The sensitivity of the SWE quantification is assessed for different GPS ambiguity resolution techniques, as the results strongly depend on the GPS processing.</p

    Analyses and localization of pectin-like carbohydrates in cell wall and mucilage of the green alga Netrium digitus

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    The unicellular, simply shaped desmid Netrium digitus inhabiting acid bog ponds grows in two phases. Prior to division, the cell elongates at its central zone, whereas in a second phase, polar tip growth occurs. Electron microscopy demonstrates that Netrium is surrounded by a morphologically homogeneous cell wall, which lacks pores. Immunocytochemical and biochemical analyses give insight into physical wall properties and, thus, into adaptation to the extreme environment. The monoclonal antibodies JIM5 and JIM7 directed against pectic epitopes with different degrees of esterification label preferentially growing wall zones in Netrium. In contrast, 2F4 marks the cell wall only after experimental de-esterification. Electron energy loss spectroscopy reveals Ca-binding capacities of pectins and gives indirect evidence for the degree of their esterification. An antibody raised against Netrium mucilage is not only specific to mucilage but also recognizes wall components in transmission electron microscopy and dot blots. These results indicate a smooth transition between mucilage and the cell wall in Netrium

    CANVAS: case report on a novel repeat expansion disorder with late-onset ataxia

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    This article presents the case of a 74-year-old female patient who first developed a progressive disease with sensory neuropathy, cerebellar ataxia and bilateral vestibulopathy at the age of 60 years. The family history was unremarkable. Magnetic resonance imaging (MRI) showed atrophy of the cerebellum predominantly in the vermis and atrophy of the spinal cord. The patient was given the syndromic diagnosis of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In 2019 the underlying genetic cause of CANVAS was discovered to be an intronic repeat expansion in the RFC1 gene with autosomal recessive inheritance. The patient exhibited the full clinical picture of CANVAS and was tested positive for this repeat expansion on both alleles. The CANVAS is a relatively frequent cause of late-onset hereditary ataxia (estimated prevalence 5‑13/100,000). In contrast to the present patient, the full clinical picture is not always present. Therefore, testing for the RFC1 gene expansion is recommended in the work-up of patients with otherwise unexplained late-onset sporadic ataxia. As intronic repeat expansions cannot be identified by next generation sequencing methods, specific testing is necessary
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