283 research outputs found

    Polymer photonic sensing skin

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    A highly flexible sensing skin with embedded polymer optical fibre Bragg gratings is characterised The response to pressure and strain compare favourably to a similar skin instrumented with silica fibre Bragg grating sensors

    Axial spectral scans of polarization dependent third harmonic generation in a multimode photonic crystal fiber

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    We demonstrate a nondestructive axial scanning technique for the spectrally resolved analysis of femtosecond nonlinear-optical transformation in photonic crystal fibers. This technique is applied to map the generation of a polarization-switched third harmonic of femtosecond Cr:forsterite laser pulses in a multimode silica photonic crystal fiber. Obtained results confirmed the intermodal phase-matching to be responsible for the observed polarization dependent multipeak third-harmonic generation. The axial scans revealed, that it is necessary to distinguish between the low and high energy excitation regime of the fiber sample. The proposed technique allows to measure the spectra of nonlinear signals generated in a photonic crystal fiber as a function of the propagation distance without cutting the fiber

    Metabolic impairment of non-small cell lung cancers by mitochondrial HSPD1 targeting

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    Background!#!The identification of novel targets is of paramount importance to develop more effective drugs and improve the treatment of non-small cell lung cancer (NSCLC), the leading cause of cancer-related deaths worldwide. Since cells alter their metabolic rewiring during tumorigenesis and along cancer progression, targeting key metabolic players and metabolism-associated proteins represents a valuable approach with a high therapeutic potential. Metabolic fitness relies on the functionality of heat shock proteins (HSPs), molecular chaperones that facilitate the correct folding of metabolism enzymes and their assembly in macromolecular structures.!##!Methods!#!Gene fitness was determined by bioinformatics analysis from available datasets from genetic screenings. HSPD1 expression was evaluated by immunohistochemistry from formalin-fixed paraffin-embedded tissues from NSCLC patients. Real-time proliferation assays with and without cytotoxicity reagents, colony formation assays and cell cycle analyses were used to monitor growth and drug sensitivity of different NSCLC cells in vitro. In vivo growth was monitored with subcutaneous injections in immune-deficient mice. Cell metabolic activity was analyzed through extracellular metabolic flux analysis. Specific knockouts were introduced by CRISPR/Cas9.!##!Results!#!We show heat shock protein family D member 1 (HSPD1 or HSP60) as a survival gene ubiquitously expressed in NSCLC and associated with poor patients' prognosis. HSPD1 knockdown or its chemical disruption by the small molecule KHS101 induces a drastic breakdown of oxidative phosphorylation, and suppresses cell proliferation both in vitro and in vivo. By combining drug profiling with transcriptomics and through a whole-genome CRISPR/Cas9 screen, we demonstrate that HSPD1-targeted anti-cancer effects are dependent on oxidative phosphorylation and validated molecular determinants of KHS101 sensitivity, in particular, the creatine-transporter SLC6A8 and the subunit of the cytochrome c oxidase complex COX5B.!##!Conclusions!#!These results highlight mitochondrial metabolism as an attractive target and HSPD1 as a potential theranostic marker for developing therapies to combat NSCLC

    Characterizations and first plasma operation of the WEST load-resilient actively cooled ICRF launchers

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    The paper discusses the characterization of the three high power steady-state and load-resilient ICRF launchers of WEST before their installation in the tokamak. These launchers have been characterized and validated in low-power experiments (milliwatt range) as well as in experiments at the nominal RF voltages and currents in the TITAN vacuum chamber (~30 kV and 915 A peak). The successful commissioning of two of the launchers during the WEST C3 campaign at ~1 MW power level is illustrated. Manual and real-time controlled impedance-matching of the launchers are discussed, as well as the validation of their load-resilience. Furthermore, several redundant and complementary protection systems have been validated and are reviewed in the paper

    The LAGUNA design study- towards giant liquid based underground detectors for neutrino physics and astrophysics and proton decay searches

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    The feasibility of a next generation neutrino observatory in Europe is being considered within the LAGUNA design study. To accommodate giant neutrino detectors and shield them from cosmic rays, a new very large underground infrastructure is required. Seven potential candidate sites in different parts of Europe and at several distances from CERN are being studied: Boulby (UK), Canfranc (Spain), Fr\'ejus (France/Italy), Pyh\"asalmi (Finland), Polkowice-Sieroszowice (Poland), Slanic (Romania) and Umbria (Italy). The design study aims at the comprehensive and coordinated technical assessment of each site, at a coherent cost estimation, and at a prioritization of the sites within the summer 2010.Comment: 5 pages, contribution to the Workshop "European Strategy for Future Neutrino Physics", CERN, Oct. 200

    A candidate gene survey of quantitative trait loci affecting chemical composition in tomato fruit

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    In tomato, numerous wild-related species have been demonstrated to be untapped sources of valuable genetic variability, including pathogen-resistance genes, nutritional, and industrial quality traits. From a collection of S. pennellii introgressed lines, 889 fruit metabolic loci (QML) and 326 yield-associated loci (YAL), distributed across the tomato genome, had been identified previously. By using a combination of molecular marker sequence analysis, PCR amplification and sequencing, analysis of allelic variation, and evaluation of co-response between gene expression and metabolite composition traits, the present report, provides a comprehensive list of candidate genes co-localizing with a subset of 106 QML and 20 YAL associated either with important agronomic or nutritional characteristics. This combined strategy allowed the identification and analysis of 127 candidate genes located in 16 regions of the tomato genome. Eighty-five genes were cloned and partially sequenced, totalling 45ā€‰816 and 45ā€‰787 bases from S. lycopersicum and S. pennellii, respectively. Allelic variation at the amino acid level was confirmed for 37 of these candidates. Furthermore, out of the 127 gene-metabolite co-locations, some 56 were recovered following correlation of parallel transcript and metabolite profiling. Results obtained here represent the initial steps in the integration of genetic, genomic, and expressional patterns of genes co-localizing with chemical compositional traits of the tomato fruit

    An Arthroscopic Device to Assess Articular Cartilage Defects and Treatment with a Hydrogel

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    The hydraulic resistance R across osteochondral tissue, especially articular cartilage, decreases with degeneration and erosion. Clinically useful measures to quantify and diagnose the extent of cartilage degeneration and efficacy of repair strategies, especially with regard to pressure maintenance, are still developing. The hypothesis of this study was that hydraulic resistance provides a quantitative measure of osteochondral tissue that could be used to evaluate the state of cartilage damage and repair. The aims were to (1) develop a device to measure R in an arthroscopic setting, (2) determine whether the device could detect differences in R for cartilage, an osteochondral defect, and cartilage treated using a hydrogel ex vivo, and (3) determine how quickly such differences could be discerned. The apparent hydraulic resistance of defect samples was ~35% less than intact cartilage controls, while the resistance of hydrogel-filled groups was not statistically different than controls, suggesting some restoration of fluid pressurization in the defect region by the hydrogel. Differences in hydraulic resistance between control and defect groups were apparent after 4Ā s. The results indicate that the measurement of R is feasible for rapid and quantitative functional assessment of the extent of osteochondral defects and repair. The arthroscopic compatibility of the device demonstrates the potential for this measurement to be made in a clinical setting

    Metal hydrides for concentrating solar thermal power energy storage

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    The development of alternative methods for thermal energy storage is important for improving the efficiency and decreasing the cost for Concentrating Solar-thermal Power (CSP). We focus on the underlying technology that allows metal hydrides to function as Thermal Energy Storage (TES) systems and highlight the current state-of-the-art materials that can operate at temperatures as low as room-temperature and as high as 1100 oC. The potential of metal hydrides for thermal storage is explored while current knowledge gaps about hydride properties, such as hydride thermodynamics, intrinsic kinetics and cyclic stability, are identified. The engineering challenges associated with utilising metal hydrides for high-temperature thermal energy storage are also addressed

    Analysis of subcellular metabolite levels of potato tubers (Solanum tuberosum) displaying alterations in cellular or extracellular sucrose metabolism

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    The expression of a heterologous invertase in potato tubers (Solanum tuberosum) in either the cytosol or apoplast leads to a decrease in total sucrose content and to an increase in glucose. Depending on the targeting of the enzyme different changes in phenotype and metabolism of the tubers occur: the cytosolic invertase expressing tubers show an increase in the glycolytic flux, accumulation of amino acids and organic acids, and the appearance of novel disaccharides; however, these changes are not observed when the enzyme is expressed in the apoplast [Roessner etĀ al. (2001). Plant Cell, 13, 11-29]. The analysis of these lines raised several questions concerning the regulation of compartmentation of metabolites in potato tubers. In the current study we addressed these questions by performing comparative subcellular metabolite profiling. We demonstrate that: (i) hexoses accumulate in the vacuole independently of their site of production, but that the cytosolic invertase expression led to a strong increase in the cytosolic glucose concentration and decrease in cytosolic sucrose, whereas these effects were more moderate in the apoplastic expressors; (ii) three out of four of the novel compounds found in the cytosolic overexpressors accumulate in the same compartment; (iii) despite changes in absolute cellular content the subcellular distribution of amino acids was invariant in the invertase overexpressing tubers. These results are discussed in the context of current models of the compartmentation of primary metabolism in heterotrophic plant tissues
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