3,131 research outputs found

    CLCA2 Interactor EVA1 Is Required for Mammary Epithelial Cell Differentiation.

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    CLCA2 is a p53-, p63-inducible transmembrane protein that is frequently downregulated in breast cancer. It is induced during differentiation of human mammary epithelial cells, and its knockdown causes epithelial-to-mesenchymal transition (EMT). To determine how CLCA2 promotes epithelial differentiation, we searched for interactors using membrane dihybrid screening. We discovered a strong interaction with the cell junctional protein EVA1 (Epithelial V-like Antigen 1) and confirmed it by co-immunoprecipitation. Like CLCA2, EVA1 is a type I transmembrane protein that is regulated by p53 and p63. It is thought to mediate homophilic cell-cell adhesion in diverse epithelial tissues. We found that EVA1 is frequently downregulated in breast tumors and breast cancer cell lines, especially those of mesenchymal phenotype. Moreover, knockdown of EVA1 in immortalized human mammary epithelial cells (HMEC) caused EMT, implying that EVA1 is essential for epithelial differentiation. Both EVA1 and CLCA2 co-localized with E-cadherin at cell-cell junctions. The interacting domains were delimited by deletion analysis, revealing the site of interaction to be the transmembrane segment (TMS). The primary sequence of the CLCA2 TMS was found to be conserved in CLCA2 orthologs throughout mammals, suggesting that its interaction with EVA1 co-evolved with the mammary gland. A screen for other junctional interactors revealed that CLCA2 was involved in two different complexes, one with EVA1 and ZO-1, the other with beta catenin. Overexpression of CLCA2 caused downregulation of beta catenin and beta catenin-activated genes. Thus, CLCA2 links a junctional adhesion molecule to cytosolic signaling proteins that modulate proliferation and differentiation. These results may explain how attenuation of CLCA2 causes EMT and why CLCA2 and EVA1 are frequently downregulated in metastatic breast cancer cell lines

    Grist: Grid-based Data Mining for Astronomy

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    The Grist project is developing a grid-technology based system as a research environment for astronomy with massive and complex datasets. This knowledge extraction system will consist of a library of distributed grid services controlled by a work ow system, compliant with standards emerging from the grid computing, web services, and virtual observatory communities. This new technology is being used to find high redshift quasars, study peculiar variable objects, search for transients in real time, and fit SDSS QSO spectra to measure black hole masses. Grist services are also a component of the "hyperatlas" project to serve high-resolution multi-wavelength imagery over the Internet. In support of these science and outreach objectives, the Grist framework will provide the enabling fabric to tie together distributed grid services in the areas of data access, federation, mining, subsetting, source extraction, image mosaicking, statistics, and visualization

    \u3ci\u3eSUB1A\u3c/i\u3e-mediated submergence tolerance response in rice involves differential regulation of the brassinosteroid pathway

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    Submergence 1A (SUB1A), is an ethylene response factor (ERF) that confers submergence tolerance in rice (Oryza sativa) via limiting shoot elongation during the inundation period. SUB1A has been proposed to restrict shoot growth by modulating gibberellic acid (GA) signaling. Our transcriptome analysis indicated that SUB1A differentially regulates genes associated with brassinosteroid (BR) synthesis during submergence. Consistent with the gene expression data, the SUB1A genotype had higher brassinosteroid levels after submergence compared to the intolerant genotype. Tolerance to submergence can be activated in the intolerant genotype by pretreatment with exogenous brassinolide, which results in restricted shoot elongation during submergence. BR induced a GA catabolic gene, resulting in lower GA levels in SUB1A plants. BR treatment also induced the DELLA protein SLR1, a known repressor of GA responses such as shoot elongation. We propose that BR limits GA levels during submergence in the SUB1A rice through a GA catabolic enzyme as part of an early response and may repress GA responses by inducing SLR1 after several days of submergence. Our results suggest that BR biosynthesis is regulated in a SUB1A-dependent manner during submergence and is involved in modulating the GA signaling and homeostasis

    Rocket Sled Based High Speed Rail Track Test Facilities

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    The present study introduces and compares several high-speed track based ground test facilities available all over the world to simulate high-speed dynamic events for selected portions of flight trajectories. The scope of performing high speed flight-testing is addressed, which is followed by the requirements of these track based test facilities. The facilities deliver flight test articles under controlled conditions to achieve high velocity impact, acceleration, aerodynamic and other related testing for small and large test articles depending upon the requirements. Sled is designed in such a way so that it can carry the test articles like aircrafts, payloads, warheads, missiles and many other ballistic systems to achieve high velocities ranging from subsonic to hypersonic by accelerating these sleds using solid rocket motors over the rail track. Such facilities provide instrumentation for large set of trial data acquisition and offline analysis for both recovery and non- recovery (impact) trials, which makes such facilities important for test, research and evaluation purposes. Here, the detailed description of test facilities, which are available in many countries such as India, United States (US), Japan, United Kingdom (UK), France, and others countries based on their technical characteristics is presented. Additionally, a brief history and introduction into basic rocket sled test facility aspects, essential technical characteristics and major features to support high speed testing at these facilities as an accurate testing technique based on quality of construction and engineering design are also covered in this paper. Compilation of available or under development facilities is done in one place which provides the information about facilities’ technological gaps. The paper concludes with an explanation of the role, major capabilities and limitations of these test facilities in the present global scenario

    Image Harvest: an open-source platform for high-throughput plant image processing and analysis

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    High-throughput plant phenotyping is an effective approach to bridge the genotype-to-phenotype gap in crops. Phenomics experiments typically result in large-scale image datasets, which are not amenable for processing on desktop computers, thus creating a bottleneck in the image-analysis pipeline. Here, we present an open-source, flexible image-analysis framework, called Image Harvest (IH), for processing images originating from high-throughput plant phenotyping platforms. Image Harvest is developed to perform parallel processing on computing grids and provides an integrated feature for metadata extraction from large-scale file organization. Moreover, the integration of IH with the Open Science Grid provides academic researchers with the computational resources required for processing large image datasets at no cost. Image Harvest also offers functionalities to extract digital traits from images to interpret plant architecture-related characteristics. To demonstrate the applications of these digital traits, a rice (Oryza sativa) diversity panel was phenotyped and genome-wide association mapping was performed using digital traits that are used to describe different plant ideotypes. Three major quantitative trait loci were identified on rice chromosomes 4 and 6, which co-localize with quantitative trait loci known to regulate agronomically important traits in rice. Image Harvest is an open-source software for high-throughput image processing that requires a minimal learning curve for plant biologists to analyze phenomics datasets. Supplementary files (2) attached below

    Solution processed large area fabrication of Ag patterns as electrodes for flexible heaters, electrochromics and organic solar cells

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    A simple method for producing patterned Ag electrodes on transparent and flexible substrates is reported. The process makes use of a laser printed toner as a sacrificial template for an organic precursor, which upon thermolysis and toner lift off produced highly conducting Ag electrodes. Thus, the process takes only a few minutes without any expensive instrumentation. The electrodes exhibited excellent adhesion and mechanical properties, important for flexible device applications. Using Ag patterned electrodes, heaters operating at low voltages, pixelated electrochromic displays as well as organic solar cells have been demonstrated. The method is extendable to produce defect-free patterns over large areas as demonstrated by roll coating

    Transparent functional oxide stretchable electronics: micro-tectonics enabled high strain electrodes

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    Fully transparent and flexible electronic substrates that incorporate functional materials are the precursors to realising nextgeneration devices with sensing, self-powering and portable functionalities. Here, we demonstrate a universal process for transferring planar, transparent functional oxide thin films on to elastomeric polydimethylsiloxane (PDMS) substrates. This process overcomes the challenge of incorporating high-temperature-processed crystalline oxide materials with low-temperature organic substrates. The functionality of the process is demonstrated using indium tin oxide (ITO) thin films to realise fully transparent and flexible resistors. The ITO thin films on PDMS are shown to withstand uniaxial strains of 15%, enabled by microstructure tectonics. Furthermore, zinc oxide was transferred to display the versatility of this transfer process. Such a ubiquitous process for the transfer of functional thin films to elastomeric substrates will pave the way for touch sensing and energy harvesting for displays and electronics with flexible and transparent characteristics

    Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance

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    Mutations in the P53 pathway are a hallmark of human cancer. The identification of pathways upon which p53-deficient cells depend could reveal therapeutic targets that may spare normal cells with intact p53. In contrast to P53 point mutations in other cancer, complete loss of P53 is a frequent event in osteosarcoma (OS), the most common cancer of bone. The consequences of p53 loss for osteoblastic cells and OS development are poorly understood. Here we use murine OS models to demonstrate that elevated Pthlh (Pthrp), cAMP levels and signalling via CREB1 are characteristic of both p53-deficient osteoblasts and OS. Normal osteoblasts survive depletion of both PTHrP and CREB1. In contrast, p53-deficient osteoblasts and OS depend upon continuous activation of this pathway and undergo proliferation arrest and apoptosis in the absence of PTHrP or CREB1. Our results identify the PTHrP-cAMP-CREB1 axis as an attractive pathway for therapeutic inhibition in OS.Mannu K Walia, Patricia MW Ho, Scott Taylor, Alvin JM Ng, Ankita Gupte, Alistair M Chalk, Andrew CW Zannettino, T John Martin, Carl R Walkle
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