1,989,415 research outputs found

    Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice

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    Biochemical studies have suggested conflicting roles for the E3 ubiquitin ligase constitutive photomorphogenesis protein 1 (Cop 1; also known as Rfwd2) in tumorigenesis, providing evidence for both the oncoprotein c-Jun and the tumor suppressor p53 as its targets. Here we present what we believe to be the first in vivo investigation of the role of Cop1 in cancer etiology. Using an innovative genetic approach to generate an allelic series of Cop1, we found that Cop1 hypomorphic mice spontaneously developed malignancy at a high frequency in the first year of life and were highly susceptible to radiation-induced lymphomagenesis. Further analysis revealed that c-Jun was a key physiological target for Cop1 and that Cop1 constitutively kept c-Jun at low levels in vivo and thereby modulated c-Jun/AP-1 transcriptional activity. Importantly, Cop1 deficiency stimulated cell proliferation in a c-Jun-dependent manner. Focal deletions of COP1 were observed at significant frequency across several cancer types, and COP1 loss was determined to be one of the mechanisms leading to c-Jun upregulation in human cancer. We therefore conclude that Cop1 is a tumor suppressor that functions, at least in part, by antagonizing c-Jun oncogenic activity. In the absence of evidence for a genetic interaction between Cop1 and p53, our data strongly argue against the use of Cop1-inhibitory drugs for cancer therapy

    Production of Gas Phase Zinc Oxide Nanoclusters by Pulsed Laser Ablation

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    We present experimental results on the photoluminescence (PL) of gas-suspended zinc oxide nanoclusters prepared during ablation of sintered ZnO targets by a pulsed ArF laser in the presence of oxygen ambient gas. The PL spectra in the UV spectral region correspond to the exciton recombination in the nanoclusters which are crystallized and cooled down to the temperature of the ambient gas in the ablation chamber. The time evolution of the spectra as well as their dependence on the ambient gas pressure are discussed.Comment: EMRS-2004, Strasbourg, France. Paper N-I.

    Defining a robust biological prior from Pathway Analysis to drive Network Inference

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    Inferring genetic networks from gene expression data is one of the most challenging work in the post-genomic era, partly due to the vast space of possible networks and the relatively small amount of data available. In this field, Gaussian Graphical Model (GGM) provides a convenient framework for the discovery of biological networks. In this paper, we propose an original approach for inferring gene regulation networks using a robust biological prior on their structure in order to limit the set of candidate networks. Pathways, that represent biological knowledge on the regulatory networks, will be used as an informative prior knowledge to drive Network Inference. This approach is based on the selection of a relevant set of genes, called the "molecular signature", associated with a condition of interest (for instance, the genes involved in disease development). In this context, differential expression analysis is a well established strategy. However outcome signatures are often not consistent and show little overlap between studies. Thus, we will dedicate the first part of our work to the improvement of the standard process of biomarker identification to guarantee the robustness and reproducibility of the molecular signature. Our approach enables to compare the networks inferred between two conditions of interest (for instance case and control networks) and help along the biological interpretation of results. Thus it allows to identify differential regulations that occur in these conditions. We illustrate the proposed approach by applying our method to a study of breast cancer's response to treatment

    Definition, Measurement and Determinants of the Consumer's Willingness to Pay: a Critical Synthesis and Directions for Further Research

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    Differentiated prices, bundling, Web auctions : firms' pricing practices are evolving. When there is no market or for customised pricing, the willingness-to-pay concept seems to be interesting. This article aims at presenting a synthesis of the marketing research stream relative to willingness to pay. First, a definition of the concept is given and compared to other similar concepts, notably reference price and acceptable price. Then the methods of measurement are presented, compared to those used to measure elasticity and criticized. Furthermore, the research on external determinants of willingness to pay is commented. Finally, numerous directions for further research are proposed.willingness to pay, price elasticity, reference price, acceptable price, conjoint analysis, contingent valuation, Vickrey auctions, BDM lottery, prices

    Ocean Industries and Marine Planning

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    Marine planning (marine spatial planning/MSP) is under development as a viable tool to address potential user conflicts in the oceans and allow for better management of ocean uses and resources. With marine planning developing in many parts of the world, especially the E.U., U.S. and Australia, it is important for industry to be part of the creation of a shared vision for a marine area, the discussion regarding whether or not to pursue a planning or other improved management effort, and the necessary elements (e.g., outreach, funding, boundaries) of such an effort. World Ocean Council, with funding from the Gordon and Betty Moore Foundation, undertook a project to inform and, as appropriate, engage a diverse range of ocean industries on marine planning and encourage the use of credible science and risk assessment. With information gathered through literature reviews, case studies, interviews, and outreach, this paper presents potential benefits of and concerns regarding marine planning from the ocean business perspective. It also offers considerations for industry to consider its role in marine planning and for planners on how and why to engage the private sector

    Marine yeast isolation and industrial application

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    Over the last century, terrestrial yeasts have been widely used in various industries, such as baking, brewing, wine, bioethanol and pharmaceutical protein production. However, only little attention has been given to marine yeasts. Recent research showed that marine yeasts have several unique and promising features over the terrestrial yeasts, for example higher osmosis tolerance, higher special chemical productivity and production of industrial enzymes. These indicate that marine yeasts have great potential to be applied in various industries. This review gathers the most recent techniques used for marine yeast isolation as well as the latest applications of marine yeast in bioethanol, pharmaceutical and enzyme production fields. Keyword

    Perceptions of the Maltese public towards local Marine Protected Areas

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    The marine environment represents a central component of Malta's local environment, and its ecosystem services play a vital role in supporting the economy as well as human well-being. Plans have been made to protect the unique ecology found within Maltese waters through the institution of five marine protected areas (MPAs). This quantitative study assessed the environmental knowledge and attitudes of the Maltese public towards the local marine environment, MPAs and education for sustainable development (ESD). A questionnaire was administered to members of the public (n = 200) at three different locations. The study found that although the Maltese public strongly appreciates the beauty of Malta's marine environment, the level of knowledge surrounding the marine environment is low. Furthermore, the research indicates that while the public agrees that the marine environment should be protected, there is a notable lack of awareness of the five local MPAs. Based on the research findings, a model linking ESD to MPAs and aiming to foster a sense of ownership among the public by encouraging their involvement in the management of local MPAs is proposed.peer-reviewe
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