4,090 research outputs found

    Global distribution of modern shallow marine shorelines. Implications for exploration and reservoir analogue studies

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    Acknowledgments Support for this work came from the SAFARI consortium which was funded by Bayern Gas, ConocoPhillips, Dana Petroleum, Dong Energy, Eni Norge, GDF Suez, Idemitsu, Lundin, Noreco, OMV, Repsol, Rocksource, RWE, Statoil, Suncor, Total, PDO, VNG and the Norwegian Petroleum Directorate (NPD). This manuscript has benefited from discussion with Bruce Ainsworth, Rachel Nanson and Christian Haug Eide. Boyan Vakarelov and Richard Davis Jr. are thanked for their constructive reviews and valuable comments that helped to improve the manuscript.Peer reviewedPostprin

    Mechanisms of type I interferons in autoimmunity and cancer

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    Interferons (IFNs) were first described in the 1950’s and has since been characterized as potent inducers of pathogen defense mechanisms. Since then, researchers have uncovered a depth of mechanisms in the IFN system extending beyond immune modulation of pathogen defense. IFNs have been described to play a role in the control of cell homeostasis as well as contributing to both the natural defense against cancer and cancer progression. The objective of the work performed in this thesis was to understand how type I IFNs are able to contribute to such a wide range of biological processes and to investigate metastatic progression of malignant melanoma. We first performed screens of miRNAs on sorted immune cells from patients treated with IFNβ. We identified miR-31-5p to be downregulated in T cells of patients treated with IFNβ. miR-31-5p was also decreased in patients with autoimmune disease, characterized by an IFN signature, further proving type I IFN regulation of miR-31-5p expression levels. We were able to show that miR-31-5p regulate metabolism of CD4+ T cells. In an attempt to get new insights into IFNAR1 signaling, we applied proximity proteomics techniques to IFNAR1. Labeled proteins were extracted and subsequently analyzed using quantitative mass spectrometry. We successfully generated interactome data that revealed insights to a possible nuclear translocation mechanism of ligand bound IFNAR1. Bromodomain (BRD) proteins are chromatin bound proteins that regulate a multitude of processes important in transcriptional regulation and epigenetic regulation of gene expression. Several BRD proteins regulate the expression of type I IFN genes and are emerging targets for new cancer drugs. We therefore aimed to identify BRD proteins that play a role in metastatic progression and plasticity of malignant melanoma. We identified that the BRD protein TRIM28 controls a plasticity switch of melanoma cells through expression of JunB. Plasticity switching of melanoma cells represent a model of metastatic progression. Recently, the role of ER stress in both protecting and killing tumors has been highlighted. We therefore aimed to identify new small molecules capable of inducing strong ER stress. We identified the IFN-inducing small molecule IMQ as a potent ER stress inducer in melanoma cells independently of TLR7/8 expression. ER stress induced by IMQ in melanoma cells lead to cell death and represents a possible pharmaceutical strategy to target and kill cancer cells. In summary, our studies provide insights to type I IFN driven mechanisms with implications for autoimmune disease and cancer

    On differential uniformity of maps that may hide an algebraic trapdoor

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    We investigate some differential properties for permutations in the affine group, of a vector space V over the binary field, with respect to a new group operation \circ, inducing an alternative vector space structure on VV .Comment: arXiv admin note: text overlap with arXiv:1411.768

    Fiber flex

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    New bend on budding

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    Gradient upon gradient

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    Totally tubular chitin

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    Axon size matters

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    Tilted tubules

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