4,146 research outputs found
Global distribution of modern shallow marine shorelines. Implications for exploration and reservoir analogue studies
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
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
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 , inducing an alternative vector space structure on .Comment: arXiv admin note: text overlap with arXiv:1411.768
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