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- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 4. |
- Carninci, P, et al.
(författare)
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The transcriptional landscape of the mammalian genome
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
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Tidskriftsartikel (refereegranskat)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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| 11. |
- Geerts, Bart, et al.
(författare)
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The COMBLE Campaign : A Study of Marine Boundary Layer Clouds in Arctic Cold-Air Outbreaks
- 2022
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 103:5, s. E1371-E1389
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Tidskriftsartikel (refereegranskat)abstract
- One of the most intense air mass transformations on Earth happens when cold air flows from frozen surfaces to much warmer open water in cold-air outbreaks (CAOs), a process captured beautifully in satellite imagery. Despite the ubiquity of the CAO cloud regime over high-latitude oceans, we have a rather poor understanding of its properties, its role in energy and water cycles, and its treatment in weather and climate models. The Cold-Air Outbreaks in the Marine Boundary Layer Experiment (COMBLE) was conducted to better understand this regime and its representation in models. COMBLE aimed to examine the relations between surface fluxes, boundary layer structure, aerosol, cloud, and precipitation properties, and mesoscale circulations in marine CAOs. Processes affecting these properties largely fall in a range of scales where boundary layer processes, convection, and precipitation are tightly coupled, which makes accurate representation of the CAO cloud regime in numerical weather prediction and global climate models most challenging. COMBLE deployed an Atmospheric Radiation Measurement Mobile Facility at a coastal site in northern Scandinavia (69°N), with additional instruments on Bear Island (75°N), from December 2019 to May 2020. CAO conditions were experienced 19% (21%) of the time at the main site (on Bear Island). A comprehensive suite of continuous in situ and remote sensing observations of atmospheric conditions, clouds, precipitation, and aerosol were collected. Because of the clouds’ well-defined origin, their shallow depth, and the broad range of observed temperature and aerosol concentrations, the COMBLE dataset provides a powerful modeling testbed for improving the representation of mixed-phase cloud processes in large-eddy simulations and large-scale models.
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| 12. |
- Arias, C, et al.
(författare)
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Diversity in orthopaedics and traumatology: a global perspective
- 2020
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Ingår i: EFORT open reviews. - : Bioscientifica. - 2058-5241 .- 2396-7544. ; 5:10, s. 743-752
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Tidskriftsartikel (refereegranskat)abstract
- Europe represents true diversity, with cultural, linguistic and geopolitical variation spanning a large geographical area. Politics for many of its 750 million inhabitants revolves around the European Union (EU) and its 27 member states. The overarching goal of the EU is to promote peace and the values of the union (inclusion, tolerance, justice, solidarity and non-discrimination).1,2 EFORT was created to connect orthopaedic associations across Europe, fostering relationships between member countries that celebrated diversity and facilitated the exchange of knowledge. Whilst the global landscape changes and politics attempts to interfere in how we live our lives, it is important to remember that a strong organization is a diverse one that evolves over time. Various initiatives exist across the global landscape to support diversity in terms of culture; gender; black, Asian and minority ethnic (BAME) groups; disability groups; lesbian, gay, bisexual, transgender and queer (or questioning) and others (LGBTQ+); and the ‘ageing’ surgeon. This article explores the creation of some of these initiatives and how they have been supported by different orthopaedic organizations. Cite this article: EFORT Open Rev 2020;5:743-752. DOI: 10.1302/2058-5241.5.200022
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| 15. |
- Kollias, Stefanos, et al.
(författare)
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Machine learning for analysis of real nuclear plant data in the frequency domain
- 2022
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Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- Machine Learning is used in this paper for noise-diagnostics to detect defined anomalies in nuclear plant reactor cores solely from neutron detector measurements. The proposed approach leverages advanced diffusion-based core simulation tools to generate large amounts of simulated data with different types of driving perturbations originating at all theoretically possible locations in the core. Specifically the CORE SIM+ modelling framework is employed, which generates these data in the frequency domain. We train using these vast quantities of simulated data state-of-the-art machine and deep learning models which are used to successfully perform semantic segmentation, classification and localisation of multiple simultaneously occurring in-core perturbations. Actual plant data are then considered, provided by two different reactors, including no labels about perturbation existence. A domain adaptation methodology is subsequently developed to extend the simulated setting to real plant measurements, which uses self-supervised, or unsupervised learning, to align the simulated data with the actual plant data and detect perturbations, whilst classifying their type and estimating their location. Experimental studies illustrate the successful performance of the developed approach and extensions are described that indicate a great potential for further research.
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| 16. |
- Kumari, S., et al.
(författare)
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Tumor Necrosis Factor Receptor Signaling in Keratinocytes Triggers Interleukin-24-Dependent Psoriasis-like Skin Inflammation in Mice
- 2013
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Ingår i: Immunity. - 1074-7613 .- 1097-4180. ; 5:39, s. 899-911
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a common chronic inflammatory skin disease with a prevalence of about 2% in the Caucasian population. Tumor necrosis factor (TNF) plays an essential role in the pathogenesis of psoriasis, but its mechanism of action remains poorly understood. Here we report that the development of psoriasis-like skin inflammation in mice with epidermis-specific inhibition of the transcription factor NF-κB was triggered by TNF receptor 1 (TNFR1)-dependent upregulation of interleukin-24 (IL-24) and activation of signal transducer and activator of transcription 3 (STAT3) signaling in keratinocytes. IL-24 was strongly expressed in human psoriatic epidermis, and pharmacological inhibition of NF-κB increased IL-24 expression in TNF-stimulated human primary keratinocytes, suggesting that this mechanism is relevant for human psoriasis. Therefore, our results expand current views on psoriasis pathogenesis by revealing a new keratinocyte-intrinsic mechanism that links TNFR1, NF-κB, ERK, IL-24, IL-22R1, and STAT3 signaling to disease initiation.
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| 19. |
- Wilm, B. J., et al.
(författare)
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Reduced field-of-view MRI using outer volume suppression for spinal cord diffusion imaging
- 2007
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 57:3, s. 625-630
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Tidskriftsartikel (refereegranskat)abstract
- A spin-echo single-shot echo-planar imaging (SS-EPI) technique with a reduced field of view (FOV) in the phase-encoding direction is presented that simultaneously reduces susceptibility effects and motion artifacts in diffusion-weighted (DW) imaging (DWI) of the spinal cord at a high field strength (3T). To minimize aliasing, an outer volume suppression (OVS) sequence was implemented. Effective fat suppression was achieved with the use of a slice-selection gradient-reversal technique. The OVS was optimized by numerical simulations with respect to T-1 relaxation times and B-1 variations. The optimized sequence was evaluated in vitro and in vivo. In simulations the optimized OVS showed suppression to < 0.25% and similar to 3% in an optimal and worst-case scenario, respectively. In vitro measurements showed a mean residual signal of < 0.95% +/- 0.42 for all suppressed areas. In vivo acquisition with 0.9 x 1.05 mm(2) in-plane resolution resulted in artifact-free images. The short imaging time of this technique makes it promising for clinical studies.
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