| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 5. |
- Adamo, Christin S., et al.
(author)
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EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis
- 2022
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 109:12, s. 2230-2252
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Journal article (peer-reviewed)abstract
- EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.
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| 6. |
- Arheimer, Berit, et al.
(author)
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The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
- 2024
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In: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
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Journal article (peer-reviewed)abstract
- The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
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| 8. |
- Gong, Lebing
(author)
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Large-scale Runoff Generation and Routing : Efficient Parameterisation using High-resolution Topography and Hydrography
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Water has always had a controlling influence on the earth’s evolution. Understanding and modelling the large-scale hydrological cycle is important for climate prediction and water-resources studies. In recent years large-scale hydrological models, including the WASMOD-M evaluated in the thesis, have increasingly become a main assessment tool for global water resources.The monthly version of WASMOD-M, the starting point of the thesis, revealed restraints imposed by limited hydrological and climate data quality and the need to reduce model-structure uncertainties. The model simulated the global water balance with a small volume error but was less successful in capturing the dynamics. In the last years, global high-quality, high-resolution topographies and hydrographies have become available. The main thrust of the thesis was the development of a daily WASMOD-M making use of these data to better capture the global water dynamics and to parameterise local non-linear processes into the large-scale model. Scale independency, parsimonious model structure, and computational efficiency were main concerns throughout the model development.A new scale-independent routing algorithm, named NRF for network-response function, using two aggregated high-resolution hydrographies, HYDRO1k and HydroSHEDS, was developed and tested in three river basins with different climates in China and North America. The algorithm preserves the spatially distributed time-delay information in the form of simple network-response functions for any low-resolution grid cell in a large-scale hydrological model.A distributed runoff-generation algorithm, named TRG for topography-derived runoff generation, was developed to represent the highly non-linear process at large scales. The algorithm, when inserted into the daily WASMOD-M and tested in same three basins, led to the same or a slightly improved performance compared to a one-layer VIC model, with one parameter less to be calibrated. The TRG algorithm also offered a more realistic spatial pattern for runoff generation.The thesis identified significant improvements in model performance when 1) local instead of global climate data were used, and 2) when the scale-independent NRF routing algorithm was used instead of a traditional storage-based routing algorithm. In the same time, spatial resolution of climate input and choice of high-resolution hydrography have secondary effects on model performance.Two high-resolution topographies and hydrographies were used and compared, and new techniques were developed to aggregate their information for use at large scales. The advantages and numerical efficiency of feeding high-resolution information into low-resolution global models were highlighted.
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