| 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. |
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| 3. |
- Rheinbay, E, et al.
(author)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Journal article (peer-reviewed)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 4. |
- Barddal, Johanna, et al.
(author)
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Reconstructing constructional semantics : The dative subject construction in Old Norse-Icelandic, Latin, Ancient Greek, Old Russian and Old Lithuanian
- 2012
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In: Studies in Language. - : John Benjamins Publishing Company. - 0378-4177 .- 1569-9978. ; 36:3, s. 511-547
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Journal article (peer-reviewed)abstract
- As the historical linguistic community is well aware, reconstructing semantics is a notoriously difficult undertaking. Such reconstruction has so far mostly been carried out on lexical items, like words and morphemes, and has not been conducted for larger and more complex linguistic units, which intuitively seems to be a more intricate task, especially given the lack of methodological criteria and guidelines within the field. This follows directly from the fact that most current theoretical frameworks are not construction-based, that is, they do not assume that constructions are form-meaning correspondences. In order to meet this challenge, we present an attempt at reconstructing constructional semantics, and more precisely the semantics of the Dative Subject Construction for an earlier stage of Indo-European. For this purpose we employ lexical semantic verb classes in combination with the semantic map model (Bar partial derivative dal 2007, Bar partial derivative dal, Kristoffersen & Sveen 2011), showing how incredibly stable semantic fields may remain across long time spans, and how reconstructing such semantic fields may be accomplished
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| 5. |
- Koenigstorfer, Joerg, et al.
(author)
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THE STATE OF PLAY BETWEEN MANAGING MAJOR SPORTS EVENTS AND HUMAN RIGHTS: A SCOPING REVIEW
- 2023
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In: Event Management. - 1525-9951. ; 27:6, s. 823-849
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Journal article (peer-reviewed)abstract
- This scoping review integrates literature from diverse perspectives to better understand when and how management of major sport events promotes or harms human rights. The authors critically review 130 peer-reviewed English language articles to identify conceptual contributions to research and practice. The findings reveal that politics and political reform, legal frameworks, and organizational actions are crucial influences in when and how management of events promotes or harms human rights. The most frequently considered rights in the literature are: equality, human trafficking related, sport as a human right, worker rights, and freedom of residence. Activism for human rights stimulates change within relevant stakeholders via collaboration, naming and shaming, in-public debates, and media coverage. The committed, transparent, and inclusive consideration of human rights in all stages of managing sport events (from bid preparation, bidding, planning, and hosting to postevent leverage) may increase the likelihood that the event has social benefits.
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