4 research outputs found
Fatores associados à dor musculoesquelética em escolares da rede pública municipal no extremo sul do Brasil
Pan-cancer analysis of whole genomes
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). 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 promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
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The ACS Survey Of Galactic Globular Clusters. VIII. Effects Of Environment On Globular Cluster Global Mass Functions
We have used observations obtained as part of the Hubble Space Telescope/ACS Survey of Galactic Globular Clusters to construct global present-day mass functions for 17 globular clusters utilizing multi-mass King models to extrapolate from our observations to the global cluster behavior. The global present-day mass functions for these clusters are well matched by power laws from the turnoff, approximate to 0.8 M(circle dot), to 0.2-0.3 M(circle dot) on the lower main sequence. The slopes of those power-law fits, alpha, have been correlated with an extensive set of intrinsic and extrinsic cluster properties to investigate which parameters may influence the form of the present-day mass function. We do not confirm previous suggestions of correlations between alpha and either metallicity or Galactic location. However, we do find a strong statistical correlation with the related parameters central surface brightness, mu(V), and inferred central density, rho(0). The correlation is such that clusters with denser cores (stronger binding energy) tend to have steeper mass functions (a higher proportion of low-mass stars), suggesting that dynamical evolution due to external interactions may have played a key role in determining alpha. Thus, the present-day mass function may owe more to nurture than to nature. Detailed modeling of external dynamical effects is therefore a requisite for determining the initial mass function for Galactic globular clusters.NASA GO-10775, NAS 5-26555Space Telescope Science InstituteInstituto de Astrofisica de Canarias 310394Ministry of Education and Science of the Kingdom of Spain AYA-2008-67913Astronom