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Sökning: WFRF:(Ball Claudia R.)

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1.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
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2.
  • Schöpf, Julia, et al. (författare)
  • Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions
  • 2024
  • Ingår i: Nature Communications. - 2041-1723. ; 15, s. 1-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in ALK variants that are oncogenic and sensitive to ALK inhibitors. Additionally, recurrent CKDN2A/MTAP co-deletions provide a rationale for PRMT5-targeted therapies. Functional studies show that FUS-TFCP2 blocks myogenic differentiation, induces transcription of ALK and truncated TERT, and inhibits DNA repair. Unlike other fusion-driven sarcomas, TFCP2-rearranged tumors exhibit genomic instability and signs of defective homologous recombination. DNA methylation profiling demonstrates a close relationship with undifferentiated sarcomas. In two patients, sarcoma was preceded by benign lesions carrying FUS-TFCP2, indicating stepwise sarcomagenesis. This study illustrates the potential of linking precision oncology with preclinical research to gain insight into the classification, pathogenesis, and therapeutic vulnerabilities of rare cancers.
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3.
  • Zanchettin, Davide, et al. (författare)
  • The Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP) : experimental design and forcing input data for CMIP6
  • 2016
  • Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 9:8, s. 2701-2719
  • Tidskriftsartikel (refereegranskat)abstract
    • The enhancement of the stratospheric aerosol layer by volcanic eruptions induces a complex set of responses causing global and regional climate effects on a broad range of timescales. Uncertainties exist regarding the climatic response to strong volcanic forcing identified in coupled climate simulations that contributed to the fifth phase of the Coupled Model Intercomparison Project (CMIP5). In order to better understand the sources of these model diversities, the Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP) has defined a coordinated set of idealized volcanic perturbation experiments to be carried out in alignment with the CMIP6 protocol. VolMIP provides a common stratospheric aerosol data set for each experiment to minimize differences in the applied volcanic forcing. It defines a set of initial conditions to assess how internal climate variability contributes to determining the response. VolMIP will assess to what extent volcanically forced responses of the coupled ocean-atmosphere system are robustly simulated by state-of-the-art coupled climate models and identify the causes that limit robust simulated behavior, especially differences in the treatment of physical processes. This paper illustrates the design of the idealized volcanic perturbation experiments in the VolMIP protocol and describes the common aerosol forcing input data sets to be used.
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  • Resultat 1-3 av 3

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