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- Schweiger, G., et al.
(författare)
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An empirical survey on co-simulation : Promising standards, challenges and research needs
- 2019
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Ingår i: Simulation (San Diego, Calif.). - : Elsevier. - 1569-190X .- 1878-1462. ; 95, s. 148-163
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Forskningsöversikt (refereegranskat)abstract
- Co-simulation is a promising approach for the modelling and simulation of complex systems, that makes use of mature simulation tools in the respective domains. It has been applied in various different domains, oftentimes without a comprehensive study of the impact to the simulation results. As a consequence, over the recent years, researchers have set out to understand the essential challenges arising from the application of this technique. This paper complements the existing surveys in that the social and empirical aspects were addressed. More than 50 experts participated in a two-stage Delphi study to determine current challenges, research needs and promising standards and tools. Furthermore, an analysis of the strengths, weakness, opportunities and threats of co-simulation utilizing the analytic hierarchy process resulting in a SWOT-AHP analysis is presented. The empirical results of this study show that experts consider the FMI standard to be the most promising standard for continuous time, discrete event and hybrid cosimulation. The results of the SWOT-AHP analysis indicate that factors related to strengths and opportunities predominate.
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- Trautmann, M., et al.
(författare)
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Phosphatidylinositol-3-kinase (PI3K)/Akt Signaling is Functionally Essential in Myxoid Liposarcoma
- 2019
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Ingår i: Molecular Cancer Therapeutics. - 1535-7163. ; 18:4, s. 834-844
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid liposarcoma (MLS) is an aggressive soft-tissue tumor characterized by a specific reciprocal t(12;16) translocation resulting in expression of the chimeric FUS-DDIT3 fusion protein, an oncogenic transcription factor. Similar to other translocation-associated sarcomas, MLS is characterized by a low frequency of somatic mutations, albeit a subset of MLS has previously been shown to be associated with activating PIK3CA mutations. This study was performed to assess the prevalence of PI3K/Akt signaling alterations in MIS and the potential of PI3Kdirected therapeutic concepts. In a large cohort of MIS, key components of the PI3K/Akt signaling cascade were evaluated by next generation seqeuncing (NGS), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). In threevi IS cell lines, PI3K activitywas inhibited by RNAi and the small-molecule PI3 K inhibitor BKM120 (buparlisib) in vitro. An MLS cell line-based avian chorioallantoic membrane model was applied for in vivo confirmation. In total, 26.8% of MLS cases displayed activating alterations in PI3K/Akt signaling components, with PIK3CA gain-of-function mutations representing the most prevalent finding (14.2%). IHC suggested PI3K/Akt activation in a far larger subgroup of MIS, implying alternative mechanisms of pathway activation. P13K-directed therapeutic interference showed that MIS cell proliferation and viability significantly depended on PI3K-mediated signals in vitro and in viva Our predinical study underlines the elementary role of PI3K/Akt signals in MLS tumorigenesis and provides a molecularly based rationale for a PI3K-targeted therapeutic approach which may be particularly effective in the subgroup of tumors carrying activating genetic alterations in P13K/Akt signaling components.
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