The novel CKLF-like Marvel Transmembrane Domain-containing gene family (CMTM) consists of 8 members (CMTM1-8). As little is known about the oncogenic impact of these genes, we aimed to systematically investigate the relevance of CMTMs to glioblastoma pathogenesis. We performed mRNA expression analyses and survival correlations in glioblastoma patients. Moreover, we analyzed the impact of RNAi-based silencing and overexpression of CMTM family genes on tumor cell proliferation and invasion in vitro. CMTMs appeared to be widely regulated in the group of glioblastomas relative to non-neoplastic brain (NB) tissue (significant upregulation for CMTM2, 3, and 6 and significant downregulation for CMTM 4 and 8). For CMTM1, 5 and 7, we found aberrant expression levels in individual tumors. Functionally, CMTM1, 3, and 7 promoted tumor cell invasion, while CMTM1 additionally enhanced cell proliferation. In a large clinically annotated dataset, higher CMTM1 and 3 expression was significantly correlated with shorter overall survival. Our data thus suggest CMTM1 and 3 as priority targets in glioblastomas. Using a human phosphokinase protein expression profiling assay, we can provide first insights into signalling of these two genes that might be conveyed by growth factor receptor, Src family kinase and WNT activation.
Safety-critical automotive systems must ful ll hard real-time constraints for reliability and safety. This paper presents a case study for the application of an AUTOSARbased language for timing modeling and analysis. We present and apply the Timing Augmented Description Language (TADL) and demonstrate a methodology for the development of a speedadaptive steer-by-wire system. We examine the impact of TADL and the methodology on the development process and the suitability and interoperability of the applied tools with respect to the AUTOSAR-based tool chain in the context of our case study.
This paper explores the possibility to include and execute source code functional mockup units on Bosch electronic control units. A prototypical realization is presented, and assumptions as well as limitations are documented. Special emphasis is laid on requirements for the contained C-code. Furthermore, aspects for an extension to adapt the FMI to the usage on automotive embedded real-time systems are summarized.
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