Black-box Integration of Heterogeneous Modeling Languages for Cyber-Physical Systems

Robots belong to a class of Cyber-Physical Systems where complex software as a mobile device has to full tasks in a complex environment. Modeling robotics applications for analysis and code generation requires modeling languages for the logical software architecture and the system behavior. The MontiArcAutomaton modeling framework integrates six independently developed modeling languages to model robotics applications: a component & connector architecture description language, automata, I/O tables, class diagrams, OCL, and a Java DSL. We describe how we integrated these languages into MontiArcAutomaton a-posteriori in a black-box integration fashion.Comment: 6 pages, 4 figures. GEMOC Workshop 2013 - International Workshop on The Globalization of Modeling Languages, Miami, Florida (USA), Volume 1102 of CEUR Workshop Proceedings, CEUR-WS.org, 201

Engineering Delta Modeling Languages

Delta modeling is a modular, yet flexible approach to capture spatial and temporal variability by explicitly representing the differences between system variants or versions. The conceptual idea of delta modeling is language-independent. But, in order to apply delta modeling for a concrete language, so far, a delta language had to be manually developed on top of the base language leading to a large variety of heterogeneous language concepts. In this paper, we present a process that allows deriving a delta language from the grammar of a given base language. Our approach relies on an automatically generated language extension that can be manually adapted to meet domain-specific needs. We illustrate our approach using delta modeling on a textual variant of statecharts.Comment: 10 pages, 8 figures. Proceedings of the 17th International Software Product Line Conference, Tokyo, September 2013, pp.22-31, ACM, 201

Integration of Heterogeneous Modeling Languages via Extensible and Composable Language Components

Effective model-driven engineering of complex systems requires to appropriately describe different specific system aspects. To this end, efficient integration of different heterogeneous modeling languages is essential. Modeling language integaration is onerous and requires in-depth conceptual and technical knowledge and ef- fort. Traditional modeling lanugage integration approches require language engineers to compose monolithic language aggregates for a specific task or project. Adapting these aggregates cannot be to different contexts requires vast effort and makes these hardly reusable. This contribution presents a method for the engineering of grammar-based language components that can be independently developed, are syntactically composable, and ultimately reusable. To this end, it introduces the concepts of language aggregation, language embed- ding, and language inheritance, as well as their realization in the language workbench MontiCore. The result is a generalizable, systematic, and efficient syntax-oriented composition of languages that allows the agile employment of modeling languages efficiently tailored for individual software projects.Comment: 12 pages, 11 figures. Proceedings of the 3rd International Conference on Model-Driven Engineering and Software Development. Angers, Loire Valley, France, pp. 19-31, 201

The Ews-ERG Fusion Protein Can Initiate Neoplasia from Lineage-Committed Haematopoietic Cells

The EWS-ERG fusion protein is found in human sarcomas with the chromosomal translocation t(21;22)(q22;q12), where the translocation is considered to be an initiating event in sarcoma formation within uncommitted mesenchymal cells, probably long-lived progenitors capable of self renewal. The fusion protein may not therefore have an oncogenic capability beyond these progenitors. To assess whether EWS-ERG can be a tumour initiator in cells other than mesenchymal cells, we have analysed Ews-ERG fusion protein function in a cellular environment not typical of that found in human cancers, namely, committed lymphoid cells. We have used Ews-ERG invertor mice having an inverted ERG cDNA cassette flanked by loxP sites knocked in the Ews intron 8, crossed with mice expressing Cre recombinase under the control of the Rag1 gene to give conditional, lymphoid-specific expression of the fusion protein. Clonal T cell neoplasias arose in these mice. This conditional Ews gene fusion model of tumourigenesis shows that Ews-ERG can cause haematopoietic tumours and the precursor cells are committed cells. Thus, Ews-ERG can function in cells that do not have to be pluripotent progenitors or mesenchymal cells

Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo

Nuclear factor interleukin-3 (Nfil3; also known as E4-binding protein 4) is a basic region leucine zipper transcription factor that has antiapoptotic activity in vitro under conditions of growth factor withdrawal. To study the role of Nfil3 in vivo, we generated gene-targeted Nfil3-deficient (Nfil3−/−) mice. Nfil3−/− mice were born at normal Mendelian frequency and were grossly normal and fertile. Although numbers of T cells, B cells, and natural killer (NK) T cells were normal in Nfil3−/− mice, a specific disruption in NK cell development resulted in severely reduced numbers of mature NK cells in the periphery. This defect was NK cell intrinsic in nature, leading to a failure to reject MHC class I–deficient cells in vivo and reductions in both interferon γ production and cytolytic activity in vitro. Our results confirm the specific and essential requirement of Nfil3 for the development of cells of the NK lineage

The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease