Timed patterns: TCOZ to timed automata

Abstract. The integrated logic-based modeling language, Timed Communicating Object Z (TCOZ), is well suited for presenting complete and coherent requirement models for complex real-time systems. However, the challenge is how to verify the TCOZ models with tool support, especially for analyzing timing properties. Specialized graph-based modeling technique, Timed Automata (TA), has powerful mechanisms for designing real-time models using multiple clocks and has well developed automatic tool support. One weakness of TA is the lack of high level composable graphical patterns to support systematic designs for complex systems. The investigation of possible links between TCOZ and TA may benefit both techniques. For TCOZ, TA’s tool support can be reused to check timing properties. For TA, a set of composable graphical patterns can be defined based on the semantics of the TCOZ constructs, so that those patterns can be re-used in a generic way. This paper firstly defines the composable TA graphical patterns, and then presents sound transformation rules and a tool for projecting TCOZ specifications into TA. A case study of a railroad crossing system is demonstrated

Molecular characterisation of canine osteosarcoma in high risk breeds

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Dogs develop osteosarcoma (OSA) and the disease process closely resembles that of human OSA. OSA has a poor prognosis in both species and disease-free intervals and cure rates have not improved in recent years. Gene expression in canine OSAs was compared with non-tumor tissue utilising RNA sequencing, validated by qRT-PCR and immunohistochemistry (n = 16). Polymorphic polyglutamine (polyQ) tracts in the androgen receptor (AR/NR3C4) and nuclear receptor coactivator 3 (NCOA3) genes were investigated in control and OSA patients using polymerase chain reaction (PCR), Sanger sequencing and fragment analysis (n = 1019 Rottweilers, 379 Irish Wolfhounds). Our analysis identified 1281 significantly differentially expressed genes (>2 fold change, p < 0.05), specifically 839 lower and 442 elevated gene expression in osteosarcoma (n = 3) samples relative to non-malignant (n = 4) bone. Enriched pathways and gene ontologies were identified, which provide insight into the molecular pathways implicated in canine OSA. Expression of a subset of these genes (SLC2A1, DKK3, MMP3, POSTN, RBP4, ASPN) was validated by qRTPCR and immunohistochemistry (MMP3, DKK3, SLC2A1) respectively. While little variation was found in the NCOA3 polyQ tract, greater variation was present in both polyQ tracts in the AR, but no significant associations in length were made with OSA. The data provides novel insights into the molecular mechanisms of OSA in high risk breeds. This knowledge may inform development of new prevention strategies and treatments for OSA in dogs and supports utilising spontaneous OSA in dogs to improve understanding of the disease in people