Exploiting the ASM method within the Model-driven Engineering paradigm

Model-driven Engineering (MDE) is an emerging approach for software development. It uses metamodels to define language (or formalism) abstract notation, so separating the abstract syntax and semantics of the language from their different concrete notations. However, metamodelling frameworks lack of a way to specify the semantics of languages, which is usually given in natural language. We claim that the MDE paradigm can gain rigor and preciseness from the integration with formal approaches, and we propose the integration with the ASMs to define a unified methodology for metamodel-based language syntax and semantics definitions

Coordinated Execution of Heterogeneous Service-Oriented Components by Abstract State Machines

Abstract. Early design and validation of service-oriented applications is hardly feasible due to their distributed, dynamic, and heterogeneous nature. In order to support the engineering of such applications and discover faults early, foundational theories, modeling notations and analysis techniques for component-based development should be revisited. This paper presents a formal framework for coordinated execution of serviceoriented applications based on the OSOA open standard Service Component Architecture (SCA) for heterogeneous service assembly and on the formal method Abstract State Machines (ASMs) for modeling notions of service behavior, interactions, and orchestration in an abstract but executable way. The proposed framework is exemplified through a Robotics Task Coordination case study of the EU project BRICS

Tolerability of Eribulin and correlation between polymorphisms and neuropathy in an unselected population of female patients with metastatic breast cancer: results of the multicenter, single arm, phase IV PAINTER study

Background Metastatic breast cancer (MBC) is an incurable disease and its treatment focuses on prolonging patients' (pts) overall survival (OS) and improving their quality of life. Eribulin is a microtubule inhibitor that increases OS in pre-treated MBC pts. The most common adverse events (AEs) are asthenia, neutropenia and peripheral neuropathy (PN). Methods PAINTER is a single arm, phase IV study, aimed at evaluating the tolerability of eribulin in MBC pts. Secondary objectives were the description of treatment efficacy and safety, the assessment of the incidence and severity of PN and its association with genetic polymorphisms. Genomic DNA was isolated from blood samples and 15 Single Nucleotide Polymorphisms (SNPs) were genotyped by Taqman specific assays. The association between PN and SNPs were evaluated by Fisher exact test. Results Starting from May 2014 until June 2018 180 pts were enrolled in this study by 20 Italian centers. 170 of these pts could be evaluated for efficacy and toxicity and 159 for polymorphisms analysis. The median age of pts was 60 years old and the biological subtypes were luminal type (64.7%), Her2 positive (18.3%) and triple negative (17%). Pts were pretreated with a median of 5 lines for MBC. The median follow up of this study was 15.4 months with a median number of 4.5 cycles administered (minimum-maximum 1-23). The median overall survival was 12 months. 48.8% of pts experienced a dose reduction, mainly for neutropenia (23.9%) and liver toxicity (12%). 65 pts (38.2%) reported at least one severe toxicity. Neutropenia and neurotoxicity were the most frequent severe AEs (15.3% and 14.7%, respectively); other reported toxicities were osteo-muscular, abdominal or tumor site pain (19.4%), liver toxicity (6.6%), pulmonary toxicity (6.5%) and dermatological toxicity (3.6%). Among the 15 evaluated SNPs, an association with PN was found for rs2233335 and rs7214723. Conclusions Eribulin is a well-tolerated treatment option in MBC. Schedule and dosage modifications were common, but toxicity rarely led to treatment discontinuation. SNPs rs2233335 (G/T and T/T) in the NDRG1 gene and rs7214723 (CC and CT) in the CAMKK1 gene were associated with PN. These findings, if validated, could allow a tailored treatment with eribulin in cancer patients. Trial registration: ClinicalTrials.gov ID: NCT02864030

A Metamodel-based Language and a Simulation Engine for Abstract State Machines

In this paper, we present a concrete textual notation, called AsmetaL, and a general-purpose simulation engine, called AsmetaS, for Abstract State Machine (ASM) specifications. They have been developed as part of the ASMETA (ASMs mETAmodelling) toolset, which is a set of tools for ASMs based on the metamodelling approach of the Model-driven Engineering. We briefly present the ASMETA framework, and we discuss how the language and the simulator have been developed exploiting the advantages offered by the metamodelling approach. We introduce the language AsmetaL used to write ASM specifications, and we provide the AsmetaL encoding of ASM specifications of increasing complexity. We explain the AsmetaS architecture, its kernel engine, and how the simulator works within the ASMETA tool set. We discuss the features currently supported by the simulator and how it has been validated