HLA-Transparent Distributed Simulation of Agent-based Systems

Applied mathematic

Functional mapping of the interaction between TDP-43 and hnRNP A2 in vivo

Nuclear factor TDP-43 has been reported to play multiple roles in transcription, pre-mRNA splicing, mRNA stability and mRNA transport. From a structural point of view, TDP-43 is a member of the hnRNP protein family whose structure includes two RRM domains flanked by the N-terminus and C-terminal regions. Like many members of this family, the C-terminal region can interact with cellular factors and thus serve to modulate its function. Previously, we have described that TDP-43 binds to several members of the hnRNP A/B family through this region. In this work, we set up a coupled minigene/siRNA cellular system that allows us to obtain in vivo data to address the functional significance of TDP-43-recruited hnRNP complex formation. Using this method, we have finely mapped the interaction between TDP-43 and the hnRNP A2 protein to the region comprised between amino acid residues 321 and 366. Our results provide novel details of protein–protein interactions in splicing regulation. In addition, we provide further insight on TDP-43 functional properties, particularly the lack of effects, as seen with our assays, of the disease-associated mutations that fall within the TDP-43 321-366 region: Q331K, M337V and G348C

iCLIP: Protein-RNA interactions at nucleotide resolution.

RNA-binding proteins (RBPs) are key players in the post-transcriptional regulation of gene expression. Precise knowledge about their binding sites is therefore critical to unravel their molecular function and to understand their role in development and disease. Individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP) identifies protein-RNA crosslink sites on a genome-wide scale. The high resolution and specificity of this method are achieved by an intramolecular cDNA circularization step that enables analysis of cDNAs that truncated at the protein-RNA crosslink sites. Here, we describe the improved iCLIP protocol and discuss critical optimization and control experiments that are required when applying the method to new RBPs

E-MDAV: A Framework for Developing Data-Intensive Web Applications

The ever-increasing adoption of innovative technologies, such as big data and cloud computing, provides significant opportunities for organizations operating in the IT domain, but also introduces considerable challenges. Such innovations call for development processes that better align with stakeholders needs and expectations. In this respect, this paper introduces a development framework based on the OMG’s Model Driven Architecture (MDA) that aims to support the development lifecycle of data-intensive web applications. The proposed framework, named E-MDAV (Extended MDA-VIEW), defines a methodology that exploits a chain of model transformations to effectively cope with both forward- and reverse-engineering aspects. In addition, E-MDAV includes the specification of a reference architecture for driving the implementation of a tool that supports the various professional roles involved in the development and maintenance of data-intensive web applications. In order to evaluate the effectiveness of the proposed E-MDAV framework, a tool prototype has been developed. E-MDAV has then been applied to two different application scenarios and the obtained results have been compared with historical data related to the implementation of similar development projects, in order to measure and discuss the benefits of the proposed approach

E-MDAV: A Framework for Developing Data-Intensive Web Applications

The ever-increasing adoption of innovative technologies, such as big data and cloud computing, provides significant opportunities for organizations operating in the IT domain, but also introduces considerable challenges. Such innovations call for development processes that better align with stakeholders needs and expectations. In this respect, this paper introduces a development framework based on the OMG’s Model Driven Architecture (MDA) that aims to support the development lifecycle of data-intensive web applications. The proposed framework, named E-MDAV (Extended MDA-VIEW), defines a methodology that exploits a chain of model transformations to effectively cope with both forward- and reverse-engineering aspects. In addition, E-MDAV includes the specification of a reference architecture for driving the implementation of a tool that supports the various professional roles involved in the development and maintenance of data-intensive web applications. In order to evaluate the effectiveness of the proposed E-MDAV framework, a tool prototype has been developed. E-MDAV has then been applied to two different application scenarios and the obtained results have been compared with historical data related to the implementation of similar development projects, in order to measure and discuss the benefits of the proposed approach

A Lightweight BPMN Extension for Business Process-Oriented Requirements Engineering

Process-oriented requirements engineering approaches are often required to deal with the effective adaptation of existing processes in order to easily introduce new or updated requirements. Such approaches are based on the adoption of widely used notations, such as the one introduced by the Business Process Model and Notation (BPMN) standard. However, BPMN models do not convey enough information on the involved entities and how they interact with process activities, thus leading to ambiguities, as well as to incomplete and inconsistent requirements definitions. This paper proposes an approach that allows stakeholders and software analysts to easily merge and integrate behavioral and data properties in a BPMN model, so as to fully exploit the potential of BPMN without incurring into the aforementioned limitation. The proposed approach introduces a lightweight BPMN extension that specifically addresses the annotation of data properties in terms of constraints, i.e., pre- and post-conditions that the different process activities must satisfy. The visual representation of the annotated model conveys all the information required both by stakeholders, to understand and validate requirements, and by software analysts and developers, to easily map these updates to the corresponding software implementation. The presented approach is illustrated by use of two running examples, which have also been used to carry out a preliminary validation activity

Process-Oriented Requirements Definition and Analysis of Software Components in Critical Systems

Requirements management is a key aspect in the development of software components, since complex systems are often subject to frequent updates due to continuously changing requirements. This is especially true in critical systems, i.e., systems whose failure or malfunctioning may lead to severe consequences. This paper proposes a three-step approach that incrementally refines a critical system specification, from a lightweight high-level model targeted to stakeholders, down to a formal standard model that links requirements, processes and data. The resulting model provides the requirements specification used to feed the subsequent development, verification and maintenance activities, and can also be seen as a first step towards the development of a digital twin of the physical system