Grid architectures and the European DataGrid

The term "Grid" is used in reference with wide area (possibly planetary) computer networks that enable very large communities of users to access massive computational facilities, ideally with the same transparency and ease that users of electrical devices, whether industrial machines or home appliances, expect from the electrical power grid. This paper introduces the basic concepts of Grid architectures, drawing upon the experience of the European DataGrid project, one of the most important enterprises in this field, aimed at providing support to scientific communities involved in High Energy Physics, Earth Observation, and Biology

Design and Synthesis of new 2-aryl substituted thiopyrano-fused pyrimidines

The molecular basis of tumour angiogenesis has been extensively studied and the Vascular Endothelial Growth Factor (VEGF) pathway has emerged as one of the most important positive modulators of this process. The various members of the VEFG family have overlapping abilities to interact with a set of tyrosine kinase receptors: VEGFR-1 and VEGFR-2 (KDR), largely expressed in endothelial cells and primarily involved in angiogenesis, and VEGFR-3, located in lymphatic vessels, where it seems to be critical in regulating lymphoangiogenesis. The demonstration that expression of VEGF and of its receptors correlates with the degree of vascularization of many experimental and clinical tumours led to the rational design and development of agents targeting this pathway The new agents range from anti-VEGF monoclonal antibodies, such as bevacizumab, to small-molecule ATP-competitive VEGFR inhibitors, including compounds from distinct heterocyclic classes. Inside the class of fused pyrimidines, those bearing the aniline substituted pyrimidine core showed to possess excellent antiangiogenic effects, and have widely been used as a basis for the design of new VEGFR-2 competitive inhibitors. In this regard, my thesis work concerned the preparation of novel benzothiopyrano- and pyridothiopyrano-fused pyrimidines, characterized by an aniline (m-substituted) group in the 2-position. Moreover, with the aim to perform critical SAR studies, the new analogue 2-benzylamino derivatives were obtained. The antiproliferative activity of new thiopyrano-fused pyrimidines will be performed on HeLa (cervix adenocarcinoma), A-431 (epidermoid carcinoma) and MSTO-211H (biphasic mesothelioma) cell lines and the results will be expressed as IC50 values, i.e. the concentration (microM) of compound able to produce 50% cell death with respect to the control culture. With the aim to investigate the mechanism of action responsible for the antiproliferative effect, the ability of new derivatives to inhibit the KDR tyrosine kinase activity will be determined by a biochemical assay performed with a recombinant human kinase insert domain receptor

Static and Dynamic Data Models for the Storage Resource Manager v2.2

We present a conceptual model for the Storage Resource Manager, the standard interface adopted for the storage systems of the Worldwide LHC Computing Grid. This model provides a clear and concise definition of the structural and behavioral concepts underlying the interface specification and is meant to support service and application development. Different languages (natural language, UML diagrams, and simple set-theoretic and logical notation) are used to describe different aspects of the model

Verifying safety properties of a nonlinear control by interactive theorem proving with the Prototype Verification System

Interactive, or computer-assisted, theorem proving is the verification of statements in a formal system, where the proof is developed by a logician who chooses the appropriate inference steps, in turn executed by an automatic theorem prover. In this paper, interactive theorem proving is used to verify safety properties of a nonlinear (hybrid) control system

A PVS-Simulink Integrated Environment for Model-Based Analysis of Cyber-Physical Systems

This paper presents a methodology, with supporting tool, for formal modeling and analysis of software components in cyber-physical systems. Using our approach, developers can integrate a simulation of logic-based specifications of software components and Simulink models of continuous processes. The integrated simulation is useful to validate the characteristics of discrete system components early in the development process. The same logic-based specifications can also be formally verified using the Prototype Verification System (PVS), to gain additional confidence that the software design complies with specific safety requirements. Modeling patterns are defined for generating the logic-based specifications from the more familiar automata-based formalism. The ultimate aim of this work is to facilitate the introduction of formal verification technologies in the software development process of cyber-physical systems, which typically requires the integrated use of different formalisms and tools. A case study from the medical domain is used to illustrate the approach. A PVS model of a pacemaker is interfaced with a Simulink model of the human heart. The overall cyber-physical system is co-simulated to validate design requirements through exploration of relevant test scenarios. Formal verification with the PVS theorem prover is demonstrated for the pacemaker model for specific safety aspects of the pacemaker design

Formal Verification in the Loop to Enhance Verification of Safety-Critical Cyber-physical Systems

Formal verification may play a central role in the development of safecontrollers, such as those found in electric drives or (semi-)autonomousvehicles, whose complexity arises from the coexistence ofmechanical and electrical subsystems with sophisticated electronic controllersthat must implement high-level control policies according to different drivingmodes, while optimizing several objectives, such as safety first and foremost,efficiency, and performance among others.  Model-driven development resorts tosimulation to assess how well the various requirements and constraints aresatisfied, but there is a growing awareness that more rigorous methods areneeded to achieve the required levels of safety.  This paper proposes aconceptual framework for the development of complex systems based on (i)higher-order logic specification, (ii) verification by theorem proving, and(iii) tight integration of verification with model-driven development andsimulation.  This framework addresses both digital and analog systems, asillustrated with some examples in different fields including implantablebiomedical systems, autonomous vehicles, and electric valve actuation

Modeling communication network requirements for an integrated clinical environment in the Prototype Verification System

Health care practices increasingly rely on complex technological infrastructure, and new approaches to the integration of information and communication technology in those practices lead to the development of such concepts as integrated clinical environments and smart intensive care units. These concepts refer to hospital settings where therapy relies heavily on inter-operating medical devices, supervised by clinicians assisted by advanced monitoring and co-ordinating software. In order to ensure safety and effectiveness of patient care, it is necessary to specify the requirements of such socio-technical systems in the most rigorous and precise way. This paper presents an approach to the formalization of system requirements for communication networks deployed in integrated clinical environment, based on the higher-order logic language of a theorem-proving environment, the Prototype Verification System

Towards a Formalization of System Requirements for an Integrated Clinical Environment

Interoperability of medical devices, and their interface to clinicians and patients, are critical issues for the safety and effectiveness of patient care. Ongoing efforts strive at establishing standards for integrated clinical environments, which may connect and co-ordinate several medical devices and interface them to patients, clinicians, and hospital information systems. In this paper, an approach to the formalization of system requirements for an integrated clinical environment is presented. The formalization relies on the higher-order logic language of the Prototype Verification System

Block-Based Models and Theorem Proving in Model-Based Development

This paper presents a methodology to integrate computer-assisted theorem proving into a standard workflow for model-based development that uses a block-based language as a modeling and simulation tool. The theorem prover provides confidence in the results of the analysis as it guides the developers towards a correct formalization of the system under developmen

Extending a user interface prototyping tool with automatic MISRA~C code generation

We are concerned with systems, particularly safety-critical systems, that involve interaction between users and devices, such as the user interface of medical devices. We therefore developed a MISRA~C code generator for formal models expressed in the PVSio-web prototyping toolkit. PVSio-web allows developers to rapidly generate realistic interactive prototypes for verifying usability and safety requirements in human-machine interfaces. The visual appearance of the prototypes is based on a picture of a physical device, and the behaviour of the prototype is defined by an executable formal model. Our approach transforms the PVSio-web prototyping tool into a model-based engineering toolkit that, starting from a formally verified user interface design model, will produce MISRA~C code that can be compiled and executed for a final product. An initial validation of our tool is presented for the data entry system of an actual medical device