Access to stem cell data and registration of pluripotent cell lines: the Human Pluripotent Stem Cell Registry (hPSCreg)

The value of human pluripotent stem cells (hPSC) in regenerative medicine has yet to reach its full potential. The road from basic research tool to clinically validated PSC-derived cell therapy products is a long and winding one, leading researchers, clinicians, industry and regulators alike into undiscovered territory. All stakeholders must work together to ensure the development of safe and effective cell therapies. Similarly, utilization of hPSC in meaningful and controlled disease modeling and drug screening applications requires information on the quality and suitability of the applied cell lines. Central to these common goals is the complete documentation of hPSC data, including the ethical provenance of the source material, the hPSC line derivation, culture conditions and genetic constitution of the lines. Data surrounding hPSC is scattered amongst diverse sources, including publications, supplemental data, researcher lab books, accredited lab reports, certificates of analyses and public data repositories. Not all of these data sources are publicly accessible nor associated with metadata nor stored in a standard manner, such that data can be easily found and retrieved. The Human Pluripotent Stem Cell Registry (hPSCreg; https://hpscreg.eu/) was started in 2007 to impart provenance and transparency towards hPSC research by registering and collecting standard properties of hPSC lines. In this chapter, we present a short primer on the history of stem cell-based products, summarize the ethical and regulatory issues introduced in the course of working with hPSC-derived products and their associated data, and finally present the Human Pluripotent Stem Cell Registry as a valuable resource for all stakeholders in therapies and disease modeling based on hPSC-derived cells

Developing a distributed electronic health-record store for India

The DIGHT project is addressing the problem of building a scalable and highly available information store for the Electronic Health Records (EHRs) of the over one billion citizens of India

Model-Based Engineering of Collaborative Embedded Systems

This Open Access book presents the results of the "Collaborative Embedded Systems" (CrESt) project, aimed at adapting and complementing the methodology underlying modeling techniques developed to cope with the challenges of the dynamic structures of collaborative embedded systems (CESs) based on the SPES development methodology. In order to manage the high complexity of the individual systems and the dynamically formed interaction structures at runtime, advanced and powerful development methods are required that extend the current state of the art in the development of embedded systems and cyber-physical systems. The methodological contributions of the project support the effective and efficient development of CESs in dynamic and uncertain contexts, with special emphasis on the reliability and variability of individual systems and the creation of networks of such systems at runtime. The project was funded by the German Federal Ministry of Education and Research (BMBF), and the case studies are therefore selected from areas that are highly relevant for Germany’s economy (automotive, industrial production, power generation, and robotics). It also supports the digitalization of complex and transformable industrial plants in the context of the German government's "Industry 4.0" initiative, and the project results provide a solid foundation for implementing the German government's high-tech strategy "Innovations for Germany" in the coming years

Re-use of tests and arguments for assesing dependable mixed-critically systems

The safety assessment of mixed-criticality systems (MCS) is a challenging activity due to system heterogeneity, design constraints and increasing complexity. The foundation for MCSs is the integrated architecture paradigm, where a compact hardware comprises multiple execution platforms and communication interfaces to implement concurrent functions with different safety requirements. Besides a computing platform providing adequate isolation and fault tolerance mechanism, the development of an MCS application shall also comply with the guidelines defined by the safety standards. A way to lower the overall MCS certification cost is to adopt a platform-based design (PBD) development approach. PBD is a model-based development (MBD) approach, where separate models of logic, hardware and deployment support the analysis of the resulting system properties and behaviour. The PBD development of MCSs benefits from a composition of modular safety properties (e.g. modular safety cases), which support the derivation of mixed-criticality product lines. The validation and verification (V&V) activities claim a substantial effort during the development of programmable electronics for safety-critical applications. As for the MCS dependability assessment, the purpose of the V&V is to provide evidences supporting the safety claims. The model-based development of MCSs adds more V&V tasks, because additional analysis (e.g., simulations) need to be carried out during the design phase. During the MCS integration phase, typically hardware-in-the-loop (HiL) plant simulators support the V&V campaigns, where test automation and fault-injection are the key to test repeatability and thorough exercise of the safety mechanisms. This dissertation proposes several V&V artefacts re-use strategies to perform an early verification at system level for a distributed MCS, artefacts that later would be reused up to the final stages in the development process: a test code re-use to verify the fault-tolerance mechanisms on a functional model of the system combined with a non-intrusive software fault-injection, a model to X-in-the-loop (XiL) and code-to-XiL re-use to provide models of the plant and distributed embedded nodes suited to the HiL simulator, and finally, an argumentation framework to support the automated composition and staged completion of modular safety-cases for dependability assessment, in the context of the platform-based development of mixed-criticality systems relying on the DREAMS harmonized platform.La dificultad para evaluar la seguridad de los sistemas de criticidad mixta (SCM) aumenta con la heterogeneidad del sistema, las restricciones de diseño y una complejidad creciente. Los SCM adoptan el paradigma de arquitectura integrada, donde un hardware embebido compacto comprende múltiples plataformas de ejecución e interfaces de comunicación para implementar funciones concurrentes y con diferentes requisitos de seguridad. Además de una plataforma de computación que provea un aislamiento y mecanismos de tolerancia a fallos adecuados, el desarrollo de una aplicación SCM además debe cumplir con las directrices definidas por las normas de seguridad. Una forma de reducir el coste global de la certificación de un SCM es adoptar un enfoque de desarrollo basado en plataforma (DBP). DBP es un enfoque de desarrollo basado en modelos (DBM), en el que modelos separados de lógica, hardware y despliegue soportan el análisis de las propiedades y el comportamiento emergente del sistema diseñado. El desarrollo DBP de SCMs se beneficia de una composición modular de propiedades de seguridad (por ejemplo, casos de seguridad modulares), que facilitan la definición de líneas de productos de criticidad mixta. Las actividades de verificación y validación (V&V) representan un esfuerzo sustancial durante el desarrollo de aplicaciones basadas en electrónica confiable. En la evaluación de la seguridad de un SCM el propósito de las actividades de V&V es obtener las evidencias que apoyen las aseveraciones de seguridad. El desarrollo basado en modelos de un SCM incrementa las tareas de V&V, porque permite realizar análisis adicionales (por ejemplo, simulaciones) durante la fase de diseño. En las campañas de pruebas de integración de un SCM habitualmente se emplean simuladores de planta hardware-in-the-loop (HiL), en donde la automatización de pruebas y la inyección de faltas son la clave para la repetitividad de las pruebas y para ejercitar completamente los mecanismos de tolerancia a fallos. Esta tesis propone diversas estrategias de reutilización de artefactos de V&V para la verificación temprana de un MCS distribuido, artefactos que se emplearán en ulteriores fases del desarrollo: la reutilización de código de prueba para verificar los mecanismos de tolerancia a fallos sobre un modelo funcional del sistema combinado con una inyección de fallos de software no intrusiva, la reutilización de modelo a X-in-the-loop (XiL) y código a XiL para obtener modelos de planta y nodos distribuidos aptos para el simulador HiL y, finalmente, un marco de argumentación para la composición automatizada y la compleción escalonada de casos de seguridad modulares, en el contexto del desarrollo basado en plataformas de sistemas de criticidad mixta empleando la plataforma armonizada DREAMS.Kritikotasun nahastuko sistemen segurtasun ebaluazioa jarduera neketsua da beraien heterogeneotasuna dela eta. Sistema hauen oinarria arkitektura integratuen paradigman datza, non hardware konpaktu batek exekuzio plataforma eta komunikazio interfaze ugari integratu ahal dituen segurtasun baldintza desberdineko funtzio konkurrenteak inplementatzeko. Konputazio plataformek isolamendu eta akatsen aurkako mekanismo egokiak emateaz gain, segurtasun arauek definituriko jarraibideak jarraitu behar dituzte kritikotasun mistodun aplikazioen garapenean. Sistema hauen zertifikazio prozesuaren kostua murrizteko aukera bat plataformetan oinarritutako garapenean (PBD) datza. Garapen planteamendu hau modeloetan oinarrituriko garapena da (MBD) non modeloaren logika, hardware eta garapen desberdinak sistemaren propietateen eta portaeraren aurka aztertzen diren. Kritikotasun mistodun sistemen PBD garapenak etekina ateratzen dio moduluetan oinarrituriko segurtasun propietateei, adibidez: segurtasun kasu modularrak (MSC). Modulu hauek kritikotasun mistodun produktu-lerroak ere hartzen dituzte kontutan. Berifikazio eta balioztatze (V&V) jarduerek esfortzu kontsideragarria eskatzen dute segurtasun-kiritikoetarako elektronika programagarrien garapenean. Kritikotasun mistodun sistemen konfiantzaren ebaluazioaren eta V&V jardueren helburua segurtasun eskariak jasotzen dituzten frogak proportzionatzea da. Kritikotasun mistodun sistemen modelo bidezko garapenek zeregin gehigarriak atxikitzen dizkio V&V jarduerari, fase honetan analisi gehigarriak (hots, simulazioak) zehazten direlako. Bestalde, kritikotasun mistodun sistemen integrazio fasean, hardware-in-the-loop (Hil) simulazio plantek V&V iniziatibak sostengatzen dituzte non testen automatizazioan eta akatsen txertaketan funtsezko jarduerak diren. Jarduera hauek frogen errepikapena eta segurtasun mekanismoak egiaztzea ahalbidetzen dute. Tesi honek V&V artefaktuen berrerabilpenerako estrategiak proposatzen ditu, kritikotasun mistodun sistemen egiaztatze azkarrerako sistema mailan eta garapen prozesuko azken faseetaraino erabili daitezkeenak. Esate baterako, test kodearen berrabilpena akats aurkako mekanismoak egiaztatzeko, modelotik X-in-the-loop (XiL)-ra eta kodetik XiL-rako konbertsioa HiL simulaziorako eta argumentazio egitura bat DREAMS Europear proiektuan definituriko arkitektura estiloan oinarrituriko segurtasun kasu modularrak automatikoki eta gradualki sortzeko

Fundamental Approaches to Software Engineering

This open access book constitutes the proceedings of the 23rd International Conference on Fundamental Approaches to Software Engineering, FASE 2020, which took place in Dublin, Ireland, in April 2020, and was held as Part of the European Joint Conferences on Theory and Practice of Software, ETAPS 2020. The 23 full papers, 1 tool paper and 6 testing competition papers presented in this volume were carefully reviewed and selected from 81 submissions. The papers cover topics such as requirements engineering, software architectures, specification, software quality, validation, verification of functional and non-functional properties, model-driven development and model transformation, software processes, security and software evolution