A First Experimentation on High-Level Tooling Support upon Fractal

International audienceIn this abstract, we present a first experimentation on tooling support based on Fractal component model. The motivations which encouraged us were to provide an homogeneous design environment for the user to specify Fractal applications

A First Experimentation on High-Level Tooling Support upon Fractal

International audienceIn this abstract, we present a first experimentation on tooling support based on Fractal component model. The motivations which encouraged us were to provide an homogeneous design environment for the user to specify Fractal applications

A Three-Tier Approach for Composition of Real-Time Embedded Software Stacks

CORE A.International audienceMany component models and frameworks have been proposed to abstract and capture concerns from Real-Time and Embedded application domains, based on high-level component-based approaches. However, these approaches tend to propose their own fixed-set abstractions and ad-hoc runtime platforms, whereas the current trend emphasizes more flexible solutions, as embedded systems must constantly integrate new functionalities, while preserving performance. In this paper, we present a two-fold contribution addressing this statement. First, we propose to express these concerns in a decoupled way from the commonly accepted structural abstractions inherent to CBSE, and provide a framework to implement them in open and extensible runtime containers. Second, we propose a three-tier approach to composition where application, containers and the underlying operating system are designed using components. Supporting a homogeneous design space allows applying optimization techniques at these three abstraction layers showing that our approach does not impact on performance. In this paper, we focus our evaluation on concerns specific to the field of real-time audio and music applications

Deep Learning of Retinal Imaging: A Useful Tool for Coronary Artery Calcium Score Prediction in Diabetic Patients

Retina fundus imaging; Deep learning; Medical imagingImatge del fons de la retina; Aprenentatge profund; Imatges mèdiquesImagen del fondo de la retina; Aprendizaje profundo; Imágenes médicasCardiovascular diseases (CVD) are one of the leading causes of death in the developed countries. Previous studies suggest that retina blood vessels provide relevant information on cardiovascular risk. Retina fundus imaging (RFI) is a cheap medical imaging test that is already regularly performed in diabetic population as screening of diabetic retinopathy (DR). Since diabetes is a major cause of CVD, we wanted to explore the use Deep Learning architectures on RFI as a tool for predicting CV risk in this population. Particularly, we use the coronary artery calcium (CAC) score as a marker, and train a convolutional neural network (CNN) to predict whether it surpasses a certain threshold defined by experts. The preliminary experiments on a reduced set of clinically verified patients show promising accuracies. In addition, we observed that elementary clinical data is positively correlated with the risk of suffering from a CV disease. We found that the results from both informational cues are complementary, and we propose two applications that can benefit from the combination of image analysis and clinical data.This research was funded by “RTI2018-095232-B-C22” grant from the Spanish Ministry of Science, Innovation and Universities (FEDER funds)

Targeting PKC iota-PAK1 signaling pathways in EGFR and KRAS mutant adenocarcinoma and lung squamous cell carcinoma

Introduction: p21-activated kinase 1 (PAK1) stimulates growth and metastasis in non-small cell lung cancer (NSCLC). Protein kinase C iota (PKC iota) is an enzyme highly expressed in NSCLC, regulating PAK1 signaling. In the present study we explored whether the PKC iota-PAK1 signaling pathway approach can be an efficient target in different types of NSCLC cell and mouse models. Methods: The effect of IPA-3 (PAK1 inhibitor) plus auranofin (PKC iota inhibitor) combination was evaluated by cell viability assay, colony formation and western blotting assay, using three types of NSCLC cell lines: EGFR or KRAS mutant adenocarcinoma and squamous cell carcinoma with PAK1 amplification. In addition, for clinical availability, screening for new PAK1 inhibitors was carried out and the compound OTSSP167 was evaluated in combination with auranofin in cell and mice models. Results: The combination of IPA-3 or OTSSP167 plus auranofin showed high synergism for inhibiting cell viability and colony formation in three cell lines. Mechanistic characterization revealed that this drug combination abrogated expression and activation of membrane receptors and downstream signaling proteins crucial in lung cancer: EGFR, MET, PAK1, PKC iota, ERK1/2, AKT, YAP1 and mTOR. A nude mouse xenograft assay demonstrated that this drug combination strongly suppressed tumor volume compared with single drug treatment. Conclusions: Combination of IPA-3 or OTSSP167 and auranofin was highly synergistic in EGFR or KRAS mutant adenocarcinoma and squamous cell carcinoma cell lines and decreased tumor volume in mice models. It is of interest to further test the targeting of PKC iota-PAK1 signaling pathways in EGFR mutant, KRAS mutant and squamous NSCLC patients

Src-Homology 2 Domain-Containing Phosphatase 2 in Resected EGFR Mutation-Positive Lung Adenocarcinoma

Funding: supported by a La Caixa Foundation grant and the Spanish Association Against Cancer (PROYE18012ROSE)EGFR mutation-positive lung adenocarcinoma (LUAD) displays impaired phosphorylation of ERK and Src-homology 2 domain-containing phosphatase 2 (SHP2) in comparison with EGFR wild-type LUADs. We hypothesize that SHP2 expression could be predictive in patients positive with resected EGFR mutation versus patients with EGFR wild-type LUAD. We examined resected LUAD cases from Japan and Spain. mRNA expression levels of AXL, MET, CDCP1, STAT3, YAP1, and SHP2 were analyzed by quantitative reverse transcriptase polymerase chain reaction. The activity of SHP2 inhibitors plus erlotinib were tested in EGFR -mutant cell lines and analyzed by cell viability assay, Western blot, and immunofluorescence. A total of 50 of 100 EGFR mutation-positive LUADs relapsed, among them, patients with higher SHP2 mRNA expression revealed shorter progression-free survival, in comparison with those having low SHP2 mRNA (hazard ratio: 1.83; 95% confidence interval: 1.05-3.23; p = 0.0329). However, SHP2 was not associated with prognosis in the remaining 167 patients with wild-type EGFR. In EGFR -mutant cell lines, the combination of SHP099 or RMC-4550 (SHP2 inhibitors) with erlotinib revealed synergism via abrogation of phosphorylated AKT (S473) and ERK1/2 (T202/Y204). Although erlotinib translocates phosphorylated SHP2 (Y542) into the nucleus, either RMC-4550 alone, or in combination with erlotinib, relocates SHP2 into the cytoplasm membrane, limiting AKT and ERK1/2 activation. Elevated SHP2 mRNA levels are associated with recurrence in resected EGFR mutation-positive LUADs, but not in EGFR wild-type. EGFR tyrosine kinase inhibitors can enhance SHP2 activation, hindering adjuvant therapy. SHP2 inhibitors could improve the benefit of adjuvant therapy in EGFR mutation-positive LUADs

Diabetic retinopathy as an independent predictor of subclinical cardiovascular disease : Baseline results of the PRECISED study

Funding This work was supported by an Integrative Excellence Project by the Spanish Institute of Health, Instituto de Salud Carlos III, grant PIE 2013/27, CIBER CV, CIBERDEM, and the European Regional Development Fund (ERDF-FEDER). The Neurovascular Research Laboratory is part of the Spanish Stroke Research Network INVICTUS+ (RD16/0019/0021).Objective Detection of subclinical cardiovascular disease (CVD) has significant impact on the management of type 2 diabetes. We examined whether the assessment of diabetic retinopathy (DR) is useful for identifying patients at a higher risk of having silent CVD. Research design and methods Prospective case-control study comprising 200 type 2 diabetic subjects without history of clinical CVD and 60 age-matched non-diabetic subjects. The presence of subclinical CVD was examined using two parameters: (1) calcium coronary score (CACs); (2) composite of CACs >400 UA, carotid plaque ≥3 mm, carotid intima-media thickness ratio >1, or the presence of ECG changes suggestive of previous asymptomatic myocardial infarction. In addition, coronary angio-CT was performed. DR was assessed by slit-lamp biomicroscopy and retinography. Results Type 2 diabetic subjects presented higher CACs than non-diabetic control subjects (p400 (area under the receiver operating characteristic curve (AUROC) 0.76). In addition, an inverse relationship was observed between the degree of DR and CACs <10 AU. The variables independently associated with the composite measurement of subclinical CVD were age, diabetes duration, the glomerular filtration rate, microalbuminuria, and the presence of DR (AUROC 0.71). In addition, a relationship (p<0.01) was observed between the presence and degree of DR and coronary stenosis. Conclusions The presence and degree of DR is independently associated with subclinical CVD in type 2 diabetic patients. Our results lead us to propose a rationalized screening for coronary artery disease in type 2 diabetes based on prioritizing patients with DR, particularly those with moderate-severe degree

Diabetic retinopathy as an independent predictor of subclinical cardiovascular disease: baseline results of the PRECISED study

Type 2 diabetes; Diabetic retinopathy; Subclinical cardiovascular diseaseDiabetis tipus 2; Retinopatia diabètica; Malalties cardiovasculars subclíniquesDiabetes tipo 2; Retinopatía diabética; Enfermedades cardiovasculares subclínicasObjective Detection of subclinical cardiovascular disease (CVD) has significant impact on the management of type 2 diabetes. We examined whether the assessment of diabetic retinopathy (DR) is useful for identifying patients at a higher risk of having silent CVD. Research design and methods Prospective case–control study comprising 200 type 2 diabetic subjects without history of clinical CVD and 60 age-matched non-diabetic subjects. The presence of subclinical CVD was examined using two parameters: (1) calcium coronary score (CACs); (2) composite of CACs >400 UA, carotid plaque ≥3 mm, carotid intima–media thickness ratio >1, or the presence of ECG changes suggestive of previous asymptomatic myocardial infarction. In addition, coronary angio-CT was performed. DR was assessed by slit-lamp biomicroscopy and retinography. Results Type 2 diabetic subjects presented higher CACs than non-diabetic control subjects (p400 (area under the receiver operating characteristic curve (AUROC) 0.76). In addition, an inverse relationship was observed between the degree of DR and CACs <10 AU. The variables independently associated with the composite measurement of subclinical CVD were age, diabetes duration, the glomerular filtration rate, microalbuminuria, and the presence of DR (AUROC 0.71). In addition, a relationship (p<0.01) was observed between the presence and degree of DR and coronary stenosis. Conclusions The presence and degree of DR is independently associated with subclinical CVD in type 2 diabetic patients. Our results lead us to propose a rationalized screening for coronary artery disease in type 2 diabetes based on prioritizing patients with DR, particularly those with moderate–severe degree.This work was supported by an Integrative Excellence Project by the Spanish Institute of Health, Instituto de Salud Carlos III, grant PIE 2013/27, CIBER CV, CIBERDEM, and the European Regional Development Fund (ERDF-FEDER). The Neurovascular Research Laboratory is part of the Spanish Stroke Research Network INVICTUS+ (RD16/0019/0021)

Road2CPS priorities and recommendations for research and innovation in cyber-physical systems

This document summarises the findings of the Road2CPS project, co-financed by the European Commission under the H2020 Research and Innovation Programme, to develop a roadmap and recommendations for strategic action required for future deployment of Cyber-Physical Systems (CPS). The term Cyber-Physical System describes hardware-software systems, which tightly couple the physical world and the virtual world. They are established from networked embedded systems that are connected with the outside world through sensors and actuators and have the capability to collaborate, adapt, and evolve. In the ARTEMIS Strategic Research Agenda 2016, CPS are described as ‘Embedded Intelligent ICT Systems’ that make products smarter, more interconnected, interdependent, collaborative, and autonomous. In the future world of CPS, a huge number of devices connected to the physical world will be able to exchange data with each other, access web services, and interact with people. Moreover, information systems will sense, monitor and even control the physical world via Cyber-Physical Systems and the Internet of Things (HiPEAC Vision 2015). Cyber-Physical Systems find their application in many highly relevant areas to our society: multi-modal transport, health, smart factories, smart grids and smart cities amongst others. The deployment of Cyber-Physical Systems (CPS) is expected to increase substantially over the next decades, holding great potential for novel applications and innovative product development. Digital technologies have already pervaded day-to-day life massively, affecting all kinds of interactions between humans and their environment. However, the inherent complexity of CPSs, as well as the need to meet optimised performance and comply with essential requirements like safety, privacy, security, raises many questions that are currently being explored by the research community. Road2CPS aims at accelerating uptake and implementation of these efforts. The Road2CPS project identifying and analysing the relevant technology fields and related research priorities to fuel the development of trustworthy CPS, as well as the specific technologies, needs and barriers for a successful implementation in different application domains and to derive recommendations for strategic action. The document at hand was established through an interactive, community-based approach, involving over 300 experts from academia, industry and policy making through a series of workshops and consultations. Visions and priorities of recently produced roadmaps in the area of CPS, IoT (Internet of Things), SoS (System-of-Systems) and FoF (Factories of the Future) were discussed, complemented by sharing views and perspectives on CPS implementation in application domains, evolving multi-sided eco-systems as well as business and policy related barriers, enablers and success factors. From the workshops and accompanying activities recommendations for future research and innovation activities were derived and topics and timelines for their implementation proposed. Amongst the technological topics, and related future research priorities ‘integration, interoperability, standards’ ranged highest in all workshops. The topic is connected to digital platforms and reference architectures, which have already become a key priority theme for the EC and their Digitisation Strategy as well as the work on the right standards to help successful implementation of CPSs. Other themes of very high technology/research relevance revealed to be ‘modelling and simulation’, ‘safety and dependability’, ‘security and privacy’, ‘big data and real-time analysis’, ‘ubiquitous autonomy and forecasting’ as well as ‘HMI/human machine awareness’. Next to this, themes emerged including ‘decision making and support’, ‘CPS engineering (requirements, design)’, ‘CPS life-cycle management’, ‘System-of-Systems’, ‘distributed management’, ‘cognitive CPS’, ‘emergence, complexity, adaptability and flexibility’ and work on the foundations of CPS and ‘cross-disciplinary research/CPS Science’