Model-driven Engineering IDE for Quality Assessment of Data-intensive Applications

This article introduces a model-driven engineering (MDE) integrated development environment (IDE) for Data-Intensive Cloud Applications (DIA) with iterative quality enhancements. As part of the H2020 DICE project (ICT-9-2014, id 644869), a framework is being constructed and it is composed of a set of tools developed to support a new MDE methodology. One of these tools is the IDE which acts as the front-end of the methodology and plays a pivotal role in integrating the other tools of the framework. The IDE enables designers to produce from the architectural structure of the general application along with their properties and QoS/QoD annotations up to the deployment model. Administrators, quality assurance engineers or software architects may also run and examine the output of the design and analysis tools in addition to the designer in order to assess the DIA quality in an iterative process

Evaluation Strategies for Datalog-based Points-To Analysis

During the last decade, several hard problems have been described and solved in Datalog in a sound way (points-to analyses, data web management, security, privacy, and trust). In this work, we describe novel evaluation strategies for this language within the context of program analyses. We first decompose any Datalog program into a program where rules have at most two atoms in their body. Then, we show that a specialized bottom-up evaluation algorithm with time and memory guarantees can be described as the on-the-fly resolution of a Boolean Equation System (Bes). The resolution computes all ground atoms in an efficient way thanks to a compact data structure with constant time access that has so far not been used in the Datalog or the Bes literature. A prototype has been developed and tested on a number of real Java projects in the context of Andersen’s points-to analysis. Experimental results show that our prototype is better than state-of-the-art solvers in terms of resolution time and memory consumption

Formal methods for industrial critical systems, preface to the special section

[EN] This special issue contains improved versions of selected papers from the workshops on Formal Methods for Industrial Critical Systems (FMICS) held in Eindhoven, The Netherlands, in November 2009 and in Antwerp, Belgium, in September 2010. These were, respectively, the 14th and 15th of a series of international workshops organized by an open working group supported by ERCIM (European Research Consortium for Informatics and Mathematics) that promotes research in all aspects of formal methods (see details in http://www.inrialpes.fr/vasy/fmics/). The FMICS workshops that have produced this special issue considered papers describing original, previously unpublished research and not simultaneously submitted for publication elsewhere, and dealing with the following themes: Design, specification, code generation and testing based on formal methods. Methods, techniques and tools to support automated analysis, certification, debugging, learning, optimization and transformation of complex, distributed, real-time and embedded systems. Verification and validation methods that address shortcomings of existing methods with respect to their industrial applicability (e.g., scalability and usability issues). Tools for the development of formal design descriptions. Case studies and experience reports on industrial applications of formal methods, focusing on lessons learned or new research directions. Impact and costs of the adoption of formal methods. Application of formal methods in standardization and industrial forums. The selected papers are the result of several evaluation steps. In response to the call for papers, FMICS 2009 received 24 papers and FMICS 2010 received 33 papers, with 10 and 14 accepted, respectively, which were published by Springer- Verlag in the series Lecture Notes in Computer Science (volumes 5825 [1] and 6371 [2]). Each paper was reviewed by at least three anonymous referees which provided full written evaluations. After the workshops, the authors of 10 papers were invited to submit extended journal versions to this special issue. These papers passed two review phases, and finally 7 were accepted to be included in the journal.his work has been partially supported by the EU (FEDER) and the Spanish MEC TIN2010-21062-C02-02 project, MICINN INNCORPORA-PTQ program, and by Generalitat Valenciana, ref. PROMETEO2011/052.Alpuente Frasnedo, M.; Joubert ., C.; Kowalewski, S.; Roveri, M. (2013). Formal methods for industrial critical systems, preface to the special section. Science of Computer Programming. 78(7):775-777. doi:10.1016/j.scico.2012.05.005S77577778

PIACERE: Programming trustworthy Infrastructure As Code in a Secure Framework

Infrastructure-as-Code (IaC), enables the automation of several deployment, configuration and management tasks. IaC has a lot of potential in cloud computing as it results in a significant saving of time when an application needs to be redeployed on a different set of resources, even running on different infrastructures. Unfortunately, IaC still suffers from some important issues, such as the large variety of competing tools or the strong orientation toward the cloud, leaving aside e.g. the edge. Also, trustworthiness and security aspects of are often left for the end of the cycle, where errors and vulnerabilities are often too late or too expensive to correct. We present here the PIACERE project, which provides tools, methods and techniques for the Infrastructure-as-Code approach. The project will make the creation of IaC more accessible to designers, developers and operators, increasing the quality, security, trustworthiness and evolvability of infrastructural code while ensuring its business continuity by providing self-healing mechanisms anticipation of failures and violations.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101000162

Conception aéroélastique optimale d'une aile de missile

Le couplage aéroélastique entre la structure évidée d'une aile de missile de croisière et le fluide en écoulement à vitesse transsonique sur cette aile est exploité pour augmenter la portée du missile. Une boucle de calcul permet de calculer la finesse du missile sous charge à l'équilibre des forces et de vérifier sa tenue structurale. Une exploration systématique de l'espace des paramètres est présentée et analysée

RIPK3-mediated cell death is involved in DUX4-mediated toxicity in facioscapulohumeral dystrophy

BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is caused by mutations leading to the aberrant expression of the DUX4 transcription factor in muscles. DUX4 was proposed to induce cell death, but the involvement of different death pathways is still discussed. A possible pro‐apoptotic role of DUX4 was proposed, but as FSHD muscles are characterized by necrosis and inflammatory infiltrates, non‐apoptotic pathways may be also involved. METHODS: We explored DUX4‐mediated cell death by focusing on the role of one regulated necrosis pathway called necroptosis, which is regulated by RIPK3. We investigated the effect of necroptosis on cell death in vitro and in vivo experiments using RIPK3 inhibitors and a RIPK3‐deficient transgenic mouse model. RESULTS: We showed in vitro that DUX4 expression causes a caspase‐independent and RIPK3‐mediated cell death in both myoblasts and myotubes. In vivo, RIPK3‐deficient animals present improved body and muscle weights, a reduction of the aberrant activation of the DUX4 network genes, and an improvement of muscle histology. CONCLUSIONS: These results provide evidence for a role of RIPK3 in DUX4‐mediated cell death and open new avenues of research

Reference gene selection for head and neck squamous cell carcinoma gene expression studies

<p>Abstract</p> <p>Background</p> <p>It is no longer adequate to choose reference genes blindly. We present the first study that defines the suitability of 12 reference genes commonly used in cancer studies (<it>ACT, ALAS, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPL27, RPS29, SHAD </it>and <it>TBP</it>) for the normalization of quantitative expression data in the field of head and neck squamous cell carcinoma (HNSCC).</p> <p>Results</p> <p>Raw expression levels were measured by RT-qPCR in HNSCC and normal matched mucosa of 46 patients. We analyzed the expression stability using geNorm and NormFinder and compared the expression levels between subgroups. In HNSCC and/or normal mucosa, the four best normalization genes were <it>ALAS, GAPDH, RPS18 </it>and <it>SHAD </it>and the most stable combination of two genes was <it>GAPDH-SHAD</it>. We recommend using <it>KALPHA-TBP </it>for the study of T1-T2 tumors, <it>RPL27-SHAD </it>for T3-T4 tumors, <it>KALPHA-SHAD </it>for N0 tumors, and <it>ALAS-TBP </it>for N+ tumors. <it>ACT, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPS29, SHAD </it>and <it>TBP </it>were slightly misregulated (<1.7-fold) between tumor and normal mucosa but can be used for normalization, depending on the resolution required for the assay.</p> <p>Conclusion</p> <p>In the field of HNSCC, this study will guide researchers in selecting the most appropriate reference genes from among 12 potentially suitable reference genes, depending on the specific setting of their experiments.</p

Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL in 2009: a French nationwide study

Background Surveillance of HIV-1 drug resistance in treated patients with plasma viral load (VL) >50 copies/mL. Methods The protease and reverse transcriptase (RT) genes were systematically sequenced in samples from 756 patients with VL >50 copies/mL in 2009. The genotyping results were interpreted for each antiretroviral drug (ARV) by using the ANRS algorithm v21. Weighted analyses were used to derive representative estimates of percentages of patients. Prevalence rates were compared with those obtained in 2004 among patients with VL >1000 copies/mL. Results Sequences were obtained for 506 patients. Sequencing was successful in 45%, 80% and 96% of samples with VL of 51-500, 501-1000 and >1000 copies/mL, respectively. Resistance or possible resistance to at least one ARV was observed in 59% of samples. Overall, 0.9% of samples contained viruses resistant to all drugs belonging to at least three drug classes. All resistance prevalence rates were significantly lower in 2009 than in 2004. Conclusion In France, where 86% of patients were receiving combination antiretroviral therapy in 2009, only 15.0% of patients had a VL >50 copies/mL, suggesting that only 8.9% of treated patients could potentially transmit resistant viruses. Only 0.08% of patients harboured viruses fully resistant to at least three antiretroviral drug classes. Further studies are needed to determine whether resistance continues to decline over tim

Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

The contemporary diagnosis of paraneoplastic neurologic syndromes (PNSs) requires an increasing understanding of their clinical, immunologic, and oncologic heterogeneity. The 2004 PNS criteria are partially outdated due to advances in PNS research in the last 16 years leading to the identification of new phenotypes and antibodies that have transformed the diagnostic approach to PNS. Here, we propose updated diagnostic criteria for PNS.A panel of experts developed by consensus a modified set of diagnostic PNS criteria for clinical decision making and research purposes. The panel reappraised the 2004 criteria alongside new knowledge on PNS obtained from published and unpublished data generated by the different laboratories involved in the project.The panel proposed to substitute "classical syndromes" with the term "high-risk phenotypes" for cancer and introduce the concept of "intermediate-risk phenotypes." The term "onconeural antibody" was replaced by "high risk" (>70% associated with cancer) and "intermediate risk" (30%-70% associated with cancer) antibodies. The panel classified 3 levels of evidence for PNS: definite, probable, and possible. Each level can be reached by using the PNS-Care Score, which combines clinical phenotype, antibody type, the presence or absence of cancer, and time of follow-up. With the exception of opsoclonus-myoclonus, the diagnosis of definite PNS requires the presence of high- or intermediate-risk antibodies. Specific recommendations for similar syndromes triggered by immune checkpoint inhibitors are also provided.The proposed criteria and recommendations should be used to enhance the clinical care of patients with PNS and to encourage standardization of research initiatives addressing PNS.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide

Objectives We studied gp41 mutations associated with failing enfuvirtide salvage therapy. Methods This multicentre study involved patients with HIV-1 plasma viral load (pVL) > 5000 copies/mL after at least 3 months of uninterrupted enfuvirtide therapy and with plasma samples available at inclusion (T0), at initial enfuvirtide failure (T1) and at last follow-up visit during continued failing enfuvirtide therapy (T2). The HR-1 and HR-2 domains of the gp41 gene were sequenced at T0, T1 and T2. Results Ninety-nine patients were enrolled. At baseline, the median pVL and CD4 cell count were 5.1 log copies/mL and 72 cells/mm3, respectively. Based on the ANRS Resistance Group algorithm, the proportion of patients harbouring viruses with enfuvirtide resistance mutations increased significantly between T0 and T1. In the HR-1 domain, the V38A/M, Q40H, N42T, N43D and L45M mutations wereselected (P < 0.02). In the HR-2 domain, no mutations were significantly selected during the follow-up. None of the mutations was associated with a CD4 cell count increment. Conclusions Mutations selected during failing enfuvirtide salvage therapy are mainly located in the HR-1 domain of the gp41 gene, between codons 38 and 45. No mutations were associated with an increase in the CD4 cell coun