Model Driven Mutation Applied to Adaptative Systems Testing

Dynamically Adaptive Systems modify their behav- ior and structure in response to changes in their surrounding environment and according to an adaptation logic. Critical sys- tems increasingly incorporate dynamic adaptation capabilities; examples include disaster relief and space exploration systems. In this paper, we focus on mutation testing of the adaptation logic. We propose a fault model for adaptation logics that classifies faults into environmental completeness and adaptation correct- ness. Since there are several adaptation logic languages relying on the same underlying concepts, the fault model is expressed independently from specific adaptation languages. Taking benefit from model-driven engineering technology, we express these common concepts in a metamodel and define the operational semantics of mutation operators at this level. Mutation is applied on model elements and model transformations are used to propagate these changes to a given adaptation policy in the chosen formalism. Preliminary results on an adaptive web server highlight the difficulty of killing mutants for adaptive systems, and thus the difficulty of generating efficient tests.Comment: IEEE International Conference on Software Testing, Verification and Validation, Mutation Analysis Workshop (Mutation 2011), Berlin : Allemagne (2011

A tool for domain-independent model mutation

Mutation is a systematic technique to create variants of a seed artefact by means of mutation operators. It has many applications in computer science, like software testing, automatic exercise generation and design space exploration. Typically, mutation frameworks are developed ad-hoc by implementing mutation operators and their application strategies from scratch, using general-purpose programming languages. However, this is costly and error-prone. To improve this situation, we propose WODEL: a domain-specific language and tool for model-based mutation that is independent of the domain meta-model. WODELenables the rapid development and application of model mutations. It provides built-in advanced functionalities like automatic generation of seed models, and static and dynamic metrics of operator coverage and applicability. It offers extension points, e.g., to post-process mutants and describe domain-specific equivalence criteria. As an example, we illustrate the usage of WODEL for the mutation of security policies, and present an empirical evaluation of its expressiveness.Work partially funded by project FLEXOR (Spanish MINECO, TIN2014- 52129-R), project DArDOS (Spanish MINECO/FEDER TIN2015-65845-C3-1- R) and the R&D programme of the Madrid Region (S2013/ICE-3006

Wodel: a domain-specific language for model mutation

This is the author's version of the work. It is posted here for your personal use. Not for redistribution. The definitive Version of Record was published in SAC '16: Proceedings of the 31st Annual ACM Symposium on Applied Computing, http://dx.doi.org/10.1145/10.1145/2851613.2851751Model-Driven Engineering (MDE) is a software engineering paradigm that uses models as main assets in all development phases. While many languages for model manipulation exist (e.g., for model transformation or code generation), there is a lack of frameworks to de ne and apply model mutations. A model mutant is a variation of an original model, created by speci c model mutation operations. Model mutation has many applications, for instance, in the areas of model trans- formation testing, model-based testing or education. In this paper, we present a domain-speci c language, called Wodel, for the speci cation and generation of model mu- tants. Wodel is domain-independent, as it can be used to generate mutants of models conforming to arbitrary meta- models. Its development environment is extensible, permit- ting the incorporation of post-processors for di erent appli- cations. As an example, we show an application consisting on the automated generation of exercises for particular do- mains (automata, class diagrams, electronic circuits, etc.).Thanks to Víctor López Rivero for the initial implementation of the Wodel IDE. Work supported by the Spanish Ministry of Economy and Competitivity (TIN2014-52129-R), the Madrid Region (S2013/ICE-3006), and the EU commission (FP7-ICT-2013-10, #611125)

A FEM-experimental approach for the development of a conceptual linear actuator based on tendril's free coiling

Within the vastness of the plant species, certain living systems show tendril structures whose motion is of particular interest for biomimetic engineers. Tendrils sense and coil around suitable grips, and by shortening in length, they erect the remaining plant body. To achieve contraction, tendrils rotate along their main axis and shift from a linear to a double-spring geometry. This phenomenon is denoted as the free-coiling phase. In this work, with the aim of understanding the fundamentals of the mechanics behind the free coiling, a reverse-engineering approach based on the finite element method was firstly applied. The model consisted of an elongated cylinder with suitable material properties, boundary, and loading conditions, in order to reproduce the kinematics of the tendril. The simulation succeeded in mimicking coiling faithfully and was therefore used to validate a tentative linear actuator model based on the plant’s working principle. More in detail, exploiting shape memory alloy materials to obtain large reversible deformations, the main tendril features were implemented into a nickel-titanium spring-based testing model. The results of the experimental tests confirmed the feasibility of the idea in terms of both functioning principles and actual performance. It can be concluded that the final set-up can be used as a base for a prototype design of a new kind of a linear actuator

Design and validation of structural health monitoring system based on bio-inspired algorithms

The need of ensure the proper performance of the structures in service has made of structural health monitoring (SHM) a priority research area. Researchers all around the world have focused efforts on the development of new ways to continuous monitoring the structures and analyze the data collected from the inspection process in order to provide information about the current state and avoid possible catastrophes. To perform an effective analysis of the data, the development of methodologies is crucial in order to assess the structures with a low computational cost and with a high reliability. These desirable features can be found in biological systems, and these can be emulated by means of computational systems. The use of bio-inspired algorithms is a recent approach that has demonstrated its effectiveness in data analysis in different areas. Since these algorithms are based in the emulation of biological systems that have demonstrated its effectiveness for several generations, it is possible to mimic the evolution process and its adaptability characteristics by using computational algorithms. Specially in pattern recognition, several algorithms have shown good performance. Some widely used examples are the neural networks, the fuzzy systems and the genetic algorithms. This thesis is concerned about the development of bio-inspired methodologies for structural damage detection and classification. This document is organized in five chapters. First, an overview of the problem statement, the objectives, general results, a brief theoretical background and the description of the different experimental setups are included in Chapter 1 (Introduction). Chapters 2 to 4 include the journal papers published by the author of this thesis. The discussion of the results, some conclusions and the future work can be found on Chapter 5. Finally, Appendix A includes other contributions such as a book chapter and some conference papers.La necesidad de asegurar el correcto funcionamiento de las estructuras en servicio ha hecho de la monitorización de la integridad estructural un área de gran interés. Investigadores en todas las partes del mundo centran sus esfuerzos en el desarrollo de nuevas formas de monitorización contínua de estructuras que permitan analizar e interpretar los datos recogidos durante el proceso de inspección con el objetivo de proveer información sobre el estado actual de la estructura y evitar posibles catástrofes. Para desarrollar un análisis efectivo de los datos, es necesario el desarrollo de metodologías para inspeccionar la estructura con un bajo coste computacional y alta fiabilidad. Estas características deseadas pueden ser encontradas en los sistemas biológicos y pueden ser emuladas mediante herramientas computacionales. El uso de algoritmos bio-inspirados es una reciente técnica que ha demostrado su efectividad en el análisis de datos en diferentes áreas. Dado que estos algoritmos se basan en la emulación de sistemas biológicos que han demostrado su efectividad a lo largo de muchas generaciones, es posible imitar el proceso de evolución y sus características de adaptabilidad al medio usando algoritmos computacionales. Esto es así, especialmente, en reconocimiento de patrones, donde muchos de estos algoritmos brindan excelentes resultados. Algunos ejemplos ampliamente usados son las redes neuronales, los sistemas fuzzy y los algoritmos genéticos. Esta tesis involucra el desarrollo de unas metodologías bio-inspiradas para la detección y clasificación de daños estructurales. El documento está organizado en cinco capítulos. En primer lugar, se incluye una descripción general del problema, los objetivos del trabajo, los resultados obtenidos, un breve marco conceptual y la descripción de los diferentes escenarios experimentales en el Capítulo 1 (Introducción). Los Capítulos 2 a 4 incluyen los artículos publicados en diferentes revistas indexadas. La revisión de los resultados, conclusiones y el trabajo futuro se encuentra en el Capítulo 5. Finalmente, el Anexo A incluye otras contribuciones tales como un capítulo de libro y algunos trabajos publicados en conferencias

Modelling bargaining behaviors within biotech clusters - Towards the "power of the weak" emergence?

If spatial and industrial economics theorical models, such as industrial districts, clusters, or learning regions propose a large analysis of differentiated coordination mecanisms, it however not really takes into account behavior of dispute dynamics, such as conflict of bargaining and power, which can explain both diversity and ambivalence of local coordinations. So, our purpose in this contribution is to bring to light that bargaining and power conflicts are at stake in coordinations structuration within territories. We base this contribution on Artificial Life simulations involving public and private local actors who bargain to share a local resource using more or less sophisticated strategies. On a methodologic point of view, our thought is based on an empirical established fact. Analysis of a biotechnology cluster in Toulouse-France (Leroux I., 2002, 2004) indeed contributes to bring to light that coordinations involving pharmaceutical industry, local communities and local research laboratories are based on direct or indirect evolving domination and concession bargaining games. If industrial firms play "the power of the weak" game, making concession of their decision power to public research laboratories, they endeavour systematically to exerce an influence or a discrimination power, by using hided and indirect means that forward by local communities.Starting from this established fact, we propose Artificial Life simulations of local bargaining games, inspired from the T. Ellingsen (1997) bargaining evolutionnary game. This is a Nash demand game under ultimatum. It leads to the interaction of obstinate agents whose demands are independent of those of the adversaries, and sophisticated agents who adapt their demand to that hoped for of their adversaries rather than gain nothing. As a result, our simulations show that bargainings between these local actors lead to an agreement which is not a perfect share, or an "universal" rule, but a compromise frequently hiding complex mecanisms of domination and concession. The main contribution of these simulations, which are based on genetic algorithms, is to put in a prominent position the variations of behavioral rules. We show how bargaining is an evolving processus based on domination and concession behaviors (influence, coercion,…) bringing to light the T. Schelling (1960) "power of the weak". This result brings to the fore the question of flexibility and phasing dynamics of power behaviors in local coordination bargainings. This model can contributes to open new researches focused on power and conflict strategies within local coordinations.

EVOLUTION OF CRISPR SYSTEM AND THEIR APPLICABILITY TO GENOME EDITING IN BACTERIA

Recombinant DNA and genetic engineering technologies have made it possible to manipulate and carry out important advances in biology. However designing reliable, safe and accurate system for genome editing in prokaryotes and eukaryotes has been an issue for a long time. Enzymes (such as polymerases, ligases, and restriction endonucleases) and the polymerase chain reaction (PCR) provided ways to isolate genes and gene fragments, as well as to introduce mutations into gens in vitro, in cells and in a model organism. Today, the field of biology is undergoing a transformative phase with the advent of easy genome engineering using RNA-programmable CRISPR-Cas9. The CRISPR-Cas9 system is an immune system present in prokaryotes that allows the identification of exogenous DNA or RNA molecules. The Cas9 endonuclease is associated with a guide RNA molecule (RNAg) that allows it to form base pairs with target DNA or RNA sequencing, allowing Cas9 to introduce a site-specific double-strand break. Thanks to this breakthrough in genetic engineering Doudna Jennifer and Charpentier Emmanuelle were awarded the Nobel Prize in Chemistry in 2020 (Doudna and Charpentier., 2014). In what follows I will talk about the applicability of this system to edit bacterial genomes by punctiform, genetic and metabolic modifications

Understanding the response to EGFR targeting therapy in non-small-cell lung cancer using -omics approach

NSCLC is the leading cause of cancer-related death worldwide. EGFR targeted therapy is used to inhibit the progress of NSCLC, but patients inevitably develop resistance to EGFRTKIs. The work presented in this thesis aimed at better understanding response and resistance mechanisms to EGFR-TKIs in NSCLC and to find novel biomarkers as well as drug targets or combination therapies for NSCLC. Paper I suggested a group of miRNAs with AAGUGC motif as oncomotif-miRNAs. Through the control of their target tumor suppressors, the oncomotif-miRNAs are part of the oncogenic signaling network that regulates NSCLC’s and other types of cancer’s cell proliferation. Paper II identified that BCL6, FGFR2, and JAK3 were upregulated after EGFR-TKI treatment. Moreover, BCL6 together with EGFR were confirmed to contribute to treatment escape. Dual targeting of BCL6 and EGFR could therefore be a potential combination therapy for treating NSCLC. Paper III reported that CDKN2A loss is associated with EGFR-TKIs sensitivity in EGFRwt NSCLC, and that BCL2L1 (encoding for BCL-xL) overexpression existed before EGFR-TKI treatment in a subset of EGFR-TKI responding cell lines. Additionally, EGFRwt/KRASwt, CDKN2A deleted NSCLC is sensitive to BCL-xL and EGFR dual inhibition, which could be a potential combination therapy for patients with this profile. These findings suggest that CDKN2A deletion can be used as a biomarker to select EGFRwt KRASwt patients for EGFRTKI based combination therapy. Paper IV identified the upregulation of AXL and GAS6, EMT, MAPK pathway reactivation, and AXL dependent CDK1 phosphorylation as potential resistance mechanisms of the thirdgeneration EGFR-TKIs. The work summarized in this thesis add new knowledge to understand the EGFR-TKI response and resistance mechanisms in NSCLC. From our work CDKN2A and oncomotifmiRNA have been identified as interesting candidates that can be investigated for use as biomarkers in NSCLC. Moreover, we propose that BCL6 or BCL-xL inhibitors together with EGFR-TKIs should be further investigated as a combination therapy