Canevas de développement agile pour l'évolution fiable de systèmes logiciels à composants et orientés services

Modern software is characterized by a need for constant and rapid evolution, such as in the mobile domain. To facilitate the development and the rapid evolution of complex systems, software engineering approaches have been proposed, such as software architecture and agile software development. However, current solutions offer poor support to enable the development of a reliable system, i.e, allow its modification while ensuring its compliance with the quality of services requirement and its good overall safety. The contribution of this PhD thesis is CALICO, an agile development framework for the design and evolution of safe component-based and service-oriented software. The agile software development relies on an iterative and incremental development cycle that allows the architect to iterate between the design of the architecture and the debug of the software in its execution context. At each iteration, the architect can evolve its software and check the consistency of its evolution through the execution of static and dynamic analysis tools. Thus, during the design and the evolution of the system, architect can use a set of metamodels to specify the structure of the architecture and its various quality of services requirement. During the deployment, CALICO instantiates the system on the target runtime platform from the models specified and keeps them synchronized with the software during its execution. By this way, the architect still has a conceptual view which allows him to reason on the critical software properties during its evolution. Moreover, in order to check these evolutions, CALICO provides a unifying framework which allows reuse of many static analysis tools of software architectures and dynamic debugging tools, that were scattered in different existing platforms. Thus, each change can be statically analyzed on the conceptual view before being propagated to the software system. Dynamic analysis are based on data values only available during the execution. The capture of these values is done through automatic instrumentation of the software system. Globally, CALICO enables reliable evolution even if the underlying platforms does not natively provide this support. Our contribution is concretized by a multi-platform implementation. The current version handles four component-based and service-oriented platforms. Moreover, the benchmarks that we have performed show that CALICO is usable for the design and development of safe applications up to 10,000 components and services, which corresponds to the maximal load of most runtime platforms.Les systèmes logiciels modernes se caractérisent par un besoin d'évolutions perpétuelles et rapides, comme par exemple dans le monde de l'informatique mobile. Pour faciliter le développe\-ment et l'évolution rapide de systèmes complexes, des approches de génie logiciel ont été proposées, telles que les architectures logicielles et la méthode de conception agile. Néanmoins, les solutions actuelles offrent peu de support pour permettre l'évolution fiable d'un système, c'est-à-dire permettre sa modification tout en garantissant le respect de ses exigences de qualités de service et de bon fonctionnement global. La contribution de cette thèse est CALICO, un canevas de développement agile pour la conception et l'évolution fiable de systèmes logiciels à composants et orientés services. Le développement agile repose sur l'utilisation d'un cycle de développement itératif et incrémental qui permet à l'architecte d'itérer entre les étapes de conception de l'architecture et de débogage du logiciel dans son environnement d'exécution. A chaque itération du cycle, l'architecte peut faire évoluer son logiciel et fiabiliser ses évolutions grâce à l'exécution d'analyses statiques et dynamiques complémentaires. Ainsi, lors de la conception et de l'évolution d'un système, l'architecte dispose d'un ensemble de métamodèles pour spécifier la structure de l'architecture de son logiciel et ses diverses exigences de qualité de services. Lors du déploiement, CALICO utilise les modèles spécifiés pour instancier le système sur la plate-forme d'exécution cible et les garde synchronisés avec le logiciel lors de son exécution. De cette façon, l'architecte dispose toujours d'une vue conceptuelle qui lui permet de raisonner sur les propriétés critiques de son logiciel lors d'une évolution. De plus, pour fiabiliser ces évolutions, CALICO offre un cadre fédérateur qui autorise la réutilisation de nombreux outils d'analyse statique des architectures logicielles et de débogage dynamique qui étaient jusqu'alors dispersés dans différentes plates-formes existantes. Ainsi, chaque évolution peut être analysée statiquement sur la vue conceptuelle avant d'être propagée au système logiciel. Les analyses dynamiques reposent quant à elles sur des valeurs disponibles à l'exécution. La capture de ces valeurs est effectuée grâce à une instrumentation automatique du système logiciel. CALICO permet donc de fiabiliser les évolutions même si les plates-formes d'exécution sous-jacentes ne le proposent pas nativement. Notre contribution se concrétise par une implémentation multi plates-formes. La version actuelle prend en charge quatre plates-formes à composants et une plate-forme à services. Par ailleurs, les tests de performances que nous avons réalisés démontrent que CALICO est utilisable pour la conception et l'évolution fiable de larges applications jusqu'à 10000 composants et services, ce qui correspond à la montée en charge maximale de la plupart des plates-formes d'exécution

Mortalidad y recurrencia de la enfermedad tromboembólica venosa en pacientes adultos: cohorte prospectiva

INTRODUCCIÓN: La enfermedad tromboembólica venosa (ETV) es una patología que aumenta con la edad. Objetivo: comparar la sobrevida de los ancianos y los jóvenes con un primer episodio de ETV aguda y sintomática. MATERIALES Y MÉTODOS: Cohorte prospectiva de casos incidentes de ETV incluidos en el Registro Institucional de Enfermedad Tromboembólica venosa (NCT01372514) del Hospital Italiano de Buenos Aires entre 2012-2014, dividido en grupos jóvenes (17-64 años) y ancianos (≥ 65 años). Todos los pacientes fueron seguidos anualmente para evaluar el tiempo a la recurrencia (progresión o nuevo evento sintomático de ETV) como eventos competitivos en contexto de muerte y sangrado mayor. Se presentaron los riesgos crudos (c) y ajustados (a). RESULTADOS: se incluyeron 446 pacientes, el 63% (292) fueron mayores de 65 años. La sobrevida fue menor en los ancianos comparados con los jóvenes (p 0.007), a los 3 meses 87% vs 95% y al año 73% vs 87%, respectivamente. Los ancianos presentaron un HRc1,71 y HR a 1.68. La recurrencia global fue 5% (IC 95% 3-8) al mes, 6% (IC 95% 4-9) a los 3 meses, 8% (IC 95% 6-11) al año y 13% (IC 95% 9-18) a los dos años. No se encontró asociación entre la edad y la recurrencia sub hazard 0.8(IC 0,34-1,86). El sangrado ocurrió en un 9% (39) de los pacientes. CONCLUSIONES: La mortalidad global en pacientes con ETV confirmada es mayor en la población anciana. No hubo diferencias en relación a la recurrencia de ETV, ni el sangrado y tampoco con la edad

Can visco-elastic phase separation, macromolecular crowding and colloidal physics explain nuclear organisation?

BACKGROUND: The cell nucleus is highly compartmentalized with well-defined domains, it is not well understood how this nuclear order is maintained. Many scientists are fascinated by the different set of structures observed in the nucleus to attribute functions to them. In order to distinguish functional compartments from non-functional aggregates, I believe is important to investigate the biophysical nature of nuclear organisation. RESULTS: The various nuclear compartments can be divided broadly as chromatin or protein and/or RNA based, and they have very different dynamic properties. The chromatin compartment displays a slow, constrained diffusional motion. On the other hand, the protein/RNA compartment is very dynamic. Physical systems with dynamical asymmetry go to viscoelastic phase separation. This phase separation phenomenon leads to the formation of a long-lived interaction network of slow components (chromatin) scattered within domains rich in fast components (protein/RNA). Moreover, the nucleus is packed with macromolecules in the order of 300 mg/ml. This high concentration of macromolecules produces volume exclusion effects that enhance attractive interactions between macromolecules, known as macromolecular crowding, which favours the formation of compartments. In this paper I hypothesise that nuclear compartmentalization can be explained by viscoelastic phase separation of the dynamically different nuclear components, in combination with macromolecular crowding and the properties of colloidal particles. CONCLUSION: I demonstrate that nuclear structure can satisfy the predictions of this hypothesis. I discuss the functional implications of this phenomenon

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

A novel inhibitor of fatty acid synthase shows activity against HER2+ breast cancer xenografts and is active in anti-HER2 drug-resistant cell lines

Introduction: Inhibiting the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of breast carcinoma cells, and this is linked to human epidermal growth factor receptor 2 (HER2) signaling pathways in models of simultaneous expression of FASN and HER2. Methods: In a xenograft model of breast carcinoma cells that are FASN+ and HER2+, we have characterised the anticancer activity and the toxicity profile of G28UCM, the lead compound of a novel family of synthetic FASN inhibitors. In vitro, we analysed the cellular and molecular interactions of combining G28UCM with anti-HER drugs. Finally, we tested the cytotoxic ability of G28UCM on breast cancer cells resistant to trastuzumab or lapatinib, that we developed in our laboratory. Results: In vivo, G28UCM reduced the size of 5 out of 14 established xenografts. In the responding tumours, we observed inhibition of FASN activity, cleavage of poly-ADPribose polymerase (PARP) and a decrease of p-HER2, p- protein kinase B (AKT) and p-ERK1/2, which were not observed in the nonresponding tumours. In the G28UCM-treated animals, no significant toxicities occurred, and weight loss was not observed. In vitro, G28UCM showed marked synergistic interactions with trastuzumab, lapatinib, erlotinib or gefitinib (but not with cetuximab), which correlated with increases in apoptosis and with decreases in the activation of HER2, extracellular signal-regulated kinase (ERK)1/2 and AKT. In trastuzumab-resistant and in lapatinib-resistant breast cancer cells, in which trastuzumab and lapatinib were not effective, G28UCM retained the anticancer activity observed in the parental cells. Conclusions: G28UCM inhibits fatty acid synthase (FASN) activity and the growth of breast carcinoma xenografts in vivo, and is active in cells with acquired resistance to anti-HER2 drugs, which make it a candidate for further pre-clinical development