MBIS: Multivariate Bayesian Image Segmentation Tool

We present MBIS (Multivariate Bayesian Image Segmentation tool), a clustering tool based on the mixture of multivariate normal distributions model. MBIS supports multi-channel bias field correction based on a B-spline model. A second methodological novelty is the inclusion of graph-cuts optimization for the stationary anisotropic hidden Markov random field model. Along with MBIS, we release an evaluation framework that contains three different experiments on multi-site data. We first validate the accuracy of segmentation and the estimated bias field for each channel. MBIS outperforms a widely used segmentation tool in a cross-comparison evaluation. The second experiment demonstrates the robustness of results on atlas-free segmentation of two image sets from scan-rescan protocols on 21 healthy subjects. Multivariate segmentation is more replicable than the monospectral counterpart on T1-weighted images. Finally, we provide a third experiment to illustrate how MBIS can be used in a large-scale study of tissue volume change with increasing age in 584 healthy subjects. This last result is meaningful as multivariate segmentation performs robustly without the need for prior knowledge.

Modelo de arquitectura para gestión cooperativa de sistemas y servicios distribuidos basado en agentes autónomos

La creciente complejidad, heterogeneidad y dinamismo inherente a las redes de telecomunicaciones, los sistemas distribuidos y los servicios avanzados de información y comunicación emergentes, así como el incremento de su criticidad e importancia estratégica, requieren la adopción de tecnologías cada vez más sofisticadas para su gestión, su coordinación y su integración por parte de los operadores de red, los proveedores de servicio y las empresas, como usuarios finales de los mismos, con el fin de garantizar niveles adecuados de funcionalidad, rendimiento y fiabilidad. Las estrategias de gestión adoptadas tradicionalmente adolecen de seguir modelos excesivamente estáticos y centralizados, con un elevado componente de supervisión y difícilmente escalables. La acuciante necesidad por flexibilizar esta gestión y hacerla a la vez más escalable y robusta, ha provocado en los últimos años un considerable interés por desarrollar nuevos paradigmas basados en modelos jerárquicos y distribuidos, como evolución natural de los primeros modelos jerárquicos débilmente distribuidos que sucedieron al paradigma centralizado. Se crean así nuevos modelos como son los basados en Gestión por Delegación, en el paradigma de código móvil, en las tecnologías de objetos distribuidos y en los servicios web. Estas alternativas se han mostrado enormemente robustas, flexibles y escalables frente a las estrategias tradicionales de gestión, pero continúan sin resolver aún muchos problemas. Las líneas actuales de investigación parten del hecho de que muchos problemas de robustez, escalabilidad y flexibilidad continúan sin ser resueltos por el paradigma jerárquico-distribuido, y abogan por la migración hacia un paradigma cooperativo fuertemente distribuido. Estas líneas tienen su germen en la Inteligencia Artificial Distribuida (DAI) y, más concretamente, en el paradigma de agentes autónomos y en los Sistemas Multi-agente (MAS). Todas ellas se perfilan en torno a un conjunto de objetivos que pueden resumirse en alcanzar un mayor grado de autonomía en la funcionalidad de la gestión y una mayor capacidad de autoconfiguración que resuelva los problemas de escalabilidad y la necesidad de supervisión presentes en los sistemas actuales, evolucionar hacia técnicas de control fuertemente distribuido y cooperativo guiado por la meta y dotar de una mayor riqueza semántica a los modelos de información. Cada vez más investigadores están empezando a utilizar agentes para la gestión de redes y sistemas distribuidos. Sin embargo, los límites establecidos en sus trabajos entre agentes móviles (que siguen el paradigma de código móvil) y agentes autónomos (que realmente siguen el paradigma cooperativo) resultan difusos. Muchos de estos trabajos se centran en la utilización de agentes móviles, lo cual, al igual que ocurría con las técnicas de código móvil comentadas anteriormente, les permite dotar de un mayor componente dinámico al concepto tradicional de Gestión por Delegación. Con ello se consigue flexibilizar la gestión, distribuir la lógica de gestión cerca de los datos y distribuir el control. Sin embargo se permanece en el paradigma jerárquico distribuido. Si bien continúa sin definirse aún una arquitectura de gestión fiel al paradigma cooperativo fuertemente distribuido, estas líneas de investigación han puesto de manifiesto serios problemas de adecuación en los modelos de información, comunicación y organizativo de las arquitecturas de gestión existentes. En este contexto, la tesis presenta un modelo de arquitectura para gestión holónica de sistemas y servicios distribuidos mediante sociedades de agentes autónomos, cuyos objetivos fundamentales son el incremento del grado de automatización asociado a las tareas de gestión, el aumento de la escalabilidad de las soluciones de gestión, soporte para delegación tanto por dominios como por macro-tareas, y un alto grado de interoperabilidad en entornos abiertos. A partir de estos objetivos se ha desarrollado un modelo de información formal de tipo semántico, basado en lógica descriptiva que permite un mayor grado de automatización en la gestión en base a la utilización de agentes autónomos racionales, capaces de razonar, inferir e integrar de forma dinámica conocimiento y servicios conceptualizados mediante el modelo CIM y formalizados a nivel semántico mediante lógica descriptiva. El modelo de información incluye además un “mapping” a nivel de meta-modelo de CIM al lenguaje de especificación de ontologías OWL, que supone un significativo avance en el área de la representación y el intercambio basado en XML de modelos y meta-información. A nivel de interacción, el modelo aporta un lenguaje de especificación formal de conversaciones entre agentes basado en la teoría de actos ilocucionales y aporta una semántica operacional para dicho lenguaje que facilita la labor de verificación de propiedades formales asociadas al protocolo de interacción. Se ha desarrollado también un modelo de organización holónico y orientado a roles cuyas principales características están alineadas con las demandadas por los servicios distribuidos emergentes e incluyen la ausencia de control central, capacidades de reestructuración dinámica, capacidades de cooperación, y facilidades de adaptación a diferentes culturas organizativas. El modelo incluye un submodelo normativo adecuado al carácter autónomo de los holones de gestión y basado en las lógicas modales deontológica y de acción.---ABSTRACT---The growing complexity, heterogeneity and dynamism inherent in telecommunications networks, distributed systems and the emerging advanced information and communication services, as well as their increased criticality and strategic importance, calls for the adoption of increasingly more sophisticated technologies for their management, coordination and integration by network operators, service providers and end-user companies to assure adequate levels of functionality, performance and reliability. The management strategies adopted traditionally follow models that are too static and centralised, have a high supervision component and are difficult to scale. The pressing need to flexibilise management and, at the same time, make it more scalable and robust recently led to a lot of interest in developing new paradigms based on hierarchical and distributed models, as a natural evolution from the first weakly distributed hierarchical models that succeeded the centralised paradigm. Thus new models based on management by delegation, the mobile code paradigm, distributed objects and web services came into being. These alternatives have turned out to be enormously robust, flexible and scalable as compared with the traditional management strategies. However, many problems still remain to be solved. Current research lines assume that the distributed hierarchical paradigm has as yet failed to solve many of the problems related to robustness, scalability and flexibility and advocate migration towards a strongly distributed cooperative paradigm. These lines of research were spawned by Distributed Artificial Intelligence (DAI) and, specifically, the autonomous agent paradigm and Multi-Agent Systems (MAS). They all revolve around a series of objectives, which can be summarised as achieving greater management functionality autonomy and a greater self-configuration capability, which solves the problems of scalability and the need for supervision that plague current systems, evolving towards strongly distributed and goal-driven cooperative control techniques and semantically enhancing information models. More and more researchers are starting to use agents for network and distributed systems management. However, the boundaries established in their work between mobile agents (that follow the mobile code paradigm) and autonomous agents (that really follow the cooperative paradigm) are fuzzy. Many of these approximations focus on the use of mobile agents, which, as was the case with the above-mentioned mobile code techniques, means that they can inject more dynamism into the traditional concept of management by delegation. Accordingly, they are able to flexibilise management, distribute management logic about data and distribute control. However, they remain within the distributed hierarchical paradigm. While a management architecture faithful to the strongly distributed cooperative paradigm has yet to be defined, these lines of research have revealed that the information, communication and organisation models of existing management architectures are far from adequate. In this context, this dissertation presents an architectural model for the holonic management of distributed systems and services through autonomous agent societies. The main objectives of this model are to raise the level of management task automation, increase the scalability of management solutions, provide support for delegation by both domains and macro-tasks and achieve a high level of interoperability in open environments. Bearing in mind these objectives, a descriptive logic-based formal semantic information model has been developed, which increases management automation by using rational autonomous agents capable of reasoning, inferring and dynamically integrating knowledge and services conceptualised by means of the CIM model and formalised at the semantic level by means of descriptive logic. The information model also includes a mapping, at the CIM metamodel level, to the OWL ontology specification language, which amounts to a significant advance in the field of XML-based model and metainformation representation and exchange. At the interaction level, the model introduces a formal specification language (ACSL) of conversations between agents based on speech act theory and contributes an operational semantics for this language that eases the task of verifying formal properties associated with the interaction protocol. A role-oriented holonic organisational model has also been developed, whose main features meet the requirements demanded by emerging distributed services, including no centralised control, dynamic restructuring capabilities, cooperative skills and facilities for adaptation to different organisational cultures. The model includes a normative submodel adapted to management holon autonomy and based on the deontic and action modal logics.

Site-specific chemical modification with polyethylene glycol of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) improves antitumor activity and reduces animal toxicity and immunogenicity

Chemical modification of proteins with polyethylene glycol (PEGylation) can increase plasma half-lives, stability, and therapeutic potency. To make a PEGylated recombinant immunotoxin with improved therapeutic properties, we prepared a mutant of anti-Tac(Fv)-PE38 (LMB-2), a recombinant immunotoxin composed of a single-chain Fv fragment of the anti-human Tac monoclonal antibody to the IL-2 receptor α subunit fused to a 38-kDa fragment of Pseudomonas exotoxin. For site-specific PEGylation of LMB-2, one cysteine residue was introduced into the peptide connector (ASGCGPE) between the Fv and the toxin. This mutant LMB-2 (cys1-LMB-2), which retained full cytotoxic activity, was then site-specifically conjugated with 5 or 20 kDa of polyethylene glycol-maleimide. When compared with unmodified LMB-2, both PEGylated immunotoxins showed similar cytotoxic activities in vitro but superior stability at 37°C in mouse serum, a 5- to 8-fold increase in plasma half-lives in mice, and a 3- to 4-fold increase in antitumor activity. This was accompanied by a substantial decrease in animal toxicity and immunogenicity. Site-specific PEGylation of recombinant immunotoxins may increase their therapeutic potency in humans.

Assessment of CO2 adsorption capacity on activated carbons by a combination of batch and dynamic tests

In this work, batch and dynamic adsorption tests are coupled for an accurate evaluation of CO2 adsorption performance for three different activated carbons obtained from olives stones by chemical activation followed by physical activation with CO2 at varying times, i.e. 20, 40 and 60 h. Kinetic and thermodynamic CO2 adsorption tests from simulated flue-gas at different temperature and CO2 pressure are carried out both in batch (a manometric equipment operating with pure CO2) and dynamic (a lab-scale fixed-bed column operating with CO2/N2 mixture) conditions. The textural characterization of the activated carbon samples shows a direct dependence of both micropore and ultramicropore volume on the activation time, hence AC60 has the higher contribution. The adsorption tests conducted at 273 and 293 K showed that, when CO2 pressure is lower than 0.3 bar, the lower the activation time the higher CO2 adsorption capacity and a ranking ωeq(AC20)>ωeq(AC40)>ωeq(AC60) can be exactly defined when T= 293 K. This result can be likely ascribed to a narrower pore size distribution of the AC20 sample, whose smaller pores are more effective for CO2 capture at higher temperature and lower CO2 pressure, the latter representing operating conditions of major interest for decarbonation of a flue-gas effluent. Moreover, the experimental results obtained from dynamic tests confirm the results derived from the batch tests in terms of CO2 adsorption capacity. It is important to highlight that the adsorption of N2 on the synthesized AC samples can be considered negligible. Finally, the importance of a proper analysis of characterization data and adsorption experimental results is highlighted for a correct assessment of CO2 removal performances of activated carbons at different CO2 pressure and operating temperature.

Characterization of Carbon Molecular Sieve Membranes Supported on Ceramic Tubes

Carbon molecular sieve membranes have been analyzed in supported and unsupported configurations in this experimental study. The membranes were used to adsorb CO2, N2 and CH4, and their adsorption data were analyzed to establish differences in rate and capacity of adsorption between the two types of samples (supported and unsupported). Experimental results show an important effect of the support, which can be considered as an additional parameter to tailor pore size on these carbon membranes. Immersion calorimetry values were measured by immersing the membranes into liquids of different molecular dimensions (dichloromethane, benzene, n-hexane, 2,2-dimethylbutane). Similarities were found between adsorption and calorimetric analysis. The pore volume of the samples analyzed ranged from 0.016 to 0.263 cm3/g. The effect of the pyrolysis temperature, either 550 or 700 °C, under N2 atmosphere was also analyzed. Quantification of the pore-size distribution of the support was done by liquid-liquid displacement porosimetry. The composite membrane was used for CO2/CH4 separation before and after pore plugging was done. The ideal selectivity factors value (4.47) was over the Knudsen theoretical factor (0.60) for membrane pyrolyzed at 600 °C, which indicates the potential application of these membranes for the separation of low-molecular weight gases.

Nd and Sr isotope record of ODP Sites 121-756 and 122-762 sediments

We have analyzed the Nd isotopic composition of both ancient seawater and detrital material from long sequences of carbonated oozes of the South Indian Ocean which are ODP Site 756 (Ninety East Ridge (-30°S), 1518 m water depth) and ODP Site 762 (Northwest Australian margin, 1360 m water depth). The measurements indicate that the epsilon-Nd changes in Indian seawater over the last 35 Ma result from changes in the oceanic circulation, large volcanic and continental weathering Nd inputs. This highlights the diverse nature of those controls and their interconnections in a small area of the ocean. These new records combined with those previously obtained at the equatorial ODP Sites 757 and 707 in the Indian Ocean (Gourlan et al., 2008, doi:10.1016/j.epsl.2007.11.054) established that the distribution of intermediate seawater epsilon-Nd was uniform over most of the Indian Ocean from 35 Ma to 10 Ma within a geographical area extending from 40°S to the equator and from -60°E to 120°E. However, the epsilon-Nd value of Indian Ocean seawater which kept an almost constant value (at about -7 to -8) from 35 to 15 Ma rose by 3 epsilon-Nd units from 15 to 10 Ma. This sharp increase has been caused by a radiogenic Nd enrichment of the water mass originating from the Pacific flowing through the Indonesian Passage. Using a two end-members model we calculated that the Nd transported to the Indian Ocean through the Indonesian Pathway was 1.7 times larger at 10 Ma than at 15 Ma. The Nd isotopic composition of ancient seawater and that of the sediment detrital component appear to be strongly correlated for some specific events. A first evidence occurs between 20 and 15 Ma with two positive spikes recorded in both epsilon-Nd signals that are clearly induced by a volcanic crisis of, most likely, the St. Paul hot-spot. A second evidence is the very large epsilon-Nd decrease recorded at ODP Sites 756 and 762 during the past 10 Ma which has never been previously observed. The synchronism between the epsilon-Nd decrease in seawater from 10 to 5 Ma and evidences of desertification in the western part of the nearly Australian continent suggests enhanced weathering inputs in this ocean from this continent as a result of climatic changes.

Geochemistry of sediments from the upwelling off Morocco

The high-productive upwelling area off Morocco is part of one of the four major trade-wind driven continental margin upwelling zones in the world oceans. While coastal upwelling occurs mostly on the shelf, biogenic particles derived from upwelling are deposited mostly at the upper continental slope. Nutrient-rich coastal water is transported within the Cape Ghir filament region at 30°N up to several hundreds of kilometers offshore. Both upwelling intensity and filament activity are dependent on the strength of the summer Trades. This study is aimed to reconstruct changes in trade wind intensity over the last 250,000 years by the analysis of the productivity signal contained in the sedimentary biogenic particles of the continental slope and beneath the Cape Ghir filament. Detailed geochemical and geophysical analyses (TOC, carbonate, C/N, delta13Corg, delta15N, delta13C of benthic foraminifera, delta18O of benthic and planktic foraminifera, magnetic susceptibility) have been carried out at two sites on the upper continental slope and one site located further offshore influenced by the Cape Ghir filament. A second offshore site south of the filament was analyzed (TOC, magnetic susceptibility) to distinguish the productivity signal related to the filament signal from the general offshore variability. Higher productivity during glacial times was observed at all four sites. However, the variability of productivity during glacial times was remarkably different at the filament-influenced site compared to the upwelling-influenced continental slope sites. In addition to climate-related changes in upwelling intensity, zonal shifts of the upwelling area due to sea-level changes have impacted the sedimentary productivity record, especially at the continental slope sites. By comparison with other proxies related to the strength and direction of the prevailing winds (Si/Al ratio as grain-size indicator, pollen) the productivity record at the filament-influenced site reflects mainly changes in trade-wind intensity. Our reconstruction reveals that especially during glacial times trade-wind intensity was increased and showed a strong variability with frequencies related to precession.