A MOLECULAR APPROACH FOR DETECTING GENETIC DAMAGE USING THE ECO R1 FAMILY OF HUMAN DNA (SEQUENCING)

A clone of the primary Eco R1 family of human DNA sequences has been used as an indicator sequence for detecting alterations induced by a toxic agent. Specific clones of this family have been examined and compared to the consensus sequence to determine the normal variability of this family. Though variations were observed, data indicated that such clones can be used to study induced DNA modifications. This DNA was exposed to the toxic agent dimethyl sulfate under various conditions and a distinct pattern of aberrations was shown to occur. It is suggested that this approach be used to characterize patterns of damage induced by various agents in the ultimate development of a system capable of monitoring human genotoxic exposure. ^

Multi-agent Architecture for Heterogeneous Reasoning under Uncertainty Combining MSBN and Ontologies in Distributed Network Diagnosis

This article proposes a MAS architecture for network diagnosis under uncertainty. Network diagnosis is divided into two inference processes: hypothesis generation and hypothesis confirmation. The first process is distributed among several agents based on a MSBN, while the second one is carried out by agents using semantic reasoning. A diagnosis ontology has been defined in order to combine both inference processes. To drive the deliberation process, dynamic data about the influence of observations are taken during diagnosis process. In order to achieve quick and reliable diagnoses, this influence is used to choose the best action to perform. This approach has been evaluated in a P2P video streaming scenario. Computational and time improvements are highlight as conclusions.

Engineering Agent Systems for Decision Support

This paper discusses how agent technology can be applied to the design of advanced Information Systems for Decision Support. In particular, it describes the different steps and models that are necessary to engineer Decision Support Systems based on a multiagent architecture. The approach is illustrated by a case study in the traffic management domain.

Agent-based modelling for cement hydration

The Agent-Based Modelling and simulation (ABM) is a rather new approach for studying complex systems withinteracting autonomous agents that has lately undergone great growth in various fields such as biology, physics, social science, economics and business. Efforts to model and simulate the highly complex cement hydration process have been made over the past 40 years, with the aim of predicting the performance of concrete and designing innovative and enhanced cementitious materials. The ABM presented here - based on previous work - focuses on the early stages of cement hydration by modelling the physical-chemical processes at the particle level. The model considers the cement hydration process as a time and 3D space system, involving multiple diffusing and reacting species of spherical particles. Chemical reactions are simulated by adaptively selecting discrete stochastic simulation for the appropriate reaction, whenever that is necessary. Interactions between particles are also considered. The model has been inspired by reported cellular automata?s approach which provides detailed predictions of cement microstructure at the expense of significant computational difficulty. The ABM approach herein seeks to bring about an optimal balance between accuracy and computational efficiency.

A multi-agent system with distributed bayesian reasoning for network fault diagnosis

In this paper, an innovative approach to perform distributed Bayesian inference using a multi-agent architecture is presented. The final goal is dealing with uncertainty in network diagnosis, but the solution can be of applied in other fields. The validation testbed has been a P2P streaming video service. An assessment of the work is presented, in order to show its advantages when it is compared with traditional manual processes and other previous systems.

I feel you: the design and evaluation of a domotic affect-sensitive spoken conversational agent

We describe the work on infusion of emotion into a limited-task autonomous spoken conversational agent situated in the domestic environment, using a need-inspired task-independent emotion model (NEMO). In order to demonstrate the generation of affect through the use of the model, we describe the work of integrating it with a natural-language mixed-initiative HiFi-control spoken conversational agent (SCA). NEMO and the host system communicate externally, removing the need for the Dialog Manager to be modified, as is done in most existing dialog systems, in order to be adaptive. The first part of the paper concerns the integration between NEMO and the host agent. The second part summarizes the work on automatic affect prediction, namely, frustration and contentment, from dialog features, a non-conventional source, in the attempt of moving towards a more user-centric approach. The final part reports the evaluation results obtained from a user study, in which both versions of the agent (non-adaptive and emotionally-adaptive) were compared. The results provide substantial evidences with respect to the benefits of adding emotion in a spoken conversational agent, especially in mitigating users' frustrations and, ultimately, improving their satisfaction.

Agent-based modeling and simulation for the design of the future european Air Traffic Management system: the experience of CASSIOPEIA

The SESAR (Single European Sky ATM Research) program is an ambitious re-search and development initiative to design the future European air traffic man-agement (ATM) system. The study of the behavior of ATM systems using agent-based modeling and simulation tools can help the development of new methods to improve their performance. This paper presents an overview of existing agent-based approaches in air transportation (paying special attention to the challenges that exist for the design of future ATM systems) and, subsequently, describes a new agent-based approach that we proposed in the CASSIOPEIA project, which was developed according to the goals of the SESAR program. In our approach, we use agent models for different ATM stakeholders, and, in contrast to previous work, our solution models new collaborative decision processes for flow traffic management, it uses an intermediate level of abstraction (useful for simulations at larger scales), and was designed to be a practical tool (open and reusable) for the development of different ATM studies. It was successfully applied in three stud-ies related to the design of future ATM systems in Europe.

Modeling Commercial Knowledge to Develop Advanced Agent-based Marketplaces for E-commerce

This paper argues about the utility of advanced knowledge-based techniques to develop web-based applications that help consumers in finding products within marketplaces in e-commerce. In particular, we describe the idea of model-based approach to develop a shopping agent that dynamically configures a product according to the needs and preferences of customers. Finally, the paper summarizes the advantages provided by this approach.

Cooperative Learning Model based on Multi-Agent Architecture for Embedded Intelligent Systems

Cooperative systems are suitable for many types of applications and nowadays these system are vastly used to improve a previously defined system or to coordinate multiple devices working together. This paper provides an alternative to improve the reliability of a previous intelligent identification system. The proposed approach implements a cooperative model based on multi-agent architecture. This new system is composed of several radar-based systems which identify a detected object and transmit its own partial result by implementing several agents and by using a wireless network to transfer data. The proposed topology is a centralized architecture where the coordinator device is in charge of providing the final identification result depending on the group behavior. In order to find the final outcome, three different mechanisms are introduced. The simplest one is based on majority voting whereas the others use two different weighting voting procedures, both providing the system with learning capabilities. Using an appropriate network configuration, the success rate can be improved from the initial 80% up to more than 90%.

Application of Agent Technology for Fault Diagnosis of Telecommunication Networks

La presente tesis doctoral contribuye al problema del diagnóstico autonómico de fallos en redes de telecomunicación. En las redes de telecomunicación actuales, las operadoras realizan tareas de diagnóstico de forma manual. Dichas operaciones deben ser llevadas a cabo por ingenieros altamente cualificados que cada vez tienen más dificultades a la hora de gestionar debidamente el crecimiento exponencial de la red tanto en tamaño, complejidad y heterogeneidad. Además, el advenimiento del Internet del Futuro hace que la demanda de sistemas que simplifiquen y automaticen la gestión de las redes de telecomunicación se haya incrementado en los últimos años. Para extraer el conocimiento necesario para desarrollar las soluciones propuestas y facilitar su adopción por los operadores de red, se propone una metodología de pruebas de aceptación para sistemas multi-agente enfocada en simplificar la comunicación entre los diferentes grupos de trabajo involucrados en todo proyecto de desarrollo software: clientes y desarrolladores. Para contribuir a la solución del problema del diagnóstico autonómico de fallos, se propone una arquitectura de agente capaz de diagnosticar fallos en redes de telecomunicación de manera autónoma. Dicha arquitectura extiende el modelo de agente Belief-Desire- Intention (BDI) con diferentes modelos de diagnóstico que gestionan las diferentes sub-tareas del proceso. La arquitectura propuesta combina diferentes técnicas de razonamiento para alcanzar su propósito gracias a un modelo estructural de la red, que usa razonamiento basado en ontologías, y un modelo causal de fallos, que usa razonamiento Bayesiano para gestionar debidamente la incertidumbre del proceso de diagnóstico. Para asegurar la adecuación de la arquitectura propuesta en situaciones de gran complejidad y heterogeneidad, se propone un marco de argumentación que permite diagnosticar a agentes que estén ejecutando en dominios federados. Para la aplicación de este marco en un sistema multi-agente, se propone un protocolo de coordinación en el que los agentes dialogan hasta alcanzar una conclusión para un caso de diagnóstico concreto. Como trabajos futuros, se consideran la extensión de la arquitectura para abordar otros problemas de gestión como el auto-descubrimiento o la auto-optimización, el uso de técnicas de reputación dentro del marco de argumentación para mejorar la extensibilidad del sistema de diagnóstico en entornos federados y la aplicación de las arquitecturas propuestas en las arquitecturas de red emergentes, como SDN, que ofrecen mayor capacidad de interacción con la red. ABSTRACT This PhD thesis contributes to the problem of autonomic fault diagnosis of telecommunication networks. Nowadays, in telecommunication networks, operators perform manual diagnosis tasks. Those operations must be carried out by high skilled network engineers which have increasing difficulties to properly manage the growing of those networks, both in size, complexity and heterogeneity. Moreover, the advent of the Future Internet makes the demand of solutions which simplifies and automates the telecommunication network management has been increased in recent years. To collect the domain knowledge required to developed the proposed solutions and to simplify its adoption by the operators, an agile testing methodology is defined for multiagent systems. This methodology is focused on the communication gap between the different work groups involved in any software development project, stakeholders and developers. To contribute to overcoming the problem of autonomic fault diagnosis, an agent architecture for fault diagnosis of telecommunication networks is defined. That architecture extends the Belief-Desire-Intention (BDI) agent model with different diagnostic models which handle the different subtasks of the process. The proposed architecture combines different reasoning techniques to achieve its objective using a structural model of the network, which uses ontology-based reasoning, and a causal model, which uses Bayesian reasoning to properly handle the uncertainty of the diagnosis process. To ensure the suitability of the proposed architecture in complex and heterogeneous environments, an argumentation framework is defined. This framework allows agents to perform fault diagnosis in federated domains. To apply this framework in a multi-agent system, a coordination protocol is defined. This protocol is used by agents to dialogue until a reliable conclusion for a specific diagnosis case is reached. Future work comprises the further extension of the agent architecture to approach other managements problems, such as self-discovery or self-optimisation; the application of reputation techniques in the argumentation framework to improve the extensibility of the diagnostic system in federated domains; and the application of the proposed agent architecture in emergent networking architectures, such as SDN, which offers new capabilities of control for the network.

A Personal Agent Architecture for Task Automation in the Web of Data. Bringing intelligence to everyday tasks

Internet está evolucionando hacia la conocida como Live Web. En esta nueva etapa en la evolución de Internet, se pone al servicio de los usuarios multitud de streams de datos sociales. Gracias a estas fuentes de datos, los usuarios han pasado de navegar por páginas web estáticas a interacturar con aplicaciones que ofrecen contenido personalizado, basada en sus preferencias. Cada usuario interactúa a diario con multiples aplicaciones que ofrecen notificaciones y alertas, en este sentido cada usuario es una fuente de eventos, y a menudo los usuarios se sienten desbordados y no son capaces de procesar toda esa información a la carta. Para lidiar con esta sobresaturación, han aparecido múltiples herramientas que automatizan las tareas más habituales, desde gestores de bandeja de entrada, gestores de alertas en redes sociales, a complejos CRMs o smart-home hubs. La contrapartida es que aunque ofrecen una solución a problemas comunes, no pueden adaptarse a las necesidades de cada usuario ofreciendo una solucion personalizada. Los Servicios de Automatización de Tareas (TAS de sus siglas en inglés) entraron en escena a partir de 2012 para dar solución a esta liminación. Dada su semejanza, estos servicios también son considerados como un nuevo enfoque en la tecnología de mash-ups pero centra en el usuarios. Los usuarios de estas plataformas tienen la capacidad de interconectar servicios, sensores y otros aparatos con connexión a internet diseñando las automatizaciones que se ajustan a sus necesidades. La propuesta ha sido ámpliamante aceptada por los usuarios. Este hecho ha propiciado multitud de plataformas que ofrecen servicios TAS entren en escena. Al ser un nuevo campo de investigación, esta tesis presenta las principales características de los TAS, describe sus componentes, e identifica las dimensiones fundamentales que los defines y permiten su clasificación. En este trabajo se acuña el termino Servicio de Automatización de Tareas (TAS) dando una descripción formal para estos servicios y sus componentes (llamados canales), y proporciona una arquitectura de referencia. De igual forma, existe una falta de herramientas para describir servicios de automatización, y las reglas de automatización. A este respecto, esta tesis propone un modelo común que se concreta en la ontología EWE (Evented WEb Ontology). Este modelo permite com parar y equiparar canales y automatizaciones de distintos TASs, constituyendo un aporte considerable paraa la portabilidad de automatizaciones de usuarios entre plataformas. De igual manera, dado el carácter semántico del modelo, permite incluir en las automatizaciones elementos de fuentes externas sobre los que razonar, como es el caso de Linked Open Data. Utilizando este modelo, se ha generado un dataset de canales y automatizaciones, con los datos obtenidos de algunos de los TAS existentes en el mercado. Como último paso hacia el lograr un modelo común para describir TAS, se ha desarrollado un algoritmo para aprender ontologías de forma automática a partir de los datos del dataset. De esta forma, se favorece el descubrimiento de nuevos canales, y se reduce el coste de mantenimiento del modelo, el cual se actualiza de forma semi-automática. En conclusión, las principales contribuciones de esta tesis son: i) describir el estado del arte en automatización de tareas y acuñar el término Servicio de Automatización de Tareas, ii) desarrollar una ontología para el modelado de los componentes de TASs y automatizaciones, iii) poblar un dataset de datos de canales y automatizaciones, usado para desarrollar un algoritmo de aprendizaje automatico de ontologías, y iv) diseñar una arquitectura de agentes para la asistencia a usuarios en la creación de automatizaciones. ABSTRACT The new stage in the evolution of the Web (the Live Web or Evented Web) puts lots of social data-streams at the service of users, who no longer browse static web pages but interact with applications that present them contextual and relevant experiences. Given that each user is a potential source of events, a typical user often gets overwhelmed. To deal with that huge amount of data, multiple automation tools have emerged, covering from simple social media managers or notification aggregators to complex CRMs or smart-home Hub/Apps. As a downside, they cannot tailor to the needs of every single user. As a natural response to this downside, Task Automation Services broke in the Internet. They may be seen as a new model of mash-up technology for combining social streams, services and connected devices from an end-user perspective: end-users are empowered to connect those stream however they want, designing the automations they need. The numbers of those platforms that appeared early on shot up, and as a consequence the amount of platforms following this approach is growing fast. Being a novel field, this thesis aims to shed light on it, presenting and exemplifying the main characteristics of Task Automation Services, describing their components, and identifying several dimensions to classify them. This thesis coins the term Task Automation Services (TAS) by providing a formal definition of them, their components (called channels), as well a TAS reference architecture. There is also a lack of tools for describing automation services and automations rules. In this regard, this thesis proposes a theoretical common model of TAS and formalizes it as the EWE ontology This model enables to compare channels and automations from different TASs, which has a high impact in interoperability; and enhances automations providing a mechanism to reason over external sources such as Linked Open Data. Based on this model, a dataset of components of TAS was built, harvesting data from the web sites of actual TASs. Going a step further towards this common model, an algorithm for categorizing them was designed, enabling their discovery across different TAS. Thus, the main contributions of the thesis are: i) surveying the state of the art on task automation and coining the term Task Automation Service; ii) providing a semantic common model for describing TAS components and automations; iii) populating a categorized dataset of TAS components, used to learn ontologies of particular domains from the TAS perspective; and iv) designing an agent architecture for assisting users in setting up automations, that is aware of their context and acts in consequence.

Detection of 400-year-old Yersinia pestis DNA in human dental pulp: An approach to the diagnosis of ancient septicemia

Ancient septicemic plague epidemics were reported to have killed millions of people for 2 millenniums. However, confident diagnosis of ancient septicemia solely on the basis of historical clinical observations is not possible. The lack of suitable infected material has prevented direct demonstration of ancient septicemia; thus, the history of most infections such as plague remains hypothetical. The durability of dental pulp, together with its natural sterility, makes it a suitable material on which to base such research. We hypothesized that it would be a lasting refuge for Yersinia pestis, the plague agent. DNA extracts were made from the dental pulp of 12 unerupted teeth extracted from skeletons excavated from 16th and 18th century French graves of persons thought to have died of plague (“plague teeth”) and from 7 ancient negative control teeth. PCRs incorporating ancient DNA extracts and primers specific for the human β-globin gene demonstrated the absence of inhibitors in these preparations. The incorporation of primers specific for Y. pestis rpoB (the RNA polymerase β-subunit-encoding gene) and the recognized virulence-associated pla (the plasminogen activator-encoding gene) repeatedly yielded products that had a nucleotide sequence indistinguishable from that of modern day isolates of the bacterium. The specific pla sequence was obtained from 6 of 12 plague skeleton teeth but 0 of 7 negative controls (P < 0.034, Fisher exact test). A nucleic acid-based confirmation of ancient plague was achieved for historically identified victims, and we have confirmed the presence of the disease at the end of 16th century in France. Dental pulp is an attractive target in the quest to determine the etiology of septicemic illnesses detected in ancient corpses. Molecular techniques could be applied to this material to resolve historical outbreaks.

A model-based approach for assessing in vivo combination therapy interactions

We present an approach for evaluating the efficacy of combination antitumor agent schedules that accounts for order and timing of drug administration. Our model-based approach compares in vivo tumor volume data over a time course and offers a quantitative definition for additivity of drug effects, relative to which synergism and antagonism are interpreted. We begin by fitting data from individual mice receiving at most one drug to a differential equation tumor growth/drug effect model and combine individual parameter estimates to obtain population statistics. Using two null hypotheses: (i) combination therapy is consistent with additivity or (ii) combination therapy is equivalent to treating with the more effective single agent alone, we compute predicted tumor growth trajectories and their distribution for combination treated animals. We illustrate this approach by comparing entire observed and expected tumor volume trajectories for a data set in which HER-2/neu-overexpressing MCF-7 human breast cancer xenografts are treated with a humanized, anti-HER-2 monoclonal antibody (rhuMAb HER-2), doxorubicin, or one of five proposed combination therapy schedules.

Ex vivo propagation of infectious sheep scrapie agent in heterologous epithelial cells expressing ovine prion protein

Transmissible spongiform encephalopathies, or prion diseases, are fatal degenerative disorders of the central nervous system that affect humans and animals. Prions are nonconventional infectious agents whose replication depends on the host prion protein (PrP). Transmission of prions to cultured cells has proved to be a particularly difficult task, and with a few exceptions, their experimental propagation relies on inoculation to laboratory animals. Here, we report on the development of a permanent cell line supporting propagation of natural sheep scrapie. This model was obtained by stable expression of a tetracycline-regulatable ovine PrP gene in a rabbit epithelial cell line. After exposure to scrapie agent, cultures were repeatedly found to accumulate high levels of abnormal PrP (PrPres). Cell extracts induced a scrapie-like disease in transgenic mice overexpressing ovine PrP. These cultures remained healthy and stably infected upon subpassaging. Such data show that (i) cultivated cells from a nonneuronal origin can efficiently replicate prions; and (ii) species barrier can be crossed ex vivo through the expression of a relevant PrP gene. This approach led to the ex vivo propagation of a natural transmissible spongiform encephalopathy agent (i.e., without previous experimental adaptation to rodents) and might be applied to human or bovine prions.

Increasing DNA repair methyltransferase levels via bone marrow stem cell transduction rescues mice from the toxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, a chemotherapeutic alkylating agent.

The chloroethylnitrosourea (CNU) alkylating agents are commonly used for cancer chemotherapy, but their usefulness is limited by severe bone marrow toxicity that causes the cumulative depletion of all hematopoietic lineages (pancytopenia). Bone marrow CNU sensitivity is probably due to the inefficient repair of CNU-induced DNA damage; relative to other tissues, bone marrow cells express extremely low levels of the O6-methylguanine DNA methyltransferase (MGMT) protein that repairs cytotoxic O6-chloroethylguanine DNA lesions. Using a simplified recombinant retroviral vector expressing the human MGMT gene under control of the phosphoglycerate kinase promoter (PGK-MGMT) we increased the capacity of murine bone marrow-derived cells to repair CNU-induced DNA damage. Stable reconstitution of mouse bone marrow with genetically modified, MGMT-expressing hematopoietic stem cells conferred considerable resistance to the cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a CNU commonly used for chemotherapy. Bone marrow harvested from mice transplanted with PGK-MGMT-transduced cells showed extensive in vitro BCNU resistance. Moreover, MGMT expression in mouse bone marrow conferred in vivo resistance to BCNU-induced pancytopenia and significantly reduced BCNU-induced mortality due to bone marrow hypoplasia. These data demonstrate that increased DNA alkylation repair in primitive hematopoietic stem cells confers multilineage protection from the myelosuppressive effects of BCNU and suggest a possible approach to protecting cancer patients from CNU chemotherapy-related toxicity.