Development of a novel platform for high-throughput gene design and artificial gene synthesis to produce large libraries of recombinant venom peptides for drug discovery

Tese de Doutoramento em Ciências Veterinárias na Especialidade de Ciências Biológicas e Biomédicas

DATA DRIVEN INTELLIGENT AGENT NETWORKS FOR ADAPTIVE MONITORING AND CONTROL

To analyze the characteristics and predict the dynamic behaviors of complex systems over time, comprehensive research to enable the development of systems that can intelligently adapt to the evolving conditions and infer new knowledge with algorithms that are not predesigned is crucially needed. This dissertation research studies the integration of the techniques and methodologies resulted from the fields of pattern recognition, intelligent agents, artificial immune systems, and distributed computing platforms, to create technologies that can more accurately describe and control the dynamics of real-world complex systems. The need for such technologies is emerging in manufacturing, transportation, hazard mitigation, weather and climate prediction, homeland security, and emergency response. Motivated by the ability of mobile agents to dynamically incorporate additional computational and control algorithms into executing applications, mobile agent technology is employed in this research for the adaptive sensing and monitoring in a wireless sensor network. Mobile agents are software components that can travel from one computing platform to another in a network and carry programs and data states that are needed for performing the assigned tasks. To support the generation, migration, communication, and management of mobile monitoring agents, an embeddable mobile agent system (Mobile-C) is integrated with sensor nodes. Mobile monitoring agents visit distributed sensor nodes, read real-time sensor data, and perform anomaly detection using the equipped pattern recognition algorithms. The optimal control of agents is achieved by mimicking the adaptive immune response and the application of multi-objective optimization algorithms. The mobile agent approach provides potential to reduce the communication load and energy consumption in monitoring networks. The major research work of this dissertation project includes: (1) studying effective feature extraction methods for time series measurement data; (2) investigating the impact of the feature extraction methods and dissimilarity measures on the performance of pattern recognition; (3) researching the effects of environmental factors on the performance of pattern recognition; (4) integrating an embeddable mobile agent system with wireless sensor nodes; (5) optimizing agent generation and distribution using artificial immune system concept and multi-objective algorithms; (6) applying mobile agent technology and pattern recognition algorithms for adaptive structural health monitoring and driving cycle pattern recognition; (7) developing a web-based monitoring network to enable the visualization and analysis of real-time sensor data remotely. Techniques and algorithms developed in this dissertation project will contribute to research advances in networked distributed systems operating under changing environments.

Geospatial Data Indexing Analysis and Visualization via Web Services with Autonomic Resource Management

With the exponential growth of the usage of web-based map services, the web GIS application has become more and more popular. Spatial data index, search, analysis, visualization and the resource management of such services are becoming increasingly important to deliver user-desired Quality of Service. First, spatial indexing is typically time-consuming and is not available to end-users. To address this, we introduce TerraFly sksOpen, an open-sourced an Online Indexing and Querying System for Big Geospatial Data. Integrated with the TerraFly Geospatial database [1-9], sksOpen is an efficient indexing and query engine for processing Top-k Spatial Boolean Queries. Further, we provide ergonomic visualization of query results on interactive maps to facilitate the user’s data analysis. Second, due to the highly complex and dynamic nature of GIS systems, it is quite challenging for the end users to quickly understand and analyze the spatial data, and to efficiently share their own data and analysis results with others. Built on the TerraFly Geo spatial database, TerraFly GeoCloud is an extra layer running upon the TerraFly map and can efficiently support many different visualization functions and spatial data analysis models. Furthermore, users can create unique URLs to visualize and share the analysis results. TerraFly GeoCloud also enables the MapQL technology to customize map visualization using SQL-like statements [10]. Third, map systems often serve dynamic web workloads and involve multiple CPU and I/O intensive tiers, which make it challenging to meet the response time targets of map requests while using the resources efficiently. Virtualization facilitates the deployment of web map services and improves their resource utilization through encapsulation and consolidation. Autonomic resource management allows resources to be automatically provisioned to a map service and its internal tiers on demand. v-TerraFly are techniques to predict the demand of map workloads online and optimize resource allocations, considering both response time and data freshness as the QoS target. The proposed v-TerraFly system is prototyped on TerraFly, a production web map service, and evaluated using real TerraFly workloads. The results show that v-TerraFly can accurately predict the workload demands: 18.91% more accurate; and efficiently allocate resources to meet the QoS target: improves the QoS by 26.19% and saves resource usages by 20.83% compared to traditional peak load-based resource allocation.

Novel efficient technologies in Europe for axle bearing condition monitoring – the MAXBE project

Axle bearing damage with possible catastrophic failures can cause severe disruptions or even dangerous derailments, potentially causing loss of human life and leading to significant costs for railway infrastructure managers and rolling stock operators. Consequently the axle bearing damage process has safety and economic implications on the exploitation of railways systems. Therefore it has been the object of intense attention by railway authorities as proved by the selection of this topic by the European Commission in calls for research proposals. The MAXBE Project (http://www.maxbeproject.eu/), an EU-funded project, appears in this context and its main goal is to develop and to demonstrate innovative and efficient technologies which can be used for the onboard and wayside condition monitoring of axle bearings. The MAXBE (interoperable monitoring, diagnosis and maintenance strategies for axle bearings) project focuses on detecting axle bearing failure modes at an early stage by combining new and existing monitoring techniques and on characterizing the axle bearing degradation process. The consortium for the MAXBE project comprises 18 partners from 8 member states, representing operators, railway administrations, axle bearing manufactures, key players in the railway community and experts in the field of monitoring, maintenance and rolling stock. The University of Porto is coordinating this research project that kicked-off in November 2012 and it is completed on October 2015. Both on-board and wayside systems are explored in the project since there is a need for defining the requirement for the onboard equipment and the range of working temperatures of the axle bearing for the wayside systems. The developed monitoring systems consider strain gauges, high frequency accelerometers, temperature sensors and acoustic emission. To get a robust technology to support the decision making of the responsible stakeholders synchronized measurements from onboard and wayside monitoring systems are integrated into a platform. Also extensive laboratory tests were performed to correlate the in situ measurements to the status of the axle bearing life. With the MAXBE project concept it will be possible: to contribute to detect at an early stage axle bearing failures; to create conditions for the operational and technical integration of axle bearing monitoring and maintenance in different European railway networks; to contribute to the standardization of the requirements for the axle bearing monitoring, diagnosis and maintenance. Demonstration of the developed condition monitoring systems was performed in Portugal in the Northern Railway Line with freight and passenger traffic with a maximum speed of 220 km/h, in Belgium in a tram line and in the UK. Still within the project, a tool for optimal maintenance scheduling and a smart diagnostic tool were developed. This paper presents a synthesis of the most relevant results attained in the project. The successful of the project and the developed solutions have positive impact on the reliability, availability, maintainability and safety of rolling stock and infrastructure with main focus on the axle bearing health.

Approche basée sur des patrons pour concevoir des logiciels d’enseignement adaptés aux technologies du Web

Les applications Web en général ont connu d’importantes évolutions technologiques au cours des deux dernières décennies et avec elles les habitudes et les attentes de la génération de femmes et d’hommes dite numérique. Paradoxalement à ces bouleversements technologiques et comportementaux, les logiciels d’enseignement et d’apprentissage (LEA) n’ont pas tout à fait suivi la même courbe d’évolution technologique. En effet, leur modèle de conception est demeuré si statique que leur utilité pédagogique est remise en cause par les experts en pédagogie selon lesquels les LEA actuels ne tiennent pas suffisamment compte des aspects théoriques pédagogiques. Mais comment améliorer la prise en compte de ces aspects dans le processus de conception des LEA? Plusieurs approches permettent de concevoir des LEA robustes. Cependant, un intérêt particulier existe pour l’utilisation du concept patron dans ce processus de conception tant par les experts en pédagogie que par les experts en génie logiciel. En effet, ce concept permet de capitaliser l’expérience des experts et permet aussi de simplifier de belle manière le processus de conception et de ce fait son coût. Une comparaison des travaux utilisant des patrons pour concevoir des LEA a montré qu’il n’existe pas de cadre de synergie entre les différents acteurs de l’équipe de conception, les experts en pédagogie d’un côté et les experts en génie logiciel de l’autre. De plus, les cycles de vie proposés dans ces travaux ne sont pas complets, ni rigoureusement décrits afin de permettre de développer des LEA efficients. Enfin, les travaux comparés ne montrent pas comment faire coexister les exigences pédagogiques avec les exigences logicielles. Le concept patron peut-il aider à construire des LEA robustes satisfaisant aux exigences pédagogiques ? Comme solution, cette thèse propose une approche de conception basée sur des patrons pour concevoir des LEA adaptés aux technologies du Web. Plus spécifiquement, l’approche méthodique proposée montre quelles doivent être les étapes séquentielles à prévoir pour concevoir un LEA répondant aux exigences pédagogiques. De plus, un répertoire est présenté et contient 110 patrons recensés et organisés en paquetages. Ces patrons peuvent être facilement retrouvés à l’aide du guide de recherche décrit pour être utilisés dans le processus de conception. L’approche de conception a été validée avec deux exemples d’application, permettant de conclure d’une part que l’approche de conception des LEA est réaliste et d’autre part que les patrons sont bien valides et fonctionnels. L’approche de conception de LEA proposée est originale et se démarque de celles que l’on trouve dans la littérature car elle est entièrement basée sur le concept patron. L’approche permet également de prendre en compte les exigences pédagogiques. Elle est générique car indépendante de toute plateforme logicielle ou matérielle. Toutefois, le processus de traduction des exigences pédagogiques n’est pas encore très intuitif, ni très linéaire. D’autres travaux doivent être réalisés pour compléter les résultats obtenus afin de pouvoir traduire en artéfacts exploitables par les ingénieurs logiciels les exigences pédagogiques les plus complexes et les plus abstraites. Pour la suite de cette thèse, une instanciation des patrons proposés serait intéressante ainsi que la définition d’un métamodèle basé sur des patrons qui pourrait permettre la spécification d’un langage de modélisation typique des LEA. L’ajout de patrons permettant d’ajouter une couche sémantique au niveau des LEA pourrait être envisagée. Cette couche sémantique permettra non seulement d’adapter les scénarios pédagogiques, mais aussi d’automatiser le processus d’adaptation au besoin d’un apprenant en particulier. Il peut être aussi envisagé la transformation des patrons proposés en ontologies pouvant permettre de faciliter l’évaluation des connaissances de l’apprenant, de lui communiquer des informations structurées et utiles pour son apprentissage et correspondant à son besoin d’apprentissage.

Estrategia y plan de mercadeo de la empresa YouTube

Esta investigación describe la situación de cómo Youtube se ha convertido a partir de sus estrategias y plan de mercadeo en la plataforma número uno en variedad de clips de películas, vídeos musicales, video de blogs, entre otros; llegando a popularizarse como una red social. Las redes sociales han desarrollado una nueva forma de comunicar y son una herramienta fundamental para la creación de conocimiento colectivo, es el caso de YouTube buscador de contenido audiovisual y red social que permite a millones de usuarios conectarse alrededor del mundo. Esta plataforma rompe las barreras culturales y de comunicación que anteriormente existían a falta de internet. En este sentido se pretende analizar a YouTube desde una perspectiva administrativa enfocada en el área de mercadeo.

Development of a numerical platform for the modeling and optimal control of liquid metal flows

The main purpose of this work is to develop a numerical platform for the turbulence modeling and optimal control of liquid metal flows. Thanks to their interesting thermal properties, liquid metals are widely studied as coolants for heat transfer applications in the nuclear context. However, due to their low Prandtl numbers, the standard turbulence models commonly used for coolants as air or water are inadequate. Advanced turbulence models able to capture the anisotropy in the flow and heat transfer are then necessary. In this thesis, a new anisotropic four-parameter turbulence model is presented and validated. The proposed model is based on explicit algebraic models and solves four additional transport equations for dynamical and thermal turbulent variables. For the validation of the model, several flow configurations are considered for different Reynolds and Prandtl numbers, namely fully developed flows in a plane channel and cylindrical pipe, and forced and mixed convection in a backward-facing step geometry. Since buoyancy effects cannot be neglected in liquid metals-cooled fast reactors, the second aim of this work is to provide mathematical and numerical tools for the simulation and optimization of liquid metals in mixed and natural convection. Optimal control problems for turbulent buoyant flows are studied and analyzed with the Lagrange multipliers method. Numerical algorithms for optimal control problems are integrated into the numerical platform and several simulations are performed to show the robustness, consistency, and feasibility of the method.

Supporting requirement elicitation and ontology testing in knowledge graph engineering

Knowledge graphs and ontologies are closely related concepts in the field of knowledge representation. In recent years, knowledge graphs have gained increasing popularity and are serving as essential components in many knowledge engineering projects that view them as crucial to their success. The conceptual foundation of the knowledge graph is provided by ontologies. Ontology modeling is an iterative engineering process that consists of steps such as the elicitation and formalization of requirements, the development, testing, refactoring, and release of the ontology. The testing of the ontology is a crucial and occasionally overlooked step of the process due to the lack of integrated tools to support it. As a result of this gap in the state-of-the-art, the testing of the ontology is completed manually, which requires a considerable amount of time and effort from the ontology engineers. The lack of tool support is noticed in the requirement elicitation process as well. In this aspect, the rise in the adoption and accessibility of knowledge graphs allows for the development and use of automated tools to assist with the elicitation of requirements from such a complementary source of data. Therefore, this doctoral research is focused on developing methods and tools that support the requirement elicitation and testing steps of an ontology engineering process. To support the testing of the ontology, we have developed XDTesting, a web application that is integrated with the GitHub platform that serves as an ontology testing manager. Concurrently, to support the elicitation and documentation of competency questions, we have defined and implemented RevOnt, a method to extract competency questions from knowledge graphs. Both methods are evaluated through their implementation and the results are promising.

One archive, many readings. Personal archives as complex networks in the semantic web

Personal archives are the archives created by individuals for their own purposes. Among these are the library and documentary collections of writers and scholars. It is only recently that archival literature has begun to focus on this category of archives, emphasising how their heterogeneous nature necessitates the conciliation of different approaches to archival description, and calling for a broader understanding of the principle of provenance, recognising that multiple creators, including subsequent researchers, can contribute to shaping personal archives over time by adding new layers of contexts. Despite these advances in the theoretical debate, current architectures for archival representation remain behind. Finding aids privilege a single point of view and do not allow subsequent users to embed their own, potentially conflicting, readings. Using semantic web technologies this study aims to define a conceptual model for writers' archives based on existing and widely adopted models in the cultural heritage and humanities domains. The model developed can be used to represent different types of documents at various levels of analysis, as well as record content and components. It also enables the representation of complex relationships and the incorporation of additional layers of interpretation into the finding aid, transforming it from a static search tool into a dynamic research platform.  The personal archive and library of Giuseppe Raimondi serves as a case study for the creation of an archival knowledge base using the proposed conceptual model. By querying the knowledge graph through SPARQL, the effectiveness of the model is evaluated. The results demonstrate that the model addresses the primary representation challenges identified in archival literature, from both a technological and methodological standpoint. The ultimate goal is to bring the output par excellence of archival science, i.e. the finding aid, more in line with the latest developments in archival thinking.

Effect Of Platform Connection And Abutment Material On Stress Distribution In Single Anterior Implant-supported Restorations: A Nonlinear 3-dimensional Finite Element Analysis.

Although various abutment connections and materials have recently been introduced, insufficient data exist regarding the effect of stress distribution on their mechanical performance. The purpose of this study was to investigate the effect of different abutment materials and platform connections on stress distribution in single anterior implant-supported restorations with the finite element method. Nine experimental groups were modeled from the combination of 3 platform connections (external hexagon, internal hexagon, and Morse tapered) and 3 abutment materials (titanium, zirconia, and hybrid) as follows: external hexagon-titanium, external hexagon-zirconia, external hexagon-hybrid, internal hexagon-titanium, internal hexagon-zirconia, internal hexagon-hybrid, Morse tapered-titanium, Morse tapered-zirconia, and Morse tapered-hybrid. Finite element models consisted of a 4×13-mm implant, anatomic abutment, and lithium disilicate central incisor crown cemented over the abutment. The 49 N occlusal loading was applied in 6 steps to simulate the incisal guidance. Equivalent von Mises stress (σvM) was used for both the qualitative and quantitative evaluation of the implant and abutment in all the groups and the maximum (σmax) and minimum (σmin) principal stresses for the numerical comparison of the zirconia parts. The highest abutment σvM occurred in the Morse-tapered groups and the lowest in the external hexagon-hybrid, internal hexagon-titanium, and internal hexagon-hybrid groups. The σmax and σmin values were lower in the hybrid groups than in the zirconia groups. The stress distribution concentrated in the abutment-implant interface in all the groups, regardless of the platform connection or abutment material. The platform connection influenced the stress on abutments more than the abutment material. The stress values for implants were similar among different platform connections, but greater stress concentrations were observed in internal connections.

Integrated Proteomics Identified Up-regulated Focal Adhesion-mediated Proteins In Human Squamous Cell Carcinoma In An Orthotopic Murine Model.

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.

Ihwg-μnir: A Miniaturised Near-infrared Gas Sensor Based On Substrate-integrated Hollow Waveguides Coupled To A Micro-nir-spectrophotometer.

A miniaturised gas analyser is described and evaluated based on the use of a substrate-integrated hollow waveguide (iHWG) coupled to a microsized near-infrared spectrophotometer comprising a linear variable filter and an array of InGaAs detectors. This gas sensing system was applied to analyse surrogate samples of natural fuel gas containing methane, ethane, propane and butane, quantified by using multivariate regression models based on partial least square (PLS) algorithms and Savitzky-Golay 1(st) derivative data preprocessing. The external validation of the obtained models reveals root mean square errors of prediction of 0.37, 0.36, 0.67 and 0.37% (v/v), for methane, ethane, propane and butane, respectively. The developed sensing system provides particularly rapid response times upon composition changes of the gaseous sample (approximately 2 s) due the minute volume of the iHWG-based measurement cell. The sensing system developed in this study is fully portable with a hand-held sized analyser footprint, and thus ideally suited for field analysis. Last but not least, the obtained results corroborate the potential of NIR-iHWG analysers for monitoring the quality of natural gas and petrochemical gaseous products.

An Integrated Framework To Improve The Concept Of Resource Specialisation.

Resource specialisation, although a fundamental component of ecological theory, is employed in disparate ways. Most definitions derive from simple counts of resource species. We build on recent advances in ecophylogenetics and null model analysis to propose a concept of specialisation that comprises affinities among resources as well as their co-occurrence with consumers. In the distance-based specialisation index (DSI), specialisation is measured as relatedness (phylogenetic or otherwise) of resources, scaled by the null expectation of random use of locally available resources. Thus, specialists use significantly clustered sets of resources, whereas generalists use over-dispersed resources. Intermediate species are classed as indiscriminate consumers. The effectiveness of this approach was assessed with differentially restricted null models, applied to a data set of 168 herbivorous insect species and their hosts. Incorporation of plant relatedness and relative abundance greatly improved specialisation measures compared to taxon counts or simpler null models, which overestimate the fraction of specialists, a problem compounded by insufficient sampling effort. This framework disambiguates the concept of specialisation with an explicit measure applicable to any mode of affinity among resource classes, and is also linked to ecological and evolutionary processes. This will enable a more rigorous deployment of ecological specialisation in empirical and theoretical studies.

Hyperhoneycomb Iridate β-li_{2}iro_{3} As A Platform For Kitaev Magnetism.

A complex iridium oxide β-Li_{2}IrO_{3} crystallizes in a hyperhoneycomb structure, a three-dimensional analogue of honeycomb lattice, and is found to be a spin-orbital Mott insulator with J_{eff}=1/2 moment. Ir ions are connected to the three neighboring Ir ions via Ir-O_{2}-Ir bonding planes, which very likely gives rise to bond-dependent ferromagnetic interactions between the J_{eff}=1/2 moments, an essential ingredient of Kitaev model with a spin liquid ground state. Dominant ferromagnetic interaction between J_{eff}=1/2 moments is indeed confirmed by the temperature dependence of magnetic susceptibility χ(T) which shows a positive Curie-Weiss temperature θ_{CW}∼+40  K. A magnetic ordering with a very small entropy change, likely associated with a noncollinear arrangement of J_{eff}=1/2 moments, is observed at T_{c}=38  K. With the application of magnetic field to the ordered state, a large moment of more than 0.35  μ_{B}/Ir is induced above 3 T, a substantially polarized J_{eff}=1/2 state. We argue that the close proximity to ferromagnetism and the presence of large fluctuations evidence that the ground state of hyperhoneycomb β-Li_{2}IrO_{3} is located in close proximity of a Kitaev spin liquid.

Modelo de inclusão digital para construção do conhecimento em qualidade de vida e atividade fisica

Universidade Estadual de Campinas. Faculdade de Educação Física