Colonoscopia virtual e DNA fecal : estudo de viabilidade como testes de rastreio do cancro colorretal

Tese de doutoramento, Cirurgia Geral (Medicina), Universidade de Lisboa, Faculdade de Medicina, 2014

Virtual power players demand response programs management based on locational marginal prices

Power systems have been suffering huge changes mainly due to the substantial increase of distributed generation and to the operation in competitive environments. Virtual power players can aggregate a diversity of players, namely generators and consumers, and a diversity of energy resources, including electricity generation based on several technologies, storage and demand response. Resource management gains an increasing relevance in this competitive context, while demand side active role provides managers with increased demand elasticity. This makes demand response use more interesting and flexible, giving rise to a wide range of new opportunities.This paper proposes a methodology for managing demand response programs in the scope of virtual power players. The proposed method is based on the calculation of locational marginal prices (LMP). The evaluation of the impact of using demand response specific programs on the LMP value supports the manager decision concerning demand response use. The proposed method has been computationally implemented and its application is illustrated in this paper using a 32 bus network with intensive use of distributed generation.

LMP based bid formation for virtual power players operating in smart grids

Power system organization has gone through huge changes in the recent years. Significant increase in distributed generation (DG) and operation in the scope of liberalized markets are two relevant driving forces for these changes. More recently, the smart grid (SG) concept gained increased importance, and is being seen as a paradigm able to support power system requirements for the future. This paper proposes a computational architecture to support day-ahead Virtual Power Player (VPP) bid formation in the smart grid context. This architecture includes a forecasting module, a resource optimization and Locational Marginal Price (LMP) computation module, and a bid formation module. Due to the involved problems characteristics, the implementation of this architecture requires the use of Artificial Intelligence (AI) techniques. Artificial Neural Networks (ANN) are used for resource and load forecasting and Evolutionary Particle Swarm Optimization (EPSO) is used for energy resource scheduling. The paper presents a case study that considers a 33 bus distribution network that includes 67 distributed generators, 32 loads and 9 storage units.

Optimal virtual cluster-based multiprocessor scheduling

Scheduling of constrained deadline sporadic task systems on multiprocessor platforms is an area which has received much attention in the recent past. It is widely believed that finding an optimal scheduler is hard, and therefore most studies have focused on developing algorithms with good processor utilization bounds. These algorithms can be broadly classified into two categories: partitioned scheduling in which tasks are statically assigned to individual processors, and global scheduling in which each task is allowed to execute on any processor in the platform. In this paper we consider a third, more general, approach called cluster-based scheduling. In this approach each task is statically assigned to a processor cluster, tasks in each cluster are globally scheduled among themselves, and clusters in turn are scheduled on the multiprocessor platform. We develop techniques to support such cluster-based scheduling algorithms, and also consider properties that minimize total processor utilization of individual clusters. In the last part of this paper, we develop new virtual cluster-based scheduling algorithms. For implicit deadline sporadic task systems, we develop an optimal scheduling algorithm that is neither Pfair nor ERfair. We also show that the processor utilization bound of us-edf{m/(2m−1)} can be improved by using virtual clustering. Since neither partitioned nor global strategies dominate over the other, cluster-based scheduling is a natural direction for research towards achieving improved processor utilization bounds.

Development of novel benzimidazole- based COX Inhibitors new synthetic strategies and screening of heterocyclic structures

Dissertação para obtenção do Grau de Doutor em Química, especialidade Química Orgânica

Which screening strategy using BMD measurements would be most cost effective for hip fracture prevention in elderly women? A decision analysis based on a Markov model.

INTRODUCTION: Hip fractures are responsible for excessive mortality, decreasing the 5-year survival rate by about 20%. From an economic perspective, they represent a major source of expense, with direct costs in hospitalization, rehabilitation, and institutionalization. The incidence rate sharply increases after the age of 70, but it can be reduced in women aged 70-80 years by therapeutic interventions. Recent analyses suggest that the most efficient strategy is to implement such interventions in women at the age of 70 years. As several guidelines recommend bone mineral density (BMD) screening of postmenopausal women with clinical risk factors, our objective was to assess the cost-effectiveness of two screening strategies applied to elderly women aged 70 years and older. METHODS: A cost-effectiveness analysis was performed using decision-tree analysis and a Markov model. Two alternative strategies, one measuring BMD of all women, and one measuring BMD only of those having at least one risk factor, were compared with the reference strategy "no screening". Cost-effectiveness ratios were measured as cost per year gained without hip fracture. Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY cohorts. RESULTS: In this model, which is mostly based on observed data, the strategy "screen all" was more cost effective than "screen women at risk." For one woman screened at the age of 70 and followed for 10 years, the incremental (additional) cost-effectiveness ratio of these two strategies compared with the reference was 4,235 euros and 8,290 euros, respectively. CONCLUSION: The results of this model, under the assumptions described in the paper, suggest that in women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry (DXA) would be more effective than no screening or screening only women with at least one risk factor. Cost-effectiveness studies based on decision-analysis trees maybe useful tools for helping decision makers, and further models based on different assumptions should be performed to improve the level of evidence on cost-effectiveness ratios of the usual screening strategies for osteoporosis.

Ligand design for molecule-based magnetic and/or conducting materials

Work in the area of molecule-based magnetic and/or conducting materials is presented in two projects. The first project describes the use of 4,4’-bipyridine as a scaffold for the preparation of a new family of tetracarboxamide ligands. Four new ligands I-III have been prepared and characterized and the coordination chemistry of these ligands is presented. This project was then extended to exploit 4,4’-bipyridine as a covalent linker between two N3O2 macrocyles. In this respect, three dimeric macrocycles have been prepared IV-VI. Substitution of the labile axial ligands of the Co(II) complex IV by [Fe(CN)6]4- afforded the self-assembly of the 1-D polymeric chain {[Co(N3O2)H2O]2Fe(CN)6}n•3H2O that has been structurally and magnetically characterized. Magnetic studies on the Fe(II) complexes V and VI indicate that they undergo incomplete spin crossover transitions in the solid state. Strategies for the preparation of chiral spin crossover N3O2 macrocycles are discussed and the synthesis of the novel chiral Fe(II) macrocyclic complex VII is reported. Magnetic susceptibility and Mössbauer studies reveal that this complex undergoes a gradual spin crossover in the solid state with no thermal hysteresis. Variable temperature X-ray diffraction studies on single crystals of VII reveal interesting structural changes in the coordination geometry of the macrocycle accompanying its SCO transition. The second project reports the synthesis and characterization of a new family of tetrathiafulvalene derivatives VIII – XII, where a heterocyclic chelating ligand is appended to a TTF donor via an imine linker. The coordination chemistries of these ligands with M(hfac)2.H2O (M( = Co, Ni, Mn, Cu) have been explored and the structural and magnetic properties of these complexes are described.

Use of cellular impedance to characterize ligand functional selectivity at G protein-coupled receptors

Les récepteurs couplés aux protéines G (RCPGs) représentent la plus grande famille de cibles thérapeutiques pour le traitement d’une panoplie de pathologies humaines. Bien que plusieurs décennies de recherche aient permis de façonner nos connaissances sur ces protéines membranaires, notre compréhension des déterminants moléculaires de leur activité signalétique reste encore limitée. De ces domaines de recherche, une avancée récente a mis à jour un nouveau phénomène, appelé sélectivité fonctionnelle des ligands, qui a bouleversé les paradigmes décrivant leu fonctionnement de ces récepteurs. Ce concept émane d’observations montrant que l’activité pharmacologique de certains ligands n’est pas nécessairement conservée sur tout le répertoire signalétiques connu du récepteur et peu se restreindre à l'activation sélective d’un sous-groupe de voies de signalisation.Ce nouveau modèle pharmacologique de l'activation des RCPG ouvre de nouvelles possibilités pour la découverte de médicaments plus efficace et sûr, ciblant les RCPGs. En effet, il permet la conception de molécules modulant spécifiquement les voies signalétiques d’intérêt thérapeutique, sans engager les autres voies qui pourraient mener à des effets secondaires indésirables ou de la tolérance. Cette thèse décrit l'utilisation d'une nouvelle approche sans marquage, basée sur la mesure du changement l'impédance cellulaire. Par la mesure des changements cellulaires, comme la morphologie, l’adhésion et/ou la redistribution des macromolécules, cette approche permet de mesurer de façon simultanée l'activité de plusieurs voies de signalisation impliqués dans ces réponses. Utilisant le récepteur β2-adrénergique (β2AR) comme modèle, nous avons démontré que les variations dans l’impédance cellulaire étaient directement liées à l’activation de multiples voies de signalisation suite à la stimulation du récepteur par son ligand. L’agoniste type du β2AR, l’isoprotérénol, s’est avéré induire une réponse d’impédance dose-dépendante constituée, dans le temps, de plusieurs caractéristiques distinctes pouvant être bloquées de façon compétitive par l’antagoniste ICI118,551 Par l’utilisation d’inhibiteurs sélectifs, nous avons été en mesure de déterminer la contribution de plusieurs voies signalétiques canoniques, comme les voies dépendantes de Gs et Gi, la production d’AMPc et l’activation de ERK1/2, sur ces changements. De plus, la dissection de la réponse d’impédance a permis d’identifier une nouvelle voie de mobilisation du Ca2+ contribuant à la réponse globale des changements initiés par la stimulation du β2AR. Dans une autre étude, nous avons rapporté que la réponse calcique induite par le β2AR serait attribuable à une transactivation Gs-dépendant du récepteur purinergique P2Y11, lui-même couplé à la protéine Gq. La mesure d’impédance permettant de distinguer et de décrire une pléiade d’activités signalétiques, nous avons émis l’hypothèse que des ligands arborant des profils signalétiques différents généreraient des réponses d’impédance distinctes. Le criblage d’une librairie de ligands spécifiques au β2AR a révélé une grande variété de signatures d’impédance. Grâce au développement d’une approche computationnelle innovatrice, nous avons été en mesure de regrouper ces signatures en cinq classes de composés, un regroupement qui s’est avéré hautement corrélé avec le profil signalétique des différents ligands. Nous avons ensuite combiné le criblage de composés par impédance avec l’utilisation d’inhibiteurs sélectifs de voies signalétiques afin d’augmenter la résolution du regroupement. En évaluant l’impact d’une voie signalétique donnée sur la signature d’impédance, nous avons été en mesure de révéler une plus grande variété de textures parmi les ligands. De plus, cette méthode s’est avérée efficace pour prédire le profil signalétique d’une librairie de composés non caractérisés, ciblant le β2AR. Ces travaux ont mené à l’élaboration d’une méthode permettant d’exprimer visuellement la sélectivité fonctionnelle de ligands et ont révélé de nouvelles classes de composés pour ce récepteur. Ces nouvelles classes de composés ont ensuite été testées sur des cardiomyocytes humains, confirmant que les composés regroupés dans différentes classes produisent des effets distincts sur la contractilité de ces cellules. Globalement, ces travaux démontrent la pertinence de l’utilisation de l’impédance cellulaire pour une évaluation précise des différences fonctionnelles parmi les composés ciblant les RCPGs. En fournissant une représentation pluridimensionnelle de la signalisation émanant des RCPGs à l’aide d’un seul essai ne requérant pas de marquage, les signatures d’impédance représentent une stratégie simple et innovante pour l’évaluation de la fonctionnalité sélective des ligands. Cette méthode pourrait être d’une grande utilité dans le processus de découverte de nouveaux médicaments.

Crystal Structures and Spectral Aspects of Mixed Ligand Transition Metal Chelates Derived from Aldehyde based ONS Donor Thiosemicarbazones

Thiosemicarbazones have emerged as an important class of ligands over a period of time, for a variety of reasons, such as variable donor properties, structural diversity and biological applications. Interesting as the coordination chemistry may be, the driving force for the study of these ligands has undoubtedly been their biological properties and the majority of the 3000 or so publications on thiosemicarbazones since 2000 have alluded to this feature. Thiosemicarbazones with potential donor atoms in their structural skeleton fascinate coordination chemists with their versatile chelating behavior. The thiosemicarbazones of aromatic aldehydes and ketones form stable chelates with transition metal cations by utilizing both their sulfur and azomethine nitrogen as donor atoms. They have been shown to possess a diverse range of biological activities including anticancer, antitumor, antibacterial, antiviral, antimalarial and antifungal properties owing to their ability to diffuse through the semipermeable membrane of the cell lines. The enhanced effect may be attributed to the increased lipophilicity of the metal complexes compared to the ligand alone.

A virtual backbone based approach for cooperative caching in mobile ad hoc networks

Cache look up is an integral part of cooperative caching in ad hoc networks. In this paper, we discuss a cooperative caching architecture with a distributed cache look up protocol which relies on a virtual backbone for locating and accessing data within a cooperate cache. Our proposal consists of two phases: (i) formation of a virtual backbone and (ii) the cache look up phase. The nodes in a Connected Dominating Set (CDS) form the virtual backbone. The cache look up protocol makes use of the nodes in the virtual backbone for effective data dissemination and discovery. The idea in this scheme is to reduce the number of nodes involved in cache look up process, by constructing a CDS that contains a small number of nodes, still having full coverage of the network. We evaluated the effect of various parameter settings on the performance metrics such as message overhead, cache hit ratio and average query delay. Compared to the previous schemes the proposed scheme not only reduces message overhead, but also improves the cache hit ratio and reduces the average delay

Dynamic management and restoration of virtual paths in broadband networks based on distributed software agents

La gestió de xarxes és un camp molt ampli i inclou molts aspectes diferents. Aquesta tesi doctoral està centrada en la gestió dels recursos en les xarxes de banda ampla que disposin de mecanismes per fer reserves de recursos, com per exemple Asynchronous Transfer Mode (ATM) o Multi-Protocol Label Switching (MPLS). Es poden establir xarxes lògiques utilitzant els Virtual Paths (VP) d'ATM o els Label Switched Paths (LSP) de MPLS, als que anomenem genèricament camins lògics. Els usuaris de la xarxa utilitzen doncs aquests camins lògics, que poden tenir recursos assignats, per establir les seves comunicacions. A més, els camins lògics són molt flexibles i les seves característiques es poden canviar dinàmicament. Aquest treball, se centra, en particular, en la gestió dinàmica d'aquesta xarxa lògica per tal de maximitzar-ne el rendiment i adaptar-la a les connexions ofertes. En aquest escenari, hi ha diversos mecanismes que poden afectar i modificar les característiques dels camins lògics (ample de banda, ruta, etc.). Aquests mecanismes inclouen els de balanceig de la càrrega (reassignació d'ample de banda i reencaminament) i els de restauració de fallades (ús de camins lògics de backup). Aquests dos mecanismes poden modificar la xarxa lògica i gestionar els recursos (ample de banda) dels enllaços físics. Per tant, existeix la necessitat de coordinar aquests mecanismes per evitar possibles interferències. La gestió de recursos convencional que fa ús de la xarxa lògica, recalcula periòdicament (per exemple cada hora o cada dia) tota la xarxa lògica d'una forma centralitzada. Això introdueix el problema que els reajustaments de la xarxa lògica no es realitzen en el moment en què realment hi ha problemes. D'altra banda també introdueix la necessitat de mantenir una visió centralitzada de tota la xarxa. En aquesta tesi, es proposa una arquitectura distribuïda basada en un sistema multi agent. L'objectiu principal d'aquesta arquitectura és realitzar de forma conjunta i coordinada la gestió de recursos a nivell de xarxa lògica, integrant els mecanismes de reajustament d'ample de banda amb els mecanismes de restauració preplanejada, inclosa la gestió de l'ample de banda reservada per a la restauració. Es proposa que aquesta gestió es porti a terme d'una forma contínua, no periòdica, actuant quan es detecta el problema (quan un camí lògic està congestionat, o sigui, quan està rebutjant peticions de connexió dels usuaris perquè està saturat) i d'una forma completament distribuïda, o sigui, sense mantenir una visió global de la xarxa. Així doncs, l'arquitectura proposada realitza petits rearranjaments a la xarxa lògica adaptant-la d'una forma contínua a la demanda dels usuaris. L'arquitectura proposada també té en consideració altres objectius com l'escalabilitat, la modularitat, la robustesa, la flexibilitat i la simplicitat. El sistema multi agent proposat està estructurat en dues capes d'agents: els agents de monitorització (M) i els de rendiment (P). Aquests agents estan situats en els diferents nodes de la xarxa: hi ha un agent P i diversos agents M a cada node; aquests últims subordinats als P. Per tant l'arquitectura proposada es pot veure com una jerarquia d'agents. Cada agent és responsable de monitoritzar i controlar els recursos als que està assignat. S'han realitzat diferents experiments utilitzant un simulador distribuït a nivell de connexió proposat per nosaltres mateixos. Els resultats mostren que l'arquitectura proposada és capaç de realitzar les tasques assignades de detecció de la congestió, reassignació dinàmica d'ample de banda i reencaminament d'una forma coordinada amb els mecanismes de restauració preplanejada i gestió de l'ample de banda reservat per la restauració. L'arquitectura distribuïda ofereix una escalabilitat i robustesa acceptables gràcies a la seva flexibilitat i modularitat.

A hearing screening protocol in a pediatric practice based on otoacoustic emissions

This paper evaluates the routine of one pediatrics facility interested in incorporating a hearing screening protocol into their practice and suggests such a protocol using distortion product otoacoustic emission tests (DPOAE).

Eye tracking and gaze based interaction within immersive virtual environments

Our eyes are input sensors which Provide our brains with streams of visual data. They have evolved to be extremely efficient, and they will constantly dart to-and-fro to rapidly build up a picture of the salient entities in a viewed scene. These actions are almost subconscious. However, they can provide telling signs of how the brain is decoding the visuals and call indicate emotional responses, prior to the viewer becoming aware of them. In this paper we discuss a method of tracking a user's eye movements, and Use these to calculate their gaze within an immersive virtual environment. We investigate how these gaze patterns can be captured and used to identify viewed virtual objects, and discuss how this can be used as a, natural method of interacting with the Virtual Environment. We describe a flexible tool that has been developed to achieve this, and detail initial validating applications that prove the concept.