Therapeutics bioconjugates: evaluation of iminoboronates as payload delivery system for cancer

The advent of bioconjugation impacted deeply the world of sciences and technology. New biomolecules were found, biological processes were understood, and novel methodologies were formed due to the fast expansion of this area. The possibility of creating new effective therapies for diseases like cancer is one of big applications of this now big area of study. Off target toxicity was always the problem of potent small molecules with high activity towards specific tumour targets. However, chemotherapy is now selective due to powerful linkers that connect targeting molecules with affinity to interesting biological receptors and cytotoxic drugs. This linkers must have very specific properties, such as high stability in plasma, no toxicity, no interference with ligand affinity nor drug potency, and at the same time, be able to lyse once inside the target molecule to release the therapeutic warhead. Bipolar environments between tumour intracellular and extracellular medias are usually exploited by this linkers in order to complete this goal. The work done in this thesis explores a new model for that same task, specific cancer drug delivery. Iminoboronates were studied due to its remarkable selective stability towards a wide pH range and endogenous molecules. A fluorescence probe was design to validate this model by creating an Off/On system and determine the payload release location in situ. A process was optimized to synthetize the probe 8-(1-aminoethyl)-7-hydroxy-coumarin (1) through a reductive amination reaction in a microwave reactor with 61 % yield. A method to conjugate this probe to ABBA was also optimized, obtaining the iminoboronate in good yields in mild conditions. The iminoboronate model was studied regarding its stability in several simulated biological environments and each half-life time was determined, showing the conjugate is stable most of the cases except in tumour intracellular systems. The construction of folate-ABBA-coumarin bioconjugate have been made to complete this evaluation. The ability to be uptaken by a cancer cell through endocytosis process and the conjugation delivery of coumarin fluorescence payload are two features to hope for in this construct.

Millennium BCP: Optimization of the branches closure process

Nowadays, a significant number of banks in Portugal are facing a bank-branch restructuring problem, and Millennium BCP is not an exception. The closure of branches is a major component of profit maximization through the reduction in operational and personnel costs but also an opportunity to approach the idea of “baking of future” and start thinking on the benefits of the digital era. This dissertation centers on a current high-impact organizational problem addressed by the company and consists in a proposal of optimization to the model that Millennium BCP uses. Even though measures of performance are usually considered the most important elements in evaluating the viability of branches, there is evidence suggesting that other general factors can be important to assess branch potential, such as the influx on branches, business dimensions of a branch and its location, which will be addressed in this project.

A multi-criteria decision support system for a routing problem in waste collection

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The non-emergency patient transport modelled as a team orienteering problem

This work presents an improved model to solve the non-emergency patients transport (NEPT) service issues given the new rules recently established in Portugal. The model follows the same principle of the Team Orienteering Problem by selecting the patients to be included in the routes attending the maximum reduction in costs when compared with individual transportation. This model establishes the best sets of patients to be transported together. The model was implemented in AMPL and a compact formulation was solved using NEOS Server. A heuristic procedure based on iteratively solving Orienteering Problems is presented, and this heuristic provides good results in terms of accuracy and computation time. Euclidean instances as well as asymmetric real data gathered from Google maps were used, and the model has a promising performance mainly with asymmetric cost matrices.

A taxonomy for the flexible job shop scheduling problem

This chapter aims at developing a taxonomic framework to classify the studies on the flexible job shop scheduling problem (FJSP). The FJSP is a generalization of the classical job shop scheduling problem (JSP), which is one of the oldest NP-hard problems. Although various solution methodologies have been developed to obtain good solutions in reasonable time for FSJPs with different objective functions and constraints, no study which systematically reviews the FJSP literature has been encountered. In the proposed taxonomy, the type of study, type of problem, objective, methodology, data characteristics, and benchmarking are the main categories. In order to verify the proposed taxonomy, a variety of papers from the literature are classified. Using this classification, several inferences are drawn and gaps in the FJSP literature are specified. With the proposed taxonomy, the aim is to develop a framework for a broad view of the FJSP literature and construct a basis for future studies.

A decision support system for a waste collection vehicle routing problem

The selective collection of municipal solid waste for recycling is a very complex and expensive process, where a major issue is to perform cost-efficient waste collection routes. Despite the abundance of commercially available software for fleet management, they often lack the capability to deal properly with sequencing problems and dynamic revision of plans and schedules during process execution. Our approach to achieve better solutions for the waste collection process is to model it as a vehicle routing problem, more specifically as a team orienteering problem where capacity constraints on the vehicles are considered, as well as time windows for the waste collection points and for the vehicles. The final model is called capacitated team orienteering problem with double time windows (CTOPdTW).We developed a genetic algorithm to solve routing problems in waste collection modelled as a CTOPdTW. The results achieved suggest possible reductions of logistic costs in selective waste collection.

Decision methods applied to solve a safety problem on a waste treatment facility

To solve a health and safety problem on a waste treatment facility, different multicriteria decision methods were used, including the PROV Exponential decision method. Four alternatives and ten attributes were considered. We found a congruent solution, validated by the different methods. The AHP and the PROV Exponential decision method led us to the same options ordering, but the last method reinforced one of the options as being the best performing one, and detached the least performing option. Also, the ELECTRE I method results led to the same ordering which allowed to point the best solution with reasonable confidence. This paper demonstrates the potential of using multicriteria decision methods to support decision making on complex problems such as risk control and accidents prevention.

Where@UM - Dependable organic radio maps

In the past decade, the research community has been dedicating considerable effort into indoor positioning systems based on Wi-Fi fingerprinting techniques, mainly due to their capability to exploit existing infrastructures. Crowdsourcing approaches, also known as organic, have been proposed recently to address the problem of creating and maintaining the corresponding radio maps. In these organic systems, the users of the system build the radio map themselves while using it to estimate their own position/location. However, most of these collaborative methods, proposed by several authors, assume that all the users are honest and committed to contribute to a good quality radio map. In this paper we assess the quality of a radio map built collaboratively and propose a method to classify the credibility of individual contributions and the reputation of individual users. Experimental results are presented for an organic indoor location system that has been used by more than one hundred users over a period of around 12 months.

Detection of dangerous situations using a smart internet of things system

The Internet of Things (IoT) is a concept that can foster the emergence of innovative applications. In order to minimize parents’s concerns about their children’s safety, this paper presents the design of a smart Internet of Things system for identifying dangerous situations. The system will be based on real time collection and analysis of physiological signals monitored by non-invasive and non-intrusive sensors, Frequency IDentification (RFID) tags and a Global Positioning System (GPS) to determine when a child is in danger. The assumption of a state of danger is made taking into account the validation of a certain number of biometric reactions to some specific situations and according to a self-learning algorithm developed for this architecture. The results of the analysis of data collected and the location of the child will be able in real time to child’s care holders in a web application.

Desenvolvimento de sistema de alarmes para incontinentes

Dissertação de mestrado em redes e serviços telemáticos

Mapeamento do uso e cobertura da terra a partir da segmentação e classificação de imagens-fração solo, sombra e vegetação derivadas do modelo linear de mistura aplicado a dados do sensor TM/Landsat5, na região do reservatório de Tucuruí - PA

Técnicas de sensoriamento remoto são fundamentais para o monitoramento das mudanças de uso da terra, principalmente em áreas extensas como a Amazônia. O mapeamento de uso da terra, geralmente é realizado por métodos de classificação manual ou digital pixel a pixel, os quais consomem muito tempo. Este estudo aborda a aplicação do modelo linear de mistura em uma imagem Landsat-TM segmentada para o mapeamento das classes de uso da terra na região do reservatório de Tucuruí-PA para os anos de 1996 e 2001.

Annular flow of viscoelastic fluids: Analytical and numerical solutions

This work provides analytical and numerical solutions for the linear, quadratic and exponential Phan–Thien–Tanner (PTT) viscoelastic models, for axial and helical annular fully-developed flows under no slip and slip boundary conditions, the latter given by the linear and nonlinear Navier slip laws. The rheology of the three PTT model functions is discussed together with the influence of the slip velocity upon the flow velocity and stress fields. For the linear PTT model, full analytical solutions for the inverse problem (unknown velocity) are devised for the linear Navier slip law and two different slip exponents. For the linear PTT model with other values of the slip exponent and for the quadratic PTT model, the polynomial equation for the radial location (β) of the null shear stress must be solved numerically. For both models, the solution of the direct problem is given by an iterative procedure involving three nonlinear equations, one for β, other for the pressure gradient and another for the torque per unit length. For the exponential PTT model we devise a numerical procedure that can easily compute the numerical solution of the pure axial flow problem

Detecção de cicatrizes de áreas queimadas baseada no modelo linear de mistura espectral e imagens índice de vegetação utilizando dados multitemporais do sensor MODIS/TERRA no estado do Mato Grosso, Amazônia brasileira

O objetivo desta pesquisa foi avaliar os dados do sensor MODIS para detectar e monitorar cicatrizes de áreas recém queimadas. Utilizamos imagens da reflectância de superfície do sensor MODIS: produto MOD09 (dia 5 de outubro) e produto MOD13A1 (meses de outubro e novembro). Foi avaliada também uma série temporal de um ano dos índices de vegetação (IV) EVI e NDVI (produto MOD13A1). Uma imagem do sensor ETM+ (dia 5 de outubro) foi utilizada como base para a delimitação dos polígonos amostrais e avaliação dos dados MODIS devido a sua melhor resolução espacial. A metodologia focou na aplicação do modelo linear de mistura espectral nas imagens reflectância para a geração das imagens fração sombra. Análises de regressão foram efetuadas para comparação entre o percentual de sombra derivado da imagem ETM+ e das imagens MODIS. As alterações multitemporais nas imagens IV foram avaliadas com base no teste de Tukey. Os resultados mostraram que a imagem fração sombra gerada a partir do produto MOD09 apresentou um R² = 0,66 (p < 0,01) em relação aos dados ETM+. Para as imagens do produto MOD13A1 não foram identificadas relações significativas. Os IV dentro dos mesmos polígonos apresentaram uma variação sazonal durante o ano. No entanto, não houve uma diminuição significativa dos valores destes índices nos meses onde foram observadas as cicatrizes de áreas recém queimadas. Portanto, o produto MOD09 mostrou-se mais eficiente que o produto MOD13A1 para a detecção de cicatrizes de áreas recém queimadas. A análise multitemporal dos IV sugeriu que não foi possível detectar este mesmo padrão na área de estudo.

Generating timed trajectories foran autonomous robot

Tese de Doutoramento Programa Doutoral em Engenharia Electrónica e Computadores