A MAP approach to evidence accumulation clustering

The Evidence Accumulation Clustering (EAC) paradigm is a clustering ensemble method which derives a consensus partition from a collection of base clusterings obtained using different algorithms. It collects from the partitions in the ensemble a set of pairwise observations about the co-occurrence of objects in a same cluster and it uses these co-occurrence statistics to derive a similarity matrix, referred to as co-association matrix. The Probabilistic Evidence Accumulation for Clustering Ensembles (PEACE) algorithm is a principled approach for the extraction of a consensus clustering from the observations encoded in the co-association matrix based on a probabilistic model for the co-association matrix parameterized by the unknown assignments of objects to clusters. In this paper we extend the PEACE algorithm by deriving a consensus solution according to a MAP approach with Dirichlet priors defined for the unknown probabilistic cluster assignments. In particular, we study the positive regularization effect of Dirichlet priors on the final consensus solution with both synthetic and real benchmark data.

Utilização do algoritmo Self-Organizing Map na caracterização de organizações públicas portuguesas.

Dissertação apresentada como requisito parcial para a obtenção do grau de mestre em Estatística e Gestão de Informação.

Caracterização da situação orçamental no poder local em indicadores orçamentais e self-organizing map.

Dissertação apresentada como requisito parcial para obtenção do grau de Mestre em Estatística e Gestão de Informação.

Análise Exploratória do Índice de Desenvolvimento Humano: uma aplicação do Self Organizing Map na segmentação dos países

Dissertação apresentada como requisito parcial para obtenção do grau de Mestre em Estatística e Gestão de Informação.

Web-application for gathering, analyzing, and processing health information about allergy data

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Adult B-Cell Acute Lymphoblastic Leukemia Cells Display Decreased PTEN Activity and Constitutive Hyperactivation of PI3K/Akt Pathway Despite High PTEN Protein Levels

Adult B-cell acute lymphoblastic leukemia remains a major therapeutic challenge, requiring a better characterization of the molecular determinants underlying disease progression and resistance to treatment. Here, using a phospho-flow cytometry approach we show that adult diagnostic B-cell acute lymphoblastic leukemia specimens display PI3K/Akt pathway hyperactivation, irrespective of their BCR-ABL status and despite paradoxically high basal expression of PTEN, the major negative regulator of the pathway. Protein kinase CK2 is known to phosphorylate PTEN thereby driving PTEN protein stabilization and concomitant PTEN functional inactivation. In agreement, we found that adult B-cell acute lymphoblastic leukemia samples show significantly higher CK2 kinase activity and lower PTEN lipid phosphatase activity than healthy controls. Moreover, the clinical-grade CK2 inhibitor CX-4945 (Silmitasertib) reversed PTEN levels in leukemia cells to those observed in healthy controls, and promoted leukemia cell death without significantly affecting normal bone marrow cells. Our studies indicate that CK2-mediated PTEN posttranslational inactivation, associated with PI3K/Akt pathway hyperactivation, are a common event in adult B-cell acute lymphoblastic leukemia and suggest that CK2 inhibition may constitute a valid, novel therapeutic tool in this malignancy.

Desenvolvimento de um head-mounted display estereoscópio

Dissertação para obtenção do Grau de Mestre em Engenharia Física

Implementing quality management systems in small and medium construction companies: a contribution to a road map for success

Leadership and Management in Engineering, January 2009

Biodiversity open map (BiodOM) - SIGWeb colaborativos e Software Geoespacial Livre e Aberto numa abordagem da neogeografia aplicada ao conhecimento da biodiversidade

Trabalho de Projeto apresentado como requisito parcial para obtenção do grau de Mestre em Ciência e Sistemas de Informação Geográfica

Using GIS to map the spatial and temporal occurrence of cholera epidemic in Camaroon

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies

Phage display as a tool for development of novel therapeutics for breast cancer

Phage display technology is a powerful platform for the generation of highly specific human monoclonal antibodies (Abs) with potential use in clinical applications. Moreover, this technique has also proven to be a reliable approach in identifying and validating new cancer-related targets. For scientific or medical applications, different types of Ab libraries can be constructed. The use of Fab Immune libraries allows the production of high quality and affinity antigen-specific Abs. In this work, two immune human phage display IgG Fab libraries were generated from the Ab repertoire of 16 breast cancer patients, in order to obtain a tool for the development of new therapeutic Abs for breast cancer, a condition that has great impact worldwide. The generated libraries are estimated to contain more than 108 independent clones and a diversity over 90%. Libraries validation was pursued by selection against BSA, a foreign and highly immunogenic protein, and HER2, a well established cancer target. Preliminary results suggested that phage pools with affinity for these antigens were selected and enriched. Individual clones were isolated, however, it was not possible to obtain enough data to further characterize them. Selection against the DLL1 protein was also performed, once it is a known ligand of the Notch pathway, whose deregulation is associated to breast cancer, making it an interesting target for the generation of function-blocking Abs. Selection resulted in the isolation of a clone with low affinity and Fab expression levels. The validation process was not completed and further effort will have to be put in this task in the future. Although immune libraries concept implies limited applicability, the library reported here has a wide range of use possibilities, since it was not restrained to a single antigen but instead thought to be used against any breast cancer associated target, thus being a valuable tool.

Map-it – Mapeamento tridimensional de interiores

A perceção tridimensional é uma área em crescente desenvolvimento. Não existindo uma tecnologia ideal capaz de percecionar todo o tipo de cenários, têm surgido estudos sobre a aplicabilidade de diferentes tecnologias de forma a obter modelos que melhor se aproximem da realidade. Propõe-se nesta dissertação o desenvolvimento de um sistema de baixo-custo de percepção tridimensional que seja portátil e acessível na sua aplicabilidade, de forma a ter a capacidade de percecionar tridimensionalmente espaços interiores com pouca iluminação, tais como as divisões de um edifício ou os canais de uma mina subterrânea. Utilizou-se a triangulação entre uma câmara digital, os pontos de uma linha laser e um emissor laser para a obtenção dos dados tridimensionais do cenário. Para isso, recorreu-se a metodologias de processamento digital de imagens para a construção dos modelos dos cenários. Para se obter a validação desta dissertação, realizaram-se testes do protótipo de forma a determinar as suas capacidades percecionais. Em primeiro lugar realizou-se uma bateria de testes de calibração onde, repetidamente, se estudaram isoladamente pontos do cenário para verificar a precisão do sensor. Após esta calibração, estudou-se a capacidade de transformação de uma linha laser projetada num conjunto de coordenadas. Finalmente testou-se a capacidade de perceção tridimensional por rotação do sensor, de forma a realizar a transformação de múltiplas projeções de linhas laser num conjunto de coordenadas em torno do sensor. Verificou-se: no teste de calibração, a obtenção de distâncias com erro médio relativo inferior a 1%; no teste da linha laser, a capacidade de perceção de profundidade de múltiplos pontos ao longo da mesma; no teste de rotação, a aquisição de múltiplos conjuntos de linhas de profundidade no cenário, por rotação do sensor. Os resultados dos testes de validação permitiram concluir a viabilidade de utilizar a triangulação na aquisição de conjuntos de coordenadas de espaços interiores.

Fate map of zebrafish left-right organizer

The organizer is a ciliated signalling transient organ, responsible for the patterning of embryo tissues during embryonic development. In higher vertebrates, such as mouse and chick, this organizer (the node and the Hensen’s node, respectively) performs dorsalventral and anteriorposterior axis definition, as well as left-right patterning of the internal organs. In lower vertebrates, such as frog and zebrafish, there is a separate specialized organ for left-right purposes called the Gastrocoel Roof Plate (GRP) and Kupffer’s Vesicle (KV), respectively. It is known that mouse and chick organizer cells give rise to structures like floor plate, notochord, hypochord and somites. Frog GRP originates all these but floor plate. In zebrafish, at 13-14 somite stage (ss) the KV finished its left-right patterning but what happens to this organizer’ cells is still poorly studied. This research attempts to understand the fate and behaviour of the KV cells. We followed the fate of KV cells by live imaging and by tight time-courses with fixed larvae. We assessed in detail their proliferative and death profile, as well as cilia length progression from 9-10 ss until 29-30 ss. We conclude that the KV cells mostly follow the evolutionarily conserved fates described for other organizers. These cells mainly incorporate the notochord and hypochord; few cells incorporate the floor plate and the somites. As a novelty, it is also hypothesized that the hypural cell fate may be among the KV cell fates.

Theranostic applications of phage display to control leishmaniasis: selection of biomarkers for serodiagnostics, vaccination, and immunotherapy

AbstractPhage display is a high-throughput subtractive proteomic technology used for the generation and screening of large peptide and antibody libraries. It is based on the selection of phage-fused surface-exposed peptides that recognize specific ligands and demonstrate desired functionality for diagnostic and therapeutic purposes. Phage display has provided unmatched tools for controlling viral, bacterial, fungal, and parasitic infections, and allowed identification of new therapeutic targets to treat cancer, metabolic diseases, and other chronic conditions. This review presents recent advancements in serodiagnostics and prevention of leishmaniasis -an important tropical parasitic disease- achieved using phage display for the identification of novel antigens with improved sensitivity and specificity. Our focus is on theranostics of visceral leishmaniasis with the aim to develop biomarker candidates exhibiting both diagnostic and therapeutic potential to fight this important, yet neglected, tropical disease.

Phage display as a tool for generation of bio-therapeutic agents for breast cancer

Notch is a conserved signalling pathway, which plays a crucial role in a multiple cellular processes such as stem cell self-renewal, cell division, proliferation and apoptosis. In mammalian, four Notch receptors and five ligands are described, where interaction is achieved through their extracellular domains, leading to a transcription activation of different target genes. Increased expression of Notch ligands has been detected in several types of cancer, including breast cancer suggesting that these proteins represent possible therapeutic targets. The goal of this work was to generate quality protein targets and, by phage display technology, select function-blocking antibodies specific for Notch ligands. Phage display is a powerful technique that allows the generation of highly specific antibodies to be used for therapeutics, and it has also proved to be a reliable approach in identifying and validating new cancer-related targets. Also, we aimed at solving the tri-dimensional structure of the Notch ligands alone and in complex with selected antibodies. In this work, the initial phase focused on the optimization of the expression and purification of a human Delta-like 1 ligand mutant construct (hDLL1-DE3), by refolding from E. coli inclusion bodies. To confirm the biological activity of the produced recombinant protein cellular functional studies were performed, revealing that treatment with hDLL1-DE3 protein led to a modulation of Notch target genes. In a second stage of this study, Antibody fragments (Fabs) specific for hDLL1-DE3 were generated by phage display, using the produced protein as target, in which one good Fab candidate was selected to determine the best expression conditions. In parallel, multiple crystallization conditions were tested with hDLL1-DE3, but so far none led to positive results.