The discovery of three lost ‘Salting’ carpets: science as a tool for revealing their history

Thesis presented at the Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, to obtain a Master degree in Conservation and Restoration,Specialization in Textiles

A regulated response to mitochondrial dysfunction modulates longevity and rates of living

Aging is a long-standing biological question of tremendous social and cultural importance. Despite this, only in the last 15 years has biology started to make significant progress in understanding the underlying mechanisms that regulate aging. This progress stemmed mainly from the use of model organisms, which allowed the discovery of several genes directly modulating longevity. Interestingly, several of these longevity genes are necessary for normal mitochondrial function, and disruption of their activity delays the aging process. This is somewhat paradoxical, considering the importance of cellular respiration for energy production and viability of eukaryotic organisms. One possible rationalization for this is that by decreasing cellular respiration, reactive oxygen species (ROS) generation is also reduced, and in that way, cellular decay and aging are delayed.(...)

Unravelling novel modes of antimicrobial action

Dissertation presented to obtain the Ph.D. degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Estimation of infection rate in epidemic models with multiple populations

Dissertação para obtenção do Grau de Mestre em Matemática e Aplicações Especialização em Actuariado, Estatística e Investigação Operacional

Planning, operations and data handling of planetary science missions

Dissertação para obtenção do Grau de Mestre em Engenharia Física

A framework for supporting knowledge representation – an ontological based approach

Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

Biological predictors of survival in limphoma and mechanisms underlying follicular lymphoma transformaion into diffuse large B cell lymphoma (vol I e II)

RESUMO: Os biomarcadores tumorais permitem identificar os doentes com maior risco de recorrência da doença, predizer a resposta tumoral à terapêutica e, finalmente, definir candidatos a novos alvos terapêuticos. Novos biomarcadores são especialmente necessários na abordagem clínica dos linfomas. Actualmente, esses tumores são diagnosticados através de uma combinação de características morfológicas, fenotípicas e moleculares, mas o prognóstico e o planeamento terapêutico estão quase exclusivamente dependentes de características clínicas. Estes factores clínicos são, na maioria dos linfomas, insuficientes numa proporção significativa dos doentes, em particular, aqueles com pior prognóstico. O linfoma folicular (LF) é, globalmente, o segundo subtipo mais comum de linfoma. É tipicamente uma doença indolente com uma sobrevida média entre os 8 e 12 anos, mas é geralmente fatal quando se transforma num linfoma agressivo de alto grau, habitualmente o linfoma difuso de grandes células B (LDGCB). Morfologicamente e funcionalmente, as células do LF recapitulam as células normais do centro germinativo na sua dependência de sobrevivência do microambiente não-tumoral, especialmente das células do sistema imunológico. Biomarcadores preditivos de transformação não existem pelo que um melhor conhecimento da biologia intrínseca de progressão do LF poderá revelar novos candidatos. Nesta tese descrevo duas abordagens distintas para a descoberta de novos biomarcadores. A primeira, o estudo da expressão global de genes ('genomics') obtidos por técnicas de alto rendimento que analisam todo o genoma humano sequenciado, permitindo identificar novas anomalias genéticas que possam representar mecanismos biológicos importantes de transformação. São descritos novos genes e alterações genómicas associados à transformação do LF, sendo especialmente relevantes as relacionadas com os eventos iniciais de transformação em LDGCB. A segunda, baseou-se em várias hipóteses centradas no microambiente do LF, rico em vários tipos de células nãomalignas. Os estudos imunoarquitectural de macrófagos, células T regulatórias e densidade de microvasos efectuado em biopsias de diagnóstico de doentes com LF tratados uniformemente correlacionaram-se significativamente, e independentemente dos critérios clínicos, com a evolução clínica e, mais importante, com o risco de transformação em LDGCB. Nesta tese, foram preferencialmente utilizadas (e optimizadas) técnicas que permitam o uso de amostras fixadas em parafina e formalina (FFPET). Estas são facilmente acessíveis a partir das biopsias de diagnóstico de rotina presentes nos arquivos de todos os departamentos de patologia, facilitando uma transição rápida dos novos marcadores para a prática clínica. Embora o FL fosse o tema principal da tese, os novos achados permitiram estender facilmente hipóteses semelhantes a outros subtipos de linfoma. Assim, são propostos e validados vários biomarcadores promissores e relacionados com o microambiente não tumoral, sobretudo dependentes das células do sistema imunológico, como contribuintes importantes para a biologia dos linfomas. Estes sugerem novas opções para a abordagem clínica destas doenças e, eventualmente, novos alvos terapêuticos.------------- ABSTRACT: Cancer biomarkers provide an opportunity to identify those patients most at risk for disease recurrence, predict which tumours will respond to different therapeutic approaches and ultimately define candidate biomarkers that may serve as targets for personalized therapy. New biomarkers are especially needed in the management of lymphoid cancers. At present, these tumours are diagnosed using a combination of morphologic, phenotypic and molecular features but prognosis and overall survival are mostly dependent on clinical characteristics. In most lymphoma types, these imprecisely assess a significant proportion of patients, in particular, those with very poor outcomes. Follicular lymphoma (FL) is the second most common lymphoma subtype worldwide. It is typically an indolent disease with current median survivals in the range of 8-12 years, but is usually fatal when it transforms into an aggressive high-grade lymphoma, characteristically Diffuse Large B Cell Lymphoma (DLBCL). Morphologically and functionally it recapitulates the normal cells of the germinal center with its survival dependency on non-malignant immune and immunerelated cells. Informative markers of transformation related to the intrinsic biology of FL progression are needed. Within this thesis two separate approaches to biomarker discovery were employed. The first was to study the global expression of genes (‘genomics’) obtained using high-throughput, wholegenome-wide approaches that offered the possibility for discovery of new genetic abnormalities that might represent the important biological mechanisms of transformation. Gene signatures associated with early events of transformation were found. Another approach relied on hypothesis-driven concepts focusing upon the microenvironment, rich in several non-malignant cell types. The immunoarchitectural studies of macrophages, regulatory T cells and microvessel density on diagnostic biopsies of uniformly treated FL patients significantly predicted clinical outcome and, importantly, also informed on the risk of transformation. Techniques that enabled the use of routine formalin fixed paraffin embedded diagnostic specimens from the pathology department archives were preferentially used in this thesis with the goal of fulfilling a rapid bench-to-beside” translation for these new findings. Although FL was the main subject of the thesis the new findings and hypotheses allowed easy transition into other lymphoma types. Several promising biomarkers were proposed and validated including the implication of several non-neoplastic immune cells as important contributors to lymphoma biology, opening new options for better treatment planning and eventually new therapeutic targets and candidate therapeutics.

Establishment and characterization of a human model of the blood-brain barrier

Dissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade N ova de Lisboa, Faculdade de Ciências e Tecnologia

Functional and structural studies of two enzymes: membrane bound kinase and Z-DNA/Z-RNA-binding protein

Dissertação para obtenção do Grau de Doutor em Sistemas de Bioengenharia

The Future of services: Uncovering latent needs through trend analysis

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Staging the Scientist: The Representation of Science and its Processes in American and British Drama

Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Estudos Ingleses e Norte Americanos

Semantic enrichment of knowledge sources supported by domain ontologies

This thesis introduces a novel conceptual framework to support the creation of knowledge representations based on enriched Semantic Vectors, using the classical vector space model approach extended with ontological support. One of the primary research challenges addressed here relates to the process of formalization and representation of document contents, where most existing approaches are limited and only take into account the explicit, word-based information in the document. This research explores how traditional knowledge representations can be enriched through incorporation of implicit information derived from the complex relationships (semantic associations) modelled by domain ontologies with the addition of information presented in documents. The relevant achievements pursued by this thesis are the following: (i) conceptualization of a model that enables the semantic enrichment of knowledge sources supported by domain experts; (ii) development of a method for extending the traditional vector space, using domain ontologies; (iii) development of a method to support ontology learning, based on the discovery of new ontological relations expressed in non-structured information sources; (iv) development of a process to evaluate the semantic enrichment; (v) implementation of a proof-of-concept, named SENSE (Semantic Enrichment kNowledge SourcEs), which enables to validate the ideas established under the scope of this thesis; (vi) publication of several scientific articles and the support to 4 master dissertations carried out by the department of Electrical and Computer Engineering from FCT/UNL. It is worth mentioning that the work developed under the semantic referential covered by this thesis has reused relevant achievements within the scope of research European projects, in order to address approaches which are considered scientifically sound and coherent and avoid “reinventing the wheel”.

Gas tungsten arc welding of NiTi shape memory alloy

Shape memory alloys are characterized by the ability of recovering their initial shape after being deformed and by superelasticity. Since the discovery of these alloys, a new field of interest emerged not only for the scientific community but also to many industries. However, these alloys present poor machinability which constitute a constrain in the design of complex components for new applications. Thus, the demand for joining techniques able to join these alloys without compromising their properties became of great importance to enlarge the complexity of existing applications. Literature shows that these alloys are joined mainly using laser welding. In the present study, similar NiTi butt joints, were produced using TIG welding. The welds were performed in 1.5 mm thick plates across the rolling direction. A special fixture and gas assist device was designed and manufactured. Also a robot arm was adapted to accommodate the welding torch to assure the repeatability of the welding parameters. Welds were successfully achieved without macroscopic defects, such as pores and distortions. Very superficial oxidation was seen on the top surface due to insufficient shielding gas flow on the weld face. The welded joints were mechanically tested and structurally characterized. Testing methods were used to evaluate macro and microstructure, as well as the phase transformation temperatures, the mechanical single and cyclic behaviour and the shape recovery ability. Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), microhardness measurements were techniques also used to evaluate the welded joints. A depletion in Ni in the fusion zone was seen, as well as a shift in Ms temperature. For strain values of 4% the accumulated irrecoverable strain was of about 30% and increased with the strain imposed during cycling. Nevertheless, a complete recovery of initial shape was observed when testing the shape memory effect on a dedicated device that introduces a deformation of 6.7%. That is, the welding procedure does not remove the ability of the specimens to recover their initial shape.

Archaeometallurgical study of the Proto-historic collection of Moinhos de Golas (North Portugal): a forecast for technological changes?

This work presents the archaeometallurgical study of a group of metallic artefacts found in Moinhos de Golas site, Vila Real (North of Portugal), that can generically be attributed to Proto-history (1st millennium BC, Late Bronze Age and Iron Age). The collection is composed by 35 objects: weapons, ornaments and tools, and others of difficult classification, as rings, bars and one small thin bent sheet. Some of the objects can typologically be attributed to Late Bronze Age, others are of more difficult specific attribution. The archaeometallurgical study involved x-ray digital radiography, elemental analysis by micro-energy dispersive X-ray fluorescence spectrometry and scanning electron microscopy with energy dispersive spectroscopy, microstructural observations by optical microscopy and scanning electron microscopy. The radiographic images revealed structural heterogeneities frequently related with the degradation of some artefacts and the elemental analysis showed that the majority of the artefacts was produced in a binary bronze alloy (Cu-Sn) (73%), being others produced in copper (15%) and three artefacts in brass (Cu-Zn(-Sn-Pb)). Among each type of alloy there’s certain variability in the composition and in the type of inclusions. The microstructural observations revealed that the majority of the artefacts suffered cycles of thermo-mechanical processing after casting. The diversity of metals/alloys identified was a discovery of great interest, specifically due to the presence of brasses. Their presence can be interpreted as importations related to the circulation of exogenous products during the Proto-history and/or to the deposition of materials during different moments at the site, from the transition of Late Bronze Age/Early Iron Age (Orientalizing period) onwards, as during the Roman period.

Identifying the urban communities of New York City using bikeshare data from NYC citibike

This study identifies a measure of the cultural importance of an area within a city. It does so by making use of origindestination trip data and the bike stations of the bike share system in New York City as a proxy to study the city. Rarely is movement in the city studied at such a small scale. The change in strength of the similarity of movement between each station is studied. It is the first study to provide this measure of importance for every point in the system. This measure is then related to the characteristics which make for vibrant city communities, namely highly mixed land use types. It reveals that the spatial pattern of important areas remains constant over differing time periods. Communities are then characterised by the land uses surrounding these stations with high measures of importance. Finally it identifies the areas of global cultural importance alongside the areas of local importance to the city.