Development of 3D in vitro models for prediction of hepatic metabolism and toxicity

The development of human cell models that recapitulate hepatic functionality allows the study of metabolic pathways involved in toxicity and disease. The increased biological relevance, cost-effectiveness and high-throughput of cell models can contribute to increase the efficiency of drug development in the pharmaceutical industry. Recapitulation of liver functionality in vitro requires the development of advanced culture strategies to mimic in vivo complexity, such as 3D culture, co-cultures or biomaterials. However, complex 3D models are typically associated with poor robustness, limited scalability and compatibility with screening methods. In this work, several strategies were used to develop highly functional and reproducible spheroid-based in vitro models of human hepatocytes and HepaRG cells using stirred culture systems. In chapter 2, the isolation of human hepatocytes from resected liver tissue was implemented and a liver tissue perfusion method was optimized towards the improvement of hepatocyte isolation and aggregation efficiency, resulting in an isolation protocol compatible with 3D culture. In chapter 3, human hepatocytes were co-cultivated with mesenchymal stem cells (MSC) and the phenotype of both cell types was characterized, showing that MSC acquire a supportive stromal function and hepatocytes retain differentiated hepatic functions, stability of drug metabolism enzymes and higher viability in co-cultures. In chapter 4, a 3D alginate microencapsulation strategy for the differentiation of HepaRG cells was evaluated and compared with the standard 2D DMSO-dependent differentiation, yielding higher differentiation efficiency, comparable levels of drug metabolism activity and significantly improved biosynthetic activity. The work developed in this thesis provides novel strategies for 3D culture of human hepatic cell models, which are reproducible, scalable and compatible with screening platforms. The phenotypic and functional characterization of the in vitro systems performed contributes to the state of the art of human hepatic cell models and can be applied to the improvement of pre-clinical drug development efficiency of the process, model disease and ultimately, development of cell-based therapeutic strategies for liver failure.

Writing/erasing 3D micro and nano wrinkles in flexible elastomers for volatile organic compounds sensor

Micro/nano wrinkled patterns on cross-linked urethane/urea polymeric flexible free standing films with two soft segments, polypropylene oxide and polybutadiene, can be induced by UV-irradiation. The ability to write/erase these 3D structures, in a controlled manner, is the main focus of this work. The imprinting of the wrinkled structures was accomplished by swelling in an appropriate solvent followed by drying the membranes after the cross-linking process and UV irradiation. The surface tailoring of the elastomeric membranes was imaged by optical microscopy, scanning electronic microscopy and by atomic force microscopy. To erase the wrinkled structures the elastomers were swollen. The swelling as well as the sol/gel fraction and the UV radiation were tuned in order to control the wrinkles characteristics. It was found that the wrinkles wavelength, in the order of microns (1±0,25μm), was stamped by the UV radiation intensity and exposure time while the wrinkles' amplitude, in the order of nanometers (150-450 nm), was highly dependent on the swelling and sol/gel fraction. A prototype for volatile organic compounds detection was developed taking advantage of the unique 3D micro/nano wrinkles features.

A cor na pintura balinesa: caracterização dos pigmentos da pintura balinesa

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Conservação e Restauro

Time – intangible tangible –

Dissertação para obtenção do Grau de Mestre em Arte e Ciência do Vidro

O Mosteiro de Sta. Maria da Vitória e a vocação moralizante das gárgulas do panteão duartino

The Portuguese monument called Batalha’s monastery has occupied an important place in Art History especially the unfinished chapels destined to be the Pantheon of the King D. Duarte. There we observe some interesting gargoyles, moral representations as an approach to the late medieval imaginary in the national context, but also common with the thoughts of King D. Duarte. Gargoyles mirrored the daily life of medieval men and women and displayed the confrontation between the religious and the social spheres by criticizing the behaviour of the sinful body, taking on an important educational role amongst audiences. This article aims to understand the moral sense and sexual behaviour that can observe in these gargoyles and its relation with the book Leal Conselheiro, written by D. Duarte some decades before.

Optimization of breast tomosynthesis image reconstruction using parallel computing

Breast cancer is the most common cancer among women, being a major public health problem. Worldwide, X-ray mammography is the current gold-standard for medical imaging of breast cancer. However, it has associated some well-known limitations. The false-negative rates, up to 66% in symptomatic women, and the false-positive rates, up to 60%, are a continued source of concern and debate. These drawbacks prompt the development of other imaging techniques for breast cancer detection, in which Digital Breast Tomosynthesis (DBT) is included. DBT is a 3D radiographic technique that reduces the obscuring effect of tissue overlap and appears to address both issues of false-negative and false-positive rates. The 3D images in DBT are only achieved through image reconstruction methods. These methods play an important role in a clinical setting since there is a need to implement a reconstruction process that is both accurate and fast. This dissertation deals with the optimization of iterative algorithms, with parallel computing through an implementation on Graphics Processing Units (GPUs) to make the 3D reconstruction faster using Compute Unified Device Architecture (CUDA). Iterative algorithms have shown to produce the highest quality DBT images, but since they are computationally intensive, their clinical use is currently rejected. These algorithms have the potential to reduce patient dose in DBT scans. A method of integrating CUDA in Interactive Data Language (IDL) is proposed in order to accelerate the DBT image reconstructions. This method has never been attempted before for DBT. In this work the system matrix calculation, the most computationally expensive part of iterative algorithms, is accelerated. A speedup of 1.6 is achieved proving the fact that GPUs can accelerate the IDL implementation.

A prestação de contas e o regime especial da invalidade das deliberações

The obligation of accountability, or the need to make known the economic and financial state of the companies, ceased to be a purely internal activity, becoming a necessity of a general nature. The knowledge of the financial state of the companies, wich is provided by accountability documents, reveals more and more elementary for all interested in the results obtained, whether in terms of profitability, either with a view to assessing the economic and financial health of the companies. This essay aims to a deeper analysis to matters of accountability, in particular, to the special invalidity scheme of corporate resolutions, wich is enshrined in art. 69º of Portuguese Companies Code. We chose to reference the accrual basis accounts approval, through the analysis of financial statements, laying down a set of principles and criteria applicable to different entities. After consideration of the special scheme versed in art. 69º, we conclude there is a certain ambiguity in the adoption of the criteria do delimit each of the hypotheses of the precept, since the legislator uses indeterminate concepts. Nevertheless, if there is a rule, this will be the annulment, and only exceptionally will apply the nullity scheme, where there is injury to the public interest and the interests of the creditors.

The influence of geometric factors on the wall shear stress distribution in realistic human coronary arteries

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para a obtenção do grau de Mestre em Engenharia Biomédica. A presente dissertação foi desenvolvida no Erasmus Medical Center em Roterdão, Holanda

Liaisons dangereuses, conservation of modern and contemporary art: a study of the synthetic binding media in Portugal

Dissertação apresentada para obtenção do Grau de Doutor em Conservação e Restauro, especialidade de Ciências da Conservação, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Bioactive beads for local sensing of proteases in 3D engineered tissues

Dissertação para obtenção do Grau de Doutor em Bioengenharia (MIT)

3D GIS modelling using ESRI's CityEngine: a case study from the University Jaume I in Castellon de la Plana Spain

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

The influence of animation on functional food intake in children

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

Uncertain Spaces: Virtual Configurations in Contemporary Art and Museums

Contém artigos apresentados na International Conference “Uncertain Spaces: Virtual Configurations in Contemporary Art and Museums”, na Fundação Calouste Gulbenkian (Lisboa), 31 Outubro - 1 de Novembro de 2014) de: Helena Barranha e Susana S. Martins - Introduction: Art, Museums and Uncertainty (pp.1-12); Alexandra Bounia e Eleni Myrivili - Beyond the ‘Virtual’: Intangible Museographies and Collaborative Museum Experiences (pp.15-32); Annet Dekker - Curating in Progress. Moving Between Objects and Processes (pp.33-54); Giselle Beiguelman - Corrupted Memories. The aesthetics of Digital Ruins and the Museum of the Unfinished (pp.55-82); Andrew Vaas Brooks - The Planetary Datalinks (pp.85-110); Sören Meschede - Curators’ Network: Creating a Promotional Database for Contemporary Visual Arts (pp.11-130); Stefanie Kogler - Divergent Histories and Digital Archives of Latin American and Latino Art in the United States – Old Problems in New Digital Formats (pp.131-156); Luise Reitstätter e Florian Bettel - Right to the City! Right to the Museum!(pp.159-182); Roberto Terracciano - On Geo-poetic systems: virtual interventions inside and outside the museum space (pp.183-210); e, Catarina Carneiro de Sousa e Luís Eustáquio - Art Practice in Collaborative Virtual Environments (pp.211-240).

Global trends in modern and contemporary islamic art

Disponível para consulta índice e introdução.

Going Public: Conservation of Contemporary Artworks. Between Backstage and Frontstage in Contemporary Art Museums

In museum studies and history of art, what happens behind the scenes of museums stays relatively unseen and unspoken about. In the arts, generally speaking, what is dismissed as irrelevant (e.g. the realm of practices) is deliberately detached from what is thought to really matter; theory, discourse, content and meaning. Up till recently, backstage activities such as conservation practices are merely discussed among specialists and museum professionals. Only the outcomes of these discussions are sometimes – if at all – explicitly communicated to a larger public. Studies into the practices of contemporary art conservation however show that practices behind the scenes play an important role in the perpetuation of these artworks. What happens behind the scenes in terms of conservation has, in several ways, important effects on the ongoing life of these artworks in a museum context. Conservation practices, I argue, should therefore become a necessary part of museum studies and history of art. How can the working practices of conservators become more visible and transparent to a diversity of audiences, including researchers? And what does this mean in terms of research methodology?