A new least-squares approach to differintegration modeling

Signal Processing, Vol. 86, nº 10

Transparent oxide thin-film transistors: production, characterization and integration

In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Nanotechnologies and Nanosciences by Universidade Nova de Lisboa Faculdade de Ciências e Tecnologia

On the relation between the fractional Brownian motion and the fractional derivatives

Physics Letters A, vol. 372; Issue 7

Introduction to fractional linear systems. Part 1 : continuous-time case

IEE Proceedings - Vision, Image, and Signal Processing, Vol. 147, nº 1

Scale-free networks and scalable interdomain routing

Trabalho apresentado no âmbito do Mestrado em Engenharia Informática, como requisito parcial para obtenção do grau de Mestre em Engenharia Informática

Microencapsulation technology: a powerful tool for human embryonic stem cells expansion and cryopreservation

Dissertation presented to obtain a Master degree in Biotechnology at the Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Natural and amyloid self-assembly of S100 proteins: structural basis of functional diversity

The S100 proteins are 10-12 kDa EF-hand proteins that act as central regulators in a multitude of cellular processes including cell survival, proliferation, differentiation and motility. Consequently, many S100 proteins are implicated and display marked changes in their expression levels in many types of cancer, neurodegenerative disorders, inflammatory and autoimmune diseases. The structure and function of S100 proteins are modulated by metal ions via Ca2+ binding through EF-hand motifs and binding of Zn2+ and Cu2+ at additional sites, usually at the homodimer interfaces. Ca2+ binding modulates S100 conformational opening and thus promotes and affects the interaction with p53, the receptor for advanced glycation endproducts and Toll-like receptor 4, among many others. Structural plasticity also occurs at the quaternary level, where several S100 proteins self-assemble into multiple oligomeric states, many being functionally relevant. Recently, we have found that the S100A8/A9 proteins are involved in amyloidogenic processes in corpora amylacea of prostate cancer patients, and undergo metal-mediated amyloid oligomerization and fibrillation in vitro. Here we review the unique chemical and structural properties of S100 proteins that underlie the conformational changes resulting in their oligomerization upon metal ion binding and ultimately in functional control. The possibility that S100 proteins have intrinsic amyloid-forming capacity is also addressed, as well as the hypothesis that amyloid self-assemblies may, under particular physiological conditions, affect the S100 functions within the cellular milieu.

Cavin 1 and cavin 2 roles on adipocyte cell function

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Managerial strategies in canning industries: A case study of early twentieth century Portugal

Business History, Vol, 51 Issue 1, p45-58

The merger of Total Portugal and CEPSA

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

Cancer theranostics: multifunctional gold nanoparticles for diagnostics and therapy

Doctorate in Biology, Specialty in Biotechnology

Perspectives and approaches for the internet of things

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

Osteoclast activity in ankylosing spondylitis patients before and after TNF-blocking therapy

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the axial skeleton. The major outcome of this disease is defined by new bone formation, commonly observed in the ligaments of the intervertebral joints, that can lead to the formation of bony spurs, known as syndesmophytes. Previous studies have shown that serum levels of TNF, IL-6 and IL-17 are increased in AS patients and may be implicated in the development of secondary osteoporosis, since these cytokines are able to induce osteoclast (OC) differentiation and, therefore, bone resorption. In this work we aimed to assess the effects of TNF-blocking therapy in the systemic inflammatory environment of AS patients with active disease as well as in OC differentiation and activity. To accomplish this objective, we cultured circulating monocytes from AS patients, before and after therapy, under osteoclastogenic conditions and we performed two functional assays (TRAP staining and resorption pit assay) and analyzed the expression of osteoclast specific genes. We have shown that AS patients with active disease have increased levels of pro-inflammatory cytokines when compared with healthy subjects. We also found that IL-17, TGF-β and osteoprotegerin are decreased after TNF-blocking therapy. Interestingly, we also observed that after TNF-blocking therapy the expression of some genes is favoring osteoclastogenesis and that differentiated OCs have increased resorption activity. These results suggest that in active AS there may be an uncoupling between inflammation and OC activity that is reset by TNF-blocking therapy.

Osteoclastogenesis, inflammatory cytokines and biomarkers of bone metabolism in psoriatic arthritis

RESUMO:A artrite psoriática (AP) é uma doença inflamatória crónica caracterizada por várias manifestações nas articulações, nas enteses e na pele. A formação de novo osso após inflamação nas enteses é um dos aspetos mais intrigantes desta doença. Os mecanismos celulares e moleculares deste processo ainda não são completamente conhecidos. Este estudo tem como objetivo compreender melhor os mecanismos subjacentes à formação e reabsorção óssea, bem como o efeito de anti-inflamatórios não esteroides (AINEs) nestes processos. Para atingir este objetivo foram quantificados biomarcadores do metabolismo ósseo e citocinas inflamatórias em doentes AP, antes e após terapêutica com AINEs. Os biomarcadores selecionados foram marcadores de remodelação óssea como CTX-I e P1NP, fatores de diferenciação e ativação de osteoclastos como o RANKL e a OPG, inibidores da via de sinalização Wnt, nomeadamente o DKK-1 e a SOST e ainda citocinas pro-inflamatórias como a IL-22 e a IL-23 e a prostaglandina PGE2. Neste contexto foram também estabelecidas culturas celulares de monócitos, isoladas de doentes AP e de controlos saudáveis. Os monócitos foram cultivados in vitro em condições não estimuladas e estimuladas e realizados dois ensaios funcionais: coloração com TRAP e ensaio de reabsorção. Foi observada uma diminuição nos níveis séricos de CTX-I e OPG em doentes AP em relação aos controlos. De igual forma os níveis séricos de SOST encontram-se significativamente mais baixos, em comparação com os controlos saudáveis. Estes valores de SOST são semelhantes aos dos doentes com espondilite anquilosante (EA), documentados anteriormente. Os ensaios com osteoclastos confirmaram a necessidade da presença de RANKL para estimulação da osteoclastogénese e que o celecoxib parece ter um papel inibitório neste processo. Os resultados obtidos sugerem que a população de doentes com AP analisados têm baixos níveis de reabsorção óssea e alguma atividade na formação óssea. --------------------------- ABSTRACT: Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by several manifestations involving the joints, enthesis and the skin. New bone formation after inflammation at enthesis site has been one of the most intriguing aspects of the disease. Cellular and molecular mechanisms in this process are still not completely understood. This study aims to understand better the mechanisms underlying bone formation and resorption and the effect of non-steroid anti-inflammatory drugs (NSAIDs) in these processes. To access that, biomarkers of bone metabolism and inflammatory cytokines were measured in PsA patients’ serum before and after NSAID therapy. These selected biomarkers were bone turnover markers such as CTX-I and P1NP, osteoclast differentiation and activation factors RANKL and OPG, Wnt pathway inhibitors DKK-1 and SOST and pro-inflammatory cytokines IL-22, IL-23 and prostaglandin PGE2. In this context monocyte cell culture was also established after PBMC isolation from PsA patients and healthy controls. Monocytes were cultured in vitro under unstimulated and stimulated conditions and two functional assays were performed: TRAP staining and resorption pit assay. It was demonstrated that CTX-I and OPG serum levels in PsA patients were lower than controls. SOST levels were extremely decreased in comparison with controls, resembling the ankylosing spondylitis patients results already documented. Osteoclast assays confirmed the need of RANKL in stimulating osteoclastogenesis and that celecoxib seems to have an inhibitor role in this process. The results obtained suggest that PsA patient population analyzed in this study have low bone resorption levels and some bone formation activity.

Cultural journalism in a digital environment : new models, practices and possibilities

Both culture coverage and digital journalism are contemporary phenomena that have undergone several transformations within a short period of time. Whenever the media enters a period of uncertainty such as the present one, there is an attempt to innovate in order to seek sustainability, skip the crisis or find a new public. This indicates that there are new trends to be understood and explored, i.e., how are media innovating in a digital environment? Not only does the professional debate about the future of journalism justify the need to explore the issue, but so do the academic approaches to cultural journalism. However, none of the studies so far have considered innovation as a motto or driver and tried to explain how the media are covering culture, achieving sustainability and engaging with the readers in a digital environment. This research examines how European media which specialize in culture or have an important cultural section are innovating in a digital environment. Specifically, we see how these innovation strategies are being taken in relation to the approach to culture and dominant cultural areas, editorial models, the use of digital tools for telling stories, overall brand positioning and extensions, engagement with the public and business models. We conducted a mixed methods study combining case studies of four media projects, which integrates qualitative web features and content analysis, with quantitative web content analysis. Two major general-interest journalistic brands which started as physical newspapers – The Guardian (London, UK) and Público (Lisbon, Portugal) – a magazine specialized in international affairs, culture and design – Monocle (London, UK) – and a native digital media project that was launched by a cultural organization – Notodo, by La Fábrica – were the four case studies chosen. Findings suggest, on one hand, that we are witnessing a paradigm shift in culture coverage in a digital environment, challenging traditional boundaries related to cultural themes and scope, angles, genres, content format and delivery, engagement and business models. Innovation in the four case studies lies especially along the product dimensions (format and content), brand positioning and process (business model and ways to engage with users). On the other hand, there are still perennial values that are crucial to innovation and sustainability, such as commitment to journalism, consistency (to the reader, to brand extensions and to the advertiser), intelligent differentiation and the capability of knowing what innovation means and how it can be applied, since this thesis also confirms that one formula doesn´t suit all. Changing minds, exceeding cultural inertia and optimizing the memory of the websites, looking at them as living, organic bodies, which continuously interact with the readers in many different ways, and not as a closed collection of articles, are still the main challenges for some media.