The emergence of product certification systems as trade barriers

This paper addresses the growing difficulties automobile manufacturers face within their after sales business: an increasing number of trade obstacles set up by import countries discriminates against the foreign suppliers and impedes the international sales of genuine parts. The purpose of the study is to explore the emergence of trade restrictive product certification systems, which affect spare parts exports of automobile manufacturers. The methodology used includes review of the literature and an empirical study based on qualitative interviews with representatives of major stakeholders of the automotive after sales business. Relevant key drivers, which initiate the introduction of technical regulations in importing countries, are identified and analysed to evaluate their effect on the emerging trade policy. The analysis of the key drivers outlines that several interacting components, such as the global competitiveness of the country, macroeconomic and microeconomic factors, and certain country-specific variables induce trade restrictive product certification systems. The findings allow for an early detection of the emergence of product certification systems and provide a means to early recognise the risks and opportunities for the sales of automotive spare parts in the automakers’ target markets. This allows the manufacturers to react immediately and adapt in time to the upcoming changes.

The role of the efflux mechanisms in multidrug resistance in Mycobacterium tuberculosis

Abstract The emergence of multi and extensively drug resistant tuberculosis (MDRTB and XDRTB) has increased the concern of public health authorities around the world. The World Health Organization has defined MDRTB as tuberculosis (TB) caused by organisms resistant to at least isoniazid and rifampicin, the main first-line drugs used in TB therapy, whereas XDRTB refers to TB resistant not only to isoniazid and rifampicin, but also to a fluoroquinolone and to at least one of the three injectable second-line drugs, kanamycin, amikacin and capreomycin. Resistance in Mycobacterium tuberculosis is mainly due to the occurrence of spontaneous mutations and followed by selection of mutants by subsequent treatment. However, some resistant clinical isolates do not present mutations in any genes associated with resistance to a given antibiotic, which suggests that other mechanism(s) are involved in the development of drug resistance, namely the presence of efflux pump systems that extrude the drug to the exterior of the cell, preventing access to its target. Increased efflux activity can occur in response to prolonged exposure to subinhibitory concentrations of anti-TB drugs, a situation that may result from inadequate TB therapy. The inhibition of efflux activity with a non-antibiotic inhibitor may restore activity of an antibiotic subject to efflux and thus provide a way to enhance the activity of current anti-TB drugs. The work described in this thesis foccus on the study of efflux mechanisms in the development of multidrug resistance in M. tuberculosis and how phenotypic resistance, mediated by efflux pumps, correlates with genetic resistance. In order to accomplish this goal, several experimental protocols were developed using biological models such as Escherichia coli, the fast growing mycobacteria Mycobacterium smegmatis, and Mycobacterium avium, before their application to M. tuberculosis. This approach allowed the study of the mechanisms that result in the physiological adaptation of E. coli to subinhibitory concentrations of tetracycline (Chapter II), the development of a fluorometric method that allows the detection and quantification of efflux of ethidium bromide (Chapter III), the characterization of the ethidium bromide transport in M. smegmatis (Chapter IV) and the contribution of efflux activity to macrolide resistance in Mycobacterium avium complex (Chapter V). Finally, the methods developed allowed the study of the role of efflux pumps in M. tuberculosis strains induced to isoniazid resistance (Chapter VI). By this manner, in Chapter II it was possible to observe that the physiological adaptation of E. coli to tetracycline results from an interplay between events at the genetic level and protein folding that decrease permeability of the cell envelope and increase efflux pump activity. Furthermore, Chapter III describes the development of a semi-automated fluorometric method that allowed the correlation of this efflux activity with the transport kinetics of ethidium bromide (a known efflux pump substrate) in E. coli and the identification of efflux inhibitors. Concerning M. smegmatis, we have compared the wild-type M. smegmatis mc2155 with knockout mutants for LfrA and MspA for their ability to transport ethidium bromide. The results presented in Chapter IV showed that MspA, the major porin in M. smegmatis, plays an important role in the entrance of ethidium bromide and antibiotics into the cell and that efflux via the LfrA pump is involved in low-level resistance to these compounds in M. smegmatis. Chapter V describes the study of the contribution of efflux pumps to macrolide resistance in clinical M. avium complex isolates. It was demonstrated that resistance to clarithromycin was significantly reduced in the presence of efflux inhibitors such as thioridazine, chlorpromazine and verapamil. These same inhibitors decreased efflux of ethidium bromide and increased the retention of [14C]-erythromycin in these isolates. Finaly, the methods developed with the experimental models mentioned above allowed the study of the role of efflux pumps on M. tuberculosis strains induced to isoniazid resistance. This is described in Chapter VI of this Thesis, where it is demonstrated that induced resistance to isoniazid does not involve mutations in any of the genes known to be associated with isoniazid resistance, but an efflux system that is sensitive to efflux inhibitors. These inhibitors decreased the efflux of ethidium bromide and also reduced the minimum inhibitory concentration of isoniazid in these strains. Moreover, expression analysis showed overexpression of genes that code for efflux pumps in the induced strains relatively to the non-induced parental strains. In conclusion, the work described in this thesis demonstrates that efflux pumps play an important role in the development of drug resistance, namely in mycobacteria. A strategy to overcome efflux-mediated resistance may consist on the use of compounds that inhibit efflux activity, restoring the activity of antimicrobials that are efflux pump substrates, a useful approach particularly in TB where the most effective treatment regimens are becoming uneffective due to the increase of MDRTB/XDRTB.

Intention recognition, commitment and their roles in the evolution of cooperation

Dissertação para obtenção do Grau de Doutor em Informática

Overcoming the “European Paradox”: The role of Regional Innovation Systems (RIS) in translating R&D investments into economic and employment growth

The emergence of the so-called “European Paradox” shows that R&D investment is not maximally effective and that increasing the scale of public R&D expenditures is not sufficient to generate employment and sustained economic growth. Increasing Governmental R&D Investment is far from being a “panacea” for stagnant growth. It is worth noting that Government R&D Investment does not have a statistically significant impact on employment, indicating the need to assess the trade-offs of policies that could lead to significant increases in government expenditure. Surprisingly, Governmental R&D Employment does not contribute to “mass-market” employment, despite its quite important role in reducing Youth-Unemployment. Despite the negative side-effects of Governmental R&D Employment on both GVA and GDP, University R&D Employment appears to have a quite important role in reducing Unemployment, especially Youth-Unemployment, while it also does not have a downside in terms of economic growth. Technological Capacity enhancement is the most effective instrument for reducing Unemployment and is a policy without any downside regarding sustainable economical development. In terms of wider policy implications, the results reinforce the idea that European Commission Research and Innovation policies must be restructured, shifting from a transnational framework to a more localised, measurable and operational approach.

The effectiveness of a teacher’s training workshop on Media Smart Program

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

The influence of off-screen landmarks on user orientation

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

Visual politics of the estado novo realized on the Alameda Dom Afonso Henriques in Lisbon – the construction of ideal citizenship?

The stylistic categorization of the Estado Novo has been intensely discussed by Portuguese art historians. The square Alameda Dom Afonso Henriques in Lisbon (Alameda) can be seen as paradigmatic for the architecture of power of the Estado Novo. The Alameda forms a gardened valley between two hills. There you find two prominent and highly propagandist buildings: The Instituto Superior Técnico (IST) and the Fonte Luminosa are dedicated to modern sciences and respectively to the harmonious contribution of nature to the city. The iconography of the Alameda as well as its incorporation into the propagandist use of urban planning in the 1930s and 1940s exemplify the visual politics during Salazarism. Urban planning programs intended to create cities that would preserve the character of a traditional catholic society and at the same time answer to the need to modernize the country and evoke the image of a progressive state. Thus, public buildings and urban squares such as the Alameda contributed to design a corporate image and to the ‘spirit’ of the regime.

Revolution in Crisis: The Ruptures of Revolution and Ruptured Revolutions Through the Ruptures of Artistic Practice

This article proposes an investigation of the history and memory of the Carnation Revolution through the lens of contemporary art. Drawing upon the argument according to which history and memory are investigated by visual artists by means other, but no less relevant, than those of professional historians, this article will argue for the importance of attending to the visual, auditory, textual, object- and research-based ways in which artists from several generations and geographies have been unearthing the repressed histories and memories of the Carnation Revolution in Portugal and of anticolonial struggles, decolonization and post-independence nation-building in Mozambique, Guinea-Bissau and Angola. The discussion focuses on several works by Ângela Ferreira, but attention will also be paid to precursors in imaging the Revolution, such as Ana Hatherly, and to a younger generation of artists such as Filipa César, Kiluanji Kia Henda and Daniel Barroca.