40 resultados para tender offers
Resumo:
The supercritical fluid technology has been target of many pharmaceuticals investigations in particles production for almost 35 years. This is due to the great advantages it offers over others technologies currently used for the same purpose. A brief history is presented, as well the classification of supercritical technology based on the role that the supercritical fluid (carbon dioxide) performs in the process.
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Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.
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The stem cell niche organization and dynamics provide valuable cues for the development of mimetic environments that could have potential to stimulate the regenerative process. We propose the use of biodegradable biomaterials to produce closed miniaturised structures able to encapsulate different cell types or bioactive molecules. In particular, capsules are fabricated using the so-called layer-by-layer technology, where the consecutive (nano-sized) layers are well stabilized by electrostatic interactions or other weak forces. Using alginate-based spherical templates containing cells or other elements (e.g. proteins, magnetic nanoparticles, microparticles) it is possible to produce liquefied capsules that may entrap the entire cargo under mild conditions. The inclusion of liquefied micropcapsules may be used to produce hierarchical compartmentalised systems for the delivery of bioactive agents. The presence of solid microparticles inside such capsules offers adequate surface area for adherent cell attachment increasing the biological performance of these hierarchical systems, while maintain both permeability and injectability. We demonstrated that the encapsulation of distinct cell types (including mesenchymal stem cells and endothelial cells) enhances the osteogenic capability of this system, that could be useful in bone tissue engineering applications.
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Tese de Doutoramento em Filosofia - Especialidade de Filosofia da Mente
Resumo:
This article offers a review of research and policy on climate change in Portugal and is organized into three main themes: scientific knowledge and assessment of climate change; policy analysis and evaluation; and public engagement. Modern scientific research on meteorology and climatology started in Portugal in the 1950s and a strong community of researchers in climate science, vulnerabilities, impacts, and adaptation has since developed, particularly in the last decade. Nevertheless, there are still many gaps in research, especially regarding the economic costs of climate change in Portugal and costs and benefits of adaptation. Governmental policies with a strong emphasis on mitigation were introduced at the end of the 1990s. As greenhouse gas emissions continued to rise beyond its Kyoto target for 2012, the country had to resort to the Kyoto Flexibility Mechanisms in order to comply. Climate change adaptation policies were introduced in 2010 but are far from being fully implemented. Regarding public engagement with climate change, high levels of concern contrast with limited understanding and rather weak behavioral dispositions to address climate change. Citizens display a heavy reliance on the media as sources of information, which are dominated by a techno-managerial discourse mainly focused on the global level. The final part of the article identifies research gaps and outlines a research agenda. Connections between policy and research are also discussed
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The safety coordination during the design phase still remains a challenge at several levels, especially when dealing with refurbishment projects. Either by lack of knowledge of the existing construction (for intervention), and its surroundings, or by the protection of the cultural and historical patrimonial values, or even, by the well known difficulty that the safety coordinator has, in his intervention in any project. The incorporation of the general principles of prevention, the difficulty of the coordinator to be heard by all the actors, to anticipate all risks associated in the construction and the prevision of the respective preventive measures, those are some examples of the obstacles that the design safety coordinator will face. This article intends to give some good practices of safety coordination acts, list all that it encompasses, and emphasizing its importance.
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A publicidade sabe que tem de procurar as estratégias mais diretas e mais eficientes na construção das suas mensagens. A ser assim, pode parecer que o imediatismo das imagens ligado às facilidades tecnológicas tenderá a secundarizar o poder da componente verbal na elaboração dos anúncios. O presente texto procura mostrar como a componente verbal é uma dimensão imprescindível da linguagem publicitária, utilizando estratégias diversificadas que podem ir da ausência (quase) absoluta de palavras até a usos em que é a própria mensagem verbal o principal elemento estruturador do anúncio.
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Risk management is of paramount importance in the success of tunnelling works and is linked to the tunnelling method and to the constraints of the works. Sequencial Excavation Method (SEM) and Tun-nel Boring Machine (TBM) method have been competing for years. This article, part of a wider study on the influence of the â Safety and Healthâ criterion in the choice of method, reviews the existing literature about the criteria usually employed to choose the tunnelling method and on the criterion â Safety and Healthâ . This crite-rion is particularly important, due to the financial impacts of work accidents and occupational diseases. This article is especially useful to the scientific and technical community, since it synthesizes the relevance of each one of the choice criteria used and it shows why â Safety and Healthâ must be a criterion in the decision mak-ing process to choose the tunnelling method.
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Aims. This paper is a report on a study analysing the effect of the umbilical cord cutting experience on fathers’ emotional involvement with their infants. Background. Participation in childbirth offers an opportunity for father and mother to share the childbirth experience, so it is vital that midwives improve the fathers’ participation in this event. Design. A quasi-experimental study with a quantitative methodology was implemented. Methods. One hundred and five fathers were recruited as part of a convenience sample in a Maternity Public Hospital in a Metropolitan City in Portugal, between January and May of 2008. The Bonding Scale, the Portuguese version of the ‘Mother-to-Infant Bonding Scale’ was used to evaluate the fathers’ emotional involvement with the neonate at different moments: before childbirth, first day after childbirth and first month after childbirth. After childbirth, the fathers were divided into three separate groups depending on their umbilical cord cutting experience. Results. The results demonstrate that the emotional involvement between father and child tends to increase during the first days after childbirth and to decrease when evaluated 1 month after birth, for fathers who did not cut the umbilical cord. However, fathers who cut the umbilical cord demonstrate an improvement in emotional involvement 1 month later. Conclusion. Results suggest that the umbilical cord cutting experience benefits the father’s emotional involvement with the neonate, supporting the benefits of his participation and empowerment in childbirth.
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O presente artigo apresenta o programa de intervenção em grupo para pais divorciados, Pais por Inteiro (PApi). Fundamentados na revisão da literatura com a qual o artigo se inicia, os objectivos gerais do programa – promover a coparentalidade positiva, a construção de um projecto de binuclearidade familiar e a reflexão e aprofundamento das trajectórias individuais de cada pai – são descritos, assim como as três macrocomponentes psicoterapêuticas ao longo das quais estes objectivos se desenvolvem – exposição dos processos de divórcio, partilha experiencial e treino de competências e mudança desenvolvimental. O artigo oferece ainda, no final, uma mais detalhada clarificação dos objectivos, materiais e actividades planeadas para cada das dez sessões que compõem o PApi.