948 resultados para fragmentation
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Dissertação de mestrado, Aquacultura e Pescas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015
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La plupart des processus cellulaires et biologiques reposent, à un certain niveau, sur des interactions protéine-protéine (IPP). Leur manipulation avec des composés chimiques démontre un grand potentiel pour la découverte de nouveaux médicaments. Malgré la demande toujours croissante en molécules capables d’interrompre sélectivement des IPP, le développement d’inhibiteurs d’IPP est fortement limité par la grande taille de la surface d’interaction. En considérant la nature de cette surface, la capacité à mimer des structures secondaires de protéines est très importante pour lier une protéine et inhiber une IPP. Avec leurs grandes capacités peptidomimétiques et leurs propriétés pharmacologiques intéressan-tes, les peptides cycliques sont des prototypes moléculaires de choix pour découvrir des ligands de protéines et développer de nouveaux inhibiteurs d’IPP. Afin d’exploiter pleinement la grande diversité accessible avec les peptides cycliques, l’approche combinatoire «one-bead-one-compound» (OBOC) est l’approche la plus accessible et puissante. Cependant, l’utilisation des peptides cycliques dans les chimiothèques OBOC est limitée par les difficultés à séquencer les composés actifs après le criblage. Sans amine libre en N-terminal, la dégradation d’Edman et la spectrométrie de masse en tandem (MS/MS) ne peuvent pas être utilisées. À cet égard, nous avons développé de nouvelles approches par ouverture de cycle pour préparer et décoder des chimiothèques OBOC de peptides cycliques. Notre stratégie était d’introduire un résidu sensible dans le macrocycle et comme ancrage pour permettre la linéarisation des peptides et leur largage des billes pour le séquençage par MS/MS. Tout d’abord, des résidus sensibles aux nucléophiles, aux ultraviolets ou au bromure de cyanogène ont été introduits dans un peptide cyclique et leurs rendements de clivage évalués. Ensuite, les résidus les plus prometteurs ont été utilisés dans la conception et le développement d’approches en tandem ouverture de cycle / clivage pour le décodage de chimiothèques OBOC de peptides cycliques. Dans la première approche, une méthionine a été introduite dans le macrocycle comme ancrage pour simultanément permettre l’ouverture du cycle et le clivage des billes par traitement au bromure de cyanogène. Dans la seconde approche, un résidu photosensible a été utilisé dans le macrocycle comme ancrage pour permettre l’ouverture du cycle et le clivage suite à une irradiation aux ultraviolets. Le peptide linéaire généré par ces approches peut alors être efficacement séquencé par MS/MS. Enfin, une chimiothèque OBOC a été préparée et criblée la protéine HIV-1 Nef pour identifier des ligands sélectifs. Le développement de ces méthodologies permttra l’utilisation de composés macrocycliques dans les chimiothèques OBOC et constitue une contribution importante en chimie médicinale pour la découverte de ligands de protéines et le développement d’inhibiteurs d’IPP.
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Tese de doutoramento, Direito (Ciências Jurídico-Económicas), Universidade de Lisboa, Faculdade de Direito, 2014
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Tese de doutoramento, Biologia (Biologia Evolutiva), Universidade de Lisboa, Faculdade de Ciências, 2014
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Tese de doutoramento, Educação (Avaliação em Educação), Universidade de Lisboa, Instituto de Educação, 2014
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Tese de doutoramento, Biologia (Biologia da Conservação), Universidade de Lisboa, Faculdade de Ciências, 2015
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The article engages with theory about the processes of spatialization of fear in contemporary Western urban space (fortification, privatization, exclusion/seclusion, fragmentation, polarization) and their relation to fear of crime and violence. A threefold taxonomy is outlined (Enclosure, Post-Public Space, Barrier), and “spaces of fear” in the city of Palermo are mapped with the aim of exploring the cumulative large-scale effects of the spatialization of fear on a concrete urban territory. Building on empirical evidence, the author suggests that mainstream theories be reframed as part of a less hegemonic and more discursive approach and that theories mainly based on the analyses of global cities be deprovincialized. The author argues for the deconstruction of the concept of “spaces of fear” in favor of the more discursive concept of “fearscapes” to describe the growing landscapes of fear in contemporary Western cities.
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This paper examines the changing production ecology of British pre-school television in light of developments since the mid-1990s and the specific role played by the BBC. Underpinning the research is the perception that pre-school television is characterised by a complex set of industry relationships and dependencies that demands content which needs to satisfy a wide range of international circumstances and commercial prerogatives. For the BBC this has created tension between its public service goals and commercial priorities. Pre-school programming began in Britain in 1950, but it was not until the mid-1990s that Britain emerged as a leading producer of pre-school programming worldwide with government/industry reports regularly identifying the children’s production sector as an important contributor to exports. The rise of pre-school niche channels (CBeebies, Nick Junior, Playhouse Disney), audience fragmentation and the internationalisation and commercialisation of markets have radically altered the funding base of children’s television and the relationships that the BBC enjoys with key players. The international success of much of its pre-school programming is based on the relationships it enjoys with independent producers who generate significant revenues from programme-related consumer products. This paper focuses on the complex and changing relationships between the BBC, independent producers, and financiers, that constitute the production ecology of pre-school television and shape its output. Within the broader setting of cultural production and global trends the paper investigates the following questions: 1) In the light of changes to the sector since the mid-1990s, what makes pre-school television significant both generally and as an ideal public service project? 2) What is the nature of the current funding crisis in British children’s television and what implications does this crisis have for the BBC’s involvement in pre-school television? 3) How is the Corporation reacting to and managing the wider commercial, cultural, regulatory and technological forces that are likely to affect its strategies for the commissioning, production and acquisition of pre-school content?
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Fabricating Ge and Si integrated structures with nanoscale accuracy is a challenging pursuit essential for novel advances in electronics and photonics. While several scanning probe-based techniques have been proposed, no current technique offers control of nanostructure size, shape, placement, and chemical composition. To this end, atomic force microscope direct write uses a high electric field (> 109 V m-1) to create nanoscale features as fast as 1 cm s-1 by reacting a liquid precursor with a biased AFM tip. In this work, I present the first results on fabricating inorganic nanostructures via AFM direct write. Using diphenylgermane (DPG) and diphenylsilane (DPS), carbon-free germanium and silicon nanostructures (SIMS, x-ray PEEM) are fabricated. For this chemistry, I propose a model that involves electron capture and precursor fragmentation under the high electric field. To verify this model, experimental data and simulations are presented. High field chemistry for DPG and DPS has also been demonstrated for both sequential deposition and the creation of nanoscale heterostuctures, in addition to microscale deposition using a flexible stamp approach. This high field chemistry approach to the deposition of organometallic precursors could offer a low-cost, high throughput alternative for future optical, electronic, and photovoltaic applications.
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Sweroside, a major active iridoid in Swertia pseudochinensis Hara, is recognized as an effective agent in the treatment of liver injury. Based on previous reports, the relatively short half-life (64 min) and poor bioavailability (approximately 0.31%) in rats suggested that not only sweroside itself but also its metabolites could be responsible for the observed hepato-protective effect. However, few studies have been carried out on the metabolism of sweroside. Therefore, the present study aimed at identifying the metabolites of sweroside in rat urine after a single oral dose (100 mg/kg). With ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS), the metabolic profile revealed 11 metabolites in rat urine, including phase I, phase II and aglycone-related products. The chemical structures of metabolites were proposed based on accurate mass measurements of protonated or deprotonated molecules and their fragmentation patterns. Our findings showed that the aglycone of sweroside (M05) and its glucuronide conjugate (M06) were principal circulating metabolites in rats. While several other metabolic transformations, occurring via reduction, N-heterocyclization and N-acetylation after deglycosylation, were also observed. Two metabolites (M05 and M06) were isolated from the rat urine for structural elucidation and identifcation of reaction sites. Both M05 and M06 were characterized by 1H, 13C and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. UHPLC/Q-TOF-MS analysis has provided an important analytical platform to gather metabolic profile of sweroside.
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This article examines John Sommerfield’s 1936 novel, May Day, a work that experiments with multiple perspectives, voices and modes. The article examines the formal experiments of the novel in order to bring into focus contemporary debates around the aesthetics of socialist realism, the politics of Popular Front anti-fascism and the relationship between writers on the left and the legacies of literary modernism. The article suggests that while leftist writers’ appropriations of modernist techniques have been noted by critics, there has been a tendency to assume that such approaches were in contravention of the aesthetics of socialist realism. Socialist realism is shown to be more a fluid and disputed concept than such readings suppose, and Sommerfield’s adaptations of modernist textual strategies are interpreted as key components of a political aesthetic directed towards the problems of alienation and social fragmentation.
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Infant sleep undergoes significant re-organization throughout the first 12 months of life, with sleep quality having significant consequences for infant learning and cognitive development. While there has been great interest in the neural basis and developmental trajectories of infant sleep in general, relatively little is known about individual differences in infant sleep and the socio-economic and cultural sources of that variability. We investigated this using questionnaire sleep data in a large, unique multi-ethnic sample of 6-7 month-olds (n=174), with families from South Asian ethnic groups in the UK (Indian, Pakistani and Bangladeshi) being especially well represented. Consistent with previous data from less variable samples, no effects of SES on sleep latency or nocturnal sleep duration emerged. However, perinatal risk factors and ethnic differences did predict daytime sleep, sleep fragmentation and sleep-onset time. While these results should be interpreted with caution due to several limitations, they likely demonstrate that even when socio-economic status and ethnicity are much less confounded than in previous studies, they have a surprisingly limited impact on individual differences in sleep patterns in young infants.
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Mestrado em Engenharia Geotécnica e Geoambiente
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Hoje em dia algumas das principais preocupações que se tem na exploração a céu aberto, são a diminuição de custos e a máxima rentabilidade dos equipamentos. São dois aspectos que estão interligados uma vez que a rentabilização dos equipamentos tem como resultado directo a diminuição dos custos de todas as operações inerentes à exploração a céu aberto e, consequentemente, a diminuição dos custos finais de produção. É por essa lógica de pensamento que se procurou perceber e compreender o funcionamento e a rentabilidade dos equipamentos em função dos diferentes estados de fracturação do maciço rochoso. Este estudo foi realizado numa pedreira a norte de Portugal e complementa outros estudos já realizados, com o objectivo de definir características do diagrama de fogo que assegurem a maior rentabilidade da referida exploração. O estudo baseia-se em determinar os rendimentos da pá carregadora calculando os tempos de ciclo, isto é, o tempo que a pá demorou a carregar, a movimentar e a descarregar o material desmontado dos vários rebentamentos. Calculou-se o rendimento do martelo demolidor na fragmentação de grandes blocos, que não entrariam directamente no britador primário, o qual também foi alvo de estudo, nomeadamente, no que diz respeito aos tempos de encravamento e de britagem, onde se tentou correlacionar esses tempos com os vários desmontes e estimou-se o consumo de energia do britador primário utilizando a equação de Bond. Por fim, realizou-se um estudo comparativo do consumo energético entre as várias fases da exploração a céu aberto. Foram realizados levantamentos geológico-geotécnicos de superfícies de descontinuidades recorrendo à técnica de amostragem linear nas superfícies do maciço rochoso para perceber o tipo de fragmentação e orientação do mesmo.