999 resultados para Cathepsin V


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This paper focuses on quantifying the benefits of pictogram based instructions relative to static images for work instruction delivery. The assembly of a stiffened aircraft panel has been used as an exemplar for the work which seeks to address the challenge of identifying an instructional mode that can be location or language neutral while at the same time optimising assembly build times and maintaining build quality. Key performance parameters measured using a series of panel build experiments conducted by two separate groups were: overall build time, the number of subject references to instructional media, the number of build errors and the time taken to correct any mistakes. Overall build time for five builds for a group using pictogram instructions was about 20% lower than for the group using image based instructions. Also, the pictogram group made fewer errors. Although previous work identified that animated instructions result in optimal build times, the language neutrality of pictograms as well as the fact that they can be used without visualisation hardware mean that, on balance, they have broader applicability in terms of transferring assembly knowledge to the manufacturing environment.

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Endothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. We found that injection of mice with recombinant Cat-S induced albuminuria and glomerular endothelial cell injury in a PAR2-dependent manner. In vivo microscopy confirmed a role for intrinsic Cat-S/PAR2 in ischemia-induced microvascular permeability. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. In human and mouse type 2 diabetic nephropathy, only CD68(+) intrarenal monocytes expressed Cat-S mRNA, whereas Cat-S protein was present along endothelial cells and inside proximal tubular epithelial cells also. In contrast, the cysteine protease inhibitor cystatin C was expressed only in tubules. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuated albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuated albumin leakage into the retina and other structural markers of diabetic retinopathy. These data identify Cat-S as a monocyte/macrophage-derived circulating PAR2 agonist and mediator of endothelial dysfunction-related microvascular diabetes complications. Thus, Cat-S or PAR2 inhibition might be a novel strategy to prevent microvascular disease in diabetes and other diseases.

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The article focuses on the recent developments as regards domestic violence within the context of the Council of Europe. Since 2007 the European Court of Human Rights has issued a series of important judgments in cases involving domestic violence. The most recent of these is Rumor v. Italy, in which the Court issued its judgment on 27 May 2014. The article analyses this case in the context of the Court’s previous jurisprudence on domestic violence. In addition, on 1 August 2014 the Council of Europe Convention on preventing and combating violence against women and domestic violence entered into force, and the article will include a number of reflections on the potential held by this Convention. No violation of the European Convention on Human Rights was found in Rumor, however the question of whether Italy would have been in breach of the provisions of the new Convention, to which it is a party, had this Convention been in force at the time of the relevant events, will be examined.

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The Grand Chamber of the European Court of Human Rights recently delivered an important judgment on Article 3 ECHR in the case of Bouyid v Belgium. In Bouyid, the Grand Chamber was called upon to consider whether slaps inflicted on a minor and an adult in police custody were in breach of Article 3 ECHR, which provides that ‘No one shall be subjected to torture or to inhuman or degrading treatment or punishment’. Overruling the Chamber judgment in the case, the Grand Chamber ruled by 14 votes to 3 that there had been a substantive violation of Article 3 in that the applicants had been subjected to degrading treatment by members of the Belgian police; it found that there had been a breach of the investigative duty under Article 3 also. In this comment, I focus on the fundamental basis of disagreement between the majority of the Grand Chamber and those who found themselves in dissent, on the question of whether there had been a substantive breach of Article 3. The crux of the disagreement lay in the understanding and application of the test of ‘minimum level of severity’, which the ECtHR has established as decisive of whether a particular form of ill-treatment crosses the Article 3 threshold, seen also in light of Article 3’s absolute character, which makes it non-displaceable – that is, immune to trade-offs of the type applicable in relation to qualified rights such as privacy and freedom of expression. I consider the way the majority of the Grand Chamber unpacked and applied the concept of dignity – or ‘human dignity’ – towards finding a substantive breach of Article 3, and briefly distil some of the principles underpinning the understanding of human dignity emerging in the Court’s analysis.

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A convite do Departamento de Línguas e Culturas da Universidade de Aveiro, formulado em finais de 2007, cerca de três dezenas de especialistas de diferentes áreas de conhecimento aceitaram escrever um ensaio cada, para integrar este volume que se destina a assinalar os 500 anos do nascimento de Fernando Oliveira, também conhecido por Fernão de Oliveira (c. 1507– – c. 1582), um Humanista genial cujo nome está intimamente associado a Aveiro. A escolha do adjectivo “genial” que figura no título e que serve para qualificar a extraordinária e multifacetada produção oliveiriana, espelho dos seus múltiplos interesses, não sendo consensual, foi intencional. Com ele pretende-se homenagear também Luís de Albuquerque, outro grande vulto da cultura e da ciência portuguesas, que, não receando as palavras, escreveu um ensaio sobre o autor intitulado «Fernando Oliveira. Um Português genial, aventureiro e insubmisso»1. Também a escolha da grafia do nome do autor foi devidamente ponderada. Seguindo as mais recentes práticas, já muito discutidas e fundamentadas2, decidimo-nos por Fernando Oliveira, por ser a forma onomástica mais moderna, inscrita no frontispício da Arte da Guerra do Mar e em todas as outras obras, com excepção da Grammatica da Lingoagem Portuguesa, onde aparece Fernão doliveyra. Respeitámos, no entanto, as opções dos autores, sobretudo dos que se dedicaram ao estudo do tratado gramatical, que ora escreveram Fernão de Oliveira, ora Fernão d’Oliveira, consentindo assim que a oscilação da grafia do nome fosse aflorando ao longo deste volume, à semelhança do que acontece no conjunto de escritos do autor. (...)

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Neste artigo, dão-se a conhecer duas versões (recolhidas da tradição oral na região de Las Hurdes, Cáceres, Espanha) dum romance de que não tinhamos notícia nem paralelos nas colecções romancísticas antigas ou modernas. O romance recria alguns episódios da morte do rei Afonso V de Leão, devido aos ferimentos produzidos por uma seta, na cidade de Viseu, em 1028. As primeiras referências a estes factos encontram-se nas primitivas crónicas asturiano-leonesas da primeira metade do séc. XII e notícias sobre eles aparecem também nos sécs. XIV, XV e XVI. O romance parece fruto dum refundidor tardio que, inspirando-se em factos históricos que conhecia, escreveu um romance, que conseguiu entrar na tradição oral de Las Hurdes, embora de modo fragmentário e mostrando acentuada debilidade narrativa. A visita de Afonso XIII à região em 1922, e a coincidência entre o seu nome e o do protagonista do romance, favoreceu, talvez, uma reactualização deste, permitindo-nos conhecer as recordações longínquas em que se inspira.

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We write to comment on the recently published paper “Defining phytoplankton class boundaries in Portuguese transitional waters: an evaluation of the ecological quality status according to the Water Framework Directive” (Brito et al., 2012). This paper presents an integrated methodology to analyse the ecological quality status of several Portuguese transitional waters, using phytoplanktonrelated metrics. One of the systems analysed, the Guadiana estuary in southern Portugal, is considered the most problematic estuary, with its upstream water bodies classified as Poor in terms of ecological status. We strongly disagree with this conclusion and we would like to raise awareness to some methodological constraints that, in our opinion, are the basis of such deceptive conclusions and should therefore not be neglected when using phytoplankton to assess the ecological status of natural waters.

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A presente dissertação visou a investigação da circulação monetária na urbe de Faro, designadamente no caso de estudo que é o da Horta da Misericórdia, desde o início do reinado de D. Sancho I (1185), até ao final do reinado de D. Afonso V (1481). Partindo de um total de 604 exemplares monetários, seleccionamos 319, que se adequavam ao âmbito proposto e ainda um ou outro a título meramente exemplificativo. Recorrendo a uma extensa base documental – se bem que com imensos hiatos no que toca a alguns monarcas em particular, como por exemplo nos casos de D. Duarte I ou ainda D. Dinis I, só para citar alguns exemplos – com a leitura crítica de algumas fontes, mormente as historiográficas e mais longínquas no passado. A partir dessa colecção numismática, procuramos inferir algumas conclusões, em alguns casos mais passíveis de resultados do que noutros. Procuramos assim, obter leituras do passado, a que a numismática nos pudesse dar mais algumas respostas minimamente plausíveis. O estudo que efectuamos permitiu-nos compreender a complexidade profunda de que se revestem os estudos numismáticos, neste caso, para este ponto específico do Algarve. Buscamos apresentar e responder a questões tais como monarcas mais representados, tipologias monetárias, metais mais utilizados, proveniências, metrologia, cerceios, contextos. Procurando oferecer uma contribuição mais, face a estudos mais latos de âmbito histórico-geográfico, neste campo específico do saber humano.

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Für die Produktion von drei Sorten stichfestem Joghurt (Natur, mit unterlegter Frucht und Mix) werden die Kosten nach einer speziellen Form der Teilkostenrechnung in Abhängigkeit von der Kapazitätsauslastung bestimmt. Es werden drei Modelle mit unterschiedlicher Kapazitätsgröße dar­gestellt: 6500, 13.000 und 26.000 Becher/h. Durch Variationen der Produktmenge, Produktionstage und Produktanteile ergeben sich Kosten zwischen 12,6 und 9,3 Pf/Becher Joghurt Natur bzw. 18,7 und 15,5 Pf/Becher Joghurt mit unterlegter Frucht bzw. 17,0 und 14,0 Pf/Becher Joghurt Mix. Je nach Produktionsbedingungen können Stückkostendifferenzen von über 20 Pfennig je kg Produkt auftreten.

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Tese de doutoramento, História (História Antiga), Universidade de Lisboa, Faculdade de Letras, 2014

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Exposure to allergens is pivotal in determining sensitization and allergic symptoms in individuals. Pollen grain counts in ambient air have traditionally been assessed to estimate airborne allergen exposure. However, the exact allergen content of ambient air is unknown. We therefore monitored atmospheric concentrations of birch pollen grain and the matched major birch pollen allergen Bet v 1 simultaneously across Europe within the EU-funded project HIALINE (Health Impacts of Airborne Allergen Information Network). Pollen count was assessed with Hirst type pollen traps at 10 l/min at sites in France, United Kingdom, Germany, Italy and Finland. Allergen concentrations in ambient air were sampled at 800l/min with a Chemvol high-volume cascade impactor equipped with stages PM>10μm, 10 μm>PM>2.5μm, and in Germany also 2.5 μm>PM>0.12μm. The major birch pollen allergen Bet v 1 was determined with an allergen specific ELISA. Bet v 1 isoform patterns were analyzed by 2D-SDS-PAGE blots and mass spectrometric identification. Basophil activation was tested in an FcεR1-humanized rat basophil cell line passively sensitized with serum of a birch pollen lmptomatic patient. Compared to 10 previous years, 2009 was a representative birch pollen season for all stations. About 90% of the allergen was found in the PM>10μm fraction at all stations. Bet v 1 isoforms pattern did not varied substantially neither during ripening of pollen nor between different geographical locations. The average European allergen release from birch pollen was 3.2 pg Bet v 1/pollen and did not vary much between the European countries. However, in all countries a >10-fold difference in daily allergen release per pollen was measured which could be explained by long range transport of pollen with a deviating allergen release. Basophil activation by ambient air extracts correlated better with airborne allergen than with pollen concentration. Although Bet v 1 is a mixture of different isoforms, its fingerprint is constant across Europe. Bet v 1 was also exclusively linked to pollen. Pollen from different days varied >10-fold in allergen release. Thus exposure to allergen is inaccurately monitored by only monitoring birch pollen grains. Indeed, a humanized basophil activation test correlated much better with allergen concentrations in ambient air than with pollen count. Monitoring the allergens themselves together with pollen in ambient air might be an improvement in allergen exposure assessment.