Convergence and quantale-enriched categories

Generalising Nachbin's theory of "topology and order", in this paper we continue the study of quantale-enriched categories equipped with a compact Hausdorff topology. We compare these $\mathcal{V}$-categorical compact Hausdorff spaces with ultrafilter-quantale-enriched categories, and show that the presence of a compact Hausdorff topology guarantees Cauchy completeness and (suitably defined) codirected completeness of the underlying quantale enriched category

P2 purinoceptors signaling in fibroblasts of rat subcutaneous tissue

Mestrado em Biologia Molecular e CelularO tecido conjuntivo parece estar envolvido na génese de diversas condições patológicas. O aumento da rigidez do tecido conjuntivo, resultante da fibrose, pode constituir um factor importante no mecanismo patogénico da dor crónica resistente a fármacos (Langevin & Sherman, 2007). Por outro lado, os nucleótidos extracelulares parecem estar envolvidos na fisiopatologia da dor crónica (Burnstock, 2001). Assim, este estudo teve como objectivo averiguar o efeito dos nucleótidos de adenina e uridina na proliferação e síntese de colagénio tipo I de fibroblastos do tecido subcutâneo de rato em cultura. Os resultados obtidos mostram que a incubação com UTP (0.3-100 M, n=5) induz um aumento da proliferação e da produção de colagénio tipo I, o qual é dependente da concentração. Contrariamente, o agonista selectivo dos receptores P2Y2, o MRS 2768 (10 μM, n=3), não teve qualquer efeito no que se refere à proliferação, mas diminuiu significativamente (P<0.05) a síntese de colagénio tipo I. Uma vez que o aumento da produção de colagénio induzida pelo UTP (100 μM) foi proporcional ao aumento do número de células (proliferação celular),podemos especular que este aumento se deve ao aumento do número de células per si do que a uma maior actividade sintética de cada célula. Assim, ao normalizar os valores do colagénio tipo I em relação aos valores obtidos do MTT para os mesmos momentos/dias, deixamos de observar diferenças estatisticamente significativas entre o controlo e as células expostas ao UTP. Uma vez que os receptores P2Y2 não parecem estar envolvidos nesta resposta do UTP (100 μM), esta poderá estar a ser mediada pela activação dos receptores P2Y4 e/ou P2Y6. Considerando que o RB-2 (10 μM, n=5), um antagonista não selectivo que actua preferencialmente no subtipo de receptores P2Y4, não foi capaz de modificar a resposta induzida pelo UTP (100 μM), os receptores P2Y4 parecem também não estar envolvidos. Por outro lado, o MRS 2578 (100 nM), um antagonista selectivo dos receptores P2Y6, atenuou de forma significativa o aumento induzido pelo UTP (100 μM). A corroborar os nossos resultados, uma análise imunocitoquímica mostrou uma imunorreactividade positiva contra os receptores P2Y2 e P2Y6, mostrando um padrão de marcação citoplasmático/membranar, o qual é típico para este tipo de receptores, ao contrário do padrão nuclear exibido pelo anticorpo contra os receptores P2Y4. Relativamente ao envolvimento dos receptores sensíveis ao ADP, os resultados obtidos mostraram que o ADPβS (10-100 μM, n=3-6), um análogo estável do ADP, não parece induzir efeitos significativamente diferentes (P>0.05) na proliferação celular. Contudo, a sua incubação continuada aumentou a produção de colagénio tipo I de forma dependente da concentração (P<0.05). De modo a identificar os receptores purinérgicos envolvidos neste efeito, testamos o ADPβS (100 μM) na presença do MRS 2179 (0.3 μM), do AR-C 66096 (0.1 μM), e do MRS 2211 (10 μM), os quais antagonizam selectivamente os receptores P2Y1, P2Y12 e P2Y13, respectivamente. O efeito facilitatório induzido pelo ADPβS (100 μM) foi atenuado de forma significativa na presença do antagonista dos receptores P2Y1, o MRS 2179 (0.3 μM, n=3), sem ser afectado pelo antagonista dos receptores P2Y12, o AR- C 66096 (0.1 μM, n=3). Pelo contrário, o MRS 2211 (10 μM, n=2) potenciou o aumento da produção de colagénio induzida pelo ADPβS (100 μM), indicando assim que a síntese de colagénio tipo I induzida pelo receptor P2Y1 pode estar a ser parcialmente influenciada por uma activação síncrona do receptor inibitório P2Y13. Por último, uma análise por imunocitoquímica mostrou que estas células apresentam imunorreactividade positiva para os receptores P2Y1 e P2Y13, exibindo um padrão citoplasmático/membranar, contrariamente ao padrão nuclear dos receptores ostentado pelo anticorpo contra os receptores P2Y12. Concluindo, a remodelação da fáscia superficial induzida pelos fibroblastos parece ser regulada por um balanço entre a activação dos receptores P2Y2 e P2Y6, assim como dos receptores P2Y13 e P2Y1. Clarificar as vias que conduzem ao processo de fibrose pode representar uma oportunidade para esclarecer o seu envolvimento na patogénese da dor crónica musculo-esquelética, bem como ser útil no desenvolvimento de novas estratégias terapêuticas.Connective tissue may be involved in the pathogenesis of a wide variety of disease conditions. Increased connective tissue stiffness due to fibrosis may be an important link to the pathogenic mechanism leading to drug-resistant chronic pain (Langevin & Sherman, 2007). In addition, extracellular nucleotides seem to be involved in the pathophysiology of chronic pain (Burnstock, 2001). Therefore, we aimed at investigating the effect of adenine and uridine nucleotides on the proliferation and synthesis of type I collagen by rat fibroblasts from subcutaneous connective tissue. The results showed that continuous incubation of UTP (0.3-100 M, n=5) concentration-dependently increased fibroblasts proliferation, as also increased the synthesis of type I collagen above the control levels. Conversely, the selective P2Y2 agonist, MRS 2768 (10 μM, n=3), was devoid of effect in what concerns proliferation, but significantly (P<0.05) decreased type I collagen synthesis. Since the increase in type I collagen synthesis induced by UTP (100 μM) was proportional to the increase in the amount of cells in the culture (fibroblasts proliferation), we speculated that such an increase could be related to the increase in the cell number rather than a higher synthetic activity. Thus, we performed a more detailed data analysis, in which we normalized type I collagen production taking into consideration the MTT values obtained at the same time points, and we observed no longer significant differences between control and UTP-exposed cells. Discounting the contribution of MRS 2768-sensitive P2Y2 receptors, UTP (100 μM)-induced increase in cells proliferation could be due to P2Y4 and/or P2Y6 receptor activation. Since RB-2 (10 μM, n=5), a non-selective antagonist that acts preferentially on the P2Y4 subtype, did not modify the effect of UTP (100 μM), P2Y4 does not seem to be involved. In turn, MRS 2578 (100 nM), which is a selective P2Y6 antagonist, significantly attenuated UTP (100 μM)-induced increase. To corroborate our results, an immunocytochemistry analysis showed a positive immunoreactivity against the P2Y2 and P2Y6 receptors exhibiting a cytoplasmic/membrane labeling pattern, which is typical for those receptors in many different cells, conversely to the nuclear labeling pattern exhibited by the antibody against the P2Y4. To investigate the involvement of ADP-sensitive P2 receptors on cell proliferation and extracellular matrix production, fibroblast cultures were continuously incubated with the stable ADP analogue, ADPβS (10-100 μM). Results obtained with ADPβS (10-100 μM, n=3-6) showed no significant (P>0.05) differences in fibroblast cells proliferation. However, a continuous incubation with ADPβS (10-100 μM, n=2-5) concentration-dependently increased type I collagen production by fibroblasts (P<0.05). In order to identify which purinoceptor(s) that could be mediating this effect, we tested ADPβS (100 μM) in the presence of MRS 2179 (0.3 μM), AR-C 66096 (0.1 μM), and MRS 2211 (10 μM), which antagonize selectively ADP-sensitive P2Y1, P2Y12 and P2Y13 receptors, respectively. The facilitatory effect of ADPβS (100 μM) was significantly attenuated in the presence of the P2Y1 antagonist, MRS 2179 (0.3 μM, n=3), without being affected by the P2Y12 antagonist, AR- C 66096 (0.1 μM, n=3). In contrast, MRS 2211 (10 μM, n=2) potentiated the effect of ADPβS (100 μM) on type I collagen synthesis, thus indicating that the P2Y1-receptor-induction of type I collagen synthesis may be partially counteracted by synchronous activation of the inhibitory P2Y13 receptor. Finally, an immunocytochemistry analysis showed that these cells exhibit immunoreactivity to P2Y1 and P2Y13 receptors with a cytoplasmic/membrane staining pattern, conversely to the nuclear pattern of P2Y12. Concluding, a delicate balance between the activation of P2Y2 and P2Y6, as well as P2Y13 and P2Y1 purinoceptors, might regulate fibroblast’s induced superficial fascia remodeling. Targeting the pathways leading to fibrosis may represent an opportunity to clarify its involvement in the pathogenesis of musculoskeletal chronic pain and it may be useful for designing novel therapeutic strategies to overcome this disease

A reabilitação urbana e o arrendamento

Dissertação apresentada à Faculdade de Direito da Universidade de Coimbra no âmbito do 2º Ciclo de Estudos em Direito, área de especialização em Ciências Jurídico-Forense

Midiatic discourse strategies: tradition in contemporary times

Proponemos un análisis de las estrategias discursivas del periódico Folha de S. Paulo sobre un grupo de excluidos, los favelados (moradores de las favelas). La problemática está en el ámbito de la crisis de los paradigmas tradicionales de la cultura, por lo que entendemos que, en una lógica jerárquica y rígida, en sus clasificaciones las representaciones constituidas son más fácilmente justificadas, pero, en un ambiente aparentemente fluido y fragmentado, como indica Canclini, ordenados por la llamada lógica post-masiva, ¿se modifican las estrategias discursivas?We propose an analysis of the discourse strategies of the newspaper Folha de S. Paulo in respect to a group of excluded persons, the favelados (residents of the slums). The problem is situated in the crisis of the traditional cultural models, understood here in a hierarchic and rigid logic, in its classification the contituted representations are more easily justified, however, in a apparent fluid and fragmented ambient, as Canclini indicates, ordered by a post-massive logic, are the discursive strategies changed

The Outstanding Agenda of the creative economy in Brazil - eppur si muove

Defendida por muchos, rechazada por otros y en general poco comprendida como propuesta más amplia sobre un mundo en dramática transformación, la economía creativa parte del reconocimiento del talento creativo –cultural o científico– como el recurso de más valor de una economía y de una sociedad que tienden a la estandarización. Con eso, es posible reproducir una dinámica de apropiación y exploración, ahora con base en la creatividad como materia prima; o, alternativamente, buscar crear las condiciones para que el talento creativo, presente en todos, sea valorado de modo más ubicuo, generando otras posibilidades de desarrollo colectivo e individual. Este artículo propone la economía creativa como base de un nuevo paradigma económico, discute la posición de la cultura como un pilar básico de ese contexto todavía en formación y trae la discusión a Brasil, país que se enorgullece de la creatividad de su gente y la tiene como rasgo pronunciado de su imagen internacional. Veremos en grandes líneas cómo la economía creativa brotó en un debate que ya lleva una década, con arranques y paradas; y lo que avanzó (o no) desde entonces, concluyendo con sugerencias puntuales para la construcción de una política más estructurada del tema.Defended by many, rejected by others and in general not understood well as a wider proposal for a world going through a dramatic transformation, the creative economy starts by recognising creative talent –cultural or scientific– as the most valuable resource of an economy and a society that tend towards standardization. With that, it is possible to reproduce a dynamic of appropriation and exploration, but still based on creativity as a raw material; or alternatively, to try to create the conditions for creative talent, present in everything, to be valued more ubiquitously, generating other possibilities for collective and individual development. This article proposes the creative economy as the base of a new economic paradigm, discusses the position of culture as a basic pillar of this area that is still forming and brings the discussion to Brazil, a country that is proud of the creativity of its people and where this creativity is a strong feature of its international image. We will see, broadly speaking, how the creative economy sprouted from a debate that has been going on for a decade, on and off; and how much it has advanced (or not) since then, concluding with detailed suggestions for the construction of a more structured policy on this topic

Molecular characterization of Olea europaea L. necrovirus transmission by fungal vectors

Abstract OMMV is an olive infecting necrovirus, likely a recombinant between TNV-D, with which it shares a high identity in its coat protein (CP), and OLV-1. Design of specific primers to use in RT-PCR, allowed for the first time molecular discrimination of OMMV from TNV-D. RT-PCR application to an olive orchard survey revealed OMMV predominance. Its transmission by Olpidium brassicae was demonstrated here for the first time and further examined. OMMV wild-type, a natural non-transmissible OMMVL11 mutant containing two mutations, a construct OMMVWT/OMMVL11 and single mutants obtained by site-directed mutagenesis were found similarly infectious. Sequencing, homology modelling and transmissibility assays showed that the single mutation of Asn residue to Tyr in position 189 of the CP amino acid sequence was located internally in the particle and abolished virus-zoospore adsorption and transmissibility. This indicates that mutation altered CP conformation on zoospore recognition sites. These findings may have important epidemiological implications in the olive crop. Caracterização molecular da transmissão de Necrovirus (Tombusviridae) de Olea europaea L. por fungos vectores OMMV é um necrovirus que infecta a oliveira e que terá surgido a partir de recombinação entre TNV-D, com o qual compartilha uma elevada identidade na cápside proteica (CP), e OLV- 1. O desenho de ‘primers’ específicos para utilização em RT-PCR permitiu, pela primeira vez, a discriminação entre OMMV e TNV-D. A aplicação de RT-PCR a um olival revelou a predominância de OMMV. A transmissão por Olpidium brassicae foi aqui pela primeira vez demonstrada e examinada. OMMV ‘wild type’, um mutante natural OMMVL11 não transmissível contendo duas mutações e mutantes obtidos por mutagénese dirigida revelaram-se igualmente infecciosos. Sequenciação, modelagem por homologia e e

Scaling relations of branching pulsatile flow

Apparently complex flow structures obey to scaling relations that enable to make it viable the study of their configuration and flow dynamics. This is the case of flow structures that exhibit several branching levels and are thought to perform optimally. Here we present scaling relations of diameters and lengths of branching cylindrical channels with pulsatile flows, and compare them with other relations published in the literature. It is shown that, under constant global volume of the flow tree, and for zero pulse frequency these scaling relations reduce to Murrays's law of consecutive diameters. Optimal scaling depends on pulse frequency, distensibility of the channel walls, and asymmetry of the daughter vessels. In case that in addition to global volume of the flow tree, the pressure head is also kept constant, a similar scaling law of channel lengths emerges that holds together with the law of diameter scaling. The effect of channel distensibility is shown to be somehow important, such that for achieving optimal performance (lowest impedance) channels with lower relative distensibility must have their diameter increased. Results are compared with those of other models for the case of some arteries

Heart rate, arterial distensibility, and optimal performance of the arterial tree

In this study we explore the ability of a previously developed model of pulsatile flow for explaining the observed reduction of arterial distensibility with heart rate. The parameters relevant for the analysis are arterial wall distensibility together with permeability and reflection coefficients of the end capillaries. A non-specific artery and the ensemble of tissues supplied by that artery were considered in the model. The blood current within that artery was equalized to the sum of all micro currents in the tissues supplied by that artery. A formula emerged that relates changes in arterial distensibility with heart rate, and also with some particular aspects of microcirculation. Then, that formula was tested with data of distensibilities of the radial and carotid arteries observed at the heart rates of 63, 90, and 110 b.p.m. The formula correctly predicted the trend of decreased distensibility with heart rate for both arteries. Moreover, due to the fact that the carotid artery supplies the brain, and because the Blood–Brain barrier is highly restrictive to colloids in the blood, for the carotid artery the formula predicted a less marked decrease in distensibility than in the case of the radial artery feeding muscle tissue, which has a greater permeability to colloids, a trend that was confirmed by data. It was found that reduction of arterial distensibility with heart rate was greater in arteries that supply end capillaries with high permeability and low reflection coefficients

Microalgal symbiosis in biotechnology

This review provides an analysis of recent published work on interactions between microorganisms, especially the ones involving mainly nutrient exchanges and at least with one microalga species. Examples of microbial partners are given, with a remark to the potential application of cultures of an autotroph and a heterotroph, which grow simultaneously, taking advantage of the complementary metabolisms. These are particularly interesting, either due to economic or sustainable aspects, and some applications have already reached the commercial stage of development. The added advantages of these symbiotic cultures are biomass, lipid, and other products productivity enhancement a better utilization of resources and the reduction or even elimination of process residues (including carbon dioxide and other greenhouse gases) to conduct an increasingly greener biotechnology. Among the several symbiotic partners referred, the microalgae and yeast cultures are the most used. The interaction between these two microorganisms shows how to enhance the lipid production for biodiesel purposes compared with separated (stand-alone) cultures