A methodology for user-oriented scalability analysis

Scalability analysis provides information about the effectiveness of increasing the number of resources of a parallel system. Several methods have been proposed which use different approaches to provide this information. This paper presents a family of analysis methods oriented to the user. The methods in this family should assist the user in estimating the benefits when increasing the system size. The key issue in the proposal is the appropriate combination of a scaling model, which reflects the way the users utilize an increasing number of resources, and a figure of merit that the user wants to improve with the larger system. Another important element in the proposal is the approach to characterize the scalability, which enables quick visual analyses and comparisons. Finally, three concrete examples of methods belonging to the proposed family are introduced in this paper.Peer ReviewedPostprint (published version

Riesgo de inversión en Life Settlements

En este trabajo, se realiza una descripción del proceso de titulización de un contrato Life Settlement. Se destacan los partícipes que intervienen en la operación y cómo éstos deben actuar para que dicha operación sea lo más eficiente y transparente. A continuación, se cuantifica el riesgo de inversión de este producto que se concentra, básicamente, en el riesgo de longevidad del asegurado. Para ello, se introducen dos medidas: la 'modified life extension duration' y la 'life extension convexity' que permiten conocer cuánto valor pierde el título si el asegurado vive por encima de su esperanza de vida

Les Ordinacions de l'hospital del Coll de Balaguer l'any 1430

L'hospital del Coll de Balaguer va ser fundat l'any 1344 per l'infant Pere (1305-1381), comte de les Muntanyes de Prades, fill de Jaume II i de Blanca d'Anjou. Es troba situat a l'actual població de l'Hospitalet de l'Infant, al sud de la comarca del Baix Camp, sobre l'antiga via de comunicació que uneix Barcelona i Tarragona amb Tortosa i València. La seva finalitat, tan diferent d'un hospital actual, era l'assistència als vianants pobres que transitaven per aquell lloc, socorrent-los amb aliments i permetent-los de passar-hi una nit. En cas de trobar-se malalts eren atesos fins al guariment

New perspectives on corpora amylacea in the human brain

Corpora amylacea are structures of unknown origin and function that appear with age in human brains and are profuse in selected brain areas in several neurodegenerative conditions. They are constituted of glucose polymers and may contain waste elements derived from different cell types. As we previously found on particular polyglucosan bodies in mouse brain, we report here that corpora amylacea present some neo-epitopes that can be recognized by natural antibodies, a certain kind of antibodies that are involved in tissue homeostasis. We hypothesize that corpora amylacea, and probably some other polyglucosan bodies, are waste containers in which deleterious or residual products are isolated to be later eliminated through the action of the innate immune system. In any case, the presence of neo-epitopes on these structures and the existence of natural antibodies directed against them could become a new focal point for the study of both age-related and degenerative brain processes

Study of the transport of substances across the blood-brain barrier with the 8D3 anti-transferrin receptor antibody

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/128014Numerous strategies have been proposed to overcome the blood-brain barrier (BBB) and efficiently deliver therapeutic agents to the brain. One of these strategies consists of linking the pharmacologically active substance to a molecular vector that acts as a molecular Trojan Horse and is capable of crossing the BBB using a receptor-mediated transcellular transport system of the brain capillary endothelial cells (BCECs). The transferrin receptor (TfR) is related to a transcytosis process in these cells, and the 8D3 monoclonal antibody (mAb), directed against the mouse TfR, is able to induce a receptor response. Thus, the 8D3 antibody could be a potential molecular Trojan Horse to transport pharmacologically active substances across the BBB. On these bases, a series of experiments were performed where the 8D3 antibody was conjugated to different cargoes, the resulting constructs were administered in vivo to mice, and the distribution and intracellular mechanisms that these constructs undergo at the BBB were studied. Our results indicated a TfR-mediated and clathrin-dependent internalization process by which the 8D3-cargo constructs enters the BCEC. The resulting endocytic vesicles follow at least two different routes. On one hand, most vesicles enter intracellular processes of vesicular fusion and rearrangement in which the cargo is guided to late endosomes, multivesicular bodies or lysosomes. On the other hand, a small but not negligible percentage of the vesicles follow a different route in which they fuse with the abluminal membrane and open towards the basal lamina, indicating a potential route for the delivery of therapeutic substances. In this route, however, the 8D3−cargo remain fixed to the abluminal membrane, indicating that the 8D3 is maintained linked to the TfR, and the cargo does not go beyond the basal membrane. Altogether, different optimization approaches need to be developed for efficient drug delivery, but receptor-mediated transport (RMT) continues to be one of the most promising strategies to overcome the BBB

Corpora amylacea in human hippocampal brain tissue are intracellular bodies that exhibit a homogeneous distribution of neoepitopes

Corpora amylacea are spherical bodies of unknown origin and function, which accumulate in the human brain during the aging process and neurodegenerative disorders. In recent work, we reported that they contain some neo-epitopes that are recognized by natural IgMs, revealing a possible link between them and the natural immune system. Here, we performed an ultrastructural study complemented with confocal microscopy in order to shed light on the formation of corpora amylacea and to precisely localize the neo-epitopes. We show that immature corpora amylacea are intracellular astrocytic structures formed by profuse cellular debris and membranous blebs entrapped in a scattered mass of randomly oriented short linear fibers. In mature corpora amylacea, the structure becomes compacted and fibrillary material constitutes the principal component. We also determined that the neo-epitopes were uniformly localized throughout the whole structure. All these observations reinforce the idea that corpora amylacea of human brain are equivalent to another type of polyglucosan bodies named PAS granules, present in mouse brain and originated from degenerative processes. All those findings support the hypothesis that corpora amylacea are involved in the entrapment of damaged materials and non-degradable products and have a role in protective or cleaning mechanisms

Exploring the elusive composition of corpora amylacea of human brain

In the current global climate change scenario, stressors overlap in space and time, and knowledge on the effects of their interaction is highly needed to understand and predict the response and resilience of organisms. Corals, among many other benthic organisms, are affected by an increasing number of global change-related stressors including warming and invasive species. In this study, the cumulative effects between warming and invasive algae were experimentally assessed on the temperate reef-builder coral Cladocora caespitosa. We first investigated the potential local adaptation to thermal stress in two distant populations subjected to contrasting thermal and necrosis histories. No significant differences were found between populations. Colonies from both populations suffered no necrosis after long-term exposure to temperatures up to 29 °C. Second, we tested the effects of the interaction of both warming and the presence of invasive algae. The combined exposure triggered critical synergistic effects on photosynthetic efficiency and tissue necrosis. At the end of the experiment, over 90% of the colonies subjected to warming and invasive algae showed signs of necrosis. The results are of particular concern when considering the predicted increase of extreme climatic events and the spread of invasive species in the Mediterranean and other seas in the future

Neo-epitopes emerging in the degenerative hippocampal granules of aged mice can be recognized by natural IgM autoantibodies

Background: Degenerative granular structures appear progressively with age in the hippocampus of most mouse strains. We recently reported that these granules contain a neo-epitope that is recognised by IgM antibodies present as contaminants in many commercial antibodies obtained from mouse ascites and mouse or rabbit serum. We hypothesise that these anti-neo-epitope IgMs are in fact natural auto-antibodies that are generated spontaneously during the foetal stage without previous contact with external antigens and whose repertoire and reactivity pattern have been determined through evolution, being remarkably stable within species and even between species. Findings: In the present work we found that mice from the ICR-CD1, BALB/C and SAMP8 strains have anti-neoepitope IgM antibodies in their plasma at all ages tested and even when maintained under specific opportunistic pathogen-free conditions. Moreover, we determined that these anti-neo-epitope IgMs are also present in rabbit, goat and rat serum. We also found that, in each mouse that presented hippocampal granules, the anti-neo-epitope IgMs contained in its plasma recognised the neo-epitopes in its own granules. Conclusions: This study led to the conclusion that anti-neo-epitope IgMs are widespread natural auto-antibodies contained in the plasma of mice and other species. The presence of these natural auto-antibodies not only explains why they are frequently found as contaminants in commercial antibodies, but also paves the way for a new approach to a treatment and diagnosis of pathological brain processes based on natural IgMs and neo-epitopes

Stable socioeconomic inequalities in ischaemic heart disease mortality during the economic crisis : A time trend analysis in 2 Spanish settings

Prior studies have identified a decrease in ischaemic heart disease mortality during the recent economic recession. The Spanish population was severely affected by the Great Recession, however, there is little evidence on its effects on socioeconomic inequalities in ischaemic heart disease mortality. This study examines trends in socioeconomic inequalities in mortality due to ischaemic heart disease (IHD). We used linked census records with mortality registers available from the Basque Country and Barcelona city for population above 25 years, between 2001 and 04, the accelerated economic growth period of 2005-08, and 2009-12, with the last period coinciding with the Great Recession. Applying Poisson models, we calculated relative and absolute indexes of inequalities by education level for each period, age group, gender, and site. We found moderate age-adjusted inequalities in IHD with a gradient of increasing rates through less educational level, but no significant evidence of increasing trends in socioeconomic inequalities in IHD mortality, rather an inverted U-shape time trend in some groups below 75 years in relative inequalities. Absolute inequalities decrease in the last period except for women from 50 to 64 years. This study shows that the economic crisis has not increased socioeconomic inequalities in IHD mortality in two geographical settings in Spain

Así saca la basura el cerebro

Si administrásemos un colorante vital como el azul de Evans a la sangre de una rata o un ratón, pasados unos minutos el animal tendría todos los órganos azulados, cual pitufo sin calzones, con excepción de su cerebro. La explicación es sencilla: en el cerebro existe una barrera, conocida como barrera hematoencefálica, que limita enormemente el intercambio de sustancias entre la sangre y dicho órgano