Plasmin-Induced Activation of Human Platelets Is Modulated by Thrombospondin-1, Bona Fide Misfolded Proteins and Thiol Isomerases

Inflammatory processes are triggered by the fibrinolytic enzyme plasmin. Tissue-type plasminogen activator, which cleaves plasminogen to plasmin, can be activated by the cross-β-structure of misfolded proteins. Misfolded protein aggregates also represent substrates for plasmin, promoting their degradation, and are potent platelet agonists. However, the regulation of plasmin-mediated platelet activation by misfolded proteins and vice versa is incompletely understood. In this study, we hypothesize that plasmin acts as potent agonist of human platelets in vitro after short-term incubation at room temperature, and that the response to thrombospondin-1 and the bona fide misfolded proteins Eap and SCN⁻-denatured IgG interfere with plasmin, thereby modulating platelet activation. Plasmin dose-dependently induced CD62P surface expression on, and binding of fibrinogen to, human platelets in the absence/presence of plasma and in citrated whole blood, as analyzed by flow cytometry. Thrombospondin-1 pre-incubated with plasmin enhanced these plasmin-induced platelet responses at low concentration and diminished them at higher dose. Platelet fibrinogen binding was dose-dependently induced by the C-terminal thrombospondin-1 peptide RFYVVMWK, Eap or NaSCN-treated IgG, but diminished in the presence of plasmin. Blocking enzymatically catalyzed thiol-isomerization decreased plasmin-induced platelet responses, suggesting that plasmin activates platelets in a thiol-dependent manner. Thrombospondin-1, depending on the concentration, may act as cofactor or inhibitor of plasmin-induced platelet activation, and plasmin blocks platelet activation induced by misfolded proteins and vice versa, which might be of clinical relevance.     

Experimental tests on the limit states of dry-jointed tuff blocks

A proper definition of the yield domains governing the frictional behaviour at contact interfaces is generally required to perform the limit analysis of 3D dry-jointed masonry block structures. However, the modelling of the actual behaviour of frictional contact interfaces under simultaneous normal and shear forces, torsion and bending moments is a topic still poorly studied, especially from the experimental point of view. In this paper the single contact interface of a system composed of two dry-jointed tuff blocks under different loading conditions is experimentally investigated. The programme includes several sets of tests based on different eccentricities of the vertical and horizontal loading implying pure strengths and interactions among shear, torsion and bending moments. The results of each set are then compared with those obtained by a recently proposed numerical model for 3D masonry block assemblages, based on the assumptions of infinite strength in compression, tension and shear for blocks and no-tension and frictional behaviour at their contact. The comparison is useful, on the one hand, as a further validation the efficacy of the previously proposed yield domains in order to be used in 3D limit analysis formulations and, on the other, to highlight which yield domains need to be better represented.     

Efficient energy-based embedding models for link prediction in knowledge graphs

We focus on the problem of link prediction in Knowledge Graphs, with the goal of discovering new facts. To this purpose, Energy-Based Models for Knowledge Graphs that embed entities and relations in continuous vector spaces have been largely used. The main limitation in their applicability lies in the parameter learning phase, which may require a large amount of time for converging to optimal solutions. In this article, we first propose an unified view on different Energy-Based Embedding Models. Hence, for improving the model training phase, we propose the adoption of adaptive learning rates. We show that, by adopting adaptive learning rates during training, we can improve the efficiency of the parameter learning process by an order of magnitude, while leading to more accurate link prediction models in a significantly lower number of iterations. We extensively evaluate the proposed learning procedure on a variety of new models: our result show a significant improvement over state-of-the-art link prediction methods on two large Knowledge Graphs, namely WordNet and Freebase.     

Reticulated Porous Foam Ceramics with Different Surface Chemistries

The aim of this study was to discuss the influence of different filter surface chemistries on the properties of foam filters. For reliable results, it is essential to ensure comparable structural properties (cell size and strut thickness) for all different surface chemistries (Al₂O₃, MgAl₂O₄, 3Al₂O₃·2SiO₂, SiO₂, and TiO₂) possess the same structural properties (cell size and strut thickness). Filters made of 100% of the investigated materials and alumina skeletons coated with the investigated materials were prepared. The coated alumina samples were sintered in one and two steps. The processing route with two sintering steps resulted in improved mechanical properties and comparable shrinkage and strut thickness. The 100% bulk foams possessed different pore sizes due to the differences of the material shrinkage. In this study, a comparison of the experimental investigated properties of the ceramic foam filters and the theoretically calculated values for foam materials derived from the bulk material properties is established.     

Distribution and identification of culturable airborne microorganisms in a Swiss milk processing facility

Airborne communities (mainly bacteria) were sampled and characterized (concentration levels and diversity) at 1 outdoor and 6 indoor sites within a Swiss dairy production facility. Air samples were collected on 2 sampling dates in different seasons, one in February and one in July 2012 using impaction bioaerosol samplers. After cultivation, isolates were identified by mass spectrometry (matrix-assisted laser desorption/ionization-time-of-flight) and molecular (sequencing of 16S rRNA and rpoB genes) methods. In general, total airborne particle loads and total bacterial counts were higher in winter than in summer, but remained constant within each indoor sampling site at both sampling times (February and July). Bacterial numbers were generally very low (<100 cfu/m³ of air) during the different steps of milk powder production. Elevated bacterial concentrations (with mean values of 391 ± 142 and 179 ± 33 cfu/m³ of air during winter and summer sampling, respectively; n = 15) occurred mainly in the “logistics area,” where products in closed tins are packed in secondary packaging material and prepared for shipping. However, total bacterial counts at the outdoor site varied, with a 5- to 6-fold higher concentration observed in winter compared with summer. Twenty-five gram-positive and gram-negative genera were identified as part of the airborne microflora, with Bacillus and Staphylococcus being the most frequent genera identified. Overall, the culturable microflora community showed a composition typical and representative for the specific location. Bacterial counts were highly correlated with total airborne particles in the size range 1 to 5 µm, indicating that a simple surveillance system based upon counting of airborne particles could be implemented. The data generated in this study could be used to evaluate the effectiveness of the dairy plant’s sanitation program and to identify potential sources of airborne contamination, resulting in increased food safety.     

Analyzing visually impaired people’s touch gestures on smartphones

Multimedia Tools and Applications - We present an analysis of how visually impaired people perform gestures on touch-screen smartphones and report their preferences, explaining the procedure and...     

Experimental study on micro manufacturing of carbon nanotube (CNT) plastic composites

In recent years, innovative materials such as carbon nanotube composites are finding growing interest in several industrial sectors, from sports and leisure to electronics, automotive, aircraft, and defence. The reinforcing influence of the carbon nanotube is of prime interest. However, technological issues concerning the production methods and the manufacturing processes of carbon nanotube components limit the industrial application of this innovative and interesting material, especially whether small features are required. For this reason, manufacturing strategy involving new production technologies must be designed and developed. This paper studies the challenges of a manufacturing chain based on two manufacturing processes: injection moulding and micro milling. A case study based on these innovative processes is reported and discussed. The propagation chain effect and the influence of each considered process parameter on cutting force and geometrical accuracy of the features (the key characteristics of the process chain) were assessed by means of statistical analysis of variance (ANOVA). The ANOVA analysis demonstrated that cutting forces in micro milling are mainly influenced by the material and percentage of carbon nanotubes, while the main parameter influencing the geometrical accuracy of micro features is the matrix material.     

Geranylgeraniol and Neurological Impairment: Involvement of Apoptosis and Mitochondrial Morphology

Deregulation of the cholesterol pathway is an anomaly observed in human diseases, many of which have in common neurological involvement and unknown pathogenesis. In this study we have used Mevalonate Kinase Deficiency (MKD) as a disease-model in order to investigate the link between the deregulation of the mevalonate pathway and the consequent neurodegeneration. The blocking of the mevalonate pathway in a neuronal cell line (Daoy), using statins or mevalonate, induced an increase in the expression of the inflammasome gene (NLRP3) and programmed cell death related to mitochondrial dysfunction. The morphology of the mitochondria changed, clearly showing the damage induced by oxidative stress and the decreased membrane potential associated with the alterations of the mitochondrial function. The co-administration of geranylgeraniol (GGOH) reduced the inflammatory marker and the damage of the mitochondria, maintaining its shape and components. Our data allow us to speculate about the mechanism by which isoprenoids are able to rescue the inflammatory marker in neuronal cells, independently from the block of the mevalonate pathway, and about the fact that cell death is mitochondria-related.     

Preparation and characterization of light‐cured methacrylate/montmorillonite nanocomposites

Polymer/clay nanocomposites were prepared from dimethacrylate monomers, commonly used in dental restorative resins, and an organically modified silicate (montmorillonite). The photopolymerization process was hardly affected by the presence of the silicate filler, and thus 2 mm thick samples containing 3 wt% clay were extensively cured. Transmission electron microscopy revealed that the montmorillonite platelets were either intercalated or exfoliated. Nevertheless, for all formulations, intermediate‐sized aggregates of about 1 µm were present and their fraction increased as the amount of filler increased. The presence of the clay was found to have no major effect on the flexural modulus and compressive yield strength of the nanocomposites. Moreover, the water uptake of nanocomposites containing 3 wt% clay was about 10–15% higher than that of unfilled monomers. Modification of the clay surface with alternative organic cations is certainly necessary in order to achieve an optimal dispersion of the clay in the polymer matrix. Copyright © 2010 Society of Chemical Industry     

Gb3 Glycosphingolipids with Fluorescent Oligoene Fatty Acids: Synthesis and Phase Behavior in Model Membranes

Glycosphingolipids are involved in a number of physiological and pathophysiological processes, and they serve as receptors for a variety of bacterial toxins and viruses. To investigate their function in lipid membranes, fluorescently labeled glycosphingolipids are highly desirable. Herein, a synthetic route to access Gb₃ glycosphingolipids with fluorescently labeled fatty acids, consisting of pentaene and hexaene moieties either at the terminus or in the middle of the acyl chain, has been developed. The fluorescent properties of the Gb₃ derivatives were investigated in small unilamellar vesicles composed of a raft-like mixture. Phase-separated giant unilamellar vesicles (GUVs) allowed the quantification of the apparent partitioning coefficients of the Gb₃ compounds by means of confocal fluorescence laser scanning microscopy. The determined partition coefficients demonstrate that the Gb₃ derivatives are preferentially localized in the liquid-disordered (l_d) phase. To analyze whether the compounds behave like their physiological counterparts, Cy3-labeled (Cy: cyanine) Shiga toxin B subunits (STxB) were specifically bound to Gb₃-doped GUVs. However, the protein was favorably localized in the l_d phase, in contrast to results reported for STxB bound to naturally occurring Gb₃, which is discussed in terms of the packing density of the lipids in the liquid-ordered (l_o) phase.