Vascular endothelial growth factor (VEGF) induces rapid prourokinase (pro-uPA) activation on the surface of endothelial cells

Vascular endothelial growth factor (VEGF) is the pivotal angiogenic growth factor activating endothelial cells to migrate, proliferate, and form capillary tubes. For an ordered endothelial cell migration, tissue invasion, and degradation of the extracellular matrix, proteolytic machinery is indispensable. Such machinery, suitable for localized proteolysis, is provided by the prourokinase-urokinase-plasmin system. Prourokinase (pro-uPA), the initial component of this system, is, however, synthesized in its inactive precursor form and as such bound to its cellular receptor uPAR. Here we identify a mechanism via which VEGF(165) interacting with its receptor VEGFR-2 rapidly induces prourokinase activation that is dependent on a change in integrin affinity, activation of matrix metalloproteinase 2 (MMP-2), and pro-uPA being bound to its surface receptor uPAR. This VEGF-induced pro-uPA activation on endothelial cells is responsible for VEGF-dependent local fibrinolytic activity and might be one of the initial steps in the angiogenic process.     

DESIGN OF REDUCED‐ORDER FUNCTIONAL OBSERVERS FOR LINEAR SYSTEMS WITH UNKNOWN INPUTS

This brief paper presents new conditions for the existence and design of reduced‐order linear functional state observers for linear systems with unknown inputs. Systematic procedures for the synthesis of reduced‐order functional observers are given. Numerical examples are given to illustrate the attractiveness and simplicity of the new design procedures.     

Mesophase behaviour of polyhedral particles

Translational and orientational excluded-volume fields encoded in particles with anisotropic shapes can lead to purely entropy-driven assembly of morphologies with specific order and symmetry. To elucidate this complex correlation, we carried out detailed Monte Carlo simulations of six convex space-filling polyhedrons, namely, truncated octahedrons, rhombic dodecahedrons, hexagonal prisms, cubes, gyrobifastigiums and triangular prisms. Simulations predict the formation of various new liquid-crystalline and plastic-crystalline phases at intermediate volume fractions. By correlating these findings with particle anisotropy and rotational symmetry, simple guidelines for predicting phase behaviour of polyhedral particles are proposed: high rotational symmetry is in general conducive to mesophase formation, with low anisotropy favouring plastic-solid behaviour and intermediate anisotropy (or high uniaxial anisotropy) favouring liquid-crystalline behaviour. It is also found that dynamical disorder is crucial in defining mesophase behaviour, and that the apparent kinetic barrier for the liquid-mesophase transition is much lower for liquid crystals (orientational order) than for plastic solids (translational order).     

Dipotassium Glycyrrhizinate on Melanoma Cell Line: Inhibition of Cerebral Metastases Formation by Targeting NF-kB Genes-Mediating MicroRNA-4443 and MicroRNA-3620—Dipotassium Glycyrrhizinate Effect on Melanoma

Glycyrrhizic acid (GA), a natural compound isolated from licorice (Glycyrrhiza glabra), has exhibited anti-inflammatory and anti-tumor effects in vitro. Dipotassium glycyrrhizinate (DPG), a dipotassium salt of GA, also has shown an anti-tumor effect on glioblastoma cell lines, U87MG and T98G. The study investigated the DPG effects in the melanoma cell line (SK-MEL-28). MTT assay demonstrated that the viability of the cells was significantly decreased in a time- and dose-dependent manner after DPG (IC₅₀ = 36 mM; 24 h). DNA fragmentation suggested that DPG (IC₅₀) induced cellular apoptosis, which was confirmed by a significant number of TUNEL-positive cells (p-value = 0.048) and by PARP-1 [0.55 vs. 1.02 arbitrary units (AUs), p-value = 0.001], BAX (1.91 vs. 1.05 AUs, p-value = 0.09), and BCL-2 (0.51 vs. 1.07 AUs, p-value = 0.0018) mRNA compared to control cells. The proliferation and wound-healing assays showed an anti-proliferative effect on DPG-IC₅₀-treated cells, also indicating an inhibitory effect on cell migration (p-values < 0.001). Moreover, it was observed that DPG promoted a 100% reduction in melanospheres formation (p-value = 0.008). Our previous microRNAs (miRs) global analysis has revealed that DPG might increase miR-4443 and miR-3620 expression levels. Thus, qPCR showed that after DPG treatment, SK-MEL-28 cells presented significantly high miR-4443 (1.77 vs. 1.04 AUs, p-value = 0.02) and miR-3620 (2.30 vs. 1.00 AUs, p-value = 0.01) expression compared to control cells, which are predicted to target the NF-kB, CD209 and TNC genes, respectively. Both genes are responsible for cell attachment and migration, and qPCR revealed significantly decreased CD209 (1.01 vs. 0.54 AUs, p-value = 0.018) and TNC (1.00 vs. 0.31 AUs, p-value = 2.38 × 10⁻⁶) mRNA expression levels after DPG compared to untreated cells. Furthermore, the migration of SK-MEL-28 cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) was attenuated by adding DPG by wound-healing assay (48 h: p-value = 0.004; 72 h: p-value = 7.0 × 10⁻⁴). In addition, the MMP-9 expression level was inhibited by DPG in melanoma cells stimulated by TPA and compared to TPA-treated cells (3.56 vs. 0.99 AUs, p-value = 0.0016) after 24 h of treatment. Our results suggested that DPG has an apoptotic, anti-proliferative, and anti-migratory effect on SK-MEL-28 cells. DPG was also able to inhibit cancer stem-like cells that may cause cerebral tumor formation.     

MIL-100(Fe) Sub-Micrometric Capsules as a Dual Drug Delivery System

Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment.     

Remote detection of a tonal anomaly in an area of hydrocarbon microseepage,Tucano basin,north-eastern Brazil

Mapping of a tonal anomaly in an area of hydrocarbon microseepage was possible using a Landsat-Thematic Mapper false-colour composite consisting of TM2/3, TM4/3 and of the difference TM2/3-TM4/3, displayed as red, green and blue, respectively. In this false-colour composite, green and yellow express variations in the vegetation cover, whereas hues of magenta are related to terrain conditions representing bleached materials, which occur close to the centre of a soil gas anomaly. Simultaneous occurrence of anomalous soil gas values with magnetic and radioactive minerals suggests that a reducing environment associated with the microseepage phenomenon created the bleached materials, identified as a tonal anomaly in the enhanced TM image.     

‘Long autonomy or long delay?’ The importance of domain in opinion mining

Nowadays, people do not only navigate the web, but they also contribute contents to the Internet. Among other things, they write their thoughts and opinions in review sites, forums, social networks, blogs and other websites. These opinions constitute a valuable resource for businesses, governments and consumers. In the last years, some researchers have proposed opinion extraction systems, mostly domain-independent ones, to automatically extract structured representations of opinions contained in those texts. In this work, we tackle this task in a domain-oriented approach, defining a set of domain-specific resources which capture valuable knowledge about how people express opinions on a given domain. These resources are automatically induced from a set of annotated documents. Some experiments were carried out on three different domains (user-generated reviews of headphones, hotels and cars), comparing our approach to other state-of-the-art, domain-independent techniques. The results confirm the importance of the domain in order to build accurate opinion extraction systems. Some experiments on the influence of the dataset size and an example of aggregation and visualization of the extracted opinions are also shown.     

Generalized Hermitian Radial Basis Functions Implicits from polygonal mesh constraints

In this work we investigate a generalized interpolation approach using radial basis functions to reconstruct implicit surfaces from polygonal meshes. With this method, the user can define with great flexibility three sets of constraint interpolants: points, normals, and tangents; allowing to balance computational complexity, precision, and feature modeling. Furthermore, this flexibility makes possible to avoid untrustworthy information, such as normals estimated on triangles with bad aspect ratio. We present results of the method for applications related to the problem of modeling 2D curves from polygons and 3D surfaces from polygonal meshes. We also apply the method to problems involving subdivision surfaces and front-tracking of moving boundaries. Finally, as our technique generalizes the recently proposed HRBF Implicits technique, comparisons with this approach are also conducted.