Dihydrotanshinone,a Natural Diterpenoid,Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor

Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.     

On sorting triangles in a delaunay tessellation

In a two-dimensional Delaunay-triangulated domain, there exists a partial ordering of the triangles (with respect to a vertex) that is consistent with the two-dimensional visibility of the triangles from that vertex. An equivalent statement is that a polygon that is star-shaped with respect to a given vertex can be extended, one triangle at a time, until it includes the entire domain. Arbitrary planar triangulations do not possess this useful property which allows incremental processing of the triangles.This work was partially supported by the National Science Foundation's US-Italy Collaborative Research Program under Grant INT-8714578 and Information, Robotics, and Intelligent Research Grant IRI-8704781.     

Two-manifold cell-decomposition of r-sets.

This paper discusses the relationships studied between manifold solids and r-sets by defining an r-set as a decomposition in two-manifold cells. This decomposition is represented as a graph (Two-manifold Cell Decomposition graph TCD) in which each node corresponds to a 2 manifold component of the regular set, while each arc or hyperarc defines a non-manifold adjacency between components. The TCD model and data structure encoding it were designed in order to be compatible with a traditional boundary architecture.     

Novel (Phenothiazinyl)Vinyl-Pyridinium Dyes and Their Potential Applications as Cellular Staining Agents

We report here the synthesis and structural characterization of novel cationic (phenothiazinyl)vinyl-pyridinium (PVP) dyes, together with optical (absorption/emission) properties and their potential applicability as fluorescent labels. Convective heating, ultrasound irradiation and mechanochemical synthesis were considered as alternative synthetic methodologies proficient for overcoming drawbacks such as long reaction time, nonsatisfactory yields or solvent requirements in the synthesis of novel dye (E)-1-(3-chloropropyl)-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium bromide 3d and its N-alkyl-2-methylpyridinium precursor 1c. The trans geometry of the newly synthesized (E)-4-(2-(7-bromo-10-ethyl-10H-phenothiazin-3-yl)vinyl)-1-methylpyridin-1-ium iodide 3b and (E)-1-methyl-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium tetrafluoroborate 3a′ was confirmed by single crystal X-ray diffraction. A negative solvatochromism of the dyes in polar solvents was highlighted by UV-Vis spectroscopy and explanatory insights were supported by molecular modeling which suggested a better stabilization of the lowest unoccupied molecular orbitals (LUMO). The photostability of the dye 3b was investigated by irradiation at 365 nm in different solvents, while the steady-state and time-resolved fluorescence properties of dye 3b and 3a′ in solid state were evaluated under one-photon excitation at 485 nm. The in vitro cytotoxicity of the new PVP dyes on B16-F10 melanoma cells was evaluated by WST-1 assay, while their intracellular localization was assessed by epi-fluorescence conventional microscopy imaging as well as one- and two-photon excited confocal fluorescence lifetime imaging microscopy (FLIM). PVP dyes displayed low cytotoxicity, good internalization inside melanoma cells and intense fluorescence emission inside the B16-F10 murine melanoma cells, making them suitable staining agents for imaging applications.     

Democratizing Journalism – How User‐Generated Content and User Communities Affect Publishers’ Business Models

Publishers, today, are struggling with their business model: Their efforts to convert traditional content into digital products seem to be insufficient as recipients expect more than simply the mere digitalization of content. Dissatisfied with solely being informed by selected journalists, modern recipients are often interested in acquiring information from various sources, in discussing with others, or even in contributing with their own content. Hence, recipients seem to evolve from being simply readers to contributors themselves. With regard to the established term ‘user‐generated content’, we refer to those co‐creating recipients as users. To underline these assumptions, the present study explores (1) users’ expectations of sources of content and (2) their willingness to provide their own content. Our findings show that both user‐generated content and professional journalists’ content is of value to users. Second, we show that users are mainly driven to contribute by their own expertise, welfare of others, and personal acceptance in the community. With this study, we consider mainly the changed user behaviour in order to derive implications of user involvement for future business models of publishers, in particular on the customer value proposition as well as key resources and key processes.     

Defining, contouring, and visualizing scalar functions on point-sampled surfaces

This paper addresses the definition, contouring, and visualization of scalar functions on unorganized point sets, which are sampled from a surface in 3D space; the proposed framework builds on moving least-squares techniques and implicit modeling. Given a scalar function f:P→R, defined on a point set P, the idea behind our approach is to exploit the local connectivity structure of the k-nearest neighbor graph of P and mimic the contouring of scalar functions defined on triangle meshes. Moving least-squares and implicit modeling techniques are used to extend f from P to the surface M underlying P. To this end, we compute an analytical approximation of f that allows us to provide an exact differential analysis of , draw its iso-contours, visualize its behavior on and around M, and approximate its critical points. We also compare moving least-squares and implicit techniques for the definition of the scalar function underlying f and discuss their numerical stability and approximation accuracy. Finally, the proposed framework is a starting point to extend those processing techniques that build on the analysis of scalar functions on 2-manifold surfaces to point sets.