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.     

Well-founded and stationary models of logic programs

We investigate the class ofstationary or partial stable models of normal logic programs. This important class of models includes all (total)stable models, and, moreover, thewell-founded model is always its smallest member. Stationary models have several natural fixed-point definitions and can be equivalently obtained as expansions or extensions of suitable autoepistemic or default theories. By taking a particular subclass of this class of models one can obtain different semantics of logic programs, including the stable semantics and the well-founded semantics. Stationary models can be also naturally extended to the class of all disjunctive logic programs. These features of stationary models designate them as an important class of models with applications reaching far beyond the realm of logic programming.Partially supported by the National Science Foundation grant #IRI-9313061.     

3D Hair sketching for real-time dynamic & key frame animations

Physically based simulation of human hair is a well studied and well known problem. But the “pure” physically based representation of hair (and other animation elements) is not the only concern of the animators, who want to “control” the creation and animation phases of the content. This paper describes a sketch-based tool, with which a user can both create hair models with different styling parameters and produce animations of these created hair models using physically and key frame-based techniques. The model creation and animation production tasks are all performed with direct manipulation techniques in real-time.     

Energy and comfort: A new type for TRNSYS

Two subroutines have been developed which permit users of the TRNSYS programme to calculate the parameters of ambiental comfort (PMV and PPD).The first subroutine deals with the calculation of the view factors inside a room for all the values of the spatial coordinates and, thus, permits the average radiant temperature to be calculated in every position. The second subroutine has been developed in accordance with the indications of the ISO 7730 standard.Both subroutines have been validated and then interfaced to TRNSYS.The integrated programme has been utilised to compare the performances of different heating systems in terms of energy consumption and comfort, maintaining the temperature of the interior constant for different climatic conditions.     

Forecasting of Turkey's net electricity energy consumption on sectoral bases

In this study forecast of Turkey's net electricity energy consumption on sectoral basis until 2020 is explored. Artificial neural networks (ANN) is preferred as forecasting tool. The reasons behind choosing ANN are the ability of ANN to forecast future values of more than one variable at the same time and to model the nonlinear relation in the data structure. Founded forecast results by ANN are compared with official forecasts.