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.     

A framework for analytical cost estimation of mechanical components based on manufacturing knowledge representation

This paper presents a novel framework for manufacturing and cost-related knowledge formalization. This artefact allows industries to capitalize the knowled     

2,4,6‐Trichlorophenol and phenol removal in methanogenic and partially‐aerated methanogenic conditions in a fluidized bed bioreactor

A fluidized bed bioreactor (FBBR) was operated for more than 575 days to remove 2,4,6‐trichlorophenol (TCP) and phenol (Phe) from a synthetic toxic wastewater containing 80 mg L^?1 of TCP and 20 mg L^?1 of Phe under two regimes: Methanogenic (M) and Partially‐Aerated Methanogenic (PAM). The mesophilic, laboratory‐scale FBBR consisted of a glass column (3 L capacity) loaded with 1 L of 1 mm diameter granular activated carbon colonized by an anaerobic consortium. Sucrose (1 g COD L^?1) was used as co‐substrate in the two conditions. The hydraulic residence time was kept constant at 1 day. Both conditions showed similar TCP and Phe removal (99.9 + %); nevertheless, in the Methanogenic regime, the accumulation of 4‐chlorophenol (4CP) up to 16 mg L^?1 and phenol up to 4 mg L^?1 was observed, whereas in PAM conditions 4CP and other intermediates were not detected. The specific methanogenic activity of biomass decreased from 1.01 ± 0.14 in M conditions to 0.19 ± 0.06 mmolCH₄ h^?1 gTKN^?1 in PAM conditions whereas the specific oxygen uptake rate increased from 0.039 ± 0.008 in M conditions to 0.054 ± 0.012 mmolO₂ h^?1 gTKN^?1, which suggested the co‐existence of both methanogenic archaea and aerobic bacteria in the undefined consortium. The advantage of the PAM condition over the M regime is that it provides for the thorough removal of less‐substituted chlorophenols produced by the reductive dehalogenation of TCP rather than the removal of the parent compound itself. Copyright © 2005 Society of Chemical Industry     

Intracellular magnesium and inositol 1,4,5-trisphosphate receptor: molecular mechanisms of interaction, physiology and pharmacology

Mass media--friend or foe? Radio, television, and/or the printed word regularly enter most of the world's households. With a better understanding between health workers and those who produce what we hear, see and read, positive messages could do much to change the habits the jeopardize health. Clear, accurate information is the first step towards improvement.     

Hardware and software architecture for power quality analysis

This paper presents a novel concept for power quality hardware and software architecture. Software tools related to detection, classification and characterization of power quality events can be integrated into a Distribution Control Center in which the interconnection between different subsystems is being carried out through the Internet allowing flexibility to the system. This system is implemented using wavelet analysis applied in all proposed algorithms. Different power quality events are taken as examples to illustrate the capabilities of the proposed method. The obtained results reveal that the proposed architecture is feasible to be implemented as an integral part of a control center system.The proposed system has the property of fast and accurate detection and classification of any power quality disturbance event and introduces a new PQ index determination that allows characterizing any type of disturbance including the non-periodic signals.     

Nonlinear Creep Damage Model for Concrete under Uniaxial Compression

An isotropic model for creep damage of concrete under uniaxial compression is proposed, where the combined effect of nonlinear viscous strain evolution and crack nucleation and propagation at high stress levels is considered. Strain splitting assumption is used for creep and damage contributions. Creep is modeled by a modified version of solidification theory. As usual in the modeling of damage of concrete, a damage index based on positive strains is introduced. As particular cases, the proposed model reduces to linear viscoelasticity for long time low stress levels whereas, for very high stresses, tertiary creep causing failure at a finite time can be described. The effect of strength variation with time is also included. The model is numerically implemented to perform time integration of nonlinear equations by means of a modified version of exponential algorithm. The model is validated through comparison with experimental results. Some numerical examples are also presented, where the roles of concrete ageing and strength variation with time are investigated.     

W‐band physical layer design issues in the context of the DAVID–DCE experiment

This paper aims at focusing on the aspects concerning the physical layer design for an innovative satellite communication experiment. Such an experiment, denoted by the acronym DAVID–DCE (Data and Video Interactive Distribution—Data Collection Experiment) is based on the exploitation of the W‐band (75–110 GHz) for high‐bit‐rate satellite transmission. The potential advantages of using of the W‐band are mainly related to the great bandwidth availability, and to the absence of interference. Moreover, an expected result of the experiment is a substantive improvement in the communication system's performances in the presence of meteorological phenomena (e.g. rain) as compared with the more conventional Ka‐band satellite transmission. On the other hand, problems to be faced concern the non‐ideal behaviours of hardware devices employed for high‐frequency digital transmission. In particular, carrier recovery and timing recovery are the most crucial signal‐processing tasks to be carefully considered in the design of the physical level of the system, because they considerably suffer from hardware impairments. The purpose of this work is to illustrate the proposed solutions in terms of the most critical modulation, demodulation and synchronization design issues, together with the effects of non‐ideal behaviours of hardware components on BER performances. Copyright © 2004 John Wiley & Sons, Ltd.     

Immobilization of an endopectinlyase on γ-alumina: Study of factors influencing the biocatalytic matrix stability

Endopectinlyase (EC 4.2.2.10) from Aspergillus japonicus was immobilized on to γ-alumina. Adsorption performed at pH 5·0 and a subsequent cross-linking phase using 0·1% glutaraldehyde were the chosen immobilization conditions. The comparison between the main biochemical parameters of the immobilized and free form of the enzyme showed that the immobilization procedure used did not affect the enzyme biochemical properties. The interactions between the carrier and the enzyme are essentially secondary bonding. In fact they depend on the pH and on the presence of phosphate ions in the medium. A tentative chemical model of the biocatalytic matrix thus obtained is proposed.