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1.
Claudia Giuseppina Fresta Giuseppe Caruso Annamaria Fidilio Chiara Bianca Maria Platania Nicol Musso Filippo Caraci Filippo Drago Claudio Bucolo 《International journal of molecular sciences》2020,21(23)
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. 相似文献
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Anaerobic co-digestion of organic wastes from households, slaughterhouses and meat processing industries was optimised in a half technical scale plant. The plant was operated for 130 days using two different substrates under organic loading rates of 10 and 12 kgCOD.m(-3).d(-1). Since the substrates were rich in fat and protein components (TKN: 12 g.kg(-1) the treatment was challenging. The process was monitored on-line and in the laboratory. It was demonstrated that an intensive and stable co-digestion of partly hydrolysed organic waste and protein rich slaughterhouse waste can be achieved in the balance of inconsistent pH and buffering NH4-N. In the first experimental period the reduction of the substrate COD was almost complete in an overall stable process (COD reduction >82%). In the second period methane productivity increased, but certain intermediate products accumulated constantly. Process design options for a second digestion phase for advanced degradation were investigated. Potential causes for slow and reduced propionic and valeric acid degradation were assessed. Recommendations for full-scale process implementation can be made from the experimental results reported. The highly loaded and stable codigestion of these substrates may be a good technical and economic treatment alternative. 相似文献
4.
OBJECTIVE: To determine the role of synovial fluid (SF) compared to peripheral blood (PB) CD45RO+ T cells in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: We examined SF and PB of 8 patients with a specific lymphocyte proliferation to Yersinia enterocolitica (n = 5) and Chlamydia trachomatis (n = 3). After depletion of the CD45RA+ T cell subset by dynabeads, the remaining T cells (> 95% CD45RO+) from PB and SF of these patients were again stimulated with these bacterial antigens. RESULTS: The mean stimulation index (SI) of these 8 patients with ReA (n = 5) and undifferentiated oligoarthritis (n = 3) was 30.3 +/- 21.86 in SF compared to 1.36 +/- 0.75 in PB. The enrichment of CD45RO+ cells influenced the antigen specific proliferative response of T cells neither in PB (SI = 1.75 +/- 1.35) nor in SF (26.1 +/- 24.05); the initial difference remained unchanged. CONCLUSION: Our findings suggest that the antigen specific lymphocyte proliferation obtained with SF cells is not due to abundance of nonspecific CD45RO+ T cells but can rather be taken as an indication of specific recognition of local bacterial antigens in ReA. 相似文献
5.
T. Braun K.-F. Becker M. Koch V. Bader R. Aschenbrenner H. Reichl 《Microelectronics Reliability》2005,45(9-11):1672
Automotive under-the-hood electronics often have to withstand temperatures up to 175 °C in combination with harsh environment conditions. This paper gives an overview about the reliability potential of epoxy based encapsulants for automotive applications. Therefore the resistance of epoxy molding compound against typical automotive fluids at temperature of use is analyzed. Six epoxy molding compounds available on the market, showing high temperature automotive potential have been carefully selected to undergo a media resistance testing. For this purpose a dedicated mold tool has been designed and manufactured to prepare these encapsulants for material testing. Thermo-mechanical, mechanical and thermal properties had been determined in initial state directly after molding and after storage in aggressive fluids typical for automotive applications as e.g. gas oil, automatic transmission fluid (ATF), brake fluid or accumulator acid at the respective temperature of use. 相似文献
6.
J.A. Bakken L. Barone D. Braun M. Caillat C. Dionisi C. Dor H. Elmamouni F. Ferroni G.L. Grazer J.T. He R. Herbiet B. Ille P. Lecomte E. Longo P.F. Loverre Y.S. Lu J.P. Martin U. Micke R.P. Mount P.A. Pirou H.-G. Sander D. Schmitz M. Schneegans D.P. Stickland R.L. Sumner K.L. Tung E. Valente M. Vivargent 《Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment》1985,228(2-3):294-302
A calorimeter of 25 bismuth germanate (BGO) crystals equipped with silicon photodiode readout has been tested at the CERN SPS in the energy range 1–50 GeV. The response for electrons has been shown to be linear in this energy range and the rms resolution obtained (
) is approximately 1%, for E > 4 GeV. The electron/pion separation was found to be better than 1:500 in the energy range 1–20 GeV. Data on lateral and longitudinal shower development were compared with the results of a Monte Carlo simulation using the SLAC-EGS program and found to be in good agreement. 相似文献
7.
On sorting triangles in a delaunay tessellation 总被引:1,自引:0,他引:1
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. 相似文献
8.
What if every public space and surface were transformed into an interactive experience - capturing our movements, gestures, sounds and actions and using these to produce new sounds, images, text and actions? Bus stops could come alive and talk back, advertisements could look back at you and talk to you and public park robotic devices could play games with you. Will public places eventually become our social barometer as well as director? Will billboards display the populace's discourse? The author look at some special streets in France where the city is literally alive with art and explores what it might mean for us to live in a world of artistic interactivity. 相似文献
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Experience with electrical diagnostic and high-potential tests, performed at the terminals of unshielded cables in older nuclear and thermal plants is presented. The three basic types of cable-low- and high-voltage power cables, control cables and instrumentation cables-that are important to the reliable operation of a generating station and large industrial plants are described, and their aging mechanisms are indicated. Dielectric testing of unshielded cables, the effect of grounding, field testing of station cables, and insulation characterization at low frequencies are discussed 相似文献