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.     

Electrical and optical properties of semi-insulating polycrystalline silicon thin films: the role of microstructure and doping

We have investigated the relationship between microstructure and electrical conductivity in semi-insulating polycrystalline silicon (SIPOS) with oxygen concentrations in the 2–35 at.% range and the effect of doping with boron, phosphorus, arsenic and erbium by ion implantation. SIPOS thin films are mixtures of silicon and silicon oxide phases. The chemical and morphological evolution of these phases upon annealing is emphasized. Electrical conductivity measurements are interpreted in terms of a physical model containing few free parameters related to the material microstructure. A direct extension of this model explains also the conductivity increase in SIPOS doped with elements of the third or the fifth group. In the last part of the paper, data of electroluminescence at 1.54 μm in Er-implanted SIPOS due to intra-4f transitions of the Er³⁺ ion are shown and discussed.     

Development of an undergraduate course – Internet-based instrumentation and control

The objective, strategy, and implementation details of a new undergraduate course, Internet-based Instrumentation and Control, are presented. The course has a companion laboratory that is supported by the National Science Foundation and industry. The combination is offered to senior-level undergraduate engineering students interested in sensing, instrumentation, control, and web programming that want to learn more about the integration of these technologies for solving real-world engineering problems. The course will also be offered to gifted high school seniors with similar interests and can serve as a vehicle to attract them to engineering disciplines. Preliminary assessment of the first offering of the course is encouraging and has shown that the course has achieved success in helping students understand concepts and master basic technologies for developing Internet-based automatic systems.     

Influence of electroosmotic treatment on the hydro-mechanical behaviour of clayey silts: preliminary experimental results

Preliminary results of an investigation focused on the influence of electrokinetic treatment on the mechanical and hydraulic behaviour of clayey soils are presented. The experimental programme aims at providing a contribution to the sustainability of contaminant extraction or containment via electroosmosis. Changes in the hydraulic and mechanical properties of two illitic clayey soils, subjected to a DC electric field, were investigated. Samples of the two soils were subjected to electrokinetic filtration, for different periods of time, and under different constant loads. Afterwards, they were tested under one-dimensional compression to detect changes in stiffness and hydraulic conductivity due to the electrical treatment. After the application of a DC field for a few hours, a small reversible increment in the average soil stiffness was observed, with respect to the untreated soil, while the hydraulic conductivity was not affected substantially. Dramatic changes of the mechanical and hydraulic soil properties, correlated to changes of the soil pH, were observed following non-conditioned electrokinetic treatment with duration of the order of days.     

Relation between microstructure, properties and spark plasma sintering (SPS) parameters of pure ultrafine WC powder

A combined experimental/numerical methodology is developed to fully consolidate pure ultrafine WC powder under a current-control mode. Three applied currents, 1900, 2100 and 2700 A, and a constant pressure of 20 MPa were employed as process conditions. The developed spark plasma sintering (SPS) finite-element model includes a moving-mesh technique to account for the contact resistance change due to sintering shrinkage and punch sliding. The effects of the heating rate on the microstructure and hardness were investigated in detail along the sample radius from both experimental and modeling points of view. The maximum hardness (2700 HV10) was achieved for a current of 1900 A at the core sample, while the maximum densification was achieved for 2100 and 2700 A. A direct relationship between the compact microstructure and both the sintering temperature and the heating rate was established.     

Preceramic organoboron–silicon polymers

Several boron-containing organosilicon polymers were synthesized from a sodium-coupling reaction of silicon and boron halides with and without alkyl halide in hydrocarbon solvents. The B–Si preceramic polymers were characterized using techniques such as IR, UV, and NMR spectrometry, gel permeation chromatography, elemental analysis, molecular weight measurement, and thermal analyses (TGA, DSC, DTA, and TMA). The chemical structures of the preceramic polymers were postulated based on the analytical results. Black ceramic materials were obtained from the precursor polymers upon thermal degradation at temperatures above 1000°C in an inert atmosphere. The precursor polymers had a ceramic yield of up to 70%. Thermogravimetric analysis of the ceramic material in air at a flow rate of 100 mL/min showed it was stable up to 1000°C with little weight gain or loss. Several methods were used to characterize the ceramic materials: XRD, solid NMR, high-temperature DTA, elemental analysis, and acid digestion. The analyses indicated that the ceramic materials comprised a mixture of silicon carbide (SiC), silicon borides (SiB₄, SiB₆), and amorphous Si–B–C ceramics, with small amounts of silica and free silicon.     

Growth dynamics in cystic fibrosis

The growth profiles of 28 cystic fibrosis patients, followed for at least three years, were analysed in order to study the dynamics of growth and to verify if any correlation with clinical events exists. Heights and weights were recorded at three-month intervals, and the patterns did not appear stable or linear, although a graphical smoothing might depict a linear pattern. Height and weight velocity profiles were plotted and all cases showed regular pulsatile patterns of height and weight velocity. By taking measurements at three-month intervals, the pulsatile rhythm was found to be associated with a circannual rhythm. When the appearance of clinical events was related to growth velocity profiles for each individual, the majority (71-82%) occurred during the descending phase of the growth velocity. An understanding of the individual pulsatile pattern of growth may actually increase the sensitivity of surveillance, and checks might be programmed according to the individual pattern, since the risk of developing an adverse clinical event is significantly greater during the slowing phase of the growth velocity.     

High-Performance Multilayer Capacitor Dielectrics from Chemically Prepared Powders

Advantages of chemically prepared powders for electronic ceramics have been demonstrated for a number of multilayer capacitor (MLC) dielectrics. A cost-efficient precipitation process was developed to produce undoped or doped crystalline barium titanate powder with a narrow particle size distribution close to 0.5 μm. More complex compositions, e.g., barium-neodymium titanate, were amorphous as precipitated but could be crystallized by calcination below 1000°C. Additional compositional modifications, to adjust electrical properties or to lower sintering temperature, were accomplished by doping the surface of the powder particles using a solution coating process. Exceptional fired densities and electrical performance were obtained.