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.     

HRTEM observation of the monoclinic-to-tetragonal m-t) phase transition in nanocrystalline ZrO2

The orientation relations m(100) || t(001), m[001] || t[110]; m(011) || t(100), m[100] || t[001]; m(100) || t(110), m[001] || t[001]; m(013) || t(116), m[001] || t[001] (indices for the primitive tetragonal cell) have been found between the tetragonal (t) and monoclinic (m) domains during the electron irradiation-induced m-t phase transition observed in-situ with HREM within isolated zirconia nanoparticles. Geometric models of the m-t interfaces are proposed.     

Acetohydroxy acid synthase and threonine deaminase activities, and the biosynthesis of isoleucine-leucine-valine in Streptococcus bovis

Acetohydroxy acid synthase (AHAS) and threonine deaminase (TD) activities were found in Streptococcus bovis and shown to be involved in the biosynthesis of the branched chain amino acids isoleucine, leucine and valine. Apparent lack of repression of AHAS synthesis by the end-products and reduced sensitivity of S. bovis growth to analogues of the branched chain amino acids suggested that secretion of isoleucine, leucine and valine in the growth medium may be a consequence of the regulatory features of AHAS. A glycyl-leucine-resistant mutant with reduced TD activity secreted a reduced amount of isoleucine and an increased amount of valine, which might be a result of the reduced rate of synthesis of the isoleucine precursor alpha-ketobutyrate and of a consequent preferential carbon flow through the valine branch of the pathway.     

Overview of recent operating experience regarding plant aging

Recent, as well as past, studies of reactor trip frequencies and other types of operating experience have shown that relatively high frequencies are likely in new plants with little accumulated operating time. In order to better understand all the factors which contribute to high frequencies in new plants, the authors have made a comparison of reactor trip frequencies between plants which went into operation in the 1960's and the early 1970's and those which have gone into operation more recently. Trip frequency versus accumulated operating time for two plant groups are compared to see the extent to which design differences (e.g., capacity, thermal margin) affect trip frequency.This paper also presents a review of some recent events in which plant age has played a major role. The events which are reviewed have been identified through the normal systematic event analysis program conducted by the NRC. Information regarding these events was obtained through followup by reviews conducted by NRC Resident Inspectors as well as event reports submitted by licensees.     

Simulation of Climate Change Effects on Hydropower Operations in Mountain Headwater Lakes,New Zealand

Future climate change is expected to have wide ranging impacts on the hydrology of mountain rivers because of changes in the magnitudes and timing of rain and snow, as well as the significant spatial variability of topography and other catchment characteristics. In New Zealand, hydropower generation in mountain basins is the primary source of electricity and renewable energy resource in the country. The goal of this study was to simulate and evaluate the potential effects of climate change on hydropower operations in three mountain headwater lakes (lakes Pukaki, Tekapo, and Ohau) in the Upper Waitaki Basin of the central South Island. The TopNet hydrological model was used to estimate catchment runoff and lake inflows based on the 1990s (baseline), 2040s, and 2090s periods. Average temperature and precipitation results from an ensemble of 12 Global Circulation Models based on the IPCC 4th Assessment Report A1B emissions scenario were used as input to TopNet. Linked hydropower lake water balance models were developed and used to simulate hydropower operations including discharge, hydroelectric power generation, and spill based on TopNet future inflow predictions, projected electricity demand, and lake storage and outflow characteristics. Our results indicate that annual lake inflows increase under future climate scenarios, but that there are seasonal effects with increasing flows in winter and early spring, and summer flows decreasing somewhat as a result of increasing temperatures and greater winter rain with less snow. Although overall hydropower generation can increase with the increasing flows and projected electricity demand, the seasonal changes result in demand being met in winter and spring with potential shortfalls in summer and autumn. Maximum annual generation can be achieved for some generating stations, but generation will decrease at other stations and more spill will likely be required through the 2090s because of the seasonal changes. Therefore flood and drought risk could also increase for downstream areas. Results also indicate that by the 2090s electricity demand could exceed generation capacity for these headwater lakes. Copyright © 2016 John Wiley & Sons, Ltd.     

Evaluation of hydraulic excavator Human–Machine Interface concepts using NASA TLX

This study evaluated newly proposed Human–Machine Interface (HMI) design concepts for improving the ergonomics of hydraulic excavators. The design concepts were based on an augmented interaction technique which involved the use of heads-up display (HUD) and coordinated control as HMI elements. Two alternative HMI designs were elaborated in order to separately evaluate the ergonomic impacts of the head-up display and the coordinated control by comparing them to the standard HMI design. The effectiveness of these three HMI designs in terms of the reduction of the operators' mental and physical workload were assessed by conducting experiments utilizing human subjects, ages 23–35 years. The National Aeronautics and Space Administration's Task Load Index (NASA TLX) method was used for collecting subjective workload scores based on a weighted average of ratings of six factors: Mental Demand, Physical Demand, Temporal Demand, Own Performance, Effort, and Frustration Level. The results showed that the type of HMI design affects different aspects of the operator's workload. Indeed, it showed how the proposed augmented interaction is an effective solution for reducing the ergonomic gaps in terms of mental workload, and to a lesser extent the physical workload, subjected by the standard HMI design.     

Activity and Selectivity of a Nanostructured CuO/ZrO2 Catalyst in the Steam Reforming of Methanol

Steam reforming of methanol for production of hydrogen can be carried out over copper based catalyst. In the work presented here, the catalytic properties of a CuO/ZrO₂ catalyst (8.5wt%) synthesised by a templating technique were investigated with respect to activity, long term stability, CO formation, and response to oxygen addition to the feed. The results were obtained using a fixed bed reactor and compared to a commercial methanol synthesis catalyst CuO/ZnO/Al₂O₃. It is shown that, depending on the time on stream, the temporary addition of oxygen to the feed has a beneficial effect on the activity of the CuO/ZrO₂ catalyst. After activation, the CuO/ZrO₂ catalyst is found to be more active (per copper mass) than the CuO/ZnO/Al₂O₃ system, more stable during time on stream (measured up to 250h), and to produce less CO. Structural characterisation by means of X-ray powder diffraction (XRD) and X-ray absorption spectroscopy (XAS) reveals that the catalyst (as prepared) consists of crystalline, tetragonal zirconia with small domain sizes (about 60Å) and small/disordered crystallites of CuO.