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1.
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   
2.
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.  相似文献   
3.
Two processes, namely shrinkage and primary fragmentation are known to be the major causes of size reduction of wood during its devolatilization in a fluidized bed combustor. A simple phenomenological model incorporating these effects to compute the average char size at the end of devolatilization is proposed. Experiments are conducted in a bubbling fluidized bed combustor using wood having three different shapes namely, cylinder, cuboid and sphere, to measure the average char size at the end of devolatilization. The model prediction of average char size agrees with the measured values within a deviation of 15%. An experimental correlation is derived to determine the number of fragments and is used to estimate the mean char size.  相似文献   
4.
A two-dimensional model is developed for the determination of devolatilization time and char yield of cylindrical wood particles in a bubbling fluidized bed combustor. By using the concept of shape factor, the model is extended to particles of cuboid shape. The model prediction of the devolatilization time agrees with the measured data (present and those reported in the literature) for cylindrical and cuboidal shaped particles within ±20% while the char yield is predicted within ±17%. Influence of some important parameters namely, thermal diffusivity, external heat transfer coefficient and shrinkage, on the devolatilization time and char yield are studied. Thermal diffusivity shows noticeable influence on devolatilization time. The external heat transfer coefficient shows little influence beyond a value of 300 W/(m2 K). However particle shrinkage shows negligible effect on the devolatilization time but has a significant influence on the char yield.  相似文献   
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A three-phase three-switch buck-type pulsewidth modulation rectifier is designed for telecom applications in this paper. The rectifier features a constant 400-V output voltage and 5-kW output power at the three-phase 400-V mains. The principle of operation and the calculation of the relative on-times of the power transistors are described. Based on analytical relationships the stresses of the active and passive components are determined and the accuracy of the given calculations is verified by digital simulations. Exemplarily, a 5-kW power converter is then designed based on the analytical expressions and on switching loss measurements from a hardware prototype constructed with insulated gate bipolar transistor/diode power modules. The loss distribution of the components, the total efficiency, and the junction temperatures of the semiconductors are then evaluated in dependency on the operating point. Finally, the trade-off between the selected switching frequency and the admissible power range for the realized design is shown and a total efficiency of 95.0% is measured on the hardware prototype, where an excellent agreement with the theoretically evaluated efficiency is shown  相似文献   
7.
The microstructure and properties of NdFeB sintered permanent magnets were analysed by different methods. Samples analysed were sintered and thermally treated. The hard magnetic Nd2Fe14B phase and amorphous neodymium-rich phase were observed by TEM. The neodymium-rich phase contained iron and boron, in elemental and in B2O3 form, which is known as a glass former. At the sintering temperature, Nd2Fe14B and the neodymium-rich phase are supersaturated with iron, which should be dissolved at the annealing temperature to react with neodymium and boron and form additional Nd2Fe14B phase. Iron precipitates of size up to 2 nm were detected in the Nd2Fe14B phase. These superparamagnetic precipitates of -Fe could affect the hard magnetic properties of NdFeB magnets.  相似文献   
8.
Automatic prediction tools play a key role in enabling the application of non-functional requirements analysis, to simplify the selection and the assembly of components for component-based software systems, and in reducing the need for strong mathematical skills for software designers. By exploiting the paradigm of Model-Driven Engineering (MDE), it is possible to automatically transform design models into analytical models, thus enabling formal property verification. MDE is the core paradigm of the KlaperSuite framework presented in this paper, which exploits the KLAPER pivot language to fill the gap between design and analysis of component-based systems for reliability properties. KlaperSuite is a family of tools empowering designers with the ability to capture and analyze quality of service views of their systems, by building a one-click bridge towards a number of established verification instruments. In this article, we concentrate on the reliability-prediction capabilities of KlaperSuite and we evaluate them with respect to several case studies from literature and industry.  相似文献   
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High T c superconducting materials based on a PbO-modified Bi-Sr-Ca-Cu-O system with various ratios between the oxides were prepared by calcination at 800 °C and firing at 855 °C. From X-ray powder diffraction analysis data, the ratio of low- and high-temperature phases was calculated. The material with the nominal composition Bi2Pb0.5Sr2Ca2.5Cu3.5O x was chosen for further experimental work. Samples fired at 800 °C contain mostly the low-temperature phase (2212). Higher firing temperatures lead to the formation of the high T c phase (2223) with T c(R=0) over 100 K. Some samples were cold pressed and refired which increased the specific density to over 80% of the theoretical density. The composition of samples was investigated by X-ray powder diffraction analysis and by energy dispersive X-ray spectroscopy. The main phase in the material fired at 800 °C, is the low T c phase 2212, and secondary phases are Ca2PbO4, unreacted CuO and traces of 2223 phase. At higher firing temperatures, the main phase is the high-temperature phase 2223. The material is still heterogeneous and contains Ca2PbO4.  相似文献   
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