Search

© 2020 Introduction: hERG block potency is widely used to calculate a drug's safety margin against its torsadogenic potential. Previous studies are confounded by use of different patch clamp electrophysiology protocols and a lack of statistical quantification of experimental variability. Since the new cardiac safety paradigm being discussed by the International Council for Harmonisation promotes a tighter integration of nonclinical and clinical data for torsadogenic risk assessment, a more systematic approach to estimate the hERG block potency and safety margin is needed. Methods: A cross-industry study was performed to collect hERG data on 28 drugs with known torsadogenic risk using a standardized experimental protocol. A Bayesian hierarchical modeling (BHM) approach was used to assess the hERG block potency of these drugs by quantifying both the inter-site and intra-site variability. A modeling and simulation study was also done to evaluate protocol-dependent changes in hERG potency estimates. Results: A systematic approach to estimate hERG block potency is established. The impact of choosing a safety margin threshold on torsadogenic risk evaluation is explored based on the posterior distributions of hERG potency estimated by this method. The modeling and simulation results suggest any potency estimate is specific to the protocol used. Discussion: This methodology can estimate hERG block potency specific to a given voltage protocol. The relationship between safety margin thresholds and torsadogenic risk predictivity suggests the threshold should be tailored to each specific context of use, and safety margin evaluation may need to be integrated with other information to form a more comprehensive risk assessment.

Additional file 1.

Direct evidence of effects of surface plasmon resonance(SPR) of gold nanorods(GNRs) on dual-band light absorption enhancement with coupling dye molecules was reported by introducing gold nanorod@SiO2(GNR@SiO2) core-shell nanoparticles into a photoelectric conversion system. GNR with asymmetric shape had unusual anisotropic SPR[transversal surface plasmon resonance(TSPR) and longitudinal surface plasmon resonance(LSPR)]. The excel-lent SPR of GNR made it a promising candidate as enhancing light absorption material to increase power conversion efficiency(PCE). The PCE was improved nearly 17.2% upon incorporating GNRs, mostly due to the increase in Jsc, while Voc and FF were unchanged. The improvement was mostly contributed by the SPR of the GNRs with coupling of N719. And there was also a complementary to N719 in visible light range. Therefore, SPR is an effective tool in improving the photocurrent and consequently enhancement of PCE. The TSPR and LSPR effects of GNRs on light harvesting were reflected in the increased monochromatic incident photon-to-electron conversion efficiency(IPCE). We also utilized finite-difference time-domain(FDTD) to investigate the light coupling of GNRs with TiO2. Compare to the base anode, the IPCE of optimized electrode showed significant improvement and peaks broadening at 500–600 nm and 610–710 nm. We got an increase in overall conversion efficiency from 6.4% to 7.5%.

Glaucoma is a neurodegenerative disorder that is generally accepted as the main cause of vision loss. In this study, we tested the hypothesis that laminin α4 (LAMA4) is implicated in glaucoma development by controlling apoptosis of retinal ganglion cells (RGCs) through the mitogen-activated protein kinase (MAPK) signaling pathway. Expression profiles and genes associated with glaucoma were searched to determine the objective gene. Intraocular pressure (IOP) rats model were established and IOP was measured. The mRNA and protein expression of LAMA4, JNK, p38 MAPK, ERK, Bcl-2, Bax, Caspase-9, and p53 was determined in concert with the treatment of H(2)O(2), si-NC, or si-LAMA4 in cultured RGCs. Viability of RGCs, reactive oxygen species (ROS) and cell apoptosis was also measured. LAMA4 was selected as the study object because of its significant difference in two expression profiles. IOP of rats with glaucoma increased significantly after model establishment, and the LAMA4 protein expression in retinal tissue of rats with glaucoma was elevated. Down-regulation of LAMA4 could inhibit the mRNA and protein expression of LAMA4, JNK, p38 MAPK, ERK, Bax, Caspase-9, and p53, as well as restrain the apoptosis and ROS of RGCs, but improve Bcl-2 expression and viability of RGCs. Collectively, the obtained data supported that downregulated LAMA4 might reduce the oxidative stress-induced apoptosis of glaucoma RGCs by inhibiting the activation of the MAPK signaling pathway.

SUMMARY Incipient faults such as those caused by tree contacts are difficult to detect by conventional relaying algorithms. These faults impact distribution feeder reliability by advancing –over time– into a full-blown fault if not detected in time. This paper proposes a combined technique using S-transform technique and Hilbert transform to extract the features of incipient fault. A least square support vector machine classifier is developed based on the features so that incipient faults can be distinguished from the normal disturbances. The comparison of the results of different feature selection methods has been conducted. The simulation results show that the proposed feature selection method is feasible and suitable. Copyright © 2012 John Wiley & Sons, Ltd.

Beacuse of the classical RPN (Region Proposal Net) exists the defect of large computation and high time complexity when extracting targets candidate region, a search mode called CRPN (Cascade Region Proposal Network) mode was proposed to ameliorate it in this paper. In order to suppress the degradation phenomenon in deep convolutional neural network training, the residual learning theory was introduced, a novel Mu-ResNet (multi-strapdown deep residual network) was proposed. Combined the Mu-ResNet with CPRN, a network model for multi-target identification of UAV was designed and tested. Compared with the network model that combines ResNet with RPN, the identification accuracy was increased nearly 2 percentage points.

The probability of crane living in reedy wetlands can reach 100%, at the same time, the area of reed, the water level and adjacent water area are main factors which control the crane’s habitat selection. We all know that all these factors are spatially heterogeneous. For the Xianghai wetland safety and to protect the Xianghai wetland habitat of crane, this paper has mainly identified a solution to these problems. The wetland information is extracted from the TM images, which reflect the whole wetland landscape and are very important for both quantitative analysis of remote sensing observation of the earth system and positioning analysis in GIS database that is automatically extracted from DEM. The DEM for Xianghai characteristics of topography is created. On the basis of the GRID SUBMODULE, applying the GIS spatial overlay analysis, the relationship between the water level and the reed area below the water level and the rating distribution maps of reed area above water level is established. When the water level reaches the altitude of 165 m, the reed area, 981.2 ha is maximum, i.e., the water level of 165 m is the optimal.

Soil sediment samples of 10 layers with a spacing of 10 cm each were collected in different floodplain zones adjacent to Huolin River in the Xianghai Nature Reserve, and contents of total N, total P and organic matters were analyzed. The results showed that contents of total N, total P and organic matters were generally decreasing with the increase of distance from sample locations to the river channel, and contents of the three items were generally higher in the upper soil layer than that in the lower soil layer. The content variations displayed how flooding functions influenced nutrient matter content variations in floodplain soils since the flood inundation frequencies of the sample locations varied. The correlation analysis displayed that there were remarkable relativities between total N, total P and organic matters within definite spatial distance from the Huolin River channel.

以三维锐钛矿TiO 2 微球为上层光散射层材料, 以商业纳米TiO 2 为下层连接材料, 采用刮刀法制备了一种新颖的双层TiO 2 薄膜, 并应用于量子点敏化太阳能电池(QDSSC)。其中, 石墨烯量子点(GQDs)采用滴液法引入, CdS/CdSe量子点采用连续离子层吸附法(SILAR)制备。采用场发射扫描电镜、透射电镜、X射线衍射、紫外-可见漫反射光谱及荧光光谱对样品进行表征。实验还制备了CdS/CdSe量子点敏化及石墨烯量子点/CdS/CdSe共敏化太阳能电池, 并研究了石墨烯量子点及CdS不同敏化周期及对电池性能影响。研究结果表明, 石墨烯量子点及CdS不同敏化周期对薄膜的光学性质、电子传输及载流子复合均有较大影响。优选条件下, TiO 2 /QGDs/CdS(4)/CdSe电池的光电转换效率为1.24%, 光电流密度为9.47 mA/cm 2 , 显著高于TiO 2 /CdS(4)/CdSe电池的这些参数(0.59%与6.22 mA/cm 2 )。这主要是由于TiO2表层吸附石墨烯量子点后增强了电子的传输, 减少了载流子的复合。

采用水热法制备了一维TiO 2 纳米棒阵列、二维TiO 2 纳米片和三维TiO 2 微球。将TiO 2 纳米棒阵列/纳米片-微球双层薄膜应用于染料敏化太阳能电池(DSSC), 研究了TiO 2 纳米片与微球的质量比对电池光电性能的影响。采用场发射扫描电镜、氮气吸附脱附等温线、X射线衍射、紫外-可见漫反射光谱、荧光光谱和电化学阻抗谱对样品进行了表征。研究表明, 纳米片与微球的质量比显著影响膜电极的光学和电学特性, 以及电池的光电性能。含50wt% TiO2纳米片膜电极具有最高的染料吸附量、最强的光吸收、最小的传输电阻和最低的荧光强度。含25wt%、50wt%、75wt%和100wt%纳米片的DSSC的效率分别为1.46%、1.71%、1.26%和1.13%。含50wt% 纳米片的电池具有最优的性能, 这是因为该组分电极具有较好的光吸收特性、较小的载流子复合速率以及较快的电子传输。

Affected by reservoir regulation, the complicated flow conditions and the traditional discharge monitoring means between Three Gorges and Gezhouba Dam are far cry from meeting demands of flood control, flood reporting and hydrological data processing. On the basis of H-ADCP on-line velocity monitoring data given by the CWRC, this paper extracts index-velocity by using wavelet analyzing techniques, handles the relationship of nonlinear mapping between index-velocity and section average velocity by making use of artificial neural network, builds an H-ADCP online discharge calculation model which can calculate the real-time sectional discharge in the Three Gorges-Gezhouba area under complicated flow conditions. The model also ensured timely and accurate hydrological data for flood control, flood reporting and hydrological data processing.

Electrochromism relates to the persistent and reversible variation in optical properties of materials driven by externally applied potentials. The changed optical transmittance in visible region brings about a different color of these materials, which are so-call electrochromic materials. Electrochromic devices (ECDs), in which electrochromic materials serve as the core layers, are composed of multiple layers and are capable of performing electrochromic behaviors. Due to their unique controllable optical properties, ECDs have promising applications in smart windows, information displays, rear-view mirrors, thermal control on the surface of spacecrafts, etc. This dissertation made investigations on the electrochromic properties, particularly cyclic properties, optical memory, electrochromic degradation, etc. of anodically coloring nickel oxide (NiOx) thin films and inorganic all-solid-state ECDs, and explored the feasibility of Al-doped ZnO coatings prepared by atmospheric pressure dielectric barrier discharge (DBD) technique. The PhD work is divided into four sections, and there are three parts included in results and discussion: In the first part, we focused on the revelation of the electrolyte-relevant cyclic properties, crystalline effect, electrochemical process and degradation mechanism of anodically coloring NiOx thin films. Firstly, NiOx thin films were cycled in aqueous and non-aqueous electrolytes, i.e. 1 M potassium hydroxide (KOH) aqueous solution and 1 M lithium perchlorate dissolved in propylene carbonate (LiClO4-PC). The evolution of the lattice structure, surface morphology, chemical composition, optical transmittance modulation, cyclic voltammograms, inserted and extracted charge capacities of NiOx thin films was evaluated as a function of the cycle number. Results showed that, in 1 M LiClO4-PC, NiOx thin films presented a better cyclic durability and a stable optical modulation approximating 41%. Secondly, in order to analyze the crystalline effect on the electrochromic properties of NiOx thin films cycled in the Li+-ion electrolyte, different substrate temperatures were set to control the crystallinity of NiOx thin films. The study presented that the enhanced crystallinity tends to decrease the optical modulation of electrochromic NiOx thin films, and that preferred orientation also was a significant factor determining their electrochromic properties. Thirdly, we proposed a new concept “in-situ electrochromic efficiency” to reveal the electrochemical origin of NiOx thin film cycled in the Li+-ion electrolyte, and to decipher the dependence of degradation on its electrochemical process. Analyses indicated that it was the oxidation of Ni2+ to Ni4+ rather than Ni3+ to Ni4+ that corresponded to the additional peaks in the coloring process, which was more reconcilable with experimental results. Besides, the irreversible reduction reaction of Ni4+ to Ni3+ was proposed to explain the activation procedure of electrochromic behavior of NiOx. The Li+-ion trapping and the variation of band structure were regarded as the major factors leading to the electrochromic degradation of NiOx thin films. The second part was devoted to studying their charge-transfer kinetics, and to improving the optical memory and cyclic properties of inorganic all-solid-state complementary ECDs. The first part paid attention to improve the optical memory of inorganic all-solid-state complementary ECD via incorporating two Ta2O5 buffer layers as electron-blocking layers, and to study its cyclic properties versus cycle number. A new seven-layer complementary ECD-2 (ITO/NiOx/Ta2O5/LiNbO3/Ta2O5/WO3/ITO) was designed and prepared by magnetron sputtering. Another ECD-1 with a typically five-layer structure (ITO/NiOx/LiNbO3/WO3/ITO) was prepared for comparison. The analysis unambiguously revealed the negative effect of electronic leakage on the electrochromic properties of ECD-1 and indicated the excellent electron-blocking capacity of Ta2O5 layers in ECD-2. Besides, we demonstrated the cyclic properties of the ECD-2, including the evolutions of its CV cycles versus cycle number and coloration efficiency. The study on deteriorating response characteristic of ECD-2 with a stable optical modulation brought a further insight into the degradation of ECDs. Then, we studied the potential dependence of dynamic behaviors of inorganic all-solid-state ECDs. The correlations of charge-transfer imbalance, optical modulation, response characteristic, and optical memory with potential were unraveled. The third part involved the preparation of Al-doped ZnO coatings using atmospheric pressure DBD technique. The effects of different synthesis parameters and annealing post-treatment on the chemical composition and physical topography of coatings were studied. The work demonstrated the feasibility of synthesizing Al-doped ZnO coatings with atmospheric pressure DBD technique., L’électrochromisme consiste en une variation permanente et réversible des propriétés optiques des matériaux sous l’effet de l’application de potentiels externes. Les montages électrochromes (ou ECDs), dont le cœur est constitué des matériaux électrochrome, sont composés de multiples couches et sont capables de présenter cette propriété d’électrochromisme. Cette thèse de doctorat a étudié les propriétés électrochromes, telles que la cyclicité, l’effet de mémoire optique, la dégradation électrochrome, etc, de couches anodiques électrochromes constitués de films minces d’oxyde de nickel, et d’ECDs inorganiques entièrement solides. Nous avons aussi étudié la faisabilité de la synthèse de couches de ZnO dopé à l’aluminium par plasma atmosphérique, à l’aide d’une décharge à barrière diélectrique (DBD). Cette thèse est divisée en trois sections :Dans la première partie, nous étudions les comportements cycliques de films minces anodiques d’oxyde de nickel (NiOx), telles que la cristallinité, la dégradation et le processus électrochimique et de leurs relations avec l’électrolyte. Dans une première approche, les films de NiOx ont été étudiés en présence d’électrolytes aqueux et non aqueux. L’évolution de la structure cristalline, de la morphologie de surface, de la composition chimique, de la transmittance optique, des voltammétries cycliques, des capacités de charge entrantes et sortantes des films minces ont été étudiés en fonction du nombre de cycles. Ensuite, nous montrons qu’une plus grande cristallinité tends à décroître la modulation optique de films électrochromes de NiOx, et qu’une orientation préférentielle est un paramètre majeur déterminant leur propriétés électrochrome. Nous montrons également une efficacité électrochromique in situ qui révèle l’origine électrochimique des films minces de NiOx dans l’électrolyte Li+-ion, et nous montrons les dépendances de la dégradation sur les processus électrochimiques. Les analyses montrent que c’est l’oxydation du Ni2+ en Ni4+ plutôt que du Ni3+ en Ni4+ qui correspond aux pics additionnels dans le processus de coloration. De plus, un processus de réduction irréversible du Ni4+ en Ni3+ est proposé pour expliquer la procédure d’activation du comportement électrochrome du NiOx. L’incorporation de l’ion Li+ est considéré comme le facteur majeur de la dégradation électrochrome des films minces de NiOx.La deuxième section est dédié à l’amélioration de l’effet de mémoire optique d’ECDs solides entièrement inorganiques, à l’étude de la cinétique de transfert de charge, et à leurs propriétés cycliques. Nos résultats montrent de manière claire l’effet négatif des fuites électroniques sur les propriétés électrochrome du montage ECD-1 (ITO/NiOx/LiNbO3/WO3/ITO) et montrent une capacité de blocage électronique des couches de Ta2O5 dans ECD-2 (ITO/NiOx/ Ta2O5/LiNbO3/ Ta2O5/WO3/ ITO) remarquable. Nous avons également étudié la détérioration de la réponse caractéristique du montage ECD-2. Enfin nous avons étudié la dépendance dynamique des comportements des différents montages en fonction du potentiel. Des corrélations avec les transferts de charge, la modulation optique, la mémoire optique et la réponse caractéristique ont été établies.La troisième section a consisté à préparer des couches de ZnO et ZnO dopé Al par plasma atmosphérique, en utilisant une décharge à barrière diélectrique. Les effets des différents paramètres de synthèse et de recuit sur la composition chimique et la topographie des couches ont été étudiés. Ce travail a démontré la faisabilité de la synthèse de couches de ZnO dopé Al par une DBD opérant à pression atmosphérique., Doctorat en Sciences, info:eu-repo/semantics/nonPublished