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Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
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Jun Dong Cho Luis Cavazos Quero Jorge Iranzo Bartolom Do Won Lee Uran Oh Inae Lee 《Color research and application》2021,46(1):103-116
A recent development in tactile technology enables an improvement in the appreciation of the visual arts for people with visual impairment (PVI). The tactile sense, in conjunction with, or a possibly as an alternative to, the auditory sense, would allow PVIs to approach artwork in a more self‐driven and engaging way that would be difficult to achieve with just an auditory stimulus. Tactile colour pictograms (TCPs), which are raised geometric patterns, are ideographic characters that are designed to enable PVIs to identify colours and interpret information by touch. In this article, three TCPs are introduced to code colours in the Munsell colour system. Each colour pattern consists of a basic cell size of 10 mm × 10 mm to represent the patterns consistently in terms of regular shape. Each TCP consists of basic geometric patterns that are combined to create primary, secondary, and tertiary colour pictograms of shapes indicating colour hue, intensity and lightness. Each TCP represents 29 colours including six hues; they were then further expanded to represent 53 colours. Two of them did not increase the cell size, the other increased the cell size 1.5 times for some colours, such as yellow‐orange, yellow, blue, and blue‐purple. Our proposed TCPs use a slightly larger cell size compared to most tactile patterns currently used to indicate colour, but code for more colours. With user experience and identification tests, conducted with 23 visually impaired adults, the effectiveness of the TCPs suggests that they were helpful for the participants. 相似文献
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为解决共享交通下的共乘用户群体发现效率低、准确率不高问题,依据R-树原理建立GeoOD-Tree索引,并在此基础上提出以最大化共乘率为目标的群体发现策略。首先,对原始时空轨迹数据进行特征提取与标定处理,挖掘有效出行起讫点(OD)轨迹;其次,针对用户起讫点轨迹的特征,建立GeoOD-Tree索引进行有效的存储管理;最后,给出以最大化共乘行程为目标的群体发现模型,并运用K最近邻(KNN)查询对搜索空间剪枝压缩,提高群体发现效率。采用西安市近12000辆出租车营运轨迹数据,选取动态时间规整(DTW)等典型算法与所提算法在查询效率与准确率上进行性能对比分析。与DTW算法相比,所提算法的准确率提高了10.12%,查询效率提高了约15倍。实验结果表明提出的群体发现策略能有效提高共乘用户群体发现的准确率和效率,可有效提升共乘出行方式的出行率。 相似文献
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Sama Rezasoltani Reza Ghanbari Mehdi Azizmohammad Looha Ehsan Nazemalhosseini Mojarad Abbas Yadegar Delisha Stewart Hamid Asadzadeh Aghdaei Mohammad Reza Zali 《International journal of molecular sciences》2020,21(23)
Abnormal activation of Toll-like receptor (TLRs) signaling can result in colon cancer development. The aim of this study was to investigate the expression of important TLRs in different histological types of colorectal polyps and evaluate their relationship with intestinal microbiota. The expression levels of TLR2, 3, 4, and 5 were analyzed in intestinal biopsy specimens of 21 hyperplastic polyp (HP), 16 sessile serrated adenoma (SSA), 29 tubular adenoma (TA), 21 villous/tubulovillous (VP/TVP) cases, and 31 normal controls. In addition, selected gut bacteria including Streptococcus bovis, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. were quantified in fecal samples using absolute qRT PCR, and, finally, the association between TLRs and these gut microbiota- was evaluated by Spearman’s correlation coefficient. Higher expression of TLR2 and TLR4 in VP/TVP and TA, and lower expression levels of TLR3 and TLR5 in all type of polyps were observed. The differences in TLR expression patterns was not only dependent on the histology, location, size, and dysplasia grade of polyps but also related to the intestinal microbiota patterns. TLR2 and TLR4 expression was directly associated with the F. nucleatum, E. faecalis, S. bovis, Porphyromonas, and inversely to Bifidobacterium, Lactobacillus, and Roseburia quantity. Furthermore, TLR3 and TLR5 expression was directly associated with Bifidobacterium, Roseburia, and Lactobacillus quantity. Our results suggest a possible critical role of TLRs during colorectal polyp progression. An abnormal regulation of TLRs in relation to gut microbial quantity may contribute to carcinogenesis. 相似文献
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Ivonne Sgura Amos S. Lawless Benedetto Bozzini 《Inverse Problems in Science & Engineering》2019,27(5):618-647
The process of electrodeposition can be described in terms of a reaction-diffusion partial differential equation (PDE) system that models the dynamics of the morphology profile and the chemical composition. Here we fit such a model to the different patterns present in a range of electrodeposited and electrochemically modified alloys using PDE constrained optimization. Experiments with simulated data show how the parameter space of the model can be divided into zones corresponding to the different physical patterns by examining the structure of an appropriate cost function. We then use real data to demonstrate how numerical optimization of the cost function can allow the model to fit the rich variety of patterns arising in experiments. The computational technique developed provides a potential tool for tuning experimental parameters to produce desired patterns. 相似文献
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《材料科学技术学报》2019,35(7):1309-1314
Degenerate pattern is a seemingly disordered morphology but it exhibits the inherently ordered crystal connected with tip-splitting and limited stability which makes it difficult to observe in the metallic system. Here we employ (100)[011] orientated planar-front seeds using directional solidification and reveal the fundamental origins of the degenerate pattern growth in an Al-4.5 wt% Cu alloy. We find that the spacing of the tip-splitting (λ) in the degenerate of the alloys followed a power law, λ∝V−0.5, and the frequency (f) of the splitting was related to the growth velocity (V) by ƒ∝V1.5. The dimensionless growth direction (θ/θ0) increased monotonously and approached 0.6 with faster velocity, attributed to its anisotropy in the interface kinetics. Once growth velocity exceeded a threshold, two types of pattern transitions from degenerate to regular dendrites were proposed. One of them exhibited a random and chaotic mode and the other underwent a rotation in growth direction. 相似文献
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The simultaneous flow of gas, oil, and water forms various flow patterns due to the complex interfacial relationships. Three-phase flow patterns are classified as the gas-liquid and liquid-liquid flow patterns. Pressure drop, void fraction, liquid holdup, and phase distribution are important characteristics of the three-phase flow. These characteristics are generally associated with the three-phase flow patterns. Hence, the knowledge about flow patterns can help to predict the overall behavior of the three-phase flow. Studies have been conducted to identify three-phase flow pattern and their characteristics at various superficial velocities of gas, oil, and water. The major purpose of the studies is to gather information about the three-phase co-current flow and use it for improvement of the efficiency of the flow systems. Therefore, the accuracy of the measurement technique is critical. Several types of flow pattern identification and measurement techniques have been developed to improve accuracy and provide high-quality results. In this article, classical and advanced techniques used for the three-phase flow identification and measurement have been reviewed. The survey will help the researchers working in the area of multiphase flow to choose the right technique based on the objectives of the studies. 相似文献
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