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Vadose Zone Heterogeneity Effect on Unsaturated Water Flow Modeling at Meso-Scale
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作者 Artur Paiva Coutinho Laurent Lassabatere +3 位作者 Thierry Winiarski Jaime Joaquim da Silva Pereira Cabral Antonio Celso Dantas Antonino Rafael Angulo-Jaramillo 《Journal of Water Resource and Protection》 2015年第4期353-368,共16页
The understanding of unsaturated flow in heterogeneous formations is a prerequisite to the understanding of pollutant transfer in the vadose zone and the proper management of infiltration basins settled over such hete... The understanding of unsaturated flow in heterogeneous formations is a prerequisite to the understanding of pollutant transfer in the vadose zone and the proper management of infiltration basins settled over such heterogeneous formations. This study addresses the effect of lithological heterogeneity of a glaciofluvial deposit on flow in the vadose zone underneath an infiltration basin settled in the Lyon suburbs. The basin had already been the subject of several previous studies, some of which demonstrated the impact of soil heterogeneity. But all of them were only based on the sedimentological study of a trench and no study addressed the potential spatial variability of results due to the spatial variability of soil heterogeneity. In this study, we model flow in the vadose zone for several case studies, including drainage, water infiltration during a rainfall event, and a complete meteorological chronic. These calculations were conducted for several sections, previously characterized in the basin using GPR and sedimentological study and compared with a blank (homogeneous section). The results clearly show that heterogeneity impacts unsaturated flow and that these impacts depend upon the section considered. Some geometrical architectural and textural parameters were proposed to explain the spatial variability and effect of the soil heterogeneity on unsaturated flow, thus establishing the first step towards modeling unsaturated flow in the basin at the meso-scale. 展开更多
关键词 ARCHITECTURAL and STRUCTURAL Indicators Ground Penetration Radar Numerical Modeling Preferential FLOW STRUCTURAL HETEROGENEITY UNSATURATED FLOW
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Gene Cloning and Bioinformatics Analysis of phoR Gene from Vibrio alginolyticus HY9901
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作者 Xiangyu LIU Peng ZHOU +4 位作者 Haiyun FENG Weijie ZHANG Huanying PANG Na WANG Xiaonan LU 《Asian Agricultural Research》 2024年第6期36-40,共5页
PhoR is a histidine kinase in a two-component regulatory system that regulates phosphorus metabolic pathways and undertakes the key mission of information transmission in pathogenic bacteria.The full-length phoR gene ... PhoR is a histidine kinase in a two-component regulatory system that regulates phosphorus metabolic pathways and undertakes the key mission of information transmission in pathogenic bacteria.The full-length phoR gene was successfully cloned from the Vibrio alginolyticus HY9901 strain.A comprehensive analysis of the cloned gene was conducted using bioinformatics.Sequence analysis revealed that the total length of the phoR gene(GenBank accession No.:KJ958404.1)is 1299 bp,with the coding region containing a total of 432 amino acid residues.The phylogenetic tree of PhoR revealed that it belongs to the same subclade as V.diabolicus.The SMART program was employed for the purpose of functional domain prediction,which revealed that PhoR possesses three major functional domains:PAS(amino acids 98-166),HisKA(amino acids 205-272),and HATPase_c(amino acids 317-429). 展开更多
关键词 VIBRIO ALGINOLYTICUS phoR GENE GENE CLONING BIOINFORMATICS analysis
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Molecular Cloning of sodB Gene from Vibrio alginolyticus HY9901 and Its Bioinformatics Analysis
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作者 Shuai YANG Yingying JIANG +4 位作者 Haiyun FENG Weijie ZHANG Na WANG Xiaonan LU Huanying PANG 《Asian Agricultural Research》 2024年第7期42-47,共6页
Vibrio alginolyticus is a zoonotic bacterium.A pair of specific primers was designed using the sodB gene sequence of Vibrio alginolyticus HY9901 in order to amplify the full length of the gene by PCR.The results indic... Vibrio alginolyticus is a zoonotic bacterium.A pair of specific primers was designed using the sodB gene sequence of Vibrio alginolyticus HY9901 in order to amplify the full length of the gene by PCR.The results indicated that the total length of the sodB gene was 585 bp and that it could encode 194 amino acids.The predicted amino acid sequence derivation indicated that the molecular weight of the protein was approximately 21.56 kDa,with an isoelectric point of 4.95.Upon prediction of the N-terminal signal peptide structure of the protein,no significant signal peptide cleavage site was observed,indicating that the protein lacked both a signal peptide and a transmembrane region.The amino acid sequence contained an N-glycosylation site,a casein kinase II phosphorylation site,a microsomal C-terminal target signal site,and a manganese and iron superoxide dismutase signal site.The probability of intracytoplasmic localization of the SodB protein was 56.5%,which was analyzed according to the subcellular localization of the protein.The amino acid sequence of the sodB gene of V.alginolyticus exhibited 98%-100%homology to other Vibrio species,clustering into the same subfamily with V.parahaem,indicating a relatively close relationship between them.In the prediction of protein structure,the proportions ofα-helix,random coil,β-sheet,and extended strand were 48.45%,30.41%,5.67%,and 15.46%,respectively.The similarity to template 1dt0.1.A reached 71.58%.A PTM site analysis revealed the presence of phosphorylation,glycosylation,ubiquitination,sumoylation,acetylation,and methylation modification sites,as well as the absence of lactylation modification sites. 展开更多
关键词 Vibrio alginolyticus Gene cloning sodB gene Bioinformatics analysis
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Ketamine,a trauma analgesic with sex-specific immunomodulatory function
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作者 Haley F.Spencer Rina Y.Berman +1 位作者 Martin Boese Kwang H.Choi 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第6期1263-1264,共2页
Ketamine,a multimodal dissociative anesthetic,produces powerful analgesia at subanesthetic doses in traumatically injured patients.As ketamine does not induce respiratory depression or hemodynamic instability,the Comm... Ketamine,a multimodal dissociative anesthetic,produces powerful analgesia at subanesthetic doses in traumatically injured patients.As ketamine does not induce respiratory depression or hemodynamic instability,the Committee on Tactical Combat Casualty Care for the US military recommends the use of subanesthetic doses of ketamine for acute pain management(Butler et al.,2014).Additionally,ketamine may have immunomodulatory effects after injury at subanesthetic doses,mediating the balance of pro-and anti-inflammatory processes(Loix et al.,2011;De Kock et al.,2013). 展开更多
关键词 doses ACUTE
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Recovery prediction of copper oxide ore column leaching by hybrid neural genetic algorithm 被引量:2
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作者 Fatemeh Sadat HOSEINIAN Aliakbar ABDOLLAHZADE +1 位作者 Saeed Soltani MOHAMADI Mohsen HASHEMZADEH 《Transactions of Nonferrous Metals Society of China》 SCIE EI CAS CSCD 2017年第3期686-693,共8页
The artificial neural network(ANN)and hybrid of artificial neural network and genetic algorithm(GANN)were appliedto predict the optimized conditions of column leaching of copper oxide ore with relations of input and o... The artificial neural network(ANN)and hybrid of artificial neural network and genetic algorithm(GANN)were appliedto predict the optimized conditions of column leaching of copper oxide ore with relations of input and output data.The leachingexperiments were performed in three columns with the heights of2,4and6m and in particle size of<25.4and<50.8mm.Theeffects of different operating parameters such as column height,particle size,acid flow rate and leaching time were studied tooptimize the conditions to achieve the maximum recovery of copper using column leaching in pilot scale.It was found that therecovery increased with increasing the acid flow rate and leaching time and decreasing particle size and column height.Theefficiency of GANN and ANN algorithms was compared with each other.The results showed that GANN is more efficient than ANNin predicting copper recovery.The proposed model can be used to predict the Cu recovery with a reasonable error. 展开更多
关键词 LEACHING copper oxide ore RECOVERY artificial neural network genetic algorithm
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Deformation-based support design for highly stressed ground with a focus on rockburst damage mitigation 被引量:3
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作者 P.K.Kaiser A.Moss 《Journal of Rock Mechanics and Geotechnical Engineering》 SCIE CSCD 2022年第1期50-66,共17页
As mines go deeper,mine designs become more fragile and effective rock support becomes a strategic element for ground control to facilitate timely construction and cost-effective access for uninterrupted production.Th... As mines go deeper,mine designs become more fragile and effective rock support becomes a strategic element for ground control to facilitate timely construction and cost-effective access for uninterrupted production.This article focuses on the design of integrated support systems for brittle ground when large displacements due to gradual bulking of stress-fractured rock or sudden violent bulking during rockbursts are induced by static and dynamic loading.It provides an overview of support design principles for a rational approach to ground control in deep mines when large deformations are anticipated near excavations.Such designs must not only account for load equilibrium but also for deformation compatibility.Most importantly,the design approach must account for the fact that the support’s displacement capacity is being consumed as it is deformed after support installation.It is therefore necessary to design for the remnant support capacity,i.e.the capacity remaining when the support is needed.Furthermore,if the support capacity can be consumed,it can also be restored by means of preventive support maintenance(PSM).The PSM concept for cost-effective ground control is introduced and illustrated by quantitative and operational evidence.Contrary to other design approaches,the deformation-based support design(DBSD)approach provides the capacity of an integrated support system as a function of imposed displacements.Reduction in this support capacity due to mininginduced deformation renders excavations increasingly more vulnerable if located within the influence of active mining and seismic activity.Because deformation measurements are robust indicators of the decay in support capacity,scanning and other displacement monitoring technologies enable measurements to verify the DBSD approach,to assess the remnant safety margin of the deformed support,and to make operational support maintenance decisions. 展开更多
关键词 Deep mining Deformation-based support design(DBSD) Cost-effective support Support consumption Preventive support maintenance(PSM)
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Nodule Formation and Development in Soybeans(Glycine max L.) in Response to Phosphorus Supply in Solution Culture 被引量:5
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作者 MIAO Shu-Jie QIAO Yun-Fa +1 位作者 HAN Xiao-Zeng M. AN 《Pedosphere》 SCIE CAS CSCD 2007年第1期36-43,共8页
Phosphorus (P) is necessary for growth and nitrogen fixation, and thus its deficiency is a major factor limiting legume production in most agricultural soils. The effect of phosphorus supply on nodule development and ... Phosphorus (P) is necessary for growth and nitrogen fixation, and thus its deficiency is a major factor limiting legume production in most agricultural soils. The effect of phosphorus supply on nodule development and its role in soybeans (Glycine max L.) was studied in a nutrient solution. Plants were inoculated with Bradyrhizobium japonicum and grown for 35 days in a glasshouse at a day and night temperature of 25℃and 15℃, respectively. Although increasing P supply increased the concentrations of P and N in the shoots and roots, the external P supply did not significantly affect the P concentration in the nodules, and the N fixed per unit nodule biomass decreased with increasing P supply. The nitrogen content in the shoots correlated well with the P content (r = 0.92**). At an inoculation level of 102 cells mL-1, the P supply did not affect the number of nodules; however, at inoculation levels of 103.5 and 105 cells mL-1, increasing P supply increased both the number and size of nodules. Irrespective of the inoculation level, increasing P supply increased the nodule biomass relative to the biomass of the host plant. It is suggested that the P deficiency specifically inhibited the nodule development and thereby the total N2 fixation. 展开更多
关键词 inoculation level nitrogen fixation NODULATION PHOSPHORUS SOYBEANS
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An operational approach to ground control in deep mines 被引量:1
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作者 A.Moss P.K.Kaiser 《Journal of Rock Mechanics and Geotechnical Engineering》 SCIE CSCD 2022年第1期67-81,共15页
As mines go deeper and get larger,mine designs become more fragile largely due to the response of the rock mass to mining.Ground control and rock support become important levers in the mine construction schedule,produ... As mines go deeper and get larger,mine designs become more fragile largely due to the response of the rock mass to mining.Ground control and rock support become important levers in the mine construction schedule,production performance,and excavation health.For example,in cave mines,the production footprint together with associated mine infrastructure are significant investments in a modern caving operation.This investment must be protected and maintained to reduce the risk of ground-related production disruptions.It is necessary to preserve the health of these excavations and their maintenance through an effective rock support design.Rock support thus becomes a strategic element in asset management.This article focuses on support design for brittle ground when displacements induced by stress-fracturing consume much of the support’s capacity.It deals with the functionality of the support in deforming ground.Several interlinked concepts are important when assessing excavation health.Designs must not only account for load equilibrium but also for deformation compatibility and capacity consumption.Most importantly,the support’s displacement capacity is being consumed when the rock mass is deformed after support installation.Hence,it is necessary to design for the support capacity remaining at the time when the support is needed.If support capacity can be consumed,it can also be restored by means of preventive support maintenance(PSM).This concept for cost-effective ground control is introduced and illustrated on operational evidence.Furthermore,how design can impact construction costs and schedule are discussed.Support is installed to provide a safe environment and preserve an operationally functional excavation.It also must assure senior management that investments in high quality support and its maintenance will substantially reduce delays and with it,costs.It is demonstrated that the use of‘gabion-like’support systems can achieve these goals.A technical summary of the‘gabion panel’support system design is presented. 展开更多
关键词 Ground control Rock support Deformation-based support design(DBSD) Gabion panel Deep mining Support consumption Preventive support maintenance(PSM) Asset management
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E+H中文网站全新改版
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《石油化工自动化》 CAS 2009年第1期74-74,共1页
关键词 中文网站 改版 行业应用 网络结构 友好性 大用户 关联性 新网站
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E+H闪耀中国国际环保展
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《石油化工自动化》 CAS 2008年第4期92-92,共1页
2008年6月26-28日,2008中国国际环境保扩展览会于大连星海会展中心隆重举行。E+H中国销售中心与E+H德国分析产品生产中心一起携分析产品首次参展这一行业盛会。
关键词 国际环境 中国 环保 会展中心 生产中心 销售中心 展览会 产品
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美不胜收——E+H闪耀Miconex 2008
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《石油化工自动化》 CAS 2008年第6期31-31,共1页
关键词 Business 国际展览中心 过程自动化 仪器仪表 企业形象 展台设计 品牌理念 CARD
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E+H新型小量程固体雷达
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《石油化工自动化》 CAS 2008年第6期13-13,共1页
关键词 固体料位 雷达技术 小量程 非接触式 工业领域
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The principles and guidelines for designing long-term agronomic experiments
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作者 Mark Conyers 《Research in Cold and Arid Regions》 2009年第1期91-97,共7页
Many of the important questions facing farming systems in the world today require long-term studies to provide meaningful information and answers. A long-term agronomic experiment (LTAE) should (1) have long-term obje... Many of the important questions facing farming systems in the world today require long-term studies to provide meaningful information and answers. A long-term agronomic experiment (LTAE) should (1) have long-term objectives; (2) study important soil processes or ecological processes; and (3) be related to the productivity and sustainability of systems. A well established LTAE can provide both insights into how the system operates and foresight into where the system goes. The prerequisites for setting up a LTAE are the secured land, continuous funding and dedicated scientists. A number of principles must be considered carefully when establishing a LTAE, (1) the site must be representative of large areas; (2) the treatments should be simple, but focusing on the big questions; (3) the plots should be large enough to allow subsequent modification of the experiment if this becomes necessary; (4) crop rotations should minimise, wherever possible, the risk of build-up of pests and diseases, and rotational phase should be considered in a rotational experiment; (5) a clearly defined experimental protocol should be developed to ensure data collected is scientifically valid and statistically analysable, but with flexibility to allow essential changes; (6) soil samples, possibly plant samples, should be achieved to provide better answer to the original questions when new, perhaps more accurate analytical techniques are developed, or answer new research questions that were not considered in the original design. The MASTER experiment in Australia was used as a case study to demonstrate how these principles are implemented in practice. 展开更多
关键词 long-term experiment SUSTAINABILITY crop rotation soil processing
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Memosens型数字式pH传感器
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《传感器世界》 2005年第9期44-44,共1页
该产品拥有一个自检传感器连接,集成电极,感应信号可从传感器转移到变送器。这种传感器拥有一个真正电隔离的pH检测点,信号从接合电缆到对潮湿和污染物不敏感的传感器的外插头上:集成电极可以使用户保存校正数据,工作时间,最小和... 该产品拥有一个自检传感器连接,集成电极,感应信号可从传感器转移到变送器。这种传感器拥有一个真正电隔离的pH检测点,信号从接合电缆到对潮湿和污染物不敏感的传感器的外插头上:集成电极可以使用户保存校正数据,工作时间,最小和最大的pH值,最小和最大的温度值。此外,当传感器被安装的时候, 展开更多
关键词 PH传感器 数字式 s型 工作时间 变送器 检测点 电隔离 污染物 pH值 温度值
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E+H新春送大礼
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《石油化工自动化》 CAS 2006年第1期106-106,共1页
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Modelling Agronomically-Suitable Sowing Date in Relation to the Risk of Frost Damage and Heat Stress of Wheat in Southern New South Wales, Australia
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作者 D. L. Liu P. Martin +3 位作者 C. Cole H. Wu E. Wang A. M. Bowman 《Journal of Agricultural Science and Technology》 2010年第4期26-36,共11页
Sowing time of wheat in south eastern Australia varies from autumn to early winter, depending on the seasonal 'break'. Wheat yields are often reduced by frost damage at flowering time and by heat-and/or water-stress... Sowing time of wheat in south eastern Australia varies from autumn to early winter, depending on the seasonal 'break'. Wheat yields are often reduced by frost damage at flowering time and by heat-and/or water-stress during grain filling. Selecting suitable varieties for specific sowing times is a complex decision farmers make because these varietal phenology and climate risks have to be assessed together. In order to help farmers make decisions, they need tools that simulate and analyse agronomically-suitable sowing dates (ASSD) for a given variety of wheat. The hypothesis underlining this study is the integration of a wheat phenology model with historical climate data is an effective approach to modelling the ASSD of current varieties used in the wheat growing areas of Southern NSW. The parameters of the wheat phenology model were based on data from five years of field experimentation across 15 sites. Data from four sites were used to examine varietal suitability in relation to sowing time and its associated risks of frost and heat damage. The optimum ASSD for any variety at 72 locations across Southern NSW was investigated. The results showed that there were substantial spatial variations in the ASSD across the target region. ASSD for a late maturing wheat genotype (EGA Gregory) can range from early March to late April, while the earliest acceptable sowing date for an early maturing spring wheat genotype (H46) can range from early to late May. The wide range of spatial variation in the earliest and latest sowing dates, as well as the varied length of sowing opportunities, highlighted the importance of being able to apply a modelling approach which can integrate information on crop phenology with climate risk for a given location. This approach would allow better decision-making on suitable varieties and sowing dates in order to minimise the risk of frost and heat damage affecting crop yield. 展开更多
关键词 Crop phenology climate risk DECISION-MAKING spatial variation break of season sowing opportunities
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3-(Tetrazol-5-yl)-2-imino-coumarins Derivatives: Synthesis, Characterization, and Evaluation on Tumor Cell Lines
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作者 Ali Bouattour Mehdi Fakhfakh +6 位作者 Souhir Abid El-Gharbi Majdi Abid Ludovic Paquin Rémy Le Guevel Thierry Charlier Houcine Ammar Jean-Pierre Bazureau 《International Journal of Organic Chemistry》 CAS 2021年第1期24-34,共11页
The first report of new 3-(tetrazol-5-yl)-2-iminocoumarin derivatives is described. The title compounds were prepared in two steps and were obtained in good yields (55-93%). They have been fully characterized by <s... The first report of new 3-(tetrazol-5-yl)-2-iminocoumarin derivatives is described. The title compounds were prepared in two steps and were obtained in good yields (55-93%). They have been fully characterized by <sup>1</sup>H, <sup>13</sup>C NMR, FTIR, UV-Visible and HRMS. They were tested for their antiproliferative activities against six representative human tumor cell lines (Huh 7-D12, Caco2, MDA-MB231, HCT 116, PC3 and NCI-H727) and HaCat keratinocytes. Among them, compound 5e was active on HCT 116 (IC<sub>50</sub> 15 μM). 展开更多
关键词 2-Iminocoumarin TETRAZOLE Fluorescence Tumor Cell Lines HCT 116
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Synthesis of New 2-Phenylamino-4<i>H</i>-chromene-3-carbonitrile Derivatives and Their Effects on Tumor Cell Lines and against Protein Kinases
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作者 Ali Bouattour Mehdi Fakhfakh +7 位作者 Souhir Abid Ludovic Paquin Rémy Le Guével Thierry Charlier Sandrine Ruchaud Stéphane Bach Jean-Pierre Bazureau Houcine Ammar 《International Journal of Organic Chemistry》 2020年第2期88-103,共16页
The synthesis of 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6(a-d)</strong> in good overall yields using an efficient and practical methodology in 3 steps has been implemented i... The synthesis of 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6(a-d)</strong> in good overall yields using an efficient and practical methodology in 3 steps has been implemented in this present work. The first step was a heterocyclization between 2-hydroxybenzaldehyde <strong>1</strong> and propanedinitrile <strong>2</strong> which produced 2-iminocoumarin <strong>3</strong> which was submitted to nitrogen/nitrogen displacement in the presence of aromatic primary amine <strong>4</strong>. In the third step, reduction of <strong>5</strong> led to the desired 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6</strong>. Compounds <strong>5(a-d)</strong> and <strong>6(a-d)</strong> were evaluated for their potential <em>in vitro</em> cytotoxicity against six selected tumor cell lines (Huh7-D12, Caco2, MDA-MB231, HCT 116, PC3 and NCI-H727) and tested for their protein kinase inhibition on eight selected protein kinases. Among them, compounds <strong>5c</strong> and <strong>6b</strong> exhibited inhibition on HsCK1e (<strong>5c</strong>: 44% and <strong>6b</strong>: 42% at 1 μM) and <strong>5c </strong>for cytotoxicity on PC3 cell lines (63% at 25 μM). 展开更多
关键词 Iminocoumarin benzopyran benzopyran 4H-chromene 2-Amino-4H-chromene Nitrogen/Nitrogen Displacement Protein Kinase Inhibition Cytotoxicity
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喷油策略耦合EGR对柴油机燃烧过程与CDPF再生性能的影响 被引量:2
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作者 陈贵升 王凯 +3 位作者 杨杰 张韦 徐劲松 雒婧 《内燃机工程》 EI CAS CSCD 北大核心 2017年第3期131-141,共11页
以匹配了可变截面几何增压系统(VGT)的D19高压共轨柴油机为研究机型,采用GT-Power和AVL FIRE构建了一维热力学整机模型和催化型微粒捕集器(CDPF)三维仿真模型,针对3 000r/min、50%负荷工况,研究了喷油策略耦合废气再循环(EGR)对燃烧过程... 以匹配了可变截面几何增压系统(VGT)的D19高压共轨柴油机为研究机型,采用GT-Power和AVL FIRE构建了一维热力学整机模型和催化型微粒捕集器(CDPF)三维仿真模型,针对3 000r/min、50%负荷工况,研究了喷油策略耦合废气再循环(EGR)对燃烧过程和CDPF再生性能的影响。研究表明:随主喷定时提前,有效燃油消耗率(BSFC)先降后升,排气温度降低,排气流量与氧浓度变化则较小,排气中一氧化氮(NO)增加,CDPF再生速率逐渐降低,颗粒物残余量、压降与CDPF出口端二氧化氮(NO_2)同时增加;随EGR率增大,BSFC和排气温度升高,排气流量、排气氧浓度、排气中NO浓度则同时降低。在主喷定时较晚时,随EGR率增大,CDPF再生速率先升后降,颗粒物残余量先降低后略升高;而在主喷定时较早时,随EGR率的增大,CDPF再生速率降低,颗粒物残余量增多。在主喷定时较晚时,提高喷油压力使BSFC和排气温度明显降低;而在主喷定时较早时,提高喷油压力导致BSFC反而快速增加。此外,随喷油压力提高,排气流量与氧浓度变化较小,排气中NO浓度增加,CDPF再生速率逐渐减小,颗粒物残余量、压降和CDPF出口端NO_2排放同时升高。总体上,相比喷油压力,主喷定时对CDPF再生过程影响更大。 展开更多
关键词 共轨柴油机 喷油策略 废气再循环 催化型微粒捕集器 再生性能
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The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy 被引量:1
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作者 Md Rakibul Alam Md Mizanur Rahman Zhiguo Li 《Genes & Diseases》 SCIE CSCD 2024年第1期321-334,共14页
Exosomes are small membrane vesicles containing microRNA,RNA,DNA fragments,and proteins that are transferred from donor cells to recipient cells.Tumor cells release exo-somes to reprogram the factors associated with t... Exosomes are small membrane vesicles containing microRNA,RNA,DNA fragments,and proteins that are transferred from donor cells to recipient cells.Tumor cells release exo-somes to reprogram the factors associated with the tumor microenvironment(TME)causing tu-mor metastasis and immune escape.Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1(PD-L1)that binds with re-ceptor program death protein 1(PD-1)and promote tumor progression by escaping immune response.Currently,some FDA-approved monoclonal antibodies are clinicallyused for cancer treatment by blocking PD-1/PD-L1 interaction.Despite notable treatment outcomes,some pa-tients show poor drug response.Exosomal PD-L1 plays a vital role in lowering the treatment response,showing resistance to PD-1/PD-L1 blockage therapy through recapitulating the ef-fect of cell surface PD-L1.To enhance therapeutic response,inhibition of exosomal PD-L1 is required.Calcium signaling is the central regulator of tumorigenesis and can regulate exosome biogenesis and secretion by modulating Rab GTPase family and membrane fusion factors.Im-mune checkpoints are also connected with calcium signaling and calcium channel blockers like amlodipine,nifedipine,lercanidipine,diltiazem,and verapamil were also reported to suppress cellular PD-L1 expression.Therefore,to enhance the PD-1/PD-L1 blockage therapy response,the reduction of exosomal PD-L1 secretion from cancer cells is in our therapeutic consider-ation.In this review,we proposed a therapeutic strategy by targeting calcium signaling to inhibit the expression of PD-L1-containing exosome levels that could reduce the anti-PD-1/PD-L1 therapy resistance and increase the patient's drug response rate. 展开更多
关键词 Calcium signaling CD8^(+)T cells Exosomal PD-L1 Exosomes biogenesis IMMUNOSUPPRESSION IMMUNOTHERAPY
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