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Synthesis of reversible PAD4 inhibitors via copper-catalyzed C-H arylation of benzimidazole

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Science China Chemistry 2019年第5期62卷 592-596页

作者： Zhengwei Guo lai shi Bo Wang Gang He Yanming Wang Gong Chen State Key Laboratory and Institute of Elemento-Organic Chemistry College of ChemistryNankai University School of Life Sciences Henan University Department of Biochemistry and Molecular Biology The Pennsylvania State University

PAD4 is a promising epigenetic drug target for various cancers and immune diseases. In this work, we applied a Cu-catalyzed C–H arylation reaction of N-heteroarene to the synthesis of complex non-covalent PAD4 inhibitors bearing a bi-heteroaryl pharmacophore. This strategy allowed us to access various analogs of C_2-aryl substituted benzimidazoles from a common benzimidazole core and easily accessible aryl iodides. Preliminary SAR studies revealed the indole motif of GSK-484 is critical to its activity. Replacing the N-cyclopropylmethyl group to N-benzyl group on the indole ring of GSK-484 resulted in more than5-fold increase in cell killing efficacy against 4T1 cell line.

关键词： C–H arylation benzimidazoles PAD4 inhibitor copper catalysis

Boron removal from metallurgical grade silicon by slag refining based on GA-BP neural network

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Rare Metals 2021年第1期40卷 237-242页

作者： shi-lai Yuan Hui-Min Lu Pan-Pan Wang Chen-Guang Tian Zhi-Jiang Gao School of Materials Science and Engineering.Beijing University of Aeronautics and Astronautics Beijing 100191China

In order to investigate the boron removal effect in slag refining process,intermediate frequency furnace was used to purify boron in SiO2-CaO-Na3 AlF6-CaSiO3 slag system at 1,550℃,and back propagation(BP)neural network was used to model the relationship between slag compositions and boron content in SiO2-CaO-Na3 AlF6-CaSiO3 slag *** BP neural network predicted error is below 2.38%.The prediction results show that the slag composition has a significant influence on boron *** the basicity of slag by adding CaO or Na3 AlF6 to CaSiO3-based slag could contribute to the boron removal,and the addition of Na3 AlF6 has a better removal effect in comparison with the addition of *** oxidizing characteristic of CaSiO3 results in the ineffective removal with the addition of *** increase of oxygen potential(pO2)in the CaO-Na3 AlF6-CaSiO3 slag system by varying the SiO2 proportion can also contribute to the boron removal in silicon *** best slag composition to remove boron was predicted by BP neural network using genetic algorithm(GA).The predicted results show that the mass fraction of boron in silicon reduces from 14.0000×10-6 to0.4366×10-6 after slag melting using 23.12%SiO2-10.44%CaO-16.83%Na3 AlF6-49.61%CaSiO3 slag system,close to the experimental boron content in silicon which is below 0.5×10-6.

关键词： Metallurgical grade silicon Boron removal Slag system Genetic algorithm-back propagation neural network

Spatial distribution model of the filling and diffusion pressure of synchronous grouting in a quasi-rectangular shield and its experimental verification

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Underground Space 2021年第6期6卷 650-664页

作者： Jun Liu Peinan Li lai shi Jie Fan Xiaoyong Kou Dezhong Huang College of Urban Railway Transportation Shanghai University of Engineering ScienceShanghai 201620China College of Environmental Science and Engineering Donghua UniversityShanghai 201620China China Railway Siyuan Survey and Design Group Co. LtdWuhanHubei 430063China Shanghai Tunnel Engineering Co. LtdShanghai 200032China

Considering that the particular geometric shape of a quasi-rectangular shield,the grout flowing law and its motion process are more complicated than those of a conventional circular *** interpret the grouting mechanical ehaviour in the special-shape shield tail void,the filling and diffusion mechanism of synchronous grouting was *** grout flowing is separated into two independent motion processes,which contains a circumferential filling and a longitudinal *** theoretical model of the grout pressure spatial distribution was derived based on the principle of fluid ***,the pressure distributions in the two directions were obtained using a case study and compared with the field measured data to verify the validation of the *** the overall spatial pattern of grout pressure distribution on the tunnel profile show a change trend dominated by the self-weight effect mostly,its local fluctuation characteristics is very abnormal relative to that of a circular shield ***,the important factors in the model were analysed,including the grout material parameters,the grouting construction parameters,and some geometry *** results show that the pressure loss along this way is positively correlated with the grout flow velocity and is sensitive to the shear yield stress of the *** pressure loss along the circumferential direction is the most sensitive to the thickness of the ring cake,and the value range suitable for the model should be 0.02-0.03 *** pressure loss along the longitudinal diffusion direction is the most sensitive to the size of the tail *** research results can provide a theoretical basis for the control of special-shape shield construction.

关键词： Tunnel engineering Quasi-rectangular shield Synchronous grouting Filling and diffusion Pressure spatial distribution model Experimental verification

Experimental and numerical simulation study on the erosion behavior of the elbow of gathering pipeline in shale gas field

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Petroleum Science 2024年第2期21卷 1257-1274页

作者： En-Bin Liu Shen Huang Ding-Chao Tian lai-Min shi Shan-Bi Peng He Zheng Petroleum Engineering School Southwest Petroleum UniversityChengdu 610500SichuanChina Chongqing Natural Gas Sales Center Natural Gas BranchSinopecChongqing400023China Zhejiang Zheneng Natural Gas Operation Co. Ltd.Hangzhou 310000ZhejiangChina School of Civil Engineering and Architecture Southwest Petroleum UniversityChengdu 610500SichuanChina Louisiana Tech Univ Trenchless Technol Ctr599 Dan Reneau DrRustonLA71270USA Southwest Oil and Gas Field Branch Natural Gas Research Institute Chengdu 610213SichuanChina

During the production period of shale gas, proppant particles and rock debris are produced together,which will seriously erode the elbows of gathering pipelines. In response to this problem, this paper takes the elbow of the gathering pipeline in the Changning Shale Gas Field as an example to test the erosion rate and material removal mechanism of the test piece at different angles of the elbow through experiments and compares the four erosion models with the experimental results. Through analysis, it is found that the best prediction model for quartz sand-carbon steel erosion is the Oka model. Based on the Oka model, FLUENT software was used to simulate and analyze the law of erosion of the elbow of the gas gathering pipeline under different gas flow velocities, gas gathering pressure, particle size, length of L1,and bending directions of the elbow. And a spiral pipeline structure is proposed to reduce the erosion rate of the elbow under the same working conditions. The results show that this structure can reduce erosion by 34%.

关键词： Shale gas Gas gathering pipeline Elbow Erosion CFD

The Sterile 20-Like Kinase Tao Controls Tissue Homeostasis by Regulating the Hippo Pathway in Drosophila Adult Midgut

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Journal of Genetics and Genomics 2014年第8期41卷 429-438页

作者： Xudong Huang lai shi Jun Cao Fangfei He Renling Li Yan Zhang Shuang Miao Longjin Jin Jia Qu Zhouhua Li Xinhua Lin School of Optometry and Ophthalmology and Eye Hospital Wenzhou Medical University State Key Laboratory of Biomembrane and Membrane Biotechnology Institute of ZoologyChinese Academy of Sciences School of Laboratory Medicine and Life Science Wenzhou Medical University School of Life Sciences Capital Normal University Division of Developmental Biology Cincinnati Children’s Hospital Medical Center

The proliferation and differentiation of adult stem cells must be tightly controlled in order to maintain resident tissue homeostasis. Dysfunction of stem cells is implicated in many human diseases, including cancer. However, the regulation of stem cell proliferation and differentiation is not fully understood. Here we show that the sterile-like 20 kinase, Tao, controls tissue homeostasis by regulating the Hippo pathway in the Drosophila adult midgut. Depletion of Tao in the progenitors leads to rapid intestinal stem cell （ISC） proliferation and midgut homeostasis loss. Meanwhile, we find that the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling activity and cytokine production are significantly increased, resulting in stimulated ISC proliferation. Furthermore, expression of the Hippo pathway downstream targets, Diapl and bantam, is dramatically increased in Tao knockdown intestines. Consistently, we show that the Yorkie （Yki） acts downstream of Tao to regulate ISC proliferation. Together, our results provide insights into our understanding of the mechanisms of stem cell proliferation and tissue homeostasis control.

关键词： Stem cell Midgut Drosophila Tissue homeostasis Tao Hippo

等离子体改性聚合物表面动力学的动态接触角法研究

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化学学报 1999年第11期57卷 1193-1198页

作者：施来顺山东工业大学化工系济南250061

不同聚合物经CF_4/CH_4等离子体处理后,在浸水过程中表面动力学衰减常数对温度通过Arrhenius关系作图,对于所研究的聚合物都有一个明显的转折点.转折点处的温度称作表面构型转变温度(T_s),大约为15℃,与表面邻近水的Drost-Hansen温度一... 详细信息

不同聚合物经CF_4/CH_4等离子体处理后,在浸水过程中表面动力学衰减常数对温度通过Arrhenius关系作图,对于所研究的聚合物都有一个明显的转折点.转折点处的温度称作表面构型转变温度(T_s),大约为15℃,与表面邻近水的Drost-Hansen温度一致.T_s以上及以下的活化能数值较小,说明表面构型变化的本质可看作是由于基团的翻转运动,而不需要整个大分子或链段的迁移运动.在浸水过程中,接触角滞后Δθ在表面构型转变温度T_s附近有转变,并有极小值,此后随着温度的升高出现极大值,继续升高温度接触角滞后Δθ又反而下降.

关键词：表面改性等离子体聚合物甲烷四氟化碳改性

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中医药临床疗效评价因果关联推断的探讨

中国中西医结合杂志 2005年第4期25卷 293-296页

作者：赖世隆广州中医药大学DME中心广州510405

简要介绍科学研究和临床医学研究中因果关联推断的一般准则,指出群体研究方法在临床研究因果关联推断中的重要作用,同时回顾了随机对照试验方法的发展历程,论述了随机对照试验的基本要求。作者认同国际上普遍接受的观点:较其它类型的研... 详细信息

简要介绍科学研究和临床医学研究中因果关联推断的一般准则,指出群体研究方法在临床研究因果关联推断中的重要作用,同时回顾了随机对照试验方法的发展历程,论述了随机对照试验的基本要求。作者认同国际上普遍接受的观点:较其它类型的研究设计,随机对照试验对推断干预措施与效应的因果关联,其真实性最强。作者强调中医药干预措施的有效性评价必须遵从因果关联推断的通用科学准则和方法。随机对照试验不仅适用于对西医药的疗效评价,对中医药临床疗效评价也具有同样的价值。

关键词：临床疗效评价因果关联中医药推断随机对照试验方法临床医学研究干预措施有效性评价科学研究临床研究群体研究研究设计真实性西医药作者

中医药临床疗效评价因果关联推断的探讨(续)

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中国中西医结合杂志 2005年第5期25卷 389-391页

作者：赖世隆广州中医药大学DME中心临床流行病学应用研究室广州510405

3 随机对照试验在干预和结局之间因果关联推断的价值　随机对照试验(randomized controlled trial, RCT)是随机对照临床试验的简称.它是指按照严格的随机方法分配合格的受试者至试验组和对照组,同期观察试验性干预措施和对照措施分别作... 详细信息

3 随机对照试验在干预和结局之间因果关联推断的价值　随机对照试验(randomized controlled trial, RCT)是随机对照临床试验的简称.它是指按照严格的随机方法分配合格的受试者至试验组和对照组,同期观察试验性干预措施和对照措施分别作用在不同组别受试者身上所产生的效应(临床结局),进而比较组间效应的异同,并对试验性干预措施与临床结局之间进行因果关联推断的前瞻性、试验性研究.……

关键词：因果关联临床疗效评价推断中医药随机对照临床试验随机对照试验临床结局干预措施试验性研究随机方法受试者对照组前瞻性效应

Ca(NO3)2 canopy spraying during physiological fruit drop period has a better influence on the tree character and fruit quality of Newhall navel orange(Citrus sinensis Osbeck)

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Journal of Integrative Agriculture 2017年第7期16卷 1513-1519页

作者： ZHENG Yong-qiang YANG Qiong JIA Xue-mei LIU Yan-mei HE Shao-lan DENG Lie XIE Rang-jin YI shi-lai Lu Qiang National Engineering Research Center for Citrus Technology/Citrus Research Institute Southwest University-Chinese Academy of Agricultural SciencesChongqing 400712P.R.China Economic Crop Technology Promotion Station Chongqing 400700P.R.China

This study aimed to provide a theoretical basis for adopting suitable cultivation measures to tackle calcium （Ca） deficiency in citrus leaves. The Newhall navel orange （Citrus sinensis Osbeck） canopy was sprayed with 20.0 mmol L-1 of Ca（NO3）2 during physiological fruit drop period, fruit expanding period, and fruit maturing period on 30, 90, and 210 days after full bloom （DAFB）, respectively, and its effects on leaf gas exchange parameters and leaf mineral nutrition and fruit quality were analyzed. The results showed that：（1） The photosynthetic rate （ACO2） at 9：00 a.m. and 16：00 p.m. of fruit expanding period with 30 and 90 DAFB Ca（NO3）2treatments slightly or significantly improved mainly by decreasing stomatal limitation and nonstomatal limitation, respectively. （2） Compared with control （CK）, the Ca concentration in leaves with 30, 90, and 240 DAFB Ca（NO3）2 treatments increased by 127.16; 97.53, and 33.33%, respectively, and the leaf magnesium concentra- tion also increased by more than 32.26%. However, Ca（NO3）2 canopy spraying on 30 DAFB significantly reduced the leaf potassium concentration, by 22.14% compared with CK. （3） Ca（NO3）2 canopy spraying on 30 DAFB decreased the second fruit drop rate by 30.55% and increased the weight per fruit by 25.04%, thus resulting in a significant increase in citrus yield. （4） Spraying Ca（NO3） on 30 DAFB mainly affected the metabolism of titratable acid （TA） to improve the maturity of citrus fruits. Whilst it improved the external quality and the coloring of citrus fruit significantly. Therefore, Ca（NO3）2 canopy spraying during physiological fruit drop period has a better influence on the tree character and fruit quality of Newhall navel orange （Citrus sinensis Osbeck）.

关键词： Ca(NO3)2 canopy spraying fruit quality high temperature Newhall navel orange