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Monetary Policy and Corporate Investment:Evidence from Chinese Micro Data 被引量:12
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作者 Ying Sophie Huang frank M.song Yizhong Wang 《China & World Economy》 SCIE 2012年第5期1-20,共20页
This paper investigates how a firm's characteristics restrict the influence of monetary policy changes on its investment behavior. Focusing on China's listed companies for a sample period from the first quarter of 2... This paper investigates how a firm's characteristics restrict the influence of monetary policy changes on its investment behavior. Focusing on China's listed companies for a sample period from the first quarter of 2002 to the first quarter of 2011, we find that quantity- oriented and price-based monetary policies have heterogeneous impacts on corporate investment behavior, but the influence of monetary policies is constrained by the liquidity, inventory, size and asset-liability ratio of a firm. Firms with higher liquidity, lower inventory level and lower asset-liability ratios are less sensitive to the impact from two kinds of monetary policies. The larger the size of the firm, the less it is subject to influenee from quantity-oriented monetary policy; it responds more to price-based monetary poliey. The policy implication is that the monetary authorities should pay attention to the importance of policy-making based on the monetary demand of mieroeconomie entities. 展开更多
关键词 micro-transmission mechanism monetary policy
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Interest Rate Pass-through in a Dual-track System:Evidence from China 被引量:7
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作者 Xuejun Jin frank M.song +1 位作者 Yizhong Wang Yi Zhong 《China & World Economy》 SCIE 2014年第4期21-39,共19页
Using the Phillips-Loretan approach, this paper verifies the degree and speed of pass- through and rigidity of different interest rates in China, as well as the response of private loan interest rates to other interes... Using the Phillips-Loretan approach, this paper verifies the degree and speed of pass- through and rigidity of different interest rates in China, as well as the response of private loan interest rates to other interest rates during 2002-2012. The results indicate that the long-term pass-through from the interbank offered rates and deposit and loan interest rates to the treasury bond rate is incomplete, but that the long-term pass-through to private loan interest rates is overshooting. The long-term pass-through from the deposit and loan interest rates to the overnight interbank offered rate is incomplete, while that to the interbank offered rates of other maturities is complete. The short-term passthrough and adjustment speed of interest rates exhibit asymmetry. Therefore, before considering a full liberalization of interest rates, it is important to further enhance the competition of the financial system and the function of different interest rate systems, such as the interhank market and bond market. 展开更多
关键词 interest rate liberalization interest rate pass-through RIGIDITY
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什那干群层凝灰岩夹层SHRIMP锆石U-Pb年代学研究及其意义 被引量:3
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作者 苏文博 李文国 +7 位作者 李惠民 宋彪 狄永军 周红英 王惠 王健 frank R Ettensohn Warren D Huff 《华北地质》 2022年第2期51-67,共17页
在内蒙古乌拉特前旗大佘太镇附近的什那干群“下岩组”中下部,第一次发现了层凝灰岩等火山沉积夹层,并对其中的层凝灰岩(NM-1191)开展了SHRIMP锆石U-Pb年代学研究,精确标定其喷发时间为1614±8 Ma。由此可以确认,什那干群整体上应... 在内蒙古乌拉特前旗大佘太镇附近的什那干群“下岩组”中下部,第一次发现了层凝灰岩等火山沉积夹层,并对其中的层凝灰岩(NM-1191)开展了SHRIMP锆石U-Pb年代学研究,精确标定其喷发时间为1614±8 Ma。由此可以确认,什那干群整体上应属于国际古元古代固结纪(Statherian Period,1800~1600 Ma)末期-中元古代盖层纪(Calymmian Period,1600~1400 Ma)初期(相当于中国中元古代长城纪(1800~1600 Ma)末期-蓟县纪(1600~1400 Ma)初期)沉积。这一新的年代地层学归属的确定,显示什那干群与毗邻的渣尔泰山群及白云鄂博群(化德群)的相应层位,应属于“三群并立”、“同时异相”的沉积古地理格局;同时这也表明,该群基本可与华北克拉通北缘-中部的大红峪组-高于庄组对比,并与南缘洛峪口组-龙家园组大体相当。结合相关资料可进一步推知,位于鄂尔多斯西缘贺兰山-千里山一带的黄旗口组-王全口组及阿拉善南缘龙首山地区墩子沟群中下部(即第一、第二岩组),也应与什那干群的层位基本一致。这一广泛存在的对比关系很可能也说明,至少到中元古代盖层纪早期,阿拉善(阴山)地块仍隶属于华北克拉通的范畴,并与鄂尔多斯西缘、燕辽盆地-华北中部带及熊耳裂谷区等,共同拥有一个统一的“泛华北”陆表海。什那干群新的年代学约束及相关地层单元年代学等时框架的建立,为重新认知该阶段华北克拉通北缘沉积-构造古地理及其演化,探讨华北克拉通与哥伦比亚超大陆关系等重要命题,提供了关键的年代地层学约束。 展开更多
关键词 什那干群 层凝灰岩 锆石U-PB年龄 同时异相 古-中元古代 华北克拉通
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Ultrathin wavy Rh nanowires as highly effective electrocatalysts for methanol oxidation reaction with ultrahigh ECSA 被引量:3
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作者 Xiaoyang Fu Zipeng Zhao +8 位作者 Chengzhang Wan Yiliu Wang Zheng Fan frank song Bocheng Cao Mufan Li Wang Xue Yu Huang Xiangfeng Duan 《Nano Research》 SCIE EI CAS CSCD 2019年第1期211-215,共5页
Direct methanol fuel cells (DMFCs) have received tremendous research interests because of the facile storage of liquid methanol vs.hydrogen.However,the DMFC today is severely plagued by the poor kinetics and rather hi... Direct methanol fuel cells (DMFCs) have received tremendous research interests because of the facile storage of liquid methanol vs.hydrogen.However,the DMFC today is severely plagued by the poor kinetics and rather high overpotential in methanol oxidation reaction (MOR).Here we report the investigation of the ultrathin Rh wavy nanowires as a highly effective MOR electrocatalyst.We show that ultrathin wavy Rh nanowires can be robustly synthesized with 2-3 nm diameters.Electrochemical studies show a current peak at the potential of 0.61 V vs.reversible hydrogen electrode (RHE),considerably lower than that of Pt based catalysts (~ 0.8-0.9 V vs.RHE).Importantly,with ultrathin diameters and favorable charge transport,the Rh nanowires catalysts exhibit an ultrahigh electrochemically active surface area determined from CO-stripping (ECSAco) of 144.2 m2/g,far exceeding that of the commercial Rh black samples (20 m2/g).Together,the Rh nanowire catalysts deliver a mass activity of 722 mA/mg at 0.61 V,considerably higher than many previously reported electrocatalysts at the same potential.The chronoamperometry studies also demonstrate good stability and CO-tolerance compared with the Rh black control sample,making ultrathin Rh wavy nanowires an attractive electrocatalyst for MOR. 展开更多
关键词 RHODIUM NANOWIRES ELECTROCATALYSIS methanol oxidation reaction (MOR)
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Search for the rare decays W^(+)→D_(s)^(+)γ and Z→D^(0)γ at LHCb 被引量:1
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作者 R.Aaij A.S.W.Abdelmotteleb +134 位作者 C.Abellan Beteta F.Abudinén T.Ackernley B.Adeva M.Adinolfi P.Adlarson H.Afsharnia C.Agapopoulou C.A.Aidala Z.Ajaltouni S.Akar K.Akiba J.Albrecht F.Alessio M.Alexander A.Alfonso Albero Z.Aliouche P.Alvarez Cartelle R.Amalric S.Amato J.L.Amey Y.Amhis L.An L.Anderlini M.Andersson A.Andreianov M.Andreotti D.Andreou D.Ao F.Archilli A.Artamonov M.Artuso E.Aslanides M.Atzeni B.Audurier S.Bachmann M.Bachmayer J.J.Back A.Bailly-reyre P.Baladron Rodriguez V.Balagura W.Baldini J.Baptista de Souza Leite M.Barbetti R.J.Barlow S.Barsuk W.Barter M.Bartolini F.Baryshnikov J.M.Basels G.Bassi B.Batsukh A.Battig A.Bay A.Beck M.Becker F.Bedeschi I.B.Bediaga A.Beiter V.Belavin S.Belin V.Bellee K.Belous I.Belov I.Belyaev G.Benane G.Bencivenni E.Ben-Haim A.Berezhnoy R.Bernet S.Bernet Andres D.Berninghoff H.C.Bernstein C.Bertella A.Bertolin C.Betancourt F.Betti Ia.Bezshyiko S.Bhasin J.Bhom L.Bian M.S.Bieker N.V.Biesuz S.Bifani P.Billoir A.Biolchini M.Birch F.C.R.Bishop A.Bitadze A.Bizzeti M.P.Blago T.Blake F.Blanc J.E.Blank S.Blusk D.Bobulska J.A.Boelhauve O.Boente Garcia T.Boettcher A.Boldyrev C.S.Bolognani R.Bolzonella N.Bondar F.Borgato S.Borghi M.Borsato J.T.Borsuk S.A.Bouchiba T.J.V.Bowcock A.Boyer C.Bozzi M.J.Bradley S.Braun A.Brea Rodriguez J.Brodzicka A.Brossa Gonzalo J.Brown D.Brundu A.Buonaura L.Buonincontri A.T.Burke C.Burr A.Bursche A.Butkevich J.S.Butter J.Buytaert W.Byczynski S.Cadeddu H.Cai R.Calabrese L.Calefice S.Cali R.Calladine M.Calvi M.Calv 《Chinese Physics C》 SCIE CAS CSCD 2023年第9期14-26,共13页
A search for the rare decays W^(+)→D_(s)^(+)γ and Z→D0γis performed using proton-proton collision data collected by the LHCb experiment at a centre-of-mass energy of 13TeV,corresponding to an integrated luminosity... A search for the rare decays W^(+)→D_(s)^(+)γ and Z→D0γis performed using proton-proton collision data collected by the LHCb experiment at a centre-of-mass energy of 13TeV,corresponding to an integrated luminosity of 2.0fb−1.No significant signal is observed for either decay mode and upper limits on their branching fractions are set using W^(+)→D_(s)^(+)γ and Z→μ+μ−decays as normalization channels.The upper limits are 6.5×10^(−4) and 2.1×10^(−3) at 95% confidence level for the W^(+)→D_(s)^(+)γ and Z→D^(0)γ decay modes,respectively.This is the first reported search for the Z→D^(0)γ decay,while the upper limit on the W+→D+sγbranching fraction improves upon the previous best limit. 展开更多
关键词 W/Z boson rare decay upper limit of branching fraction
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气相合成铋纳米颗粒的多维MonteCarlo模拟
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作者 尚诚 徐祖伟 +2 位作者 赵海波 何松 frank Einar Kruis 《工程热物理学报》 EI CSCD 北大核心 2023年第12期3313-3318,共6页
气相合成是纳米颗粒的主要生产途经之一,对其复杂颗粒动力学事件及气固多相流过程的模拟具有重要指导意义。本研究首次提出了群平衡Monte Carlo下的高效颗粒迁移方法,在GPU架构下进行了气相合成铋纳米颗粒的多维CFD-PBMC模拟。作为颗粒... 气相合成是纳米颗粒的主要生产途经之一,对其复杂颗粒动力学事件及气固多相流过程的模拟具有重要指导意义。本研究首次提出了群平衡Monte Carlo下的高效颗粒迁移方法,在GPU架构下进行了气相合成铋纳米颗粒的多维CFD-PBMC模拟。作为颗粒合成源头事件,比较了不同成核模型对纳米颗粒的影响,成核速率的差异直接影响了成核区域大小及蒸气浓度分布,使得停留时间较长的边界处颗粒差异显著。与实验测量结果对比,当前模拟颗粒浓度均偏高而体积偏小。 展开更多
关键词 气相合成 多维PBMC 成核理论 GPU
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Estimation of genetic parameters and their sampling variances for quantitative traits in the type 2 modified augmented design 被引量:1
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作者 frank M.You Qijian song +4 位作者 Gaofeng Jia Yanzhao Cheng Scott Duguid Helen Booker Sylvie Cloutier 《The Crop Journal》 SCIE CAS CSCD 2016年第2期107-118,共12页
The type 2 modified augmented design(MAD2) is an efficient unreplicated experimental design used for evaluating large numbers of lines in plant breeding and for assessing genetic variation in a population. Statistical... The type 2 modified augmented design(MAD2) is an efficient unreplicated experimental design used for evaluating large numbers of lines in plant breeding and for assessing genetic variation in a population. Statistical methods and data adjustment for soil heterogeneity have been previously described for this design. In the absence of replicated test genotypes in MAD2, their total variance cannot be partitioned into genetic and error components as required to estimate heritability and genetic correlation of quantitative traits, the two conventional genetic parameters used for breeding selection. We propose a method of estimating the error variance of unreplicated genotypes that uses replicated controls, and then of estimating the genetic parameters. Using the Delta method, we also derived formulas for estimating the sampling variances of the genetic parameters.Computer simulations indicated that the proposed method for estimating genetic parameters and their sampling variances was feasible and the reliability of the estimates was positively associated with the level of heritability of the trait. A case study of estimating the genetic parameters of three quantitative traits, iodine value, oil content, and linolenic acid content, in a biparental recombinant inbred line population of flax with 243 individuals, was conducted using our statistical models. A joint analysis of data over multiple years and sites was suggested for genetic parameter estimation. A pipeline module using SAS and Perl was developed to facilitate data analysis and appended to the previously developed MAD data analysis pipeline(http://probes.pw.usda.gov/bioinformatics_ tools/MADPipeline/index.html). 展开更多
关键词 Broad-sense HERITABILITY Genetic correlation Sampling variance MODIFIED AUGMENTED DESIGN
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Macroeconomic Uncertainty, Fund Demand and Corporate Investment
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作者 Yizhong Wang frank M. song 《Frontiers of Economics in China-Selected Publications from Chinese Universities》 2015年第2期365-391,共27页
Using a unique set of data on fund use by China's listed companies, this paper examines how macroeconomic uncertainty works on corporate investment. The study shows that macroeconomic uncertainty affects corporate in... Using a unique set of data on fund use by China's listed companies, this paper examines how macroeconomic uncertainty works on corporate investment. The study shows that macroeconomic uncertainty affects corporate investment behavior through the three channels of external demand, liquidity demand and long-term fund demand, However, the result is influenced by expectations and can differ across firms depending on their economic cycle, shareholder character, industrial character and the financial constraints they are exposed to. Specifically, high macroeconomic uncertainty can weaken the positive roles of these channels, especially those of external demand and liquidity demand, in driving corporate investment. During economic upturns, the effect of these channels is the most evident among state-owned firms, manufacturing firms and low cash dividend firms. The lessons from this study are that macroeconomic policies should be leveraged taking account of the channels through which economic shocks find their way, and monetary policies have to be implemented by targeting microscopic fund demand. 展开更多
关键词 macroeconomic uncertainty fund demand corporate investment monetary policy
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Educational, psychosocial, and clinical impact of SARS-CoV-2 (COVID-19) pandemic on medical students in the United States
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作者 Veronica frank Anjali Doshi +8 位作者 Natalie L Demirjian Brandon K K Fields Catherine song Xiaomeng Lei Sravanthi Reddy Bhushan Desai Drayton C Harvey Steven Cen Ali Gholamrezanezhad 《World Journal of Virology》 2022年第3期150-169,共20页
BACKGROUND The coronavirus disease 2019(COVID-19)pandemic altered education,exams,and residency applications for United States medical students.AIM To determine the specific impact of the pandemic on US medical studen... BACKGROUND The coronavirus disease 2019(COVID-19)pandemic altered education,exams,and residency applications for United States medical students.AIM To determine the specific impact of the pandemic on US medical students and its correlation to their anxiety levels.METHODS An 81-question survey was distributed via email,Facebook and social media groups using REDCapTM.To investigate risk factors associated with elevated anxiety level,we dichotomized the 1-10 anxiety score into low(≤5)and high(≥6).This cut point represents the 25th percentile.There were 90(29%)shown as low anxiety and 219(71%)as high anxiety.For descriptive analyses,we used contingency tables by anxiety categories for categorical measurements with chi square test,or mean±STD for continuous measurements followed by t-test or Wilcoxson rank sum test depending on data normality.Least Absolute Shrinkage and Selection Operator was used to select important predictors for the final multivariate model.Hierarchical Poisson regression model was used to fit the final multivariate model by considering the nested data structure of students clustered within State.RESULTS 397 medical students from 29 states were analyzed.Approximately half of respondents reported feeling depressed since the pandemic onset.62%of participants rated 7 or higher out of 10 when asked about anxiety levels.Stressors correlated with higher anxiety scores included“concern about being unable to complete exams or rotations if contracting COVID-19”(RR 1.34;95%CI:1.05-1.72,P=0.02)and the use of mental health services such as a“psychiatrist”(RR 1.18;95%CI:1.01-1.3,P=0.04).However,those students living in cities that limited restaurant operations to exclusively takeout or delivery as the only measure of implementing social distancing(RR 0.64;95%CI:0.49-0.82,P<0.01)and those who selected“does not apply”for financial assistance available if needed(RR 0.83;95%CI:0.66-0.98,P=0.03)were less likely to have a high anxiety.CONCLUSION COVID-19 significantly impacted medical students in nu 展开更多
关键词 Medical student SARS-CoV-2 ANXIETY Stress PSYCHOLOGICAL Impact clinical
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一种环境友好成膜型生物胶对蚊幼虫的杀灭作用(英文)
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作者 frank k leung yirong song +2 位作者 jing li phillip leung rose wang 《中华卫生杀虫药械》 CAS 2016年第5期421-426,共6页
目的评估一种成膜型生物胶的物理特性、生物毒性,以及对水中蚊幼和蛹的杀灭作用。方法采用标准的药物毒理学模型鼠成纤维细胞进行毒性试验;利用人尿测试抗菌活性;采用100~1 000μm碳颗粒测试生物附着性与成膜的弹性;利用蚊幼和蚊蛹测... 目的评估一种成膜型生物胶的物理特性、生物毒性,以及对水中蚊幼和蛹的杀灭作用。方法采用标准的药物毒理学模型鼠成纤维细胞进行毒性试验;利用人尿测试抗菌活性;采用100~1 000μm碳颗粒测试生物附着性与成膜的弹性;利用蚊幼和蚊蛹测试生物胶的灭蚊活性。结果该生物胶处理的大鼠成纤维细胞细胞正常生长,它对细胞染色质和细胞核无毒;它具有抗菌作用;该物质具有良好的成膜性,能够在数秒内形成塑料膜状的薄膜,且具有高弹性。一滴生物胶能够形成直径几英寸的膜。大力搅拌时,生物胶变成白色泡沫;该生物胶具有生物附着性,当生物胶形成的膜完全覆盖水面时,能够杀死100%的蚊子幼虫和蛹。结论这种生物胶具有易于使用,无毒,成膜快、环境友好的特点,完全覆盖水面后能够在24 h杀灭所有蚊幼虫和蛹。 展开更多
关键词 成膜型生物胶 环境友好 无毒 蚊幼虫 新型蚊幼杀灭技术 生物粘性膜
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Ten decadal advances in fungal biology leading towards human well‑being
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作者 Ausana Mapook·Kevin DHyde Kevin D.Hyde +27 位作者 Khadija Hassan Blondelle Matio Kemkuignou Adela Cmokova frank Surup Eric Kuhnert Pathompong Paomephan Tian Cheng Sybren de Hoog Yinggai song Ruvishika S.Jayawardena Abdullah M.S.Al‑Hatmi Tokameh Mahmoudi Nadia Ponts Lena Studt‑Reinhold Florence Richard‑Forget K.W.Thilini Chethana Dulanjalee L.Harishchandra Peter E.Mortimer Huili Li Saisamorm Lumyong Worawoot Aiduang Jaturong Kumla Nakarin Suwannarach Chitrabhanu S.Bhunjun Feng‑Ming Yu Qi Zhao Doug Schaefer Marc Stadler 《Fungal Diversity》 SCIE 2022年第5期547-614,共68页
Fungi are an understudied resource possessing huge potential for developing products that can greatly improve human well-being.In the current paper,we highlight some important discoveries and developments in applied m... Fungi are an understudied resource possessing huge potential for developing products that can greatly improve human well-being.In the current paper,we highlight some important discoveries and developments in applied mycology and interdisciplinary Life Science research.These examples concern recently introduced drugs for the treatment of infections and neurological diseases;application of–OMICS techniques and genetic tools in medical mycology and the regulation of mycotoxin production;as well as some highlights of mushroom cultivaton in Asia.Examples for new diagnostic tools in medical mycology and the exploitation of new candidates for therapeutic drugs,are also given.In addition,two entries illustrating the latest developments in the use of fungi for biodegradation and fungal biomaterial production are provided.Some other areas where there have been and/or will be significant developments are also included.It is our hope that this paper will help realise the importance of fungi as a potential industrial resource and see the next two decades bring forward many new fungal and fungus-derived products. 展开更多
关键词 Biomaterial CRISPR Drug development Morel cultivation Mushroom cultivation Mycotoxin biosynthesis Plastic degradation
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The shift in the abundance of two Stipa species in response to land use change is associated with their divergent reproductive strategies
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作者 Xiaoshuai Wang frank Yonghong Li +4 位作者 Yuanheng Li Xin song Xudong Guo Xiangyang Hou Taogetao Baoyin 《Journal of Plant Ecology》 SCIE CSCD 2019年第4期722-729,共8页
Aims The divergent changes of plant species under land use changes are key mechanisms underlying vegetation succession.Stipa grandis steppe and Stipa krylovii steppe are two plant commu-nities widely distributed on th... Aims The divergent changes of plant species under land use changes are key mechanisms underlying vegetation succession.Stipa grandis steppe and Stipa krylovii steppe are two plant commu-nities widely distributed on the Mongolian Plateau.They have been speculated to be able to succeed into each other under different land use types and intensities based on the observa-tions on their presence and abundance at the sites with dif-ferent land use history.However,no direct evidence,neither the underlying mechanisms,have been reported for this specu-lation.Here,we verified this speculation and explored the underlying mechanisms in the typical steppe region of Inner Mongolia.Methods We investigated the abundance and reproductive behavior of S.kry-lovii and S.grandis under different land use types and intensities.We used 18 grassland paddocks to run a 6-year experiment with 6 management treatments(T0-unused,T1-grazing monthly in plant growing season,T2,T4,T6-grazing in different months in plant growing season,and T8-mowing)replicated three times.We measured the relative density and cover of S.krylovii and S.grandis using line sampling method and examined their number and bio-mass of vegetative and reproductive tillers using quadrat method in each paddock after treatments for 4 and 6 years.We also de-termined these plant attributes in 14 pairs of heavily versus lightly used grassland plots in a wide area(150 km×200 km)of the typical steppe region.Important Findings 1.Grazing largely and mowing moderately decreased the density ratio and coverage ratio of S.grandis to S.krylovii in grasslands(P<0.05),and the differences in these ratios between grazed and unused grasslands increased with time.2.Grazing,but not mowing,significantly enhanced the relative density(N_(rep)=reproductive tiller number/total tiller number)of,and biomass allocation(B_(rep)=reproductive tiller biomass/total bio-mass)to,reproductive tillers of S.krylovii(P<0.05),but not S.gran-dis.This grazing enhancement to sexual reproduction of S.krylovii,and additio 展开更多
关键词 reproductive tiller vegetative tiller SUCCESSION GRAZING MOWING
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嗜铬细胞瘤和副神经节瘤的影像学 被引量:2
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作者 张艾米(译) 宋少莉(审校) 《中华核医学与分子影像杂志》 CAS CSCD 北大核心 2022年第4期248-256,共9页
影像学在嗜铬细胞瘤(PCC)和副神经节瘤(PGL)的诊疗中起着至关重要的作用,常用于指导治疗。肿瘤相关易感基因的发现使人们对临床和影像学表型有了更好的了解。功能显像在PCC和PGL亚型中具有灵敏度和特异性优势,因此有着重要意义。目前已... 影像学在嗜铬细胞瘤(PCC)和副神经节瘤(PGL)的诊疗中起着至关重要的作用,常用于指导治疗。肿瘤相关易感基因的发现使人们对临床和影像学表型有了更好的了解。功能显像在PCC和PGL亚型中具有灵敏度和特异性优势,因此有着重要意义。目前已有几种靶向PCC和PGL特定受体和代谢过程的放射性药物被开发,包括^(131)I/^(123)I-间碘苄胍、6-氟-18-L-3,4-二羟基苯丙氨酸、^(18)F-FDG和^(68)Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)-生长抑素类似物,其中2种已被用于治疗。该文重点关注目前用于PCC和PGL的显像方法,这些方法因临床表型和基因表型而异。 展开更多
关键词 嗜铬细胞瘤 副神经节瘤 生长抑素 MIBG DOTATATE FDOPA FDG
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醛酮还原酶AKR1Cs的表达纯化及其催化还原福美司坦的作用研究
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作者 孔熙 陶思雯 +8 位作者 frank Heinrich WIELAND 杨佑喆 Alexander Tobias TEICHMANN 马根 陈木兰 解河崧 王海 汪贵林 万闰兰 《生物化学与生物物理进展》 SCIE CAS CSCD 北大核心 2019年第12期1209-1217,共9页
乳腺癌是女性最常见的恶性肿瘤之一,芳香化酶抑制剂(AIs)是辅助治疗乳腺癌的重要手段.福美司坦(4-OHA)作为固醇类AIs,不可逆地抑制芳香化酶的活性,可有效治疗乳腺癌.多项研究表明,醛酮还原酶(AKR1Cs)参与许多固醇类及其衍生物的代谢而... 乳腺癌是女性最常见的恶性肿瘤之一,芳香化酶抑制剂(AIs)是辅助治疗乳腺癌的重要手段.福美司坦(4-OHA)作为固醇类AIs,不可逆地抑制芳香化酶的活性,可有效治疗乳腺癌.多项研究表明,醛酮还原酶(AKR1Cs)参与许多固醇类及其衍生物的代谢而间接治疗多种激素依赖性疾病,从而成为治疗靶点.我们推测AKR1Cs可能参与4-OHA的特异性代谢而影响其疗效.本文通过体外原核表达纯化成功得到4种具有酶活性的AKR1Cs蛋白亚型,采用荧光法检测AKR1Cs对4-OHA的催化效率,并检测AKR1Cs酶抑制剂对其催化还原4-OHA的影响.结果发现4种AKR1Cs蛋白亚型均能催化还原4-OHA,其中AKR1C4能快速还原4-OHA,转化率几乎为100%,其次是AKR1C3和AKR1C1,转化效率为30%左右,AKR1C2对4-OHA的还原性最低,转化效率只有20%左右.同时抑制剂对AKR1Cs表现出明显的剂量-效应关系,非线性回归分析得到抑制剂对AKR1C3和AKR1C4的亲和性较强,IC50值分别为47.4μmol/L和54.68μmol/L,而对AKR1C1和AKR1C2的抑制力相对较弱,IC50值分别为77.37μmol/L和82.24μmol/L.以上结果表明,4-OHA能被肝脏中特异性表达的AKR1C4快速代谢,从代谢角度揭示了4-OHA口服用药效果不理想的原因.因此,本研究阐明了4-OHA肠胃外或经皮给药的优势并奠定了理论基础,也为今后利用纳米药物载体和开展该药物衍生物的深入研究提供了新思路. 展开更多
关键词 AKR1Cs 福美司坦 转化效率 IC50
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