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崔彩莲教授课题组

 

 

  崔彩莲  北京大学教授,博士生导师

  联系方式

  地址:北京市海淀区学院路38

  北京大学神经科学研究所

邮编:100191

  电话:(010)-82801120

  传真:(010)-82801120

  Email: clcui@bjmu.edu.cnclcuimclean@gmail.com

 

      崔彩莲教授1982年12月毕业于西安医科大学临床医学专业。曾先后在陕西中医学院、北京医科大学、北京大学神经生物学系任教。1993年加盟北京医科大学神经科学研究中心,开始从事药物成瘾的神经生物学基础及电针治疗药物成瘾的疗效机制研究至今。2005年至2006年作为访问学者在美国哈佛大学医学院进行药物成瘾的合作研究。实验室目前主要主要采用行为药理学、分子生物学、电生理学、形态学及蛋白质生物化学等方法研究药物成瘾的神经生物学基础及电针治疗药物成瘾的机制。

 

目前研究兴趣:

1.      谷氨酸能突触可塑性在药物成瘾记忆形成、维持、消退及再唤起中的作用及其分子机制:在动物吗啡及海洛因CPP和SA模型上,应用行为药理学、电生理学、分子生物学,蛋白质生物化学,形态学等手段,研究前脑NMDA受体各亚基在药物成瘾记忆过程中的变化,以及对谷氨酸突触效能(LTP和LTD)的影响及其涉及的主要下游信号分子。用NR2B过表达转基因大鼠与野生型大鼠检测其对吗啡诱导的成瘾记忆的差异性。以期寻找维持药物成瘾记忆的关键分子。

2.      药物成瘾对脑冲动控制环路的影响及其分子机制:在认知冲动及运动冲动动物模型上,采用清醒自由活动大鼠多通道同步记录技术,检测吗啡处理及戒断大鼠脑冲动控制环路神经元及神经元集群放电活动的改变,环路涉及主要核团阿片、多巴胺及谷氨酸受体及受体后信号通路在吗啡成瘾大鼠冲动行为及神经元放电活动改变中的作用。探讨阿片成瘾个体冲动行为增强是否与其脑冲动控制环路神经元放电活动改变相关,以及所涉及的主要分子。

3.      慢性吗啡依赖与戒断不同时间点大鼠VTA区DA能神经元形态与放电活动改变以及电针的干预作用:用形态学、电生理学及分子生物学方法,观察VTA区DA能神经元在药物处理及撤药的不同时间点DA能神经元形态及放电模式改变规律性,对再次给予小剂量药物的电生理学反应与药物强化行为反应的改变及其主要机制。

4.     电针镇痛个体差异的基因及蛋白质谱研究(合作研究):应用基因表达谱和蛋白质组学技术,分别对低频(2 Hz)和高频(100 Hz)EA镇痛高反应(high responder)和低/无反应(low responder/non-responder)的大鼠中枢痛相关脑区组织,进行基因谱和蛋白质组学检测,筛选编码电针镇痛的“有效基因”或“特异基因”及相关功能蛋白。分析EA镇痛效应是否与中枢镇痛与抗镇痛基因及蛋白水平的表达差异相关。

近年主要基金来源:

1.  科技部重大基础研究计划(973)项目分课题(2015CB553503):精神活性物质成瘾记忆的形成和消除,骨干;课题起始年月:2015.1-2019.12

2.  国家自然科学基金面上项目(81471353):成体齿状回神经干细胞microRNA-132/212在阿片成瘾中的作用及分子机制, 负责人;课题起始年月:2015.1-2018.12

3.  国家自然科学基金面上项目(31271163):海马-前额叶皮层谷氨酸能投射在成瘾记忆提取中的作用及机制,负责人;课题起始年月:2013.1-2016.12

4.  国家自然科学基金创新研究群体科学基金(81221002):精神疾病的神经可塑性机制, 骨干;课题起始年月:2013.1-2015.12

5.  科技部重大基础研究计划(973)项目分课题(2013CB531905):针药复合麻醉镇痛机制, 骨干;课题起始年月:2013.1-2017.12

6.  国家自然科学基金面上项目(30570583):选择性损毁伏核对大鼠天然奖赏和吗啡奖赏效应影响的比较研究,负责人;课题起始年月:2006.1-2008.12

7.  国家自然科学基金面上项目(30770690):外周电刺激抑制可卡因成瘾冲动的作用及机制研究,负责人;课题起始年月:2008.1-2010.12

8.  国家自然科学基金面上项目(30370466):2Hz EA抑制吗啡CPP的机制研究,负责人;课题起始年月:2004.1-2006.12

9.  教育部211工程II期基金,阿片成瘾的学习记忆机制研究,子课题负责人;课题起始年月:2003-2006

10.  科技部重大基础研究计划(973)项目分课题(2009CB522003):阿片类物质精神依赖的神经生物学机制,负责人;课题起始年月:2009.01-

11.  科技部重大基础研究计划(973)项目分课题(2003CB515407):抗精神活性物质依赖和复发其他干预手段及其作用机理研究,负责人;课题起始年月:2004.1-2008.12

12.  卫生部“十一五”支撑计划基金项目(2007BAI07B03)“对已有防复吸疗法的临床再评估”,子课题负责人; 课题起始年月:2008.1- 2010.12

13.  科技部重大基础研究计划(973)项目(2007CB512500):“基于临床的针麻镇痛的基础研究”子课题“针麻镇痛中高级中枢痛觉信息调制回路的作用”(2007CB512501),子课题负责人;课题起始年月:2007.7-2011.8

14.  北京大学工学院-医学部生物医学工程联合研究基金项目:经皮穴位电刺激镇痛机制的脑功能核磁共振定量实验研究,负责人;课题起始年月:2009.6 -

15.  国家基础科学人才培养基金项目(89100-217755109):“前脑NR2B 过表达大鼠药物成瘾易感性研究”,负责人;课题起止年月:2007.1-.

16.  美国国立卫生院(NIH)重点项目(P01 AT 002038)分课题:替代医学干预药物成瘾-外周刺激防治可卡因成瘾,主要执行人;课题起始年月:2004.10-

17.  国家科技部973 前期重点基金(2001 50 号),阿片成瘾与复吸的神经机制及非药物抗复吸的研究,子课题负责人,课题起始年月:2002.1-

18.  北京大学神经科学研究所-中国中医研究院针灸所合作基金:经皮穴位电刺激(TEAS)中枢响应的fMRI 研究,负责人;课题起始年月:2011.12-

 

近期代表性论著:(CA: corresponding author)

1.       Feifei Ge, Na Wang, Cailian CuiCA, Yijing Li, Yan Liu, Yaoying Ma, Shuli Liu, Haolin Zhang, Xiaowei Sun Glutamatergic projections from the entorhinal cortex to dorsal dentate gyrus mediate context-Induced reinstatement of heroin seeking. Neuropsychopharmacology, 2017, 15 February 2017; doi:10.1038.[Epub ahead of print]

2.       Yijing Li, Xingjie Ping, Chong Qi, Fang Shen, Linlin Sun, Xiaowei Sun, Feifei Ge, Guogang Xing, Cailian CuiCA, Re-exposure to morphine-associated context facilitated long-term potentiation in the vSUB-NAc glutamatergic pathway via GluN2B-containing receptor activation, Addiction Biology, 2017, 22(2):435-445

3.       Junkai Wang, Yunli Fan, Yue Dong, Mengying Ma, Yi Ma, Yuru Dong, Yajuan Niu, Yin Jiang, Hong Wang, Zhiyan Wang, Liuzhen Wu, Hongqiang Sun, Cailian CuiCA. Alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Plos one, 2016 Aug 30;11(8):e0161956

4.       Yan Liu, Xin-Juan Wang, Na Wang, Cai-Lian CuiCAand Liu-Zhen WuCA.Electroacupuncture Ameliorates Propofol-Induced Cognitive Impairment via an Opioid Receptor-Independent Mechanism. The American Journal of Chinese Medicine, 2016, 44(4):705-719.

5.       YJ Li, XJ Ping, P Yu, J Liang, F Shen, JS Han, CL CuiCA. Over-expression of the GluN2B subunit in the forebrain facilitates the acquisition of morphine-related positive and aversive memory in rats. Behav Brain Res,2016, 311: 416–424.

6.       F Shen, XW Wang, FF Ge; YJ Li, CL CuiCA. Essential role of the NO signaling pathway in the hippocampal CA1 in morphine-associated memory depends on glutaminergic receptors. Neuropharmacology,2016, 102: 216-228

7.       Li YJ, Zuo YF, Yu P, Ping XJ, Cui CLCA. Role of basolateral amygdala dopamine D2 receptors in impulsive choice in acute cocaine-treated rats. Behav Brain Res.2015, 287: 187–195.

8.       Lv XF, Sun LL, Cui CLCA, Han JS.NAc shell Arc/Arg3.1 Protein Mediates Reconsolidation of Morphine CPP by Increase GluR1 Cell Surface Expression: Activation of ERK coupled CREB Is Required. Int J Neuropsychopharmacol.2015;18(9). pii: pyv030.

9.       Qi C, Wang XJ, Ge FF, Li YJ, Shen F, Wang JK, Cui CLCA. mGluR5 in the Nucleus Accumbens Shell Regulates Morphine-associated Contextual Memory through Reactive Oxygen Species Signaling. Addict Biology, 2015, 20(5):927-940.

10.     Fang Shen, Na Wang, Chong Qi, Yi-Jing Li, Cai-Lian CuiCA. The NO/sGC/PKG signaling pathway in the NAc shell is necessary for the acquisition of morphine-induced place preference.  Behav Neurosci .2014, 128(4):446-59.

11.     Ke Wang, Xiao-Hui Xiang, Nan Qiao, Jun-Yi Qi, Li-Bo Lin, Rong Zhang, Xiao-jing Shou, Xing-Jie Ping, Ji-Sheng Han, Jing-Dong Han, Guo-Ping ZhaoCA, Cai-Lian CuiCA.  Genomewide Analysis of Rat Periaqueductal Gray-Dorsal Horn Reveals Time-, Region- and Frequency-Specific mRNA Expression Changes in Response to Electroacupuncture Stimulation. Scientific Reports. 2014, 4: 6713.

12.     Xiang XH, Chen YM, Zhang JM, Tian JH, Han JS, Cui CLCA. Low- and high-frequency transcutaneous electrical acupoint stimulation induces different effects on cerebral μ-opioid receptor availability in rhesus monkeys. J Neurosci Res. 2014, 92(5): 555-63.

13.     Yin Jiang, Jing Liu, Junling Liu, Jisheng Han, Xiaoying Wang and Cai-Lian CuiCA. Cerebral blood flow-based evidence for mechanisms of low- versus high-frequency transcutaneous electric acupoint stimulation analgesia: a perfusion fMRI study in human. Neuroscience 2014; (268): 180–193.

14.     Zhang Y, Jiang Y, Glielmi CB, Li L, Hu X, Wang X, Han J, Zhang J, Cui CLCA, Fang J. Long-duration transcutaneous electric acupoint stimulation alters small-world brain functional networks. Magn Reson Imaging. 2013, 31(7): 1105-11.

15.     Hu L, Jing XH, Cui CL, Xing GG, Zhu B. NMDA receptors in the midbrain play a critical role in dopamine-mediated hippocampal synaptic potentiation caused by morphine. Addict Biol.,2014, 19(3): 380-391.

16.     Lin-Lin Sun, Ling Hu, Yi-Jing Li, Cai-Lian CuiCA. Mesoaccumbens dopamine signaling alteration underlies behavioral transition from tolerance to sensitization to morphine rewarding properties during morphine withdrawal. Brain Struc Funct, 2014;219(5):1755-71

17.     Yin Jiang, Hong Wang, Zhenyu Liu, Yuru Dong, Yue Dong, Xiaohui Xiang, Lijun Bai, Jie Tian, Liuzhen Wu, Jisheng Han, Cailian CuiCA. Manipulation of and sustained effects on the human brain induced by different modalities of acupuncture: an fMRI study. PLoS, 2013; 28;8(6):e66815.

18.     Shen F, Li YJ, Shou XJ,Cui CLCA. Role of the NO/sGC/PKG signaling pathway of hippocampal CA1 in morphine-induced reward memory. Neurobiology of Learning and Memory, 2012 (98): 130–138.

19.     Xu Y , Lv XF , Cui CLCA, Ge FF, Li YJ, Zhang HL. Essential role of NR2B-containing NMDA receptor–ERK pathway in nucleus accumbens shell in morphine-associated contextual memory. Brain Research Bulletin, 2012; (89) 22– 30.

20.     Wang K, Zhang R, Xiang XH, He F, Lin LB, Ping XJ, Yu L, Han JS, Zhao GPCA, Zhang QHCA, Cui CLCA. Differences in Neural-Immune Gene Expression Response in Rat Spinal Dorsal Horn Correlates with Variations in Electroacupuncture Analgesia. PLoS, 2012; 7(8) e42331.

21.     Wang K, Zhang R, He F, Lin LB, Xiang XH, Ping XJ, Han JS, Zhao GP, Zhang QHCA, Cui CLCA.  Electroacupuncture Frequency-Related Transcriptional Response in Rat Arcuate Nucleus Revealed Region-Distinctive Changes in Response to Low- and High-Frequency Electroacupuncture. Journal of Neuroscience Research, 2012;90:1464–1473.

22.     Liang J, Ma SS, Li YJ, Ping XJ, Hu Ling, Cui CLCA. Dynamic Changes of Tyrosine Hydroxylase and Dopamine Concentrations in the Ventral Tegmental Area-Nucleus Accumbens Projection During the Expression of Morphine-Induced Conditioned Place Preference in Rats. Neurochem Res. 2012:(37)1482-1489.

23.     Xiang XH, Jiang Y, Ni Yanjun, Fan M, Shen F,Wang XW, Han JS, Cui CLCA. Catechol-O-methyltransferase polymorphisms do not play a significant role in pain perception in male Chinese Han population. Physiol Genomics. 2012;(44)318-328.

24.     Jiang Y, Hao Y, Zhang Y, Liu J, Wang XY, Han JS, Fang J, Zhang JCA, Cui CLCA. Thirty minute transcutaneous electric acupoint stimulation modulates resting state brain activities: A perfusion and BOLD fMRI study. Brain Res. 2012;(1457)13-25.

25.     Yue Zhang, Christopher B. Glielmi, Yin Jiang, Jing Wang, Xiaoying Wang, Jing Fang, Cailian Cui, Jisheng Han, Xiaoping Hu, Jue Zhang. Simultaneous CBF and BOLD mapping of high frequency acupuncture induced brain activity. Neuroscience Letters, 2012, 530: 12–17.

26.     Yan-fang Zuo, Xin-sheng Wang, Cai-Lian CuiCA, Fei Luo, Peng Yu, Xue-Wei Wang. Cocaine-induced impulsive choices are accompanied by impairing delay-dependent anticipatory activity in basolateral amygdale. J Cognitive Neurosci, 2011 24:1, 196–211.

27.     Xingjie Ping, Yaoying Ma, Yijing Li, Chong Qi, Xiaowei Sun, Xiufang Lv, Cai-Lian CuiCA. Essential Role of Protein Kinase C in Morphine-Induced Rewarding Memory. Neuropharmacology, 2011, 62(2):959-966.

28.     Xiu-Fang Lv, Ya Xu, Ji-Sheng Han, Cai-Lian CuiCA. Expression of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) in the nucleus accumbens is critical for the acquisition, expression and reinstatement of morphine-induced conditioned place preference.  Behavioural Brain Research, 2011, 223: 182–191.

29.     Hong-Yu Li, Rong Zhang, Cai-Lian Cui, Ji-Sheng Han, Liu-Zhen WuCA. Damage of Splenic T Lymphocyte Proliferation and Differentiation and Its Normalization by Electro- acupuncture in Morphine-Dependent Mice Mode. eCAM , 2011, doi:10.1155/2011/424092

30.     Gui-Bin Wang, Liu-Zhen Wu, Peng Yu, Yi-Jing Li, Xing-Jie Ping,Cai-Lian CuiCA. Multiple 100 Hz electroacupuncture treatments produced cumulative effect on the suppression of morphine withdrawal syndrome: Central preprodynorphin mRNA and p-CREB implicated. Peptides, 2011, 32: 713–721.

31.     Yao-Ying Ma,Peng Yu,Chang-Yong Guo,Cai-Lian CuiCA. Effects of Ifenprodil on Morphine-Induced Conditioned Place Preference and Spatial Learning and Memory in Rats. Neurochemical Research,2011, 36: 383–391.

32.     Jisheng Han, Cailian Cui, Liuzhen Wu. Acupuncture-related techniques for the treatment of opiate addiction: A case of translational medicine. Front. Med, 2011;5(2):141-50.

33.     Jing Liang, Xing-Jie Ping, Yi-Jing Li, Yao-Ying Ma, Liu-Zhen Wu, Ji-Sheng Han, Cai-Lian CuiCA. Morphine-induced conditioned place preference in rats is inhibited by electroacupuncture at 2 Hz: Role of enkephalin in the Nucleus Accumbens. Neuropharmacology, 2010, 58: 233–240.

34.     Ke Wang, Xiao-Hui Xiang, Fei He, Li-Bo Lin, Rong Zhang, Xing-Jie Ping, Qing-Hua Zhang, Ji-Sheng Han, Cai-Lian CuiCA, Guo-Ping Zhao. Transcriptome profiling analysis reveals region-distinctive changes of gene expression in the CNS in response to moderate restraint stress. Journal of neurochemistry, 2010, 113: 1436-1446.

35.     Hu L, Chu NN, Sun LL, Zhang R, JS Han,CL CuiCA. Electroacupuncture treatment reverses morphine-induced physiological changes in dopaminergic neurons within the ventral tegmental area. Addiction Biology, 2009, 14(4):431-437.

36.     Yao-Ying Ma, Li Meng, Chang-Yong Guo, Ji-Sheng Han, David Yue-Wei Lee,Cai-Lian CuiCA. Dose- and time-dependent, context-induced elevation of dopamine and its metabolites in the nucleus accumbens of morphine-induced CPP rats. Brain Research, 2009, 204: 192–199.

37.     Yi-Jing Li, Fei Zhong, Peng Yu, Ji-Sheng Han, Cai-Lian CuiCA, Liu-Zhen WuCA. Electroacupuncture treatment normalized sleep disturbance in morphine withdrawal rats. eCAM 2011;2011:361054.

38.     CL CuiCA, LZ Wu, F Luo. Acupuncture for the treatment of drug addiction. Neurochemical Research, 2008, 33(10): 2013-2022.

39.     David H Overstreet,Cai-Lian Cui,Yao-Ying Ma,Chang-Yong Guo,Ji-Sheng Han,ScottE Lukas,David YW Lee. Electroacupuncture Reduces Voluntary Alcohol Intake in Alcohol-preferring Rats via an Opiate-sensitive Mechanism. Neurochemical Research,2008, 33(10): 2166-2170.

40.     Ning-ning Chu, Wei Xia, Peng Yu, Ling Hu, Rong Zhang, Cai-lian CuiCA. Chronic morphine-induced neuronal morphological changes in the ventral tegmental area in rats are reversed by electroacupuncture treatment. Addiction Biology, 2008, 13: 47-51.

41.     Wei Xia, Ning-Ning Chu, Jing Liang, Yi-Jing Li, Rong Zhang, Ji-Sheng Han, Cai-Lian CuiCA. Electroacupuncture of 2 Hz Has a Rewarding Effect: Evidence from a Conditioned Place Preference Study in Rats. eCAM 2011;2011:730514.

42.     Y Chou, CL Cui, SD SCHLUSSMAN, J C CHOI, A HO, JS HAN, MJ KREEK. Effects of cocaine place conditioning, chronic escalating-dose “binge” pattern cocaine administration and acute withdrawal on orexin/hypocretin gene expression in lateral hypothalamus of fischer and Sprague-dawley rats. Neuroscience, 2008,153: 1225-1234.

43.     Yao-Ying Ma, Xiang-Dang Shi, Ji-Sheng Han, Cai-Lian CuiCA. Peripheral electrical stimulation-induced suppression of morphine-induced CCP in rats: a role for dopamine in the nucleus accumbens. Brain Research, 2008, 1212: 63-70.

44.     Ning-ning CHU, Yan-fang ZUO, Li MENG, David Yue-Wei Lee, Ji-sheng HAN, Cai-Lian CUICA. Peripheral electrical stimulation reversed the cell size reduction and increased BDNF level in the ventral tegmental area in chronic morphine treated. Brain Research, 2007, 1182: 90-97.

45.     YF Zuo, JY Wang, JH Chen, ZM Qiao, JS Han, CL CuiCA, F Luo. A comparison between spontaneous electroencephalographic activities induced by morphine and morphine-related environment in rats. Brain Research, 2007, 1136: 88-101

46.     Yao-Ying Ma, Ning-Ning Chu, Chang-Yong Guo, Ji-Sheng Han, Cai-Lian CuiCA.NR2B Containing NMDA Receptor Is Required for Morphine- But Not Stress-Induced Reinstatement. Experimental Neurology, 2007, 203:309-319.

47.     Jing LIANG Yijing LI, Xingjie PING, Peng Yu, Yanfang ZUO, Liuzhen WU, Ji-Sheng HAN and Cai-lian CuiCA. The possible involvement of endogenous ligands for mu-, delta- and kappa-opioid receptors in modulating morphine-induced CPP expression in rats. Peptides, 2006, 27: 3307-3314.

48.     Ma Y.Y., Guo C.Y., Yu P., Lee D.Y., Han J.S., Cui CLCA. The role of NR2B containing NMDA receptor in place preference conditioned with morphine and natural reinforcers in rats. Experimental Neurology, 2006, 200: 343–355.

49.     Ji-huan Chen, Jing Liang, Gui-bin Wang, Ji-sheng Han, Cai-lian CuiCA. Repeated 2 Hz peripheral electrical stimulations suppress morphine-induced CPP and improve spatial memory ability in rats. Experimental Neurology, 2005, 194 (2): 550-556.

50.     Dong Ji , Zi-Ye Sui , Yao-Ying Ma, Fei Luo , Cai-lian CuiCA, Ji-Sheng Han. NMDA receptor in nucleus accumbens is implicated in morphine withdrawal in rats. Neurochemical Research, 2004, 29(11): 2113-2120.

51.     Guo-Hong Cui, Xiao-Wei Ren, Liu-Zhen Wu, Ji-Sheng Han and Cai-Lian CuiCA. Electro-acupuncture Facilitates Recovery of Male Sexual Behavior in Morphine Withdrawal Rats. Neurochemical Research, 2004. 29(2): 397-401.

52.     Shi XD, Wang GB, Ma YY, Ren YH, Luo F, Cui CLCA, Han JS. Repeated peripheral electrical stimulations suppress both morphine-induced CPP and reinstatement of extinguished CPP in rats: accelerated expression of PPE and PPD mRNA in nucleus accumbens implicated. Mol. Brain Research. 2004, 130: 124–133.

53.     Xiang-Dang Shi, Wei Ren, Gui-Bin Wang, Fei Luo, Han JS and Cui CLCA. Brain opioid-receptors are involved in mediating peripheral electric stimulation-induced inhibition of morphine conditioned place preference in rats. Brain Research, 2003, 981: 23-29.

54.     Yan-Hua Ren, Bin Wang, Fei Luo, Cai-Lian Cui, Ji-Wang Zheng, Ji-sheng Han. Peripheral electric stimulation attenuates the expression of cocaine-induced place preference in rats. Brain Research, 2002, 957: 129-135.

55.     Cui CL, Wu LZ, Han JS. Spinal kappa-opioid system plays an important role in morphine withdrawal syndrome in the rats. Neuroscience Letters, 2000,295: 45-48.

56.     LZ Wu, CL Cui, JB Tian, et al. Suppression of morphine withdrawal by electroacupuncture in rats: dynorphin and k–opioid receptor implicated. Brain Res. 1999, 851: 290-296.

57.     Han JS, Wu LZ, Cui CL. Heroin addicts treated with Transcutaneous electrical nerve stimulation of identified frequencies. Regulatory Peptides, 1994, 54: 115-116.

58.     Yao-Ying Ma, Carlos Cepeda and Cai-Lian Cui. The role of striatal NMDA receptors in drug addiction. International Review of Neurobiology, in: Novel Approaches to Studying Basal Ganglia and Related Neuropsychiatric Disorders, Burlington: Academic Press, 2009, pp.131-146.

59.     Ji-Sheng Han and Cai-Lian Cui, Chapter 49 Acupuncture. In: Ruiz P et al (eds) Substance abuse - a comprehensive text book, 5th ed. Wolters Kluwer / Lippincott Williams and Wilkins, 2011, pp 466-476.