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Convergence of normal stem cell and cancer stem cell developmental stage:Implication for differential therapies

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World Journal of Stem Cells 2011年第9期3卷 83-88页

作者： Shengwen Calvin Li Katherine L Lee Jane Luo Jiang F Zhong william g loudon Neuro-Oncology Research Laboratory Center for Neuroscience and Stem Cell ResearchChildren's Hospital of Orange CountyUniversity of California Irvine455 South Main StreetOrangeCA 92868United States Beckman Coulter Inc.250 South Kraemer BoulevardBreaCA 92821United States Department of Pathology Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033United States Department of Neurological Surgery University of California IrvineOrangeCA 92862United States

Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental *** postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and *** can be the key to the elaboration of anti-cancer-based *** this article,we focus on a controversial new theme relating to *** may have a critical stage characterized as a "therapeutic window",which can be identified by asso-ciation of molecular,biochemical and biological *** such a stage can allow the production of more effective therapies (*** stem cells) to treat several *** importantly,confirming the existence of a similar therapeutic window during the conversion of normal stem cells to malignant CSC may lead to targeted therapy specifically against *** conversion information may be derived from investigating the biological behaviour of both normal stem cells and cancerous stem ***,there is little knowledge about the cellular and molecular mechanisms that govern the initiation and maintenance of *** on co-evolution and interdependence of cancer with normal tissues may lead to a useful treatment paradigm of *** crosstalk between normal stem cells and cancer formation may converge developmental stages of different types of stem cells (*** stem cells,CSC and embryonic stem cells).The differential studies of the convergence may result in novel therapies for treating cancers.

关键词： Neural stem cell Cancer stem cell Convergence Therapeutic

Training stem cells for treatment of malignant brain tumors

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World Journal of Stem Cells 2014年第4期6卷 432-440页

作者： Shengwen Calvin Li Mustafa H Kabeer Long T Vu Vic Keschrumrus Hong Zhen Yin Brent A Dethlefs Jiang F Zhong John H Weiss william g loudon Neuro-On-cology and Stem Cell Research Laboratory Center for Neurosci-ence ResearchChildren’s Hospital of Orange CountyUniversity of California-IrvineOrangeCA 92868United States Department of Neurology University of California IrvineOrangeCA 92862United States Department of Pathology University of Southern CaliforniaLos AngelesCA 90033United States

The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for pa-tients. Here, we perform a literature review to identify the problems in the field. given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution(i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.

关键词： Stem cells Malignant brain tumors Engineered tissue graft Organotypic slice model

The Physiological Response during Divergent Thinking

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Journal of Behavioral and Brain Science 2016年第1期6卷 28-37页

作者： gareth H. loudon gina M. Deininger Cardiff School of Art and Design Cardiff Metropolitan University Cardiff UK Centre for Creativity Ltd. Newport UK

Our research studied the physiological response of participants during a creative task to investigate if a person’s psychophysiological state was correlated with divergent thinking performance. We used heart rate variability as our physiological measure. We asked 50 participants to perform a cognitive task that assessed their divergent thinking skills and recorded their heart rate and heart rate variability (HRV) before and during the task. Frequency domain analysis was performed on the HRV. The results showed that there was a significant negative correlation between log-transformed low frequency HRV power and the number of “divergent thinking” words generated. Our results suggest that a person’s psychophysiological state is correlated with their divergent thinking performance, and that attention and motivation may be important factors, however this needs further research. Our findings also suggest that being in a relaxed state before the start of a creative task is not a predictor of creative performance.

关键词： Creativity Divergent Thinking Heart Rate Variability Attention Motivation

The Physiological Response to Drawing and Its Relation to Attention and Relaxation

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Journal of Behavioral and Brain Science 2017年第3期7卷 111-124页

作者： gareth H. loudon gina M. Deininger Centre for Creativity Ltd. Newport UK Cardiff School of Art & Design Cardiff Metropolitan University Cardiff UK

The main purpose of this study was to analyze the physiological response of participants during a creative activity and compare the results to their physiological response during states of high attention and relaxation. Our interest was not only about the relationship between creativity and attention, but also about the role of valence and arousal. We used heart rate variability (HRV) as our physiological measure. We asked twenty-two participants to undertake three activities: a stroop test;a relaxation activity;and a drawing activity. After each activity, the participants were asked to reflect on their levels of attention, relaxation and enjoyment. The results showed significant physiological differences between the three activities: mean heart rate, F(2, 42) = 8.96, p = 0.001;log-transformed low frequency HRV power, F(1.43, 30.07) = 18.12, p g-transformed high frequency HRV power, F(2, 42) = 6.25, p = 0.004. Overall, the results suggested that participants had high levels of attention during the drawing activity, with positive valence. The results also suggested that participants’ levels of arousal differed between the three activities. The implications of these results are described in the discussion.

关键词： Creativity Heart Rate Variability Attention Arousal Valence

Function of Casein kinase 1 in circadian clock:a study of CK1 inhibitors

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Function of Casein kinase 1 in circadian clock:a study of CK...

The Role of Casein Kinase 1 in Circadian Timing

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Andrew S.I.loudon Michael Hastings Faculty of Life Sciences University of ManchesterManchesterM13 9PTUK Division of Neurobiology MRC Laboratory of Molecular BiologyCambridgeCB2 OQHUK

Circadian pacemaking requires the orderly synthesis,posttranslational modification,and degradation of clock *** mammals,mutations in casein kinase 1(CK1)εorδcan alter the circadian period,but theparticular functions of the WT isoforms within the pacemaker remain *** selectively targeted WT CK1εand CK1δusing pharmacological inhibitors(PF-4800567 and PF-670462,respectively)alongside genetic knockout and knockdown to reveal that CK1 activity is essential to molecular ***,CK1δis theprincipal regulator of the clock period:pharmacological inhibition ofCK1δ,but not CKle,significantly lengthened circadian rhythms in locomotor activity in vivo and molecular oscillations in the suprachiasmatic nucleus(SCN)and peripheral tissue slices in *** lengthening mediated by CK1δinhibition was accompanied by nuclear retention of PER2 protein both in vitro and in ***,phase mapping of the molecular clockwork in vitro showed that PF-670462 treatment lengthened the period in a phase-specific manner,selectively extending the duration of PER2-mediated transcriptional feedback. These findings suggested that CK1δinhibition might be effective in increasing the amplitude and synchronization of disrup-ted circadian *** was tested using arrhythmic SCN slices derived from Vipr2mice,in which PF- 670462 treatment transiently restored robust circadian rhythms of PER2::Luc ***,in mice rendered behaviorally arrhythmic by the Vipr2mutation or by constant light,daily treatment with PF-670462 elicited robust 24-h activity cycles that persisted throughout ***,selective pharmacological targeting of the endogenous circadian regulator CK1δoffers an avenue for therapeutic modulation of perturbed circadian behavior.

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The Role of Casein Kinase 1 in Circadian Timing

“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Michael H.Hastings Andrew S.I.loudon MRC Laboratory of Molecular Biology Neurobiology DivisionHills RdCambridge CB2 0QHU.K. Faculty of Life Sciences University of ManchesterA.V.Hill BuildingOxford RoadManchesterM13 9PT

Post-translational modifications of key clock proteins are essential regulators circadian clocks,with phosphorylation by casein kinase 1 as a key step in the degradation pathway of mammalian PER *** the role （s） of theεandδisoforms of CK1 are unclear, not least because CK1εnull mice exhibit near-normal circadian behavioural rhythms. Questions remain,therefore,as to whether both enzymes are active regulators of the circadian clock,and how they interact with specific clock *** using novel pharmacological inhibitors targeting either CK1εor CK1δcombined with gene knock-out,and knock-down,we define their respective roles in the mammalian *** CK1ε-selective drug（PF-4800567） had no significant action on circadian rhythmicity in wild-type and CK1εnull animals,tissues or *** did,however,counteract the acceleration of circadian period of behavioural activity and clock gene oscillation observed in the CK1ε *** contrast,CK1δinhibitor（PF- 670462） dose-dependently lengthened the circadian period of wild-type and CK1εnull mice in terms of in vivo behaviour,as well as clock gene oscillations in the SCN,peripheral tissues and *** gene-specific SiRNA and ShRNA in cell lines and primary cells,we confirmed that CK1εknockdown had little impact on the circadian clockwork,while CK1δknock-down significantly reduced the amplitude of oscillation and lengthened circadian *** determine the mechanism of action of CK1δin setting circadian period,we examined the effects of inhibitor on PER2 protein *** high doses,PF-670462 caused a reversible arrhythmia in cell cultures, which was accompanied by prolonged nuclear retention of *** treatment of SCN slices with PF-670462 caused desynchrony between left and right SCN（splitting） and ultimately cellular dys-rhythmia and sustained PER2 *** suggests that CK1 enzymes are crucial for nuclear clearance of the target PER2 *** retention of PER2 in the nucleus ma

关键词： Casein kinase 1 Circadian Period Inhibitor Suprachiasmatic

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无限词汇特定人汉语语音识别系统

无限词汇特定人汉语语音识别系统

第三届全国人机语音通讯学术会议

作者：苑宝生高雨青洪小文 gareth H．loudon Apple-ISS Research Centre National University of SingaporeHeng Mui Keng TerraceKent Ridge 0511Singapore Apple-ISS Research Centre National University of SingaporeHeng Mui Keng TerraceKent Ridge 0511Singapore Apple-ISS Research Centre National University of SingaporeHeng Mui Keng TerraceKent Ridge 0511Singapore Apple-ISS Research Centre National University of SingaporeHeng Mui Keng TerraceKent Ridge 0511Singapore

这里介绍的是一个用来语音输入汉字的特定人语音识别系统。这个系统不仅可以识别全部汉语单音字,而且还能够识别另外5,000常用多字词,因而构成一个无限定词汇系统。基于一种优化的声母、韵母音节相关模型,系统的识别率可达到首选94％及... 详细信息

这里介绍的是一个用来语音输入汉字的特定人语音识别系统。这个系统不仅可以识别全部汉语单音字,而且还能够识别另外5,000常用多字词,因而构成一个无限定词汇系统。基于一种优化的声母、韵母音节相关模型,系统的识别率可达到首选94％及五个候选99％。本文还将介绍为了使系统实用化而做的减少训练用语音数据的一些研究结果。

关键词：语音识别无限词汇声母、韵母音节相关模型优化训练

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肠激惹综合征患者小肠运动的门诊研究

临床与病理杂志 1994年第4期14卷 250-250页

作者： loudon-MA 李开顺

０６０肠激惹综合征患者小肠运动的门诊研究［英］／ＬｏｕｄｏｎＭＡ…／／Ｇｕｔ．一１９９３，３４（ｓｕｐｐｌｌ）．一Ｓ５５肠激惹综合征（ＩＢＳ）是引起慢性腹痛和排便习惯不规则的常见原因之一。肠道动力的改变可能是其发病机... 详细信息

０６０肠激惹综合征患者小肠运动的门诊研究［英］／ＬｏｕｄｏｎＭＡ…／／Ｇｕｔ．一１９９３，３４（ｓｕｐｐｌｌ）．一Ｓ５５肠激惹综合征（ＩＢＳ）是引起慢性腹痛和排便习惯不规则的常见原因之一。肠道动力的改变可能是其发病机制之一。作者在５０例ＩＢＳ患者（ｌ...

关键词：肠激惹综合征小肠运动患者门诊

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腹部钝器伤的检查

英国医学杂志中文版 2008年第4期11卷 222-226页

作者： Jan O Jansen Steven R Yule Malcolm A loudon 陈继业(刘毅) 董家鸿(校) Department of Surgery Aberdeen Royal Infirmary Aberdeen AB25 2ZN Department of Radiology Aberdeen Royal Infirmary 不详

隐匿性出血是腹部创伤后死亡的第二大常见原因。同时，对于那些创伤后早期存活的患者，如果腹部损伤未得到及时发现常常会导致后期病情恶化甚至死亡。因而，选择合适的检查方法可帮助外科医师制定合适的治疗方案，并且可以减少创伤后各... 详细信息

隐匿性出血是腹部创伤后死亡的第二大常见原因。同时，对于那些创伤后早期存活的患者，如果腹部损伤未得到及时发现常常会导致后期病情恶化甚至死亡。因而，选择合适的检查方法可帮助外科医师制定合适的治疗方案，并且可以减少创伤后各种并发症的发生。因此，采取合适并且快捷的检查方式是非常重要的。

关键词：腹部损伤检查方式钝器伤创伤后早期存活病情恶化治疗方案隐匿性