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Transcriptomic Profiling of Human Pluripotent Stem Cell-derived Retinal Pigment Epithelium over Time

Genomics, Proteomics & Bioinformatics 2021年第2期19卷 223-242页

作者： Grace E.Lidgerwood Anne Senabouth Casey J.A.Smith-Anttila Vikkitharan Gnanasambandapillai Dominik C.Kaczorowski Daniela Amann-Zalcenstein Erica L.fletcher Shalin H.Naik Alex W.Hewitt Joseph E.Powell Alice Pebay Department of Anatomy and Neuroscience The University of MelbourneParkvilleVIC 3010Australia Department of Surgery The University of MelbourneParkvilleVIC 3010Australia Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC 3002Australia Garvan Weizmann Centre for Cellular Genomics Garvan Institute of Medical ResearchThe Kinghorn Cancer CentreDarlinghurstNSW 2010Australia Single Cell Open Research Endeavour The Walter and Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Immunology Division The Walter and Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Department of Medical Biology The University of MelbourneParkvilleVIC 3010Australia School of Medicine Menzies Institute for Medical ResearchUniversity of TasmaniaHobartTAS 7005Australia UNSW Cellular Genomics Futures Institute School of Medical SciencesUniversity of New South WalesSydneyNSW 2052Australia

Human pluripotent stem cell(h PSC)-derived progenies are immature versions of cells,presenting a potential limitation to the accurate modelling of diseases associated with maturity or ***,it is important to characterise how closely cells used in culture resemble their native *** order to select appropriate time points of retinal pigment epithelium(RPE)cultures that reflect native counterparts,we characterised the transcriptomic profiles of the h PSC-derived RPE cells from 1-and 12-month *** differentiated the human embryonic stem cell line H9 into RPE cells,performed single-cell RNA-sequencing of a total of 16,576 cells to assess themolecular changes of the RPE cells across these two culture time *** results indicate the stability of the RPE transcriptomic signature,with no evidence of an epithelial–mesenchymal transition,and with the maturing populations of the RPE observed with time in *** of Gene Ontology pathways revealed that as the cultures age,RPE cells upregulate expression of genes involved in metal binding and antioxidant *** might reflect an increased ability to handle oxidative stress as cells *** with native human RPE data confirms a maturing transcriptional profile of RPE cells in *** results suggest that long-term in vitro culture of RPE cells allows the modelling of specific phenotypes observed in native mature *** work highlights the transcriptional landscape of h PSC-derived RPE cells as they age in culture,which provides a reference for native and patient samples to be benchmarked against.

关键词： Human embryonic stem cell Human pluripotent stem cell Retinal pigment epithelium Single-cell RNA sequencing Ageing

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影响正常幼儿词汇发育的个体和家庭因素的研究

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中华儿科杂志 2004年第12期42卷 908-912页

作者：郝波梁卫兰王爽季成叶张致祥左启华 Tardif T fletcher P 北京大学第一医院妇产科 100034 北京大学第一医院儿科 100034 北京大学公共卫生学院妇女保健与儿少卫生系 100083 美国密西根大学香港大学

目的　了解幼儿词汇发育水平及影响幼儿词汇发育的个体和家庭社会因素。方法采用现况定量研究方法。用多阶段分层不等比例抽样方法在北京 4个城区中的 2个城区抽取样本。用“中文早期语言与沟通发展量表”(CCDI)及个人背景问卷 ,对北京... 详细信息

目的　了解幼儿词汇发育水平及影响幼儿词汇发育的个体和家庭社会因素。方法采用现况定量研究方法。用多阶段分层不等比例抽样方法在北京 4个城区中的 2个城区抽取样本。用“中文早期语言与沟通发展量表”(CCDI)及个人背景问卷 ,对北京城区 10 5 6名 16～ 30个月正常幼儿的母亲或日间照顾人进行面对面问卷调查。用两样本成组秩和检验比较同年龄不同性别幼儿词汇发育水平 ,用单因素相关分析和多重回归分析方法探讨影响幼儿词汇发展的因素。结果　 16个月时 ,男童会说 2 2个词 ,女童会说 84个词 ;2 9～ 30个月时 ,男童会说 72 5个词 ,女童会说 75 2个词。调查地区 16～ 30个月龄正常幼儿词汇水平高于以往讲英语儿童的文献报道。部分月龄组女童词汇得分中位数高于男童。单因素和多重回归分析结果显示 ,母亲受教育程度高、父亲年轻、幼儿开始说话月龄早、幼儿气质情绪随和、幼儿身长较高、女孩、月龄大等因素有利于幼儿词汇发展。结论　北京城区正常幼儿词汇发育水平较高。部分个体和家庭因素可能对幼儿词汇发育有影响。

关键词：正常幼儿男童女童发育水平单因素影响词汇家庭因素得分

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从风景到风景的空间

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缤纷 2009年第12期 61-67,60页

作者： Moria Joe fletcher Marmol Radziner&Associates

过去20年间,Marmol Radziner+Associates公司一直专注于加州南部地区的设计、重建及施工工作,充分吸收了现代派的精髓并将其作为建筑元素在一系列项目中进行诠释。在阳光加州杂乱无序的拓展和低级公寓的冲击中,那种被人们遗忘的"轻松休... 详细信息

过去20年间,Marmol Radziner+Associates公司一直专注于加州南部地区的设计、重建及施工工作,充分吸收了现代派的精髓并将其作为建筑元素在一系列项目中进行诠释。在阳光加州杂乱无序的拓展和低级公寓的冲击中,那种被人们遗忘的"轻松休闲的生活方式"

关键词：建筑元素杂乱无序施工工作南部地区私密性自然式南加州赖特努特建筑概念

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肿瘤组织病理诊断

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丛书名：世界权威医学著作译丛

2001年

作者：（美）Christopher.D.M.fletcher 周庚寅等主译

本书全面系统地介绍了全身各种良、恶性肿瘤组织的病理诊断方法、多种镜下所见的病理改变及其特征。

ISBN: (纸本)7533119819

本书全面系统地介绍了全身各种良、恶性肿瘤组织的病理诊断方法、多种镜下所见的病理改变及其特征。

关键词：肿瘤学学科:病理学学科:组织学生物学科:诊断病理学组织学

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Report of Haemophilus Influenzae serotype a intracranial infections in older children

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Pediatric Investigation 2023年第2期7卷 132-136页

作者： Varvara Probst Fadi Shahoud Aaron fletcher Osborne Ana Alvarez Nizar Maraqa Ayesha Mirza Department of Pediatrics University of Florida College of Medicine-JacksonvilleJacksonvilleFloridaUSA Department of Pediatrics Division of Infectious Diseases and ImmunologyUniversity of Florida College of Medicine-JacksonvilleJacksonvilleFloridaUSA

Introduction:Haemophilus influenzae(Hi)is subdivided into typeable(a-f)and non-typeable *** serotype b(Hib)has historically been one of the important pathogens responsible for invasive ***,after widespread Hib vaccination,the emergence of other Hi serotypes,specifically Hi serotype a(Hia),was noted during the last few decades,mostly in children younger than 5 years of *** presentation:We present two cases of severe intracranial infections with detected Hia in patients>5 years of age within a short time frame and within the same geographic ***:Epidemiological studies and surveillance on Hia-related illnesses in all age groups worldwide are needed to better understand the clinical and epidemiological characteristics of *** can establish a platform to develop a candidate vaccine against Hia that might protect children of all ages.

关键词： Haemophilus influenzae serotype b intracranial infection vaccine epidemiology

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Relationships between Microsclerotia Content and Hyperspectral Reflectance Data in Soybean Tissue Infected by Macrophomina phaseolina

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American Journal of Plant Sciences 2014年第25期5卷 3737-3744页

作者： Reginald S. fletcher James R. Smith Alemu Mengistu Jeffery D. Ray Crop Production Systems Research Unit Agricultural Research Service United States Department of Agriculture Stoneville USA Crop Genetics Research Unit Agricultural Research Service United States Department of Agriculture Stoneville USA Crop Genetics Research Unit Agricultural Research Service United States Department of Agriculture Jackson USA

Alternative methods are needed to assess the severity of charcoal rot disease [Macrophomina phaseolina (Tassi) Goid] in soybean [Glycine max (L.)] plant tissue. The objective of this study was to define the relationship between light reflectance properties and microsclerotia content of soybean stem and root tissue. Understanding that relationship could lead to using spectral reflectance data as a tool to assess the severity of charcoal rot disease in soybean plants, thus reducing human bias associated with qualitative analysis of soybean plant tissue and cost and time issues connected with quantitative analysis. Hyperspectral reflectance measurements (400-2490 nm) were obtained with a non-imaging spectroradiometer of non-diseased and charcoal rot diseased ground stem and root tissue samples of six soybean genotypes (“Clark”, “LD00-3309”, “LG03- 4561-14”, “LG03-4561-19”, “Saline”, and “Y227-1”). Relationships between the reflectance measurements and tissue microsclerotia content were evaluated with Spearman correlation (rs) analysis (p < 0.05). Moderate (rs = ±0.40 to ±0.59), strong (rs = ±0.60 to ±0.79), and very strong (rs = ±0.80 to ±1.00) negative and positive statistically significant (p < 0.05) monotonic relationships were observed between tissue spectral reflectance values and tissue microsclerotia content. Near-infrared and shortwave-infrared wavelengths had the best relationships with microsclerotia content in the ground tissue samples, with consistent results obtained with near-infrared wavelengths in that decreases in near-infrared spectral reflectance values were associated with increases in microsclerotia content in the stem and root tissue of the soybean plants. The findings of this study provided evidence that relationships exist between tissue spectral reflectance and tissue microsclerotia content of soybean plants, supporting spectral reflectance data as a means for assessing variation of microsclerotia content in soybean plants. Future research shou

关键词： Hyperspectral Stem-Root Tissue Charcoal Rot Macrophomina phaseolina Soybeans

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Serotonin uptake rates in platelets from angiotensin II-induced hypertensive mice

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Health 2013年第4期5卷 31-39页

作者： Preeti Singh Terry W. fletcher Yicong Li Nancy J. Rusch Fusun Kilic Department of Biochemistry and Molecular Biology College of Medicine The University of Arkansas for Medical Sciences Little Rock USA Department of Pharmacology and Toxicology College of Medicine The University of Arkansas for Medical Sciences Little Rock USA

Angiotensin II (Ang II) is a critical component of the reninangiotensin system that contributes to hypertension. Although platelets in blood from hypertensive subjects have an abnormal biological profile, it is unclear if circulating Ang II influences platelet aggregation or thrombus formation. One of the abnormalities presented to the platelets during hypertension is an elevated plasma concentration of serotonin (5-HT) caused by reduced 5-HT uptake secondary to loss of the 5-HT transporter (SERT) on the platelet plasma membrane. In the current study, we evaluated in vivo platelet function after 7 days of subcutaneous Ang II infusion to establish hypertension in mice and additionally assessed the biology of isolated platelets exposed to Ang II in vitro. The administration of Ang II elevated systolic blood pressure, but markers of platelet activation including P-selectin and PEJon/A staining were not changed. However, the aggregation response to collagen was reduced in isolated platelets from Ang II-infused mice, which also showed reduced 5-HT uptake by SERT. In vitro exposure of isolated platelets to Ang II also resulted in a loss of surface SERT associated with a reduced aggregation response to collagen. These abnormalities were reversed by increasing concentra tions of the Ang II receptor antagonist, valsartan. Interestingly, SERT KO mice failed to fully develop hypertension in response to Ang II infusion and isolated platelets from these animals were insensitive to the anti-aggregatory influence of Ang II. Thus, Ang II blunts the aggregation responses of platelets and the mechanism underlying this action may involve a loss of SERT on the platelet plasma membrane. The latter event depletes intracellular 5-HT in platelets, an event that is associated with reduced aggregation. The widespread use of antihypertensive drugs that target the renin-angiotensin system suggest the potential clinical utility of our findings and emphasize the importance of understanding the i

关键词： Serotonin Angiotensin Platelet Hypertension

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Understanding the Experiences of Anxiety in Community Dwelling Older Adults—Understanding Anxiety in Older Adults

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Open Journal of Nursing 2017年第11期7卷 1197-1208页

作者： Margaret H. Roberts Paul L. Merrick Richard B. fletcher Kirsty Furness School of Clinical Sciences Auckland University of Technology Auckland New Zealand School of Psychology Massey University Auckland New Zealand

Objectives: Anxiety is commonly reported as being experienced by older adult patients. However most of the theories on anxiety in older adults are developed from clinical measures rather than open-ended questionnaires. Consequently, little is known about the day to day experiences of anxiety in the lives of older adults, and the functional impairment that may result. Method: Community dwelling older adults (n = 135) were administered an open-ended questionnaire eliciting their experiences of anxiety using a cognitive behavioural framework. Directed content analysis was applied to discover the shared experiences of anxiety in older adults. Results: Although 64% of older adults reported avoidance behaviour that appeared anxiety driven, they generally denied experiencing anxiety themselves. Thought content and processes were idiosyncratic however commonalities were thinking positively (34%), problem solving (31%), rumination (31%) and difficulty concentrating (19%). A broad range of physical symptoms including those that may relate to medical conditions and depression were reported as resulting from anxiety, most commonly headaches (26%) and gastrointestinal disturbances (26%). Conclusion: Anxiety driven behaviours were common and appeared to negatively impact their quality of life through avoidance behaviours. Older adults may benefit from education to destigmatise the experiences of anxiety and improve reporting of functional impairment due to anxiety.

关键词： Anxiety Beliefs Qualitative Methods Assessment Older-Adults

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Sharing Clinical Trial Data： A Proposal from the International Committee of Medical Journal Editors

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Chinese Medical Journal 2016年第2期129卷 127-128页

作者： Darren B Taichman Joyce Backus Christopher Baethge Howard Bauchner Peter W de Leeuw Jeffrey M Drazen John fletcher Frank Frizelle Irish Groves Abraham Haileamlak Astrid James Christine Laine Larry Peiperl Anja Pinborg Peush Sahni Si-Nan Wu ICMJE Executive Deputy Editor Annals of Internal Medicine Library Operations National Library of Medicine German Medical Journal (Deutsches Arzteblatt) Editor-in-Chief Journal of the American Medical Association (JAMA) and the JAMA Network Editor-in-Chief The Dutch Medical Journal (Nederlands Tijdschrift voor Geneeskunde) Editor-in-Chief New England Journal of Medicine Editor-in-Chief Canadian Medical Association Journal Editor-in-Chief New Zealand Medical Journal Head of Research British Medical Journal Editor-in-Chief Ethiopian Journal of Health Sciences Deputv Editor The Lancet Editor-in-Chief Annals of Internal Medicine Chief Editor Public Library of Science (PLOS) Medicine Scientific Editor-ln-Chief Danish Medical Journal (Ugeskrift for Laeger) Representative and Past President World Association of Medical Editors Representative Chinese Medical Journal

The International Committee of Medical Journal Editors （ICMJE） believes that there is an ethical obligation to responsibly share data generated by interventional clinical trials because participants have put themselves at risk. In a growing consensus, many funders around the world - foundations, government agencies, and industry - now mandate data sharing. Here, we outline ICMJE＇s proposed requirements to help meet this obligation. We encourage feedback on the proposed requirements. Anyone can provide feedback at www. *** by April 18, 2016.

关键词： Clinical Trial Data International Committee of Medical Journal Editors Share

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墨西哥深海酒店

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设计 2016年第18期29卷 30-31页

作者： Jacob Joe fletcher

这栋建筑顺应地势，面向大海层层跌落。中部的空间开敞宽阔，平静的水池向前延伸，和远处的大海无缝连接。数间占据了最佳视野的家庭套间利用了地势，隐藏在水面之下，丝毫不露踪迹。高大的多层建筑环绕基地的三侧对称而建，如同一个个... 详细信息

这栋建筑顺应地势，面向大海层层跌落。中部的空间开敞宽阔，平静的水池向前延伸，和远处的大海无缝连接。数间占据了最佳视野的家庭套间利用了地势，隐藏在水面之下，丝毫不露踪迹。高大的多层建筑环绕基地的三侧对称而建，如同一个个孤岛，悬浮于水面之上。海上几道圆滑的弧线划过水面，形成了交织的步道。步道的尽端，室外休息平台略低于水面，保证开阔的视野不受干扰。黑色的池底铺装让浅浅的水池看起来似乎深不见底，和纯白色的建筑体量形成了鲜明对比。

关键词：墨西哥酒店深海多层建筑无缝连接休息平台水面地势

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