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Gene therapy: light is finally in the tunnel

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Protein & Cell 2011年第12期2卷 973-989页

作者： Huibi Cao robert S.Molday Jim Hu Programme in Physiology and Experimental Medicine Hospital for Sick ChildrenDepartments of Laboratory Medicine and Pathobiologyand PaediatricsUniversity of TorontoTorontoOntario M5G1X8Canada Department of Biochemistry and Molecular Biology 2350 Health Sciences MallUniversity of British ColumbiaVancouverB.C.V6T 1Z3Canada

After two decades of ups and downs,gene therapy has recently achieved a milestone in treating patients with Leber’s congenital amaurosis(LCA).LCA is a group of inherited blinding diseases with retinal degeneration and severe vision loss in early *** in several genes,including RPE65,cause the *** adenoassociated virus as a vector,three independent teams of investigators have recently shown that RPE65 can be delivered to retinal pigment epithelial cells of LCA patients by subretinal injections resulting in clinical benefits without side ***,considering the whole field of gene therapy,there are still major obstacles to clinical applications for other *** obstacles include innate and immune barriers to vector delivery,toxicity of vectors and the lack of sustained therapeutic gene ***,new strategies are needed to overcome these hurdles for achieving safe and effective gene *** this article,we shall review the major advancements over the past two decades and,using lung gene therapy as an example,discuss the current obstacles and possible solutions to provide a roadmap for future gene therapy research.

关键词： gene therapy transgenes viral vector non-viral vector helper-dependent adenoviral vector adenoassociated virus lentivirus cystic fibrosis transmembrane conductance regulator(CFtR) host immune responses

Data-Driven Discovery in Mineralogy: Recent Advances in Data Resources, Analysis, and Visualization

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Engineering 2019年第3期5卷 397-405页

作者： robert M. Hazen robert.t. downs Ahmed Eleish Peter Fox Olivier C. Gagné Joshua J. Golden Edward S. Grew Daniel R. Hummer Grethe Hystad Sergey V. Krivovichev Congrui Li Chao Liu Xiaogang Ma Shaunna M. Morrison Feifei Pan Alexander J. Pires Anirudh Prabhu Jolyon Ralph Simone E. Runyon Hao Zhong Geophysical Laboratory Carnegie Institution for Science Washington DC 20015 USA Department of Geology and Geophysics University of Wyoming Laramie WY 82071-2000 USA Department of Geosciences The University of Arizona Tucson AZ 85721-0077 USA tetherless World Constellation Rensselaer Polytechnic Institute Troy NY 12180 USA School of Earth and Climate Sciences University of Maine Orono ME 04469 USA Department of Geology Southern Illinois University Carbondale IL 62901 USA Mathematics Statistics and Computer Science Purdue University Northwest Hammond IN 46323-2094 USA Kola Science Centre of the Russian Academy of Sciences Apatity Murmansk Region 184209 Russia Department of Computer Science University of Idaho Moscow ID 83844-1010 USA *** Mitcham CR4 4FD UK

Large and growing data resources on the diversity, distribution, and properties of minerals are ushering in a new era of data-driven discovery in mineralogy. the most comprehensive international mineral database is the IMA database, which includes information on more than 5400 approved mineral species and their properties, and the *** data source, which contains more than 1 million species/locality data on minerals found at more than 300 000 localities. Analysis and visualization of these data with diverse techniques—including chord diagrams, cluster diagrams, Klee diagrams, skyline diagrams, and varied methods of network analysis—are leading to a greater understanding of the co-evolving geosphere and biosphere. New data-driven approaches include mineral evolution, mineral ecology, and mineral network analysis—methods that collectively consider the distribution and diversity of minerals through space and time. these strategies are fostering a deeper understanding of mineral co-occurrences and, for the first time, facilitating predictions of mineral species that occur on Earth but have yet to be discovered and described.

关键词： Mineral evolution ecology Skyline diagrams Network analysis Cluster Chord Klee

Application of Advanced Analytics and Visualization in Mineral Systems

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Acta Geologica Sinica(English Edition) 2019年第S01期93卷 55-55页

作者： Shaunna M.MORRISON Anirudh PRABHU Ahmed ELEISH PAN Feifei ZHONG Hao HUANG Fang Peter FOX MA Xiaogang Jolyon RALPH Joshua J.GOLDEN robert.t.downs LIU Chao Simone E.RUNYON robert M.HAZEN Geophysical Laboratory Carnegie Institution for Science1530 P Street NWWashington DC 20005USA Rensselaer Polytechnic Institute 1008th StTroyNY 12180USA University of Idaho 875 Perimeter DrMoscowID 83844USA *** University of Arizona TucsonAZ 85721USA University of Wyoming 1000 E University AveLaramieWY 82071USA

the key to answering many compelling and complex questions in Earth,planetary,and life science lies in breaking down the barriers between scientific fields and harnessing the integrated,multi-disciplinary power of Earth,planetary,and bioscience data *** have a unique opportunity to integrate large and rapidly expanding"big data"resources,to enlist powerful analytical and visualization methods,and to answer multi-disciplinary questions that cannot be addressed by one field alone.

关键词： minerals network analysis data-driven discovery mineral evolution mineral ecology

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一类可维修系统的失效间时间矩的计算

无线电通信技术 1982年第4期 55-64页

作者： P.K.W.chan t.downs 邵长新

本文导出了确定一类可维修系统的失效间时间矩的计算法,这类系统的部件有予定的失效分布。这类系统一般是非马尔柯夫过程的并且这里所用的方法是用多步法来近似计算系统的性质。对于这类所考虑的系统的一次矩(平均失效间时间)的计算,在... 详细信息

本文导出了确定一类可维修系统的失效间时间矩的计算法,这类系统的部件有予定的失效分布。这类系统一般是非马尔柯夫过程的并且这里所用的方法是用多步法来近似计算系统的性质。对于这类所考虑的系统的一次矩(平均失效间时间)的计算,在本杂志以前的一期中曾作为未解决的问题提出过。

关键词：系统失效电路板所有线路板数学分析矩阵马尔柯夫链方程概率矢量

Buffer Standards for Physiological pH of the Buffer N-(2-Acetamido)-2-aminoethanesulfonic Acid from 5°C to 55°C

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Open Journal of Physical Chemistry 2011年第3期1卷 118-123页

作者： Blake M. Bodendorfer Zachary M. downs Isaac B. Henson Lakshmi N. Roy Rabindra N. Roy Jessica M. Stegner Jaime A. Veliz Joshua t. Wollen 不详

Electromotive force (emf) measurements of the Cell Pt(s), H2(g)|ACES(m1) + NaACES(m2) + NaCl (m3)| AgCl, Ag(s) have been carried out from 5°C to 55°C . the agreement of pH values between two calculated (extended Debye-Hückel and liquid junction correction) is very good. two buffer solutions without the chloride ion and seven buffer solutions with NaCl, at an ionic strength (I = 0.16 ***-1) similar to that of physiological fluids, have been studied. the pH values for these buffer solutions have been evaluated in the temperature range of 5°C to 55°C using the extended Debye-Hückel equation of the Bates-Guggenheim convention. Values of the residual liquid junction potential (δEj) between the ACES solutions and the saturated KCl calomel electrode solution have been estimated at 25°C and 37°C from the previously determined Ej values using the flowing junction cell to determine the operational pH values at 25°C and 37°C. these ACES buffer solutions are recommended as secondary standard reference solutions for pH measurements in the range of physiological applicati on at I = 0.16 ***-1.

关键词： Buffer Emf pH Zwitterionic

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塑造文明和心灵的巨人及其思想

2006年

作者：（美）罗伯特·宾厄姆·唐斯（downs robert Bingham）王宏方孟海英齐慧甫译

本书选取了一些典型人物的经典著作,上起《圣经》，下迄1966年的《寂静的春天》，共涉及到了人类历史上几百个重要人物和近百种图书。

ISBN: (数字)7508037995

ISBN: (纸本)7508037995

本书选取了一些典型人物的经典著作,上起《圣经》，下迄1966年的《寂静的春天》，共涉及到了人类历史上几百个重要人物和近百种图书。

关键词：历史、地理世界史通史

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眩晕

Buffer Standards for the Biochemical pH of the Zwitterionic Buffer <i>N</i>-tris-(Hydroxymethyl) Methyl-2-Aminoethanesulfonic Acid (tES) from 5℃ to 55℃

1959年

作者：（美）唐德威（D.downs De weese）殷明德译

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Open Journal of Physical Chemistry 2012年第1期2卷 41-46页

作者： Rabindra N. Roy Lakshmi N. Roy Blake M. Bodendorfer Zachary M. downs Stephen D. Rocchio Joshua t. Wollen Jessica M. Stegner Isaac B. Henson Nicholas W. Grove Lauren A. Dieterman Hoffman Department of Chemistry Drury University Springfield USA

the authors have undertaken the determination of pH values for one buffer solution of tES without NaCl and nine buffer solutions with NaCl yielding an ionic strength I = ***-1. similar to that of blood. these buffer solutions have been evaluated in the temperature range of 5℃ to 55℃ using an extended version of the Debye-Hückel equation. the pH values are reported using 1) the Debye-Hückel extension of the Bates-Guggenheim convention in the tempera- ture range 5℃ to 55℃ and 2) with and without liquid junction correction at 25℃ and 37℃. these tES buffer solutions are recommended as secondary standard references for pH measurements in the range of pH 7.2 to 7.5 for physiological application with an ionic strength of I = 0.16 ***-1.

关键词： Ionic Strength Liquid Junction Potentials Second Dissociation Constant Buffer Solutions Activity Coefficients

先天性甲状腺功能减退患儿的神经发育结果:首次t4剂量和达到t4、tSH目标剂量时所需时间的比较

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世界核心医学期刊文摘（儿科学分册） 2006年第6期2卷 25-26页

作者： Selva K.A. Harper A. downs A. 王经纬 Children's Diabetes and Endocrine Center Legacy Emanuel Hospital 501 N. Graham Street Portland OR 97229 United States Dr.

Objectives: to compare neurodevelopmental outcomes in severe and moderate congenital hypothyroidism (CH) among 3 different initial L-thyroxine doses and to examine the effect of the time to thyroid function normalization on neurodevelopmental outcomes. Study design: Neurodevelopmental assessments of 31 subjects included the Mullen Scales of Early Learning, Wechsler Preschool and Primary Scale of Intelligence-Revised, Wechsler Intelligence Scale for Children, Wide-Range Achievement test, and Child Behavioral Checklist. Results: Subjects started on higher initial L-thyroxine doses (50 μg) had full-scale IQ scores 11 points higher than those started on lower (37.5 μg) initial doses. However, verbal IQ, performance IQ, and achievement scores did not differ among the 3 treatment cohorts. Subjects with moderate CH had higher full-scale IQ scores than subjects with severe CH, regardless of the initial treatment dose. Subjects who took longer than 2 weeks to normalize thyroid function had significantly lower cognitive, attention, and achievement scores than those who achieved normal thyroid function at 1 or 2 weeks of therapy. Conclusions: Initial L-thyroxine dose and faster time to normalization of thyroid function are important to optimal neurodevelopmental outcome. In severe CH, it is important to choose an initial dose at the higher end of the recommended range to achieve these goals.

关键词：先天性甲状腺功能减退目标剂量神经发育首次时间患儿 tSH 左旋甲状腺素 t4 甲状腺功能正常