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Supramolecular approaches for insulin stabilization without prolonged duration of action

Acta Pharmaceutica Sinica B 2023年第5期13卷 2281-2290页

作者： Rolande Meudom Yanxian zhang Michael A.VandenBerg Lei Zou Yi Wolf zhang Matthew J.Webber danny Hung-Chieh Chou Division of Endocrinology and Diabetes Department of PediatricsSchool of MedicineStanford UniversityPalo AltoCA 94305USA Department of Biochemistry School of MedicineUniversity of UtahSalt Lake CityUT 84112USA Department of Chemical Engineering University of Notre DameNotre DameIN 46556USA

Aggregation represents a significant challenge for the long-term formulation stability of insulin *** supramolecular PEGylation of insulin with conjugates of cucurbit[7]uril and polyethylene glycol(CB[7]-PEG)has been shown to stabilize insulin formulations by reducing aggregation *** prolonged in vivo duration of action,arising from sustained complex formation in the subcutaneous depot,limits the application scope for meal-time insulin uses and could increase hypoglycemic risk several hours after a *** affinity of CB[7]in binding the B1-Phe residue on insulin is central to supramolecular PEGylation using this ***,here we synthesized N-terminal acid-modified insulin analogs to reduce CB[7]interaction affinity at physiological pH and reduce the duration of action by decreasing the subcutaneous depot effect of the *** insulin analogs show weak to no interaction with CB[7]-PEG at physiological pH but demonstrate high formulation stability at reduced ***,N-terminal modified analogs have in vitro and in vivo bioactivity comparable to native ***,in a rat model of diabetes,the acid-modified insulin formulated with CB[7]-PEG offers a reduced duration of action compared to native insulin formulated with CB[7]-*** work extends the application of supramolecular PEGylation of insulin to achieve enhanced stability while reducing the risks arising from a subcutaneous depot effect prolonging in vivo duration of action.

关键词： Diabetes mellitus Insulin aggregation Supramolecular PEGylation Selective N-Terminal modification N-terminal acid-modified insulin Subcutaneous depot Hypoglycemia Subcutaneous administration

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WHERE THERE IS MOTIVATION, THERE IS A WAY IN LANGUAGE TEACHING AND LEARNING

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中国英语教学：英文版 2004年第4期27卷 118-119,74页

作者： zhangJu danny InnerMongoliaUniversityfortheNationalities

A retrospective review of motivation in language learning and teaching shows that motivation is a complex phenomenon, which includes many components: the individual's drive, need for achievement and success, curiosity and desire for stimulation and new experience, communicative need, attitudes toward the second language community and teachers, sell-image and so on. All these factors play a key role in every kind of learning situation. One should pay great attention to the inspiration of motivation in language study no matter if he is a teacher or a student.

关键词：语言教学学习过程学习动机学习态度语言交流

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AntVis:A web-based visual analytics tool for exploring ant movement data

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Visual Informatics 2020年第1期4卷 58-70页

作者： Tianxiao Hu Hao Zheng Chen Liang Sirou Zhu Natalie Imirzian Yizhe zhang Chaoli Wang David P.Hughes danny Z.Chen Facebook Inc.Menlo ParkCA 94025United States University of Notre Dame Notre DameIN 46556United States Carnegie Mellon University PittsburghPA 15213United States Pennsylvania State University University ParkPA 16802United States

We present AntVis,a web-based visual analytics tool for exploring ant movement data collected from the video recording of ants moving on tree *** goal is to enable domain experts to visually explore massive ant movement data and gain valuable insights via effective visualization,filtering,and *** is achieved through a deep learning framework for automatic detection,segmentation,and labeling of ants,ant movement clustering based on their trace similarity,and the design and development of five coordinated views(the movement,similarity,timeline,statistical,and attribute views)for user interaction and *** demonstrate the effectiveness of AntVis with several case studies developed in close collaboration with domain ***,we report the expert evaluation conducted by an entomologist and point out future directions of this study.

关键词： Ant movement Object detection Image segmentation Visual analytics Knowledge discovery

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拍卖行化身多元艺术空间——嘉德艺术中心

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设计家 2018年第1期 102-106页

作者： Marcel Holmberg Sun Ke Emily Liang Cecilia Lei Yingda Ahrens Mark Biemans Kim Bjarke Catarina Canas Alicia Casals Michael Cavander Jeffrey Cheng Patrick Conway Dyno Du Nicolaz Frez Brian Fung Daniel Hawkins Xinran Ji Philipp Kramer Emeline Laurencon Yuyang Lin Mavis Liu Wymen Lo Max Ma Rafael Merino John Murphey Marcin Olszowski Kevin Ou Kevin Park Yanyadech Phornphong Aaron Powers Klementina Savickaite Jim Shi Chiara Storino Joseph Tang Yang Tao Elena Yang Quentin Yiu Francis Young Lei Yu danny zhang Bruno Zhao Weiwei zhang Yi Zhu Catarina Canas Brian Fung Paloma Hernaiz Marcel Holmberg Tait Kaplan Jaime Oliver Joseph Tang Beijing Institute of Architectural Design (BIAD) Beijing Buro Ole Scheeren MQ-Studio Shanghai(Hotel)

嘉德艺术中心紧邻紫禁城,作为一座全新的综合文化机构,将北京的古城韵味与现代大都会的蓬勃生机以及多元艺术融为一体.嘉德艺术中心是世界上第一个量身定制的拍卖行总部,在北京的中心创建了一个全新的多元艺术机构类型.建筑提供博物馆... 详细信息

嘉德艺术中心紧邻紫禁城,作为一座全新的综合文化机构,将北京的古城韵味与现代大都会的蓬勃生机以及多元艺术融为一体.嘉德艺术中心是世界上第一个量身定制的拍卖行总部,在北京的中心创建了一个全新的多元艺术机构类型.建筑提供博物馆硬件质量的展示空间和最先进的艺术品保护设施,同时也是一个灵活丰富的文化空间,与餐馆、酒店、公共交通基础设施结合在一起.

关键词：艺术中心拍卖行艺术空间化身交通基础设施机构类型文化空间量身定制

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Cathodic Hydrogen as Electron Donor in Enhanced Reductive Dechlorination

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Chinese Journal of Chemical Engineering 2013年第12期21卷 1386-1390页

作者：张瑞玲路晓霞 danny D. Reible 焦刚珍秦松岩 School of Environmental Science and Safety Engineering Tianjin University of Technology Tianjin 300384 China Anchor Qea LLC Austin TX 78746 USA Department of Civil & Environmental Engineering Texas Tech University Lubbock TX 79409-1023 USA

In situ capping is an attractive and cost-effective method for remediation of contaminated sediments,but few studies on enhancing contaminant degradation in sediment caps have been reported,especially for chlorinated *** enhanced bioactive barrier is a new process for in situ remediation for reducible compounds in soil or *** primary objective of this study is to determine if electrodes in sediment could create a redox gradient and provide electron acceptor/donor to stimulate degradation of chlorinated *** results demonstrate that graphite electrodes lead to sustainable evolution of hydrogen,displaying zero-order kinetics in the initial stages with different *** constant rates of hydrogen evolution at 3,4,and 5 V are1.05,2.54,and 4.3 nmol·L 1·d 1,*** higher voltage can produce more hydrogen,but it could not keep long time because the over potentials on electrode surfaces prevent its *** study shows that 4 V is more appropriate for hydrogen *** measured and evaluated concentration of 1,2,3,5-tetrachlorobenzene in pore water of sediment and concentration of sulfate show that dechlorination is inhibited at higher concentration of sulfate.

关键词： hydrogen electrode reductive dechlorination capping

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Intervertebral disc development and disease-related genetic polymorphisms

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Genes & Diseases 2016年第3期3卷 171-177页

作者： Jason W.Ashley Motomi Enomoto-Iwamoto Lachlan J.Smith Robert L.Mauck danny Chan Joseph Lee Martin F.Heyworth Howard An Yejia zhang Department of Orthopedic Surgery Perelman School of MedicineUniversity of PennsylvaniaUSA Department of Surgery Division of Orthopaedic SurgeryChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA School of Biomedical Sciences The University of Hong KongHong Kong Department of Orthopedic Surgery University of ChicagoChicagoILUSA Corporal Michael J.Crescenz Veterans Affairs Medical Center PhiladelphiaPAUSA Department of Medicine Perelman School of MedicineUniversity of PennsylvaniaUSA Department of Orthopedic Surgery Rush University Medical CenterChicagoILUSA Department of Physical Medicine&Rehabilitation Perelman School of MedicineUniversity of PennsylvaniaUSA

The intervertebral disc(IVD)comprises a gelatinous inner core(nucleus pulposus;NP)and concentric rings(annulus fibrosus;AF).The NP,an important structure for shock absorption in the vertebrate spinal motion segment,can be traced back to the notochord in ontogenetic *** vertebrates,the notochord undergoes mucinoid changes,and had been considered vestigial until ***,observed correlations between IVD degeneration and back pain in humans have renewed interest in the IVD in biomedical *** its mechanical contribution to development,the notochord is also an essential signaling center,which coordinates formation of the neural tube and *** pertinent signaling molecules,particularly TGF-b and bone morphogenetic proteins(BMPs),continue to play roles in the adult tissues and have been utilized for tissue *** factors are major determinants of who will develop IVD degeneration and related back pain,and seem to correlate better with disc degeneration and back pain than do external forces on the *** summary,the spinal column is a landmark development in *** directing the development of the IVD may also contribute to its maintenance,degeneration,and ***,structural genes as well as genes responsible for maintenance of the structure are related to IVD ***,genes responsible for inflammation may play a dual role in exacerbating degeneration or facilitating repair responses depending on the context.

关键词： Back pain Development Intervertebral disc(IVD) Notochord Regeneration

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A single-cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration

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Bioactive Materials 2022年第3期7卷 281-298页

作者： Peng Guo Xizhe Liu Penghui zhang Zhongyuan He Zhen Li Mauro Alini RGeoff Richards Sibylle Grad Martin J.Stoddart Guangqian Zhou Xuenong Zou danny Chan Wei Tian Dafu Chen Manman Gao Zhiyu Zhou Shaoyu Liu Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury Department of Orthopaedic SurgeryThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenChina Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina AO Research Institute Davos DavosSwitzerland Shenzhen Key Laboratory of Anti-aging and Regenerative Medicine Department of Medical Cell Biology and GeneticsHealth Sciences CenterShenzhen UniversityShenzhenChina School of Biomedical Sciences LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina Laboratory of Bone Tissue Engineering Beijing Laboratory of Biomedical MaterialsBeijing Research Institute of Orthopaedics and TraumatologyBeijing JiShuiTan HospitalBeijingChina Department of Sport Medicine Inst Translat MedThe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People’s HospitalShenzhenChina

The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined,which significantly limits the application of such bioactive ***,the transcriptional landscapes of different osteogenic microenvironments,including three-dimensional(3D)hydroxyapatite(HA)scaffolds and osteogenic medium(OM),for mesenchymal stromal cells(MSCs)in vitro were mapped at single-cell *** findings suggested that an osteogenic process reminiscent of endochondral ossification occurred in HA scaffolds through sequential activation of osteogenic-related signaling pathways,along with inflammation and angiogenesis,but inhibition of adipogenesis and ***,we revealed the mechanism during OM-mediated osteogenesis involves the ZBTB16 and WNT signaling *** of MSCs was also *** vitro ossification of LRRC75A+MSCs was shown to have better utilization of WNT-related ossification process,and PCDH10+MSCs with superiority in hydroxyapatite-related osteogenic *** findings provided further understanding of the cellular activity modulated by OM conditions and HA scaffolds,providing new insights for the improvement of osteogenic *** atlas provides a blueprint for research on MSC heterogeneity and the osteogenic microenvironment of HA scaffolds and a database reference for the application of bioactive materials for bone regeneration.

关键词： inflammation bioactive finding

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多功能热泵冷热水机组研究及在医院设计中的应用探索

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机电信息 2014年第31期 85-93页

作者：张圆郝玲 danny Chen 中国中建设计集团有限公司医疗专业院北京100044 台湾东元空调江西东成空调设备有限公司江西南昌330000

由于医院需要具有24 h热水供应能力,如何在满足使用需求的情况下节能减排,通过项目实际设计过程,提出了热泵冷凝热回收加热生活热水的解决方案,介绍了多功能热泵冷热水机组空调系统方案设计思路与国外运行案例数据的分析。

关键词：医院多功能热泵冷热水机组冷凝热回收生活热水

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Opportunities to search for extraterrestrial intelligence with the FAST

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Research in Astronomy and Astrophysics 2020年第5期20卷 193-204页

作者： Di Li Vishal Gajjar Pei Wang Andrew Siemion Zhi-Song zhang Hai-Yan zhang You-Ling Yue Yan Zhu Cheng-Jin Jin Shi-Yu Li Sabrina Berger Bryan Brzycki Jeff Cobb Steve Croft Daniel Czech David DeBoer Julia DeMarines Jamie Drew J.Emilio Enriquez Nectaria Gizani Eric J.Korpela Howard Isaacson Matthew Lebofsky Brian Lacki David H.E.MacMahon Morgan Nanez Chen-Hui Niu Xin Pei danny C.Price Dan Werthimer Pete Worden Yunfan Gerry zhang Tong-Jie zhang FAST Collaboration CAS Key Laboratory of FAST National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Department of Astronomy University of California BerkeleyBerkeley CA 94720USA SETI Institute Mountain ViewCA 94043USA Department of Astrophysics/IMAPP Radboud UniversityNijmegenNetherlands University of Malta Institute of Space Sciences and AstronomyMalta Space Sciences Laboratory University of CaliforniaBerkeleyBerkeley CA 94720USA Breakthrough Initiatives NASA Research ParkMoffett Field CA 94043USA Hellenic Open University School of Science&TechnologyParodos AristotelousPerivola PatronGreece University of Southern Queensland QLD 4350Australia Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China Centre for Astrophysics&Supercomputing Swinburne University of TechnologyHawthornVIC 3122Australia Department of Astronomy Beijing Normal UniversityBeijing 100875China Institute of Astronomical Science Dezhou UniversityDezhou 253023China

The discovery of ubiquitous habitable extrasolar planets,combined with revolutionary advances in instrumentation and observational capabilities,has ushered in a renaissance in the search for extraterrestrial intelligence(SETI).Large scale SETI activities are now underway at numerous international *** Five-hundred-meter Aperture Spherical radio Telescope(FAST)is the largest single-aperture radio telescope in the world,and is well positioned to conduct sensitive searches for radio emission indicative of *** is one of the five key science goals specified in the original FAST project plan.A collaboration with the Breakthrough Listen Initiative was initiated in 2016 with a joint statement signed both by *** Yan,the then director of National Astronomical Observatories,Chinese Academy of Sciences(NAOC),and *** Worden,Chairman of the Breakthrough Prize *** this paper,we highlight some of the unique features of FAST that will allow for novel SETI *** identify and describe three different signal types indicative of a technological source,namely,narrow band,wide-band artificially dispersed and modulated ***,we propose observations with FAST to achieve sensitivities never before *** nearby exoplanets,such as TESS targets,FAST will be sensitive to an EIRP of 1.9×1011 W,well within the reach of current human *** the Andromeda Galaxy,FAST will be able to detect any Kardashev type II or more advanced civilization there.

关键词： Search for Extraterrestrial Intelligence Five-hundred-meter Aperture Spherical radio Telescope

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从投资视角看中国—东盟经济一体化

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中国周边外交学刊 2018年第1期 161-186页

作者：张淼黄子坚马来亚大学中国研究所

在国内和区域市场以及贸易协定的相互推动下,东盟与中国的经济一体化正不断加强。尽管区域贸易协定已极大推进了中国跨国企业在东盟地区的参与,但一个重要问题是,东南亚国家的中小企业是否愿意参与并从这一区域经济一体化中受益。本文... 详细信息

在国内和区域市场以及贸易协定的相互推动下,东盟与中国的经济一体化正不断加强。尽管区域贸易协定已极大推进了中国跨国企业在东盟地区的参与,但一个重要问题是,东南亚国家的中小企业是否愿意参与并从这一区域经济一体化中受益。本文主要考察了中国跨国企业在东盟与当地中小企业的互动。通过对奇瑞汽车的案例研究,本文发现,虽然中国跨国企业的业务受国家'走出去'战略与优惠的区域贸易协定的影响较大,但东道国的国家政策对外国企业的进入也有重要影响。奇瑞在马来西亚的经验显示,中国跨国企业在当地的联系与溢出效应有限,因为大多数企业都极大依赖于其当地伙伴企业的贸易网络。本文认为,奇瑞需调整其区域战略,使其在国际价值链中占据更重要的地位,以促进企业的发展和国际竞争力.

关键词：跨国企业中小企业地区经济一体化中国—东盟关系

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