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Fast fluorescence lifetime imaging techniques:A review on challenge and development

Journal of Innovative Optical Health Sciences 2019年第5期12卷 3-29页

作者： Xiongbo Liu Danying Lin Wolfgang becker Jingjing Niu Bin Yu Liwei Liu Junle Qu Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Physics and Optoelectronic Engineering Shenzhen University Shenzhen 518060 P.R.China becker&hickl gmbh Nunsdorfer Ring 7-9 Berlin 12277Germany

Fluorescence lifetime imaging microscopy(FLIM)is increasingly used in biomedicine,material science,chemistry,and other related research fields,because of its advantages of high specificity and sensitivity in monitoring cellular microenvironments,studying interaction between proteins,metabolic state,screening drugs and analyzing their efficacy,characterizing novel materials,and diagnosing early ***,there is a large interest in obtaining FLIM data within an acquisition time as short as ***,there is currently a technology that advances towards faster and faster FLIM ***,the maximum speed of a recording technique is only part of the *** acquisition time of a FLIM image is a complex function of many *** include the photon rate that can be obtained from the sample,the amount of information a technique extracts from the decay functions,the fficiency at which it determines fluorescence decay parameters from the recorded photons,the demands for the accuracy of these parameters,the number of pixels,and the lateral and axial resolutions that are obtained in biological *** from a discussion of the parameters which determine the acquisition time,this review will describe existing and emerging FLIM techniques and data analysis algo-rithms,and analyze their performance and recording speed in biological and biomedical applications.

关键词： Fluorescence lifetime imaging microscopy(FLIM) acquisitin time imaging speed dead time photon fficiency time domain frequency domain scanning wide-field imaging time-correlated single photon counting(TCSPC) gated detection gated image intensifer modulated inage intensifier SPAD array detector

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Fast repetition rate fs pulsed lasers for advanced PLIM microscopy

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Journal of Innovative Optical Health Sciences 2019年第5期12卷 86-94页

作者： Sviatlana Kalinina Alexander Jelzow Tobias Plotzing Angelika Rück University of Ulm Core Facility Confocal and Multiphoton MicroscopyN24 Albert-Einstein-Allee 1189081 UlmGermany becker&hickl gmbh Nahmitzer Damm 3012277 BerlinGermany Laser Quantum gmbh Max-Stromeyer-Str.11678467 KonstanzGermany

Simultaneous metabolic and oxygen imaging is promising to follow up therapy response,dis-ease development and to determine prognostic *** of metabolic coenzymes is now widely accepted to be the most reliable method to determine cellular ***,oxygen consumption has to be taken into account to understand treatment *** phosphorescence lifetimne of oxygen sensors is able to indicate local oxygen *** phosphorescence lifetime imaging(PLIM)dyes based on ruthenium(I)coordination com-plexes are useful,in detaill TLD1433 which possesses a variety of different triplet states,enables complex photochemistry and redox *** is usally reached by two photon exci-tation of the drug with a femtosecond(fs)pulsed Ti:Sapphire laser working at 80 MHz repe-tition rate and(time-correlated single photon counting)(TCSPC)detection *** interesting question was whether it is possible to follow up PLIM 1using faster repetition *** repetition rates could be advantageous for the induction of specific photochemical reactions because of similar light doses used normally in standard CW light *** this,a default 2p-FLIM-PLIM system was expanded by adding a second fs pulsed laser("helixx")which provides 50 fs pulses at a repetition rate of 250 MHz,more than 2.3 w average power and tunable from 720 nm to 920 *** laser beam was coupled into the AOM instead of the default 80 MHz *** demonstrated siuccessful applications of the 250 MHz laser for PLIM which correlates well with measurements done by excitation with the conventional 80MHx laser source.

关键词： Multiphoton microscopy axygen consumption phosphorescence lifetime microscopy fast repetition rate excitation short laser pulses Ru(I)complexes

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THAI experimental research on hydrogen risk and source term related safety systems

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Frontiers in Energy 2021年第4期15卷 887-915页

作者： Sanjeev GUPTA Martin FREITAG Gerhard POSS becker Technologies gmbh Rahmannstrasse 11Eschborn 65760Germany

In the defense-in-depth concept employed for the safety of nuclear installations,maintaining integrity of containment as the last barrier is of high importance to limit the release of radioactivity to the environment in case of a severe *** active and passive safety systems implemented in containments of light water reactors(LWRs)are designed to limit the consequences of such *** the performance and reliability of such systems under accident conditions is critical to the safety of nuclear *** the aftermath of the Fukushima accident,there has been focus on re-examining the existing safety systems to demonstrate their capabilities for a broader range of boundary conditions comprising both the early as well as the late phases of an *** addition to the performance testing of safety systems,their interaction with containment atmosphere needs detailed investigations to evaluate the effects of operation of safety systems on H2 risk and fission product(FP)behavior in containment,which may ultimately have an impact on the source term to the *** this context,an extensive containment safety related experimental research has been conducted in a thermalhydraulics,hydrogen,aerosols,and iodine test facility(THAI,60 m3,single vessel)/(THAI+,80 m3,two interconnected vessels).Related to the subject of this paper,experimental investigations covered performance testing of various safety and mitigation systems,i.e.,containment spray,passive autocatalytic recombiner(PAR),pressure suppression pool(water pools),and effects of their operation on H2 risk and in-containment FP *** experimental results have provided a better phenomenological understanding and database for validation and further improvement of a safety analysis tool based on computation fluid dynamic(CFD)and lumped parameter(LP)modeling *** paper summarizes the main insights obtained from the aforesaid THAI experimental research covering safety systems

关键词： severe accident containment safety mitigation H2 risk source term

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A pilot study of the dynamics of tissue oxygenation in vivo using time-resolved phosphorescence imaging

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Journal of Innovative Optical Health Sciences 2021年第5期4卷 15-24页

作者： Natalia Kazachkina Julia Lymar Vladislav Shcheslavskiy Alexander Savitsky A.N.Bach Institute of Biochemistry Research Center of Biotechnology of the Russian Academy of Sciences Moscow 119071Russian Federation Institute of Experimental Oncology and Biomedical Technologies Privolzhsky Research Medical University Sq Minin and Pozharsky10/1603005 Nizhny Novgorod Russian Federation becker and hickl gmbh Nunsdorfer Ring 7-912277 BerlinGermany

Oxygenation of tissues plays an important role in the development and progression of tumor to treatment *** of metalloporphyrines phosphorescence quenching by oxygen is one of the ways to measure dynamics of the oxygen concentration in the tissues by phosphorescence lifetime imaging of meso-tetra(sulfophenyl)tetrabenzoporphyrin Pd(Ⅱ)(TBP)using the time-correlated single photon counting(TCSPC)*** has been shown that phosphorescence lifetime of the sensor in S37 tumor in vivo varied in the range of 130 to 290μs after both topical and intravenous administration of *** indicates that oxygen level in tumors was lower compared to normal tissues where TBP phosphorescence has not been *** lifetimes of TBP increased in the solid tumor and in the muscle after photodynamic therapy of solid tumor that demonstrates oxygen consumption during treatment and possibly stopping the blood flow and hence the oxygen supply to the tissues.

关键词： Phosphorescence oxygen sensor metalloporphyrines TCSPC

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Model Experiments on Melting of Alloys with Low Melting Temperature in a Medium with High Melting Temperature

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Journal of Iron and Steel Research International 1999年第2期6卷 1-9页

作者： becker Jens-Ulrik Oeters Franz Thyssen-Krupp Stahl gmbh Technical University Berlin

Experiments of alloy melting were carried out in water/HCl H 2O eutectic model system. The eutectic has a solid liquid equilibrium temperature of -74 ℃. 5 cm diameter spheres of the eutectic in which three thermocouples in the core, on the edge and in the middle between them had been positioned were cooled to -196 ℃ in liquid nitrogen. After cooling the spheres were immersed into water of 10 ℃, and the changes of temperatures with time in the three thermocouples were measured. In some experiments the temperature on the outer side of the spheres where an ice shell grew up was also measured. In these experiments, the growing rate of the shell was additionally determined. The results for the first minute of the melting process, where the system can be considered as one dimensional, were described by an exact solution of Fouriers equation. The density of liquid ferromanganese at 1 500 ℃ was measured.

关键词： alloy melting model experiment

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Antidiabetic profiling of veramycins,polyketides accessible by biosynthesis,chemical synthesis and precursor-directed modification

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Organic Chemistry Frontiers 2022年第6期9卷 1604-1615页

作者： Denis Dardić Nils Böhringer Alberto Plaza Florian Zubeil Juliane Pohl Svenja Sommer Leo Padva Jonathan becker Maria A.Patras Mona-Katharina Bill Michael Kurz Luigi Toti Sven W.Görgens Sören M.M.Schuler AndréBillion Oliver Schwengers Paulus Wohlfart Alexander Goesmann Norbert Tennagels Andreas Vilcinskas Peter E.Hammann Till F.Schäberle Armin Bauer Fraunhofer Institute for Molecular Biology and Applied Ecology(IME) Branch for Bioresources35392 GießenGermany Justus-Liebig-University Gießen 35392 GießenGermany Sanofi-Aventis Deutschland gmbh R&D Integrated Drug Discovery65926 Frankfurt am MainGermany Sanofi-Aventis Deutschland gmbh R&D German Hub65926 Frankfurt am MainGermany German Center of Infection Research(DZIF) Partner Site Gießen-Marburg-Langen35392 GießenGermany

Seven new polyketides,termed veramycins,were isolated from a Streptomyces *** the Sanofi microbial strain collection along with their known congeners NFAT-133 and *** A,anα-pyrone congener of TM-123 and NFAT-133 showed an increased baseline deoxy-glucose uptake in the absence of insulin in a modified L6 rat skeletal muscle cell line(L6 GLUT4 AS160-like cells).In addition,both compounds slightly increased the sensitivity to insulin in this cell *** syntheses of NFAT-133,TM-123 and veramycin A were accomplished starting from a central building block,which bears the three contiguous stereogenic centers of this polyketide *** approach enables an efficient,selective and flexible access to all possible isomers of the stereotriad for further exploration of this series as a potential anti-diabetic lead structure as exemplified by the synthesis of an NFAT-133 ***,the corresponding biosynthetic gene cluster(BGC)was identified by genome sequencing and gene *** on feeding experiments,a biosynthetic pathway was proposed,which enabled access to new veramycin A analogs by precursor-directed biosynthesis.

关键词： synthesis directed isomers

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Identification of fungal fossils and novel azaphilone pigments in ancient carbonised specimens of Hypoxylon fragiforme from forest soils of Chatillon-sur-Seine(Burgundy)

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Fungal Diversity 2018年第5期92卷 345-356页

作者： Frank Surup Abolfazl Narmani Lucile Wendt Sebastian Pfutze Robin Kretz Kevin becker Cle ment Menbrives Alain Giosa Michelle Elliott Christophe Petit Manfred Rohde Marc Stadler Dept.Microbial Drugs Helmholtz-Zentrum für Infektionsforschung GmbHInhoffenstrasse 738124 BraunschweigGermany German Centre for Infection Research(DZIF) Partner Site Hannover-Braunschweig38124 BraunschweigGermany Department of Plant Protection Faculty of AgricultureUniversity of TabrizTabrizIran University of Paris 1 Panthéon-Sorbonne UMR 7041Archéologies EnvironnementalesParisFrance Helmholtz-Zentrum für Infektionsforschung gmbh Central Facility for MicroscopyInhoffenstrasse 738124 BraunschweigGermany

Fungal stromata were recently discovered in association with charcoal and burnt soil aggregates during an archaeological survey in the Chaˆtillon-sur-Seine forest *** wood and soil in the samples were dated to the medieval period(between 738 and 1411 AD).Light microscopy and scanning electron microscopy revealed that a few of the stromatal fragments still contained *** macromorphological characters were described and secondary metabolite profiles were generated using high performance liquid chromatography with diode array and mass spectrometric detection(HPLC–DAD/MS).The combination of these two data lines then allowed species *** of the fragments were assigned to Hypoxylon fragiforme,the type species of the Hypoxylaceae(Xylariales).Two further species whose stromata grew on the fossil charcoal could be tentatively identified as Jackrogersella cohaerens and(more tentatively)as Hypoxylon *** three species are still commonly encountered in the forests of Central Europe ***,the HPLC-HRMS data of *** suggested the presence of unknown azaphilone dimers and of further new *** archaeological compounds were compared to fresh stromata of *** collected in Germany and subjected to the same analytical *** the major components in both samples were identified as the known mitorubrin type azaphilones and orsellinic acid,the chemical structures of seven novel complex azaphilone pigments,for which we propose the trivial names rutilins C-D and fragirubrins A-E,were elucidated using spectral methods(NMR and CD spectroscopy,high resolution mass spectrometry).It appears that these pigments had indeed persisted for millennia in the fossil stromata.

关键词： Biodiversity Chemotaxonomy Phylogeny Sordariomycetes Xylariales Structure elucidation

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Mutation Status of KRAS, BRAF, PIK3CA and Expression Level of AREG and EREG Identify Responders to Cetuximab in a Large Panel of Patient Derived Colorectal Carcinoma Xenografts of All Four UICC Stages

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Journal of Cancer Therapy 2013年第2期4卷 678-693页

作者： Paulina Pechanska M.becker T.Mayr B.Hinzmann H.-P.Adams I.Klaman K.-H.Kretschmar K.Kretschmar K.Stecker R.Mantke R.Pauli J.Pertschy K.Hertel K.Ridwelski K.Hellwig M.Pross C.Radke I.Fichtner J.Hoffmann A.Rosenthal Signature Diagnostics AG PotsdamGermany Experimental Pharmacology&Oncology Berlin-Buch gmbh BerlinGermany Stadtisches Klinikum Brandenburg gmbh Klinik fur Allgemein-und ViszeralchirurgieInstitut fur PathologieBrandenburg an der HavelGermany Katholisches Krankenhaus St.Johann Nepomuk Klinik fur Allgemeine ChirurgieErfurtGermany HELIOS Klinikum Erfurt Institut fur PathologieErfurtGermany Klinikum Magdeburg Klinik für Allgemein-und ViszeralchirurgieInstitut fur PathologieMagdeburgGermany DRK Kliniken Berlin-Kopenik Klinik fur ChirurgieInstitut fur PathologieBerlinGermany Max Delbruck Center fur Molekulare Medizin(MDC) Experimentale PharmakologieBerlinGermany.

To advance preclinical testing of novel targeted drugs in colorectal cancer (CRC) we established a panel of 133 mouse xenograft models from fresh tumor specimens of 239 patients with CRC of all four UICC stages. A subgroup of 67 xenograft models was treated with cetuximab, bevacizumab and oxaliplatin as single agents. Mutation status of KRAS (G12, G13, A146T), BRAF (V600E) and PIK3CA (E542K, E545K, H1047R) was assessed in all xenografts by allelespecific real-time PCR. KRAS codon 61 was assessed by conventional sequencing. AREG and EREG expression levels were analyzed by real-time PCR expression assays. In the treatment experiment we observed response rates of 27% (18/67) for cetuximab, 3% (2/67) for bevacizumab, and 6% (4/67) for oxaliplatin. Classification based on KRAS, BRAF and PIK3CA mutation status identified 15 of the responders (sensitivity 83%, confidence interval at p = 0.05 (CI): 59% - 96%), and 38 nonresponders (specificity 78%, CI: 63% - 88%). If any mutation except in KRAS codon 13 were considered, the classifier reached sensitivity of 94% and specificity of 69%. We improved specificity of the classifiers to 90% and 86% respectively by adding AREG and EREG RNA expression thresholds retrospectively. In patient-derived xenograft models, we found a predictive classifier for response to cetuximab that is more accurate than established biomarkers. We confirmed its potential performance in primary human tumors. For patients, the classifier’s sensitivity promises increased response rates and its specificity limits unnecessary toxicity. Given the scope of our xenograft models across all UICC stages, this applies not only to mCRC but also to the adjuvant setting of earlier stages. The xenograft collection allows to mimic randomized phase II trials and to test novel drugs effectively as single agents or in combinations. It also enables the development of highly accurate companion diagnostics as demonstrated by us for cetuximab.

关键词： Colorectal Cancer Xenograft Mutation Biomarker Cetuximab

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质子转移反应质谱仪的技术改进及其在新领域中的应用

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生命科学仪器 2011年第5期9卷 23-25页

作者： Philipp SULZER Alfons JORDAN Lukas MARK Christopher A. MAYHEW Kurt becker Tilmann D. MARK IONICON Analytik gmbh Eduard-Bodem-Gasse 3 6020 InnsbruckAustria Molecular PhysicsGroup School of Physics and Astronomy University of Birmingham Edgbaston Birmingham U.K. Dr Dept. of Physics Polytechnic Institute of New York University Brooklyn NY U.S.A. Dr. T~ Institut fur Ionenphysik und Angewandte Physik Leopold Franzens Universitat （Innsbruck Austria）l

质子转移反应质谱仪(PTR-MS)拥有着独特的发展历程。1995年,世界上只有两个刊物报道这个相对陌生的技术。现在PTR-MS技术已经比较成熟,本文就其最新技术发展和新领域应用进行深入地讨论。

关键词：质子转移反应技术改进质谱仪应用最新技术

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Measurement of the integrated luminosities of the data taken by BESⅢ at √s=3.650 and 3.773 GeV

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Chinese Physics C 2013年第12期37卷 1-6页

作者：麦迪娜 M.N.Achasov O.Albayrak D.J.Ambrose 安芬芬安琪白景芝 R.Baldini Ferroli 班勇 J.becker J.V.Bennett M.Bertani 边渐鸣 E.Boger O.Bondarenko I.Boyko S.Braun R.A.Briere V.Bytev 蔡浩蔡啸 O.Cakir A.Calcaterra 曹国富 S.A.Cetin 常劲帆 G.Chelkov 陈刚陈和生陈江川陈玛丽陈申见陈旭荣陈元柏程和平初元萍 D.Cronin-Hennessy 代洪亮代建平 D.Dedovich 邓子艳 A.Denig I.Denysenko M.Destefanis 丁伟民丁勇董燎原董明义杜书先方建房双世 L.Fava 封常青 P.Friedel 傅成栋傅金林 O.Fuks 高原宁耿聪 K.Goetzen 龚文煊 W.Gradl M.Greco 顾旻皓顾运厅管颖慧郭爱强郭立波郭墩郭玉萍韩艳良 F.A.Harris 何康林何苗何振亚 T.Held 衡月昆侯治龙胡深胡海明胡继峰胡涛黄光明黄光顺黄金书黄亮黄性涛黄勇 T.Hussain 姬长胜纪全姬清平季晓斌季筱璐姜丽丽江晓山焦健斌焦铮金大鹏金山景繁凡 N.Kalantar-Nayestanaki M.Kavatsyuk B.Kloss B.Kopf M.Kornicer W.Kuehn 赖蔚 J.S.Lange M.Lara P.Larin M.Leyhe 李春花李澄李翠李德民李飞李刚李海波李家才李康李蕾李培荣李秋菊李卫东李卫国李晓玲李小男李学潜李秀荣李志兵梁昊梁勇飞梁羽铁廖广瑞 D.X.LinLin 刘北江 C.L.Liu 刘春秀刘福虎刘芳刘峰刘宏邦刘汇慧刘怀民刘觉平刘凯刘魁勇刘佩莲刘倩刘树彬刘翔刘玉斌刘振安刘志强刘智青 H.Loehner 娄辛丑鲁公儒吕海江吕军光吕晓睿卢云鹏罗成林罗民兴 T.Luo 罗小兰吕蒙马凤才马海龙马秋梅马斯马天马骁妍 F.E.Maas M.Maggiora Q.A.Malik 冒亚军毛泽普 J.G.Messchendorp 阂建闵天觉 R.E.Mitchell 莫晓虎 H.Moeini C.Morales Morales K.Moriya N.Yu.Muchnoi H.Muramatsu Y.Nefedov I.B.Nikolaev 宁哲 S.Nisar 马鹏欧阳群 S.Pacetti J.W.Park M.Pelizaeus 彭海平 K.Peters 平加伦平荣刚 R.Poling E.Prencipe 祁鸣钱森乔从丰秦丽清秦小帅秦瑶秦中华邱进发 K.H.Rashid C.F.Redmer 荣刚阮向东 A.Sarantsev 邵明沈成平沈肖雁盛华义 M.R.Shepherd 宋维民宋新颖 S.Spataro B.Spruck 孙功星孙俊峰孙胜森孙勇杰孙永昭孙志嘉孙振田唐昌建唐晓 I.Tapan E.H.Thorndike D.Toth M.Ullrich I.Uman G.S.Varner 王斌王东王大勇王科王亮亮王灵淑王萌王平王佩良王庆娟王思广王雄飞汪晓莲 Y.D.WangYadi 王贻芳王亚乾王铮王志刚王志宏王至勇魏代会韦江波 P.Weidenkaff 文群刚文硕频 M.Werner U.Wiedner 伍灵慧吴宁吴硕星吴蔚吴智夏力钢夏宇肖振军谢宇广修青磊许国发徐庆君徐庆年徐新平许志蕊薛镇严亮鄢文标闺文成颜永红杨洪勋杨迎杨永栩叶桦叶梅叶铭汉俞伯祥喻纯旭于海旺俞洁晟于帅鹏苑长征n 袁野 A.A.Zafar A.Zallo 臧石磊曾云张丙新张炳云张驰张长春张达华张宏浩章红宇张敬庆张家文张建勇张景芝张丽丽张书华张晓杰张学尧张瑶张银鸿张子平张振宇张正好赵光赵京伟赵雷赵玲赵明刚赵强赵书俊赵天池赵祥虎赵豫斌赵政国 A.Zhemchugov 郑波郑建平郑阳恒钟彬周莉周详周晓康周小蓉朱凯朱科军朱相雷朱莹春朱永生朱自安庄建邹冰松邹佳恒 Institute of High Energy Physics Chinese Academy of Sciences G.I.Budker Institute of Nuclear Physics SB RAS (BINP) Also at the Novosibirsk State University Carnegie Mellon University Pittsburgh University of Rochester Rochester University of Science and Technology of China INFN Laboratori Nazionali di Frascati Peking University Bochum Ruhr-University Indiana University Bloomington University of Minnesota Minneapolis Joint Institute for Nuclear Research Also at the Moscow Institute of Physics and Technology KVI University of Groningen Universitaet Giessen Wuhan University Ankara University Dogol Caddesi Dogus University Nanjing University Lanzhou University Huangshan College Johannes Gutenberg University of Mainz University of Turin INFN Shandong University Liaoning University Zhengzhou University University of Eastern Piedmont Tsinghua University GSI Helmholtzcentre for Heavy Ion Research gmbh GuangXi University University of Chinese Academy of Sciences Nankai university Nanjing Normal University University of Hawaii Central China Normal University Henan Normal University University of the Punjab Helmholtz Institute Mainz Hangzhou Normal University Seoul National University Sun Yat-Sen University Sichuan University Shanxi University Henan University of Science and Technology Also at University of Texas at Dallas Zhejiang University COMSATS Institute of Information Technology INFN and University of Perugia University of Minnesota Also at the PNPI Beihang University Uludag University Guangxi Normal University Hunan University Soochow University China Center of Advanced Science and Technology University of South China

Data sets were collected with the BESⅢ detector at the BEPCⅡ collider at the center-of-mass energy of √s=3.650 GeV during May 2009 and at √s=3.773 GeV from January 2010 to May 2011. By analyzing the large angle Bhabha scattering events, the integrated luminosities of the two data sets are measured to be （44.49±0.02±0.44） pb-1 and （2916.94±0.18±29.17） pb-1, respectively, where the first error is statistical and the second error is systematic.

关键词： Bhabha scattering events integrated luminosity cross section

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