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浅谈固相微萃取的理论和条件优化

现代科学仪器 2024年第4期41卷 29-35页

作者：王玮 Stephan Altmaier 默克化工技术(上海)有限公司上海200120 merck Life Sciences kgaa DarmstadtGermany

固相微萃取是一种简便高效的方法,无需使用任何有机或化学试剂,即可实现对液相或顶空的挥发性或非挥发性物质的高选择性富集。SPME是一种与GC、HPLC联用技术相结合、具有广泛的分析线性范围等优点。本项目拟采用高效液相色谱-质谱联用技... 详细信息

固相微萃取是一种简便高效的方法,无需使用任何有机或化学试剂,即可实现对液相或顶空的挥发性或非挥发性物质的高选择性富集。SPME是一种与GC、HPLC联用技术相结合、具有广泛的分析线性范围等优点。本项目拟采用高效液相色谱-质谱联用技术,通过调控色谱柱的极性、膜厚、连续采样等多种方法,实现对样品中微量目标化合物的高纯度、高稳定性的检测。

关键词：固相微萃取(SPME) 样品制备样品萃取

LC-MS/MS测定生活饮用水中27种PFAS化合物

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现代科学仪器 2024年第4期41卷 50-56页

作者：王玮 Stephan Altmaier 默克化工技术(上海)有限公司上海200120 merck Life Sciences kgaa DarmstadtGermany

建立了超高效液相色谱-串联质谱(UHPLC-MS/MS)同时测定生活饮用水中27种PFAS(全氟和多氟烷基物质)的分析方法。水样采用固相萃取富集浓缩的样品前处理过程,离子化模式为:ESI-,多反应监测模式(MRM)进行定性分析;外标法进行定量分析。27种... 详细信息

建立了超高效液相色谱-串联质谱(UHPLC-MS/MS)同时测定生活饮用水中27种PFAS(全氟和多氟烷基物质)的分析方法。水样采用固相萃取富集浓缩的样品前处理过程,离子化模式为:ESI-,多反应监测模式(MRM)进行定性分析;外标法进行定量分析。27种PFAS化合物在0.005-0.2mg/L线性浓度范围内具有良好的线性响应,相关系数R2均大于0.9990。加标回收率为82.9%-108%,相对标准偏差为1.6-8.6%,27种PFAS化合物的定量限为3.0-5.0μg/kg。该方法可用于饮用水中PFAS的检测和分析,具有较高的准确性和可靠性。以期为市场监管部门的监督抽查提供技术支撑。

关键词：超高效液相色谱-串联质谱 PFAS 生活饮用水

Glass transition temperature prediction of disordered molecular solids

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npj Computational Materials 2021年第1期7卷 1633-1639页

作者： Kun-Han Lin Leanne Paterson Falk May Denis Andrienko Max Planck Institute for Polymer Research Ackermannweg 1055128 MainzGermany merck kgaa 64293 DarmstadtGermany

Glass transition temperature,Tg,is the key quantity for assessing morphological stability and molecular ordering of films of organic semiconductors.A reliable prediction of Tg from the chemical structure is,however,challenging,as it is sensitive to both molecular interactions and analysis of the heating or cooling *** combining a fitting protocol with an automated workflow for forcefield parameterization,we predict Tg with a mean absolute error of~20℃for a set of organic compounds with Tg in the 50–230℃*** study establishes a reliable and automated prescreening procedure for the design of amorphous organic semiconductors,essential for the optimization and development of organic light-emitting diodes.

关键词： automated prediction transition

AZ~ 15nXT Photoresist for Lift-off Applications

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高分子通报 2014年第12期 170-178页

作者： CHEN Chun-wei TOUKHY Medhat BOGUSZ Zachary MEYER Stephen LIU Wei-hong LU Ping-hung AZ Electronic Materials USA Corp.(A Subsidiary of merck kgaa DarmstadtGermany)

AZ15nXT is a chemically-amplified negative-tone thick film *** resist has vertical profile and is widely used for redistribution layer(RDL)and through silicon vias(TSV)*** lift-off applications,however,the inverted profile is *** this paper,we report the effects of process conditions on the resist profile and process window for lift off applications.

关键词： Chemically amplified Thick film Lift-off Negative photoresist Inverted profile

Boron-modified perhydropolysilazane towards facile synthesis of amorphous SiBN ceramic with excellent thermal stability

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Journal of Advanced Ceramics 2022年第7期11卷 1104-1116页

作者： Ying ZHAN Wei LI Tianshu JIANG Claudia FASEL Emmanuel III RICOHERMOSO Jan BERNAUER Zhaoju YU Zhenghao WU Florian MÜLLER-PLATHE Leopoldo MOLINA-LUNA Ralf GROTTENMÜLLER Ralf RIEDEL Department of Materials and Earth Sciences Technical University of DarmstadtD-64287 DarmstadtGermany College of Materials Key Laboratory of High Performance Ceramic Fibers(Xiamen University)Ministry of EducationXiamen 361005China Eduard-Zintl-Institut für Anorganische und Physikalische Chemie Technical University of DarmstadtD-64287 DarmstadtGermany merck kgaa Performance MaterialsD-64293DarmstadtGermany

SiBN ceramics are widely considered to be the most promising material for microwavetransparent applications in harsh environments owing to its excellent thermal stability and low dielectric *** work focuses on the synthesis and ceramization of single-source precursors for the preparation of SiBN ceramics as well as the investigation of the corresponding microstructural evolution at high temperatures including molecular dynamic ***-and chlorine-free perhydropolysilazanes were reacted with borane dimethyl sulfide complex at different molar ratios to synthesize single-source precursors,which were subsequently pyrolyzed and annealed under N2 atmosphere(without ammonolysis)to prepare SiBN ceramics at 1100,1200,and 1300℃with high ceramic yield in contrast to previously widely-used ammonolysis synthesis *** obtained amorphous SiBN ceramics were shown to have remarkably improved thermal stability and oxidation resistance compared to amorphous silicon ***,the experimental results have been combined with molecular dynamics simulation to further study the amorphous structure of SiBN and the atomic-scale diffusion behavior of Si,B,and N at 1300℃.Incorporation of boron into the Si–N network is found to suppress the crystallization of the formed amorphous silicon nitride and hence improves its thermal stability in N2 atmosphere.

关键词： polymer-derived ceramics(PDCs) SiBN crystallization molecular dynamics oxidation resistanc

TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies

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World Journal of Gastroenterology 2009年第47期15卷 5924-5935页

作者： Bruno Christian Koehler Toni Urbanik Binje Vick Regina Johanna Boger Steffen Heeger Peter R Galle Marcus Schuchmann Henning Schulze-Bergkamen First Department of Medicine Johannes Gutenberg-University Mainz55101 MainzGermany Steffen HeegerMerck KGaAMS-D Global Clinical Development Unit-Oncology64293 DarmstadtGermany National Center of Tumor Diseases Department of Medical OncologyUniversity Clinic of Heidelberg69120 HeidelbergGermany

AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering *** cellswere treated with kinase inhibitors and chemotherapeutic *** induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis *** resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor ***,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC ***, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and ***:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in

关键词： Hepatocellular carcinoma Apoptosis Tumor necrosis factor-related apoptosis inducing ligand BCL-xL MCL-1 5-fluorouracil Doxorubicin Sorafenib Phosphoinositol-3-kinase (Mitogen-activated protein kinase)/(extracellular signal regulated kinase) kinase c-Jun N-terminal kinase

应用三阶梯系统结构设计万维网上运行的系统(英文)

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应用三阶梯系统结构设计万维网上运行的系统(英文)

Cetuximab plus irinotecan in pretreated metastatic colorectal cancer patients:The ELSIE study

“科技增强国力，青年开创未来——携手走向辉煌的新世纪”中国科协第三届青年学术年会

作者：彭卫国 merck kgaa DarmstadtGermany

企业信息系统软件已经经历了从传统的二阶梯client/server到intranet三阶梯系统结构。这一设计将复杂的商业逻辑与用户显示分离开来,并将其移到运算能力更强的主机上。分机的负担可随之减小到最小程度。这是基于恰当地结合当前的万维网... 详细信息

企业信息系统软件已经经历了从传统的二阶梯client/server到intranet三阶梯系统结构。这一设计将复杂的商业逻辑与用户显示分离开来,并将其移到运算能力更强的主机上。分机的负担可随之减小到最小程度。这是基于恰当地结合当前的万维网技术(HTML,Java),分散系统标准(RMI,DCOM,CORBA)以及数据库的连接。其优点是反映时间短,应变能力强。作为例子,我们还介绍了一个100%的纯Java方法。三阶梯系统结构可以用来作为一种普遍的系统开发设计,另外还可用作融合其它数据的方法。

关键词：三阶梯系统结构软件设计万维网 JDBC CORBA

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World Journal of Gastroenterology 2011年第14期17卷 1879-1888页

作者： Robert Lim Yan Sun Seock-Ah Im Ruey-Kuen Hsieh Tsz Kok Yau Anthony Bonaventura Arkom Cheirsilpa Regina Esser Matthias Mueser Suresh Advani Department of Hematology-Oncology National University Hospital 119074 Singapore Singapore Department of Medical Oncology Cancer Hospital and Institute Chinese Academy of Medical Science Beijing 100021 China Division of Hematology-Oncology Department of Internal Medicine Seoul National University Hospital Seoul 110-744 South Korea Department of Oncology-Hematology Mackay Memorial Hospital Taipei 104 Taiwan China Department of Clinical Oncology Pamela Youde Nethersole Eastern Hospital Hong Kong China Department of Medical Oncology Calvary Mater Newcastle Hospital Waratah New South Wales 2298. Australia National Cancer Institute Bangkok 10400 Thailand Global Clinical Development Unit Oncology Merck KGaA Darmstadt 64293 Germany Medical Affairs Oncology Asia Pacific Merck Serono 609927 Singapore Singapore Jaslok Hospital and Research Centre Mumbai 400026 India

AIM:To evaluate the efficacy and safety of cetuxim-ab plus irinotecan in irinotecan-refractory metastatic colorectal cancer (mCRC) patients from South-East Asia and Australia. METHODS:In this open-label,phase Ⅱ study,the main eligibility criteria were epidermal growth factor receptor-positive mCRC with progressive disease within 3 mo of an irinotecan-based regimen as the most recent chemotherapy. Patients received cetuximab 400 mg/m2 initially,then 250 mg/m2 every week,with the same regimen of irinotecan on which the patients had progressed (4 pre-defined regim-ens allowed). The prim-ary objective was evaluation of progression-free survival (PFS) at 12 wk. Secondary objectives included a further investigation of PFS,and an assessment of the overall response rate (ORR),duration of response,time to treatment failure (TTF),overall survival and the safety profile. RESULTS:One hundred and twenty nine patients were enrolled from-25 centers in the Asia-Pacific region and of these 123 received cetuximab plus irinotecan. The most common recent irinotecan regimen used was 180 mg/m2 every 2 wk which had been used in 93 patients (75.6%). The PFS rate at 12 wk was 50% (95% confidence interval (CI,41-59) and m-edian PFS tim-e was 12.1 wk (95% CI:9.7-17.7). The ORR was 13.8% (95% CI:8.3-21.2) and disease control rate was 49.6% (95% CI:40.5-58.8). Median duration of response was 31.1 wk (95% CI:18.0-42.6) and median overall survival was 9.5 mo (95% CI,7.5-11.7). The median TTF was 11.7 wk (95% CI:9.1-17.4). Treatment was generally well tolerated. The most common grade 3/4 adverse events were diarrhea (13.8%),neutropenia (8.9%),rash (5.7%) and vomiting (5.7%).CONCLUSION:In patients from Asia and Australia,this study confirm-s the activity and safety of cetuxim-ab plus irinotecan observed in previous studies in Europe and South America.

关键词： Epidermal growth factor receptor Cetuximab Irinotecan Metastatic colorectal cancer Asia

Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial

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World Journal of Gastroenterology 2010年第25期16卷 3133-3143页

作者： Janja Ocvirk Thomas Brodowicz Fritz Wrba Tudor E Ciuleanu Galina Kurteva Semir Beslija Ivan Koza Zsuzsanna Pápai Diethelm Messinger Ugur Yilmaz Zsolt Faluhelyi Suayib Yalcin Demetris Papamichael Miklós Wenczl Zrinka Mrsic-Krmpotic Einat Shacham-Shmueli Damir Vrbanec Regina Esser Werner Scheithauer Christoph C Zie-linski Institute of Oncology 1000 Ljubljana Slovenia Clinical Division of Oncology Department of Medicine I Medical University of Vienna 1090 Vienna Austria Clinical Institute of Pathology Medical University of Vienna 1090 Vienna Austria Institutul Oncologic Cluj 400015 Cluj-Nap-oca Romania Department of Oncology National Specialized Hospital of Active Treatment in Oncology 1754 Sofi a Bulgaria Institute of Oncology Clinical Center of Sara-jevo University 71000 Sarajevo Bosnia-Herzegovina Department of Oncology National Cancer Institute 83310 Bratislava Slovak Republic AEK Onkologiai Osztaly 1122 Budapest Hungary Biometrics IST GmbH 68219 Mannheim Germany Department of Gastroenterology 9 Eylül Univer-sity Medical Faculty 35340 Izmir Turkey Oncology Department Veszprém County Hos-pital 8200 Veszprém Hungary Institute of Oncology Ankara Hacettepe Univer-sity 06100 Ankara Turkey Department of Medical Oncology Bank of Cyprus Oncology Center 2006 Nicosia Cyprus Department of Oncoradiology Markusovszky Teaching Hospital 9700 Szombathely Hungary Department of Medical Oncology Uni-versity Hospital for Tumors 10000 Zagreb Croatia Oncology Division Tel-Aviv Souraski Medical Center Tel Aviv 64239 Israel KBC Rebro Oncology Department 10000 Zagreb Croatia merck kgaa D64293 Darmstadt Germany

AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56%vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated. CONCLUSION: This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC.

关键词： Cetuximab 5-fluorouracil folinic acid and oxaliplatin 5-fluorouracil folinic acid and irinotecan KRAS Metastatic colorectal cancer