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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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Perspective on ultramicroporous carbon as sulphur host for Li-S batteries

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Journal of Energy Chemistry 2021年第8期30卷 242-256,I0006页

作者： Helen Maria Joseph Maximilian fichtner Anji Reddy Munnangi ASTUTE 2020 College of EngineeringSwansea UniversityFabian WaySA18EN SwanseaUnited Kingdom Helmholtz institute Ulm(HiU)Electrochemical Energy Storage Helmholtzstraße 1189081 UlmGermany institute of Nanotechnology Karlsruhe Institute of TechnologyP.O.Box 3640D-76021 KarlsruheGermany College of Engineering Swansea UniversityFabian WaySA18EN SwanseaUnited Kingdom

Lithium-sulphur(Li-S)batteries are currently considered as next-generation battery *** is an attractive positive electrode for lithium metal batteries,mainly due to its high capacity(1675 m Ah g^(-1))and high specific energy(2600 Wh kg^(-1)).The electrochemical reaction of lithium with sulphur in non-aqueous electrolytes results in the formation of electrolyte soluble intermediate *** dissolved polysulphides shuttle to the anode and get reduced at the anode resulting in Li metal *** solubility of polysulphide gradually reduces the amount of sulphur in the cathode,thereby limiting the cycle life of Li-S *** strategies have been proposed to improve the cycling stability of Li-S batteries.A unique approach to eliminate the polysulphide shuttle is to use ultramicroporous carbon(UMC)as a host for *** pore size of UMC which is below 7A,is the bottleneck for carbonate solvents to access sulphur/polysulphides confined in the pores,thereby preventing the polysulphide *** perspective article will emphasise the role of UMC host in directing the lithiation mechanism of sulphur and in inhibiting polysulphide dissolution,including the resulting parasitic reaction on the lithium ***,the challenges that need to be addressed by UMC-S based Li-S batteries,and the strategies to realise high power density,high Coulombic efficiency,and resilient Li-S batteries will be discussed.

关键词： Lithium-sulphur batteries Ultramicroporous carbon Sulphur Cathode Composites

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A review on current anode materials for rechargeable Mg batteries

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Journal of Magnesium and Alloys 2020年第4期8卷 963-979页

作者： Dajian Li Yuan Yuan Jiawei Liu Maximilian fichtner Fusheng Pan Karlsruhe institute of Technology Institute for Applied Materials-Applied Materials Physics(IAM-AWP)Hermann-von-Helmholtz-Platz 176344 Eggenstein-LeopoldshafenGermany National Engineering Research Center for Magnesium Alloys(CCMG) College of Materials Science and EngineeringChongqing University400044 ChongqingChina Karlsruhe institute of Technology Institute of Nanotechnology(1NT)Hermann-von-Helmholtz-Platz 176344 Eggenstein-LeopoldshafenGermany Helmholtz-institute Ulm(HiU) Helmholtzstr.1189081 UlmGermany

There is an increasing demand for rechargeable batteries in high-performance energy storage *** current dominating Li-ion batteries are limited by price,resource availability,as well as their theoretical *** that the community has started to explore alternative battery *** a promising multivalent battery type,rechargeable magnesium batteries(RMBs)have attracted increasing attention because of high safety,high volumetric energy density,and low cost thanks to abundant resource of ***,the development of high-performance anodes is still hampered by formation of passivating layers on the Mg ***,dendrites can also grow under certain conditions with pure Mg anodes,which requires further studies for reliable operation window and ***,this review specifically aims to provide an overview on the often overlooked yet very important anode materials of RMBs,with the hope to inspire more attention and research efforts for the achievement of over-all better performance of future RMBs.c 2020 Published by Elsevier *** behalf of Chongqing University.

关键词： Rechargeable Mg batteries Anode materials

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Comparison of hyperthermic intraperitoneal chemotherapy regimens for treatment of peritoneal-metastasized colorectal cancer

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World Journal of Gastrointestinal Oncology 2020年第8期12卷 903-917页

作者： Julia Spiegelberg Hannes Neeff Philipp Holzner Mira Runkel Stefan fichtner-Feigl Torben Glatz Department of General and Visceral Surgery Medical Center–University of FreiburgFreiburg 79106Germany Department of Surgery Marien Hospital HerneRuhr-University BochumHerne 44625Germany

BACKGROUND Cytoreductive surgery(CRS)in combination with hyperthermic intraperitoneal chemotherapy(HiPEC)improves patient survival in colorectal cancer(CRC)with peritoneal carcinomatosis(PC).Commonly used cytotoxic agents include mitomycin C(MMC)and *** have reported varying results,and the evidence for the choice of the HiPEC agent and uniform procedure protocols is *** To evaluate therapeutic benefits and complications of CRS+MMC vs oxaliplatin HiPEC in patients with peritoneal metastasized CRC as well as prognostic *** One hundred and two consecutive patients who had undergone CRS and HiPEC for CRC PC between 2007 and 2019 at the Medical Center of the University Freiburg regarding interdisciplinary cancer conference decision were retrospectively *** and MMC were used in 68 and 34 patients,*** patient’s demographics and tumour characteristics,operative details,postoperative complications and survival were *** were stratified and graded using Clavien/Dindo *** outcome factors were identified using univariate and multivariate analysis of *** The two groups did not differ significantly regarding baseline *** found no difference in median overall survival between MMC and oxaliplatin *** postoperative complications,patients treated with oxaliplatin HiPEC suffered increased complications(66.2%vs 35.3%;P=0.003),particularly intestinal atony,intraabdominal infections and urinary tract infection,and had a prolonged intensive care unit stay compared to the MMC group(7.2 d vs 4.4 d;P=0.035).Regarding univariate analysis of survival,we found primary tumour factors,nodal positivity and resection margins to be of prognostic value as well as peritoneal cancer index(PCi)-score and the completeness of cytoreduction regarding peritoneal *** analysis of survival confirmed primary distant metastasis and primary tumour resec

关键词： Colorectal cancer Peritoneal carcinomatosis Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Chemotherapy Mitomycin

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Effects of local neighbourhood diversity on crown structure and productivity of individual trees in mature mixed-species forests

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Forest Ecosystems 2021年第2期8卷 345-356页

作者： Louis Georgi Matthias Kunz Andreas fichtner Karl Friedrich Reich Anne Bienert Hans-Gerd Maas Goddert von Oheimb Technische Universität Dresden Institute of General Ecology and Environmental ProtectionPienner Straße 701737 TharandtGermany Leuphana University of Lüneburg Institute of EcologyUniversitätsallee 121335 LüneburgGermany Technische Universität Dresden Institute of Photogrammetry and Remote SensingHelmholtzstraße 1001069 DresdenGermany

Background:Species-specific genotypic features,local neighbourhood interactions and resource supply strongly influence the tree stature and growth *** mixed-species forests,diversity-mediated biomass allocation has been suggested to be a fundamental mechanism underlying the positive biodiversity-productivity *** evidence,however,is rare about the impact of local neighbourhood diversity on tree characteristics analysed at a very high level of *** address this issue we analysed these effects on the individual-tree crown architecture and tree productivity in a mature mixed forest in northern ***:Our analysis considers multiple target tree species across a local neighbourhood species richness gradient ranging from 1 to *** applied terrestrial laser scanning to quantify a large number of individual mature trees(N=920)at very high *** evaluated two different neighbour inclusion approaches by analysing both a fixed radius selection procedure and a selection based on overlapping *** and conclusions:We show that local neighbourhood species diversity significantly increases crown dimension and wood volume of target ***,we found a size-dependency of diversity effects on tree productivity(basal area and wood volume increment)with positive effects for large-sized trees(diameter at breast height(DBH)>40 cm)and negative effects for small-sized(DBHis,the neighbour inclusion approach has a significant impact on the *** scientific studies and the validation of growth models we recommend a neighbour selection by overlapping crowns,because this seems to be the relevant scale at which local neighbourhood interactions *** local neighbourhood diversity promotes individual-tree productivity in mature European mixed-species forests,we conclude that a small-scale species mixture should be considered in management plans.

关键词： Biodiversity Tree growth Crown architecture Quantitative structure models Terrestrial laser scanning Neighbour classification

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Sclerosing angiomatoid nodular transformation of the spleen, a rare cause for splenectomy: Two case reports

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World Journal of Clinical Cases 2020年第1期8卷 103-109页

作者： Sophia Chikhladze Ann-Kathrin Lederer Stefan fichtner-Feigl Uwe A Wittel Martin Werner Konrad Aumann Department of General and Visceral Surgery Medical Center-University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburg 79106Germany Center for Complementary Medicine Department of Infection Prevention and Hospital EpidemiologyMedical Center-University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburg 79106Germany institute of Surgical Pathology Medical Center-University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburg 79106Germany

BACKGROUND Sclerosing angiomatoid nodular transformation(SANT)is a rare benign disease of the spleen with unknown *** symptoms are inhomogeneous,and suspicious splenic lesion often found incidentally,leading to splenectomy,as malignancy cannot securely be ruled *** is made histologically after *** SUMMARY Two cases of German,white,non-smoking,and non-drinking patients of normal weight are *** first one is a 26-year-old man without medical history who was exhibiting an undesired weight loss of 10 kg and recurring vomiting for about 18 *** second one is a 65-year-old woman with hypertension who had previously undergone gynecological surgery,suffering from a lasting feeling of abdominal *** showed radiologically an inhomogeneous splenic lesion leading to splenectomy approximately 6 and 9 wk after surgical *** diagnoses of SANT were made ***-up went well,and both were treated according to the recommendation for asplenic *** SANT is a rare cause of splenectomy and an incidental histological *** research should focus on clinical and radiological diagnosis of SANT as well as on treatment of patients with asymptomatic and small findings.

关键词： Splenectomy Sclerosing angiomatoid nodular transformation Spleen Abdominal discomfort Gastrointestinal dysfunction Case report

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On the Quantum Zeno Effect and Time Series Related to Quantum Measurements

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Applied Mathematics 2013年第10期4卷 61-69页

作者： Karl-Heinz fichtner Kei inoue School of Mathematics and Computer Science Institute of Applied MathematicsFriedrich-Schiller-Universitat JenaJenaGermany Department of Electrical Engineering Faculty of EngineeringTokyo University of ScienceYamaguchiSanyoonodaJapan

Our main aim is to prove a more general version of the quantum Zeno effect. Then we discuss some examples of the quantum Zeno effect. Furthermore, we discuss a possibility that based on the quantum Zeno effect and certain experiments one could check whether, from the statistical point of view, a concrete system behaves like a quantum system. The more general version of quantum Zeno effect can be helpful to prove that the brain acts like in a quantum system. The proof of our main result is based on certain formulas describing probability distributions of time series related to quantum measurements.

关键词： Quantum Zeno Effect Quantum Measurements Time Series

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E65/E75:高性能精梳机的新境界

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纺织导报 2006年第12期 65-69页

作者： Stephan fichtner Rieter(立达)机械有限公司

Rieter公司的新一代精梳机E 65/E 75从工艺上和技术上把精梳技术推向了高性能的新纪元.现在450钳次/min的钳速已经在车间实际生产条件下实现.下面详细介绍新一代精梳机E 65/E 75的工艺特性及其精梳条的特点和对后道工序的积极作用.

关键词：精梳机性能 Rieter公司工艺特性生产条件后道工序精梳条技术

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五次插值样条在NC过程链中的应用研究

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机械科学与技术 2002年第S1期21卷 75-77页

作者：田锡天杨海成 fichtner 西北工业大学西安710072 德国德累斯顿工业大学

对几种五次样条插值算法的性质及其在 NC铣削轨迹处理、CNC技术及逆向工程中的可使用性进行了研究 ,并讨论了曲线参数化方法。

关键词：五次样条插值曲线拟合数控铣削

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Electrochemical top-down synthesis of C-supported Pt nanoparticles with controllable shape and size:Mechanistic insights and application

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Nano Research 2021年第8期14卷 2762-2769页

作者： Batyr Garlyyev Sebastian Watzele Johannes fichtner Jan Michalicka Alexander Schokel Anatoliy Senyshyn Andrea Perego Dingjie Pan Hany A.El-Sayed Jan M.Macak Plamen Atanassov iryna V.Zenyuk Aliaksandr S.Bandarenka Physics of Energy Conversion and Storage Technical University of MunichJames Franck Strafle 185748 Garching Germany Central European institute of Technology Brno University of TechnologyPurkynova 12361200 BrnoCzech Republic Deutsches Elektronen Synchrotron(DESY) Notkestr.8522607HamburgGermany Heinz Maier-Leibnitz-Zentrum(MLZ) Technische Universitat MiinchenLichtenbergstr.185748 Garching Germany Department of Chemical Engineering National Fuel Cell Research Center University of CaliforniaIrvine92697-2580 CaliforniaUSA Department of Material Science and Engineering University of CaliforniaIrvine92697-2580 CaliforniaUSA Chair of Technical Electrochemistry Technical University of MunichLichtenbergstrafie 485748 Garching Germany

in this work,we demonstrate the power of a simple top-down electrochemical erosion approach to obtain Pt nanoparticle with controlled shapes and sizes(in the range from-2 to-10 nm).Carbon supported nanoparticles with narrow size distributions have been synthesized by applying an alternating voltage to macroscopic bulk platinum structures,such as disks or *** using any surfactants,the size and shape of the particles can be changed by adjusting simple parameters such as the applied potential,frequency and electrolyte *** instance,application of a sinusoidal AC voltage with lower frequencies results in cubic nanoparticles;whereas higher frequencies lead to predominantly spherical *** the other hand,the amplitude of the,sinusoidal signal was found to affect the particle size;the lower the amplitude of the applied AC signal,the smaller the resulting particle ***/C catalysts prepared by this approach showed 0.76 A/mg mass activity towards the oxygen reduction reaction which is-2 times higher than the state-of-the-art commercial Pt/C catalyst(0.42 A/mg)from *** addition to this,we discussed the mechanistic insights about the nanoparticle formation pathways.

关键词： electrochemical synthesis platinum nanoparticles oxygen reduction reaction

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