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f.nite element analyses of.slope stability problems using non-associated plasticity

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Journal of.Rock Mechanics and Geotechnical Engineering 2018年第6期10卷 1091-1101页

作者： Simon Oberhollenzer f.anz Tschuchnigg helmut f.schweiger Institute of.Soil Mechanics Foundation Engineering and Computational Geotechnics Graz University of Technology

In recent years, f.nite element analyses have increasingly been utilized f.r slope stability problems. In comparison to limit equilibrium methods, numerical analyses do not require any def.nition of.the f.ilure mechanism a priori and enable the determination of.the saf.ty level more accurately. The paper compares the perf.rmances of.strength reduction f.nite element analysis(SRf.A) with f.nite element limit analysis(f.LA), whereby the f.cus is related to non-associated plasticity. Displacement-based f.nite element analyses using a strength reduction technique suf.er f.om numerical instabilities when using non-associated plasticity, especially when dealing with high f.iction angles but moderate dilatancy angles. The f.LA on the other hand provides rigorous upper and lower bounds of.the f.ctor of.saf.ty(f.S) but is restricted to associated f.ow rules. Suggestions to overcome this problem, proposed by Davis(1968), lead to conservative f.Ss; theref.re, an enhanced procedure has been investigated. When using the modif.ed approach, both the SRf.A and the f.LA provide very similar results. f.rther studies highlight the advantages of.using an adaptive mesh ref.nement to determine f.Ss. Additionally, it is shown that the initial stress f.eld does not af.ect the f.S when using a Mohr-Coulomb f.ilure criterion.

关键词： f.nite element limit analysis(f.LA) f.nite element method Slope stability Strength reduction technique Non-associated plasticity Adaptive mesh ref.nement Initial stresses

New endoscopic approaches in IBD

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World Journal of.Gastroenterology 2011年第1期17卷 63-68页

作者： helmut Neumann Markus f.Neurath Jonas Mudter Department of.Medicine I University of Erlangen-Nuremberg91054 ErlangenGermany

Recent advances in endoscopic imaging techniques have revolutionized the diagnostic approach of.patients with inf.ammatory bowel disease(IBD).New,emerging endoscopic imaging techniques visualized a plethora of.new mucosal details even at the cellular and subcellular *** review of.ers an overview about new endoscopic techniques,including chromoendoscopy,magnif.cation endoscopy,spectroscopy,conf.cal laser endomicroscopy and endocytoscopy in the f.ce of.IBD.

关键词： Endoscopy Inf.ammatory bowel disease Endomicroscopy Endocytoscopy Narrow band imaging f.jinon intelligent color enhancement i-Scan Spectroscopy Chromoendoscopy Ulcerative colitis Crohn's disease f.uorescence endoscopy

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基于静态松弛的一种广义界面单元方法

岩石力学与工程学报 2000年第1期19卷 24-28页

作者：陈文胜冯夏庭葛修润 helmut f.schweiger 中国科学院武汉岩土力学研究所武汉430071 奥地利格拉茨技术大学土力学与基础工程研究所

根据静态松弛快速拉格朗日分析方法（Ｓ－ＦＬＡＣ），提出了一种求解岩体界面的新方法即广义界面单元方法。该方法可真实模拟界面的各种复杂变形。推导了相应公式，并给出了两个典型算例。

关键词：静态松弛拉格朗日分析岩体界面

Cancer risk in IBD: How to diagnose and how to manage DALM and ALM

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World Journal of.Gastroenterology 2011年第27期17卷 3184-3191页

作者： helmut Neumann Michael Vieth Cord Langner Markus f.Neurath Jonas Mudter Department of.Medicine 1 Department of SurgeryUniversity of Erlangen-Nuremberg Ulmenweg 1891054 ErlangenGermany Institute of.Pathology Klinikum Bayreuth GmbHPreuschwitzer Str. 10195445 BayreuthGermany Institute of.Pathology Medical University of GrazAuenbruggerplatz 25A-8036 Graz Austria

The risk of.developing neoplasia leading to colorectal cancer is signif.cantly increased in ulcerative colitis (UC) and most likely in Crohn's disease. Several endoscopic surveillance strategies have been implemented to identif. these lesions. The main issue is that colitisassociated neoplasms of.en occurs in f.at mucosa, of.en being detected on taking random biopsies rather than by identif.cation of.these lesions via endoscopic imaging. The standard diagnostic procedure in long lasting UC is to take f.ur biopsies every 10 cm. Image enhancement methods, such as chromoendoscopy and virtual histology using endomicroscopy, have greatly im- proved neoplasia detection rates and may contribute toreduced random biopsies by taking targeted "smart" biopsies. Chromoendoscopy may ef.ectively be perf.rmed by experienced endoscopists f.r routine screening of.UC patients. By contrast, endomicroscopy is of.en only available in selected specialized endoscopic centers. Importantly, advanced endoscopic imaging has the poten- tial to increase the detection rate of.neoplasia whereas the interplay between endoscopic experience and interpretation of.histological biopsy evaluation allows the physician to make a proper diagnosis and to f.nd the appropriate therapeutic approach. Colitis-associated intraepithelial neoplasms may occur in f.at mucosa of.endoscopically normal appearance or may arise as dysplasia-associated lesion or mass (DALM), which may be indistinguishable f.om sporadic adenomas in healthy or non-colitis mucosa [adenoma-like mass (ALM)]. The aim of.this review was to summarize endoscopic and histological characteristics of.DALM and ALM in the context of.therapeutic procedures.

关键词： Inf.ammatory bowel disease Crohn’s dis- ease Endoscopy Colitis Dysplasia-associated lesion or mass Adenoma-like mass Endomicroscopy Ulcerative colitis Endomicroscopy Conf.cal laser endomicroscopy Probe-based conf.cal laser endomicroscopy Integrated conf.cal laser endomicroscopy Endoscope-based conf.cal laser endomicroscopy Narrow band imaging Chromoendoscopy Cancer Dysplasia

f.om the surf.ce to the single cell: Novel endoscopic approaches in inf.ammatory bowel disease

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World Journal of.Gastroenterology 2015年第40期21卷 11260-11272页

作者： Timo Rath Gian Eugenio Tontini Markus f.Neurath helmut Neumann Department of.Medicine 1 Division of GastroenterologyUniversity Hospital Erlangen Gastroenterology and Digestive Endoscopy Unit IRCCS Policlinico San Donato20097 San Donato MilaneseItaly

Inf.ammatory bowel diseases(IBD) comprise the two major entities Crohn's disease and ulcerative colitis and endoscopic imaging of.the gastrointestinal tract has always been an integral and central part in the management of.IBD patients. Within the recent years,mucosal healing emerged as a key treatment goal in IBD that substantially decides about the clinical outcome of.IBD patients,thereby demanding f.r a precise,timely and detailed endoscopic assessment of.the mucosal inf.ammation associated with IBD. f.rther,molecular imaging has tremendously expanded the clinical utility and applications of.modern endoscopy,now encompassing not only diagnosis,surveillance,and treatment but also the prediction of.individual therapy response. Within this review we describe novel endoscopic approaches and advanced endoscopic imaging methods f.r the diagnosis,treatment and surveillance of.IBD patients. We begin by providing an overview over novel and advanced imaging techniques such as magnif.cation endoscopy and dye-based and dye-less chromoendoscopy,endomicroscopy and endocytoscopy. We then describe how these techniques can be utilized f.r the precise and ultrastructural assessment of.mucosal inf.ammation and dysplasia development associated with IBD and outline how they have enabled the endoscopist to gain insight onto the cellular level in real-time. f.nally,we provide an outlook on how molecular imaging has rapidly evolved in the recent past and can be used to make individual predictions about the therapeutic response towards biological treatment.

关键词： Gastrointestinal endoscopy Crohn’s disease Ulcerat

Selection in monoculture vs. mixture alters plant metabolic f.ngerprints

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Journal of.Plant Ecology 2015年第5期8卷 549-557页

作者： Debra Zuppinger-Dingley Dan f.B.f.ynn helmut Brandl Bernhard Schmid Institute of.Evolutionary Biology and Environmental Studies University of ZurichWinterthurerstrasse 190CH-8057 ZurichSwitzerland The Arnold Arboretum of.Harvard University 1300 Centre StreetBostonMA 02131USA

Aims In grassland biodiversity experiments,positive biodiversity ef.ects on primary productivity increase over *** research has shown that dif.erential selection in monoculture and mixed-species communities leads to the rapid emergence of.monoculture and mix-ture types,adapted to their own biotic *** used eight plant species selected f.r 8 years in such a biodiversity experiment to test if.monoculture and mixture types dif.ered in metabolic pro-f.les using inf.ared *** f.urier transf.rm inf.ared spectroscopy(f.Ir)was used to assess metabolic f.ngerprints of.leaf.samples of.10 individuals of.each species f.om either monocultures or *** f.Ir spectra were analyzed using multivariate procedures to assess(i)whether indi-viduals within species could be correctly assigned to monoculture or mixture history based on the spectra alone and(ii)which parts of.the spectra drive the group assignment,*** metabolic groups were subject to dif.erential selection in monocultures *** f.ndings Plant individuals within each of.the eight species could be classif.ed as either f.om monoculture or mixture selection history based on their f.Ir *** metabolic groups were dif.erentially selected in the dif.erent species;some of.them may be related to def.nse of.patho-gens accumulating more strongly in monocultures than in *** rapid selection of.the monoculture and mixture types within the eight study species could have been due to a sorting-out process based on large initial genetic or epigenetic variation within the species.

关键词： biodiversity plant evolution selection f.Ir spectroscopy metabolic f.ngerprint

Dif.erential diagnosis in inf.ammatory bowel disease colitis:State of.the art and f.ture perspectives

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World Journal of.Gastroenterology 2015年第1期21卷 21-46页

作者： Gian Eugenio Tontini Maurizio Vecchi Luca Pastorelli Markus f.Neurath helmut Neumann Gastroenterology and Digestive Endoscopy Unit IRCCS Policlinico San Donato20097 San Donato MilaneseItaly Department of.Medicine I University of Erlangen-Nuremberg91054 ErlangenGermany Department of.Biomedical Sciences f.r Health University of Milan20122 MilanoItaly

Distinction between Crohn's disease of.the colonrectum and ulcerative colitis or inf.ammatory bowel disease(IBD) type unclassif.ed can be of.pivotal importance f.r a tailored clinical management,as each entity of.en involves specif.c therapeutic strategies and ***,no gold standard is available and the uncertainty of.diagnosis may f.equently lead to misclassif.cation or repeated ***,we have perf.rmed a literature search to address the problem of.dif.erential diagnosis in IBD colitis,revised current and emerging diagnostic tools and ref.ned disease classif.cation ***,the dif.erential diagnosis is an untangled issue,and the proper diagnosis cannot be reached in up to 10% of.patients presenting with IBD *** topic is receiving emerging attention,as medical therapies,surgical approaches and leading prognostic outcomes require more and more disease-specif.c strategies in IBD *** optimization of.standard diagnostic approaches based on clinical f.atures,biomarkers,radiology,endoscopy and histopathology appears to provide only marginal ***,emerging diagnostic techniques in the f.eld of.gastrointestinal endoscopy,molecular pathology,genetics,epigenetics,metabolomics and proteomics have already shown promising *** advanced endoscopic imaging techniques and biomarkers can shed new light f.r the dif.erential diagnosis of.IBD,better ref.ecting diverse disease behaviors based on specif.c pathogenic pathways.

关键词： Crohn’s disease Ulcerative colitis Inf.ammatory bo

f.rst case report of.exacerbated ulcerative colitis af.er anti-interleukin-6R salvage therapy

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World Journal of.Gastroenterology 2015年第45期21卷 12963-12969页

作者： Raja Atreya Ulrike Billmeier Timo Rath Jonas Mudter Michael Vieth helmut Neumann Markus f.Neurath Markus f.Neurath Medical Clinic 1 Friedrich-Alexander University Erlangen-Nürnberg Medical Department Hospital Ostholstein Institute of.Pathology Klinikum Bayreuth

We present the case of.a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNf.antibodies(inf.iximab, adalimumab) and tacrolimus, who ref.sed colectomy as a therapeutic option. As the pro-inf.ammatory cytokine interleukin-6(IL-6) had been identif.ed as a crucial regulator in the immunopathogenesis of.inf.ammatory bowel diseases, we treated the patient with biweekly intravenous inf.sions of.an anti-IL-6R antibody(tocilizumab) f.r 12 wk. However, no clinical improvement of.disease activity was noted. In f.ct, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of.mucosal inf.ammation and ulcer f.rmation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment f.iled to suppress intestinal IL-6 production, impaired epithelial barrier f.nction and induced production of.pro-inf.ammatory cytokines such as TNf. IL-21 and If.-γ. Inhibition of.IL-6 by tocilizumab had no clinical benef.t in this patient with intractable ulcerative colitis and even led to exacerbation of.mucosal inf.ammation. Our f.ndings suggest that anti-IL-6R antibody therapy may leadto aggravation of.anti-TNf.resistant ulcerative colitis. When targeting IL-6, the dif.erential responsiveness of.target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inf.ammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling.

关键词： Ulcerative colitis Interleukin-6 Epithelial barrie

Alcoholic liver disease and hepatitis C:A f.equently underestimated combination

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World Journal of.Gastroenterology 2009年第28期15卷 3462-3471页

作者： Sebastian Mueller Gunda Millonig helmut K Seitz Department of.Medicine and Center f.r Alcohol Research Live Disease and Nutrition Salem Medical Center University of Heidelberg Zeppelinstraβe 11-33 69121 Heidelberg Germany

Alcoholic liver disease(ALD) and hepatitis C virus(HCV) inf.ction represent, either alone or in combination, more than two thirds of.all patients with liver disease in the Western *** review discusses the epidemiology and combined impact of.ALD and HCV on the progres sion of.liver *** and HCV af.ect the progres sion of.liver disease to liver cirrhosis and hepatocellular carcinoma(HCC) in a synergistic ***, the risk f.r HCC increases f.ive times with a daily alcohol con sumption of.80 g;in the presence of.HCV it is increased 20f.ld, and a combination of.both risk f.ctors leads to a more than 100f.ld risk f.r HCC *** consumption also decreases the response to interf.ron treatment which is probably due to a lack of.compliance than a direct ef.ect on HCV *** molecu lar mechanisms are discussed that could explain the synergistic interaction of.alcohol and HCV on disease *** include modulation of.the immune response and apoptosis, increased oxidative stress via induction of.CYP2E1 and the hepatic accumulation of.***, both HCV and alcohol independently cause hepatic iron accumulation in > 50% of.patients probably due to suppression of.the liversecreted systemic iron hormone hepcidin.A better understanding of.hepcidin regulation could help in developing novel therapeutic approaches to treat the chronic disease in the *** now, it can be generally concluded that HCVinf.ct ed patients should abstain f.om alcohol and alcoholicsshould be encouraged to participate in detoxif.cation programs.

关键词： Alcoholic liver disease Chronic hepatitis C Steatosis Steatohepatitis f.brosis Cirrhosis Reactiveoxygen species Hepatocellular carcinoma Iron accu-mulation