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In vivo detection of mucosal healing-involved histiocytes by confocal laser endomicroscopy

World Journal of Gastroenterology 2012年第32期18卷 4447-4449页

作者： Gheorghe Hundorfean Abbas Agaimy Mircea T Chiriac Walter GeiBdrfer Jochen Wacker markus f neurath Jonas Mudter Medical ClinicⅠ University of ErlangenNuremberg91054 ErlangenGermany Institute of Pathology University of Erlangen-Nuremberg91054 ErlangenGermany Microbiology Institute-Clinical Microbiology Immunology and HygieneUniversity of Erlangen-Nuremberg91054 ErlangenGermany Medical Clinic Ⅲ University of Erlangen-Nuremberg91054 ErlangenGermany

Histiocytes have a pivotal role in wound repair and intestinal epithelial recovery-the most important goal to sustain gut ***,an in vivo description of colonic histiocytes by confocal laser endomicroscopy(CLE) is ***,we report the case of a 45-yearsold male patient who was referred to our clinic with weight loss and a history of two consecutive Clostridium difficile colitis episodes,the latter cured 3 wk before present *** microbiology was *** colonoscopy showed atrophy and a light mucosal oedema in the distal *** on-going endoscopy,we performed a fluorescein-aided CLE which revealed large polygonal(histiocytes-like) cells with copious cytoplasm and large nuclei in the lamina propria of the sigmoid colon as well as regenerative epithelial *** assessment of biopsies from the same areas confirmed the endomicroscopical findings:Periodic acid-Schiff-and CD68-positive foamy histiocytes in the colonic lamina propria and an advanced epithelial *** stool microbiology was repeatedly negative and polymerase chain reaction-analysis from colonic biopsies could not detect any mRNA for Thropheryma whippleii and common pathogens,we interpreted this particular setting as a mucosal healing process after consecutive Clostridium difficile *** conclusion,by describing these colonic histiocytes,we highlight the clinical usefulness of CLE in describing the entity of histiocytes in vivo and in real-time during the process of post-infectious mucosal healing in the colon.

关键词： Endomicroscopy Mucosal healing Advanced colonic imaging Colonic histiocytes

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first case report of exacerbated ulcerative colitis after 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(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNf, IL-21 and IfN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNf resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation 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

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Advances in hepatitis C therapy: What is the current state-what come's next?

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World Journal of Hepatology 2016年第3期8卷 139-147页

作者： Steffen Zopf Andreas E Kremer markus f neurath Juergen Siebler Medical Department 1 University of Erlangen Nuremberg

Chronic hepatitis C virus(HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver *** is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ***,treatment of HCV has undergone a revolutionary change in recent *** admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents(DAA).Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal *** rates of sustained virological response(SVR) rates can be achieved with these novel *** in difficult to treat populations such as patients with liver cirrhosis,HCV-human immunodeficiency virus co-infections,after liver transplantion,or with chronic kidney disease comparable high rates of SVR can be *** anticipated 2nd generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or posttransplant *** 2nd generations DAAs will have higher resistance barriers,higher antiviral effects and a pan-genotypic *** review highlights the current state of the art of antiviral treatment in hepatitis Cand gives an outlook for upcoming therapies.

关键词： hepatitis C virus direct antiviral agents sustained virological response liver transplantation renal impairment cirrhosis

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Comparison of Hemospray~? and Endoclot? for the treatment of gastrointestinal bleeding

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World Journal of Gastroenterology 2019年第13期25卷 1592-1602页

作者： francesco Vitali Andreas Naegel Raja Atreya Steffen Zopf Clemens Neufert Juergen Siebler markus f neurath Timo Rath Ludwig Demling Endoscopy Center of Excellence Division of Gastroenterology Friedrich-Alexander-University

BACKGROUND Gastrointestinal(GI) bleeding is a common indication for endoscopy. for refractory cases, hemostatic powders(HP) represent "touch-free" *** To analyze short term(ST-within 72 h-) and long-term(LT-within 30 d-) success for achieving hemostasis with HP and to directly compare the two agents Hemospray(HS) and Endoclot(EC).METHODS HP was applied in 154 consecutive patients(mean age 67 years) with GI *** were followed up for 1 mo(mean follow-up: 3.2 mo).RESULTS Majority of applications were in upper GI tract(89%) with following bleeding sources: peptic ulcer disease(35%), esophageal varices(7%), tumor bleeding(11.7%), reflux esophagitis(8.7%), diffuse bleeding and erosions(15.3%). Overall ST success was achieved in 125 patients(81%) and LT success in 81 patients(67%). Re-bleeding occurred in 27% of all patients. In 72 patients(47%), HP was applied as a salvage hemostatic therapy, here ST and LT success were 81% and64%, with re-bleeding in 32%. As a primary hemostatic therapy, ST and LT success were 82% and 69%, with re-bleeding occurring in 22%. HS was more frequently applied for upper GI bleeding(P = 0.04)CONCLUSION Both HP allow for effective hemostasis with no differences in ST, LT success and re-bleeding.

关键词： Hemostatic powder Gastrointestinal bleeding Hemospray Endoclot Haemostasis

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The effect of Laves phases and nano-precipitates on the electrochemical corrosion resistance of Mg-Al-Ca alloys under alkaline conditions

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Journal of Magnesium and Alloys 2024年第6期12卷 2447-2461页

作者： markus felten Veronika Chaineux Siyuan Zhang Ali Tehranchi Tilmann Hickel Christina Scheu Joshua Spille Marta Lipińska-Chwałek Joachim Mayer Benjamin Berkels Marcus Hans Imke Greving Silja flenner Sandra Sefa Daniela Zander Chair of Corrosion and Corrosion Protection RWTH Aachen UniversityAachen 52072 Germany Max-Planck-Institut für Eisenforschung GmbH Düsseldorf 40237 Germany Central facility for Electron Microscopy RWTH Aachen UniversityAachen 52074 Germany Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons Forschungszentrum Jülich GmbHJülich 52428Germany Mathematical Image and Signal Processing Aachen Institute for Advanced Study in Computational Engineering ScienceRWTH Aachen UniversityAachen 52062 Germany Materials Chemistry RWTH Aachen UniversityAachen 52074 Germany Institute of Materials Physics Helmholtz-Zentrum HereonGeesthacht 21502 Germany

The electrochemical corrosion mechanisms of Mg alloys were extensively studied in previous investigations of different chemical com-positions,modified surface states and various electrolyte ***,recent research focused on the active state of Mg dissolution,leading to unresolved effects of secondary phases adjacent to a stableα-solid solution passive *** present study investigates the fundamental electrochemical corrosion mechanisms of three different Laves phases with varying phase morphologies and phase fractions in the passive state of Mg-Al-Ca *** microstructure was characterized by(transmission-)electron microscopy and synchrotron-based transmission X-ray *** electrochemical corrosion resistance was determined with a standard three-electrode setup and advanced in-situ flow cell measurements.A new electrochemical activity sequence(C15>C36>α-Mg>C14)was obtained,as a result of a stable passive layer formation on theα-solid ***,nm-scale Mg-rich precipitates were identified within the Laves phases,which tend to inhibit the corrosion kinetics.

关键词： Laves phase STEM Magnesium Corrosion Passive layer

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Demonstrating grating-based phase-contrast imaging of laser-driven shock waves

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Matter and Radiation at Extremes 2024年第4期9卷 90-97页

作者： Leonard Wegert Stephan Schreiner Constantin Rauch Bruno Albertazzi Paulina Bleuel Eric frojdh Michel Koenig Veronika Ludwig Artem SMartynenko Pascal Meyer Aldo Mozzanica Michael Müller Paul Neumayer markus Schneider Angelos Triantafyllidis Bernhard Zielbauer Gisela Anton Thilo Michel Stefan funk Plasma Physics Department GSI Helmholtzzentrum fur SchwerionenforschungPlanckstraBe 164291 DarmstadtGermany Erlangen Centre for Astroparticle Physics(ECAP) Friedrich-Alexander-Universität Erlangen-NurnbergNikolaus-Fiebiger-StraBe 291058 ErlangenGermany LULI-CNRS CEASorbonne UniversitésEcole PolytechniqueInstitut Polytechnique de ParisF-91120 Palaiseau CedexFrance Paul Scherrer Institut(Psi) Forschungsstrasse 1115232VilligenSwitzerland Karlsruhe Institute of Technology Institute of Microstructure TechnologyHermann-von-Helmholtz-Platz 176344 Eggenstein-LeopoldshafenGermany

Single-shot X-ray phase-contrast imaging is used to take high-resolution images of laser-driven strong shock *** a two-grating Talbot interferometer,we successfully acquire standard absorption,differential phase-contrast,and dark-field images of the shocked *** agreement is demonstrated between experimental data and the results of two-dimensional radiation hydrodynamics simulations of the laser-plasma *** main sources of image noise are identified through a thorough assessment of the interferometer’s *** acquired images demonstrate that grating-based phase-contrast imaging is a powerful diagnostic tool for high-energy-density *** addition,we make a novel attempt at using the dark-field image as a signal modality of Talbot interferometry to identify the microstructure of a foam target.

关键词： interaction shock phase

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Genetic composition,genetic diversity and small-scale environmental variation matter for the experimental reintroduction of a rare plant

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Journal of Plant Ecology 2016年第6期9卷 805-813页

作者： Daniel Prati markus Peintinger markus fischer Institute of Plant Sciences University of BernAltenbergrain 21CH-3013 BernSwitzerland Oeschger Centre for Climate Change Research University of BernZähringerstrasse 25CH-3012 BernSwitzerland WSL-Eidgenössische forschungsanstalt für Wald Schnee und LandschaftZürcherstrasse 111CH-8903 BirmensdorfSwitzerland

Aims Reintroduction has become an important tool for the management of endangered plant *** tested the little-explored effects of small-scale environmental variation,genotypic composition(*** of genotypes)and genotypic diversity on the population survival of the regionally rare clonal plant Ranunculus *** this species of periodically inundated lakeshores,genetic differentiation had been reported between populations and between short-flooded and long-flooded microsites within *** We established 306 experimental test populations at a previously unoccupied lakeshore,comprising either monocultures of 32 genotypes,mixtures of genotypes within populations or mixtures of genotypes between *** 2000,three years after planting out at the experimental site,a long-lasting flood caused the death of half of the experimental *** 2003,an extreme drought resulted in the lowest summer water levels ever *** findings Despite these climatic extremes,27%of the established populations survived in December *** success of experimental populations largely differed between ***,the success of genotype monocultures depended on genotype and source *** differentiation between microsites played a minor role for the success of *** the flood,populations planted with genotypes from different source populations increased in abundance,whereas populations with genotypes from single source populations and genotype monocultures *** 2014,several small patches of Ranunculus clones were still present,but plants were strongly intermingled,which precluded their assignment to the original *** conclude that sources for reintroductions need to be selected ***,mixtures of plants from different populations appear to be the best choice for successful reintroduction,at least in unpredictably varying environments.

关键词： conservation management global change lakeshore Ranunculus reptans

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t-Private and t-Secure Auctions

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Journal of Computer Science & Technology 2008年第5期23卷 694-710页

作者： markus Hinkelmann Andreas Jakoby Peer Stechert Institut für Theoretische Informatik Universitt zu Lübeck Germany fachgruppe Didaktik der Informatik und E-Learning Universitt Siegen Germany

In most of the auction systems the values of bids are known to the auctioneer. This allows him to manipulate the outcome of the auction. Hence, one might be interested in hiding these values. Some cryptographically secure protocols for electronic auctions have been presented in the last decade. Our work extends these protocols in several ways. On the basis of garbled circuits, i.e., encrypted circuits, we present protocols for sealed-bid auctions that fulfill the following requirements： 1） protocols are information-theoretically t-private for honest but curious parties; 2） the number of bits that can be learned by malicious adversaries is bounded by the output length of the auction; 3） the computational requirements for participating parties are very low： only random bit choices and bitwise computation of the XOR-function are necessary. Note that one can distinguish between the protocol that generates a garbled circuit for an auction and the protocol to evaluate the auction. In this paper we address both problems. We will present a t-private protocol for the construction of a garbled circuit that reaches the lower bound of 2t ＋ 1 parties, and finally, we address the problem of bid changes in an auction. a more randomness efficient protocol for （t ＋ 1）^2 parties

关键词： multi-party private and secure computation garbled circuits private auctions

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Ultrahigh numerical aperture meta-fibre for flexible optical trapping

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Light(Science & Applications) 2021年第4期10卷 589-599页

作者： Malte Plidschun Haoran Ren Jisoo Kim Ronny forster Stefan A.Maier markus A.Schmidt Leibniz Institute of Photonic Technology 07745 JenaGermany Abbe Center of Photonics and faculty of Physics FSU Jena07745 JenaGermany Chair in Hybrid Nanosystems Nanoinstitute MunichLMU Munchen80539 MunchenGermany Department of Physics Imperial College LondonLondon SW72AZUK Otto Schott Institute of Material Research FSU Jena07745 JenaGermany

Strong focusing on diffraction-limited spots is essential for many photonic applications and is particularly relevant for optical trapping;however,all currently used approaches fail to simultaneously provide flexible transportation of light,straightforward implementation,compatibility with waveguide circuitry,and strong ***,we demonstrate the design and 3D nanoprinting of an ultrahigh numerical aperture meta-fibre for highly flexible optical *** into account the peculiarities of the fibre environment,we implemented an ultrathin meta-lens on the facet of a modified single-mode optical fibre via direct laser writing,leading to a diffraction-limited focal spot with a recordhigh numerical aperture of up to NA≈*** unique capabilities of this flexible,cost-effective,bio-and fibre-circuitrycompatible meta-fibre device were demonstrated by optically trapping microbeads and bacteria for the first time with only one single-mode fibre in combination with diffractive *** study highlights the relevance of the unexplored but exciting field of meta-fibre optics to a multitude of fields,such as bioanalytics,quantum technology and life sciences.

关键词： optical waveguide fibre

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Omicron:Master of immune evasion maintains robust ACE2 binding

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1360-1362页

作者： markus Hoffmann Lu Zhang Stefan Pohlmann Infection Biology Unit German Primate Center—Leibniz Institute for Primate ResearchGöttingenGermany Georg-August-University Göttingen GöttingenGermany

The spike(S)protein of the SARS-CoV-2 Omicron variant is highly mutated but the impact of these mutations on viral entry into cells and its inhibition by antibodies has been unclear.A recent study published in Science by Mannar et *** shows that these mutations are compatible with robust ACE2 binding and allow for efficient evasion of neutralizing *** emergence of SARS-CoV-2 variants has become a hallmark of the COVID-19 *** of concern(VOC)harbor mutations in the viral S protein that can increase transmissibility,potentially by promoting S protein binding to the cellular receptor ACE2.

关键词： ACE2 maintain

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