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Polymorphisms in NF-κB,PXR,LXR,PPARγ and risk of inflammatory bowel disease

World Journal of Gastroenterology 2011年第2期17卷 197-206页

作者： Vibeke Andersen Jane Christensen anja ernst Bent A Jacobsen Anne Tjφnneland Henrik B Krarup Ulla Vogel Department of Medical Viborg Regional Hospital Institute of Cancer Epidemiology Danish Cancer Society Department of Clinical Biochemistry Aarhus University Hospital Department of Medical Gastroenterology Aarhus University Hospital National Food Institute Technical University of Denmark Institute for Science Systems and ModelsUniversity of Roskilde National Research Centre for the Working Environment

AIM:To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease(IBD) . METHODS:Genotypes of nuclear factor(NF) -κB(NFKB1) NFκB-94ins/del(rs28362491) ;peroxisome proliferatoractivated receptor(PPAR) -γ(PPARγ) PPARγPro12Ala(rs1801282) and C1431T(rs 3856806) ;pregnane X receptor(PXR) (NR1I2) PXR A-24381C(rs1523127) ,C8055T(2276707) ,and A7635G(rs 6785049) ;and liver X receptor(LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn's disease patients,495 ulcerative colitis(UC) patients,and 779 healthy *** ratio(OR) and 95%CI were estimated by logistic regression models. RESULTS:The PXR A7635G variant,the PPARγPro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC(OR:1.31,95% CI:1.03-1.66,P=0.03,OR:2.30,95%CI:1.04-5.08,P=0.04,and OR:1.41,95%CI:1.00-1.98,P=0.05,respectively) compared to the corresponding homozygous wild-type *** never smokers,PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD(OR:1.41,95%CI:1.05-1.91,P=0.02,OR:1.63,95%CI:1.21-2.20,P=0.001,and OR:2.02,95%CI:1.36-2.99,P=0.0005,respectively) compared to the respective homozygous variant *** A7635G(rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease(OR:1.34,95%CI:1.03-1.75 and OR:2.49,95%CI:1.24-5.03,respectively) . CONCLUSION:Common PXR and LXR polymorphisms may contribute to risk of IBD,especially among never smokers.

关键词： Crohn's disease Genetic susceptibility Single nucleotide polymorphisms Smoking status Transcription factors Ulcerative colitis

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Reactivity against microsatellite instability-induced frameshift mutations in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2015年第1期21卷 221-228页

作者： Florian Kuehn ernst Klar anja Bliemeister Michael Linnebacher Department of General ThoracicVascular and Transplantation SurgeryMolecular Oncology and ImmunotherapyUniversity of Rostock18057 RostockGermany

AIM: To analyze the cellular immune response towards microsatellite-instability(MSI)-induced frameshift-peptides(FSPs) in patients suffering from inflammatory bowel disease(IBD) with and without thiopurine-based immunosuppressive ***: Frequencies of peripheral blood T cell responses of IBD patients(n = 75) against FSPs derived from 14 microsatellite-containing candidate genes were quantified by interferon-γ enzyme-linked immunospot.T cells derived from 20 healthy individuals served as ***: Significant T cell reactivities against MSIinduced FSPs were observed in 59 of 75 IBD patients(78.7%).This was significantly more as we could observe in 20 healthy controls(P = 0.001).Overall,the reactivity was significantly influenced by thiopurine treatment(P = 0.032) and duration of disease(P = 0.002) but not by duration or cumulative amount of thiopurine therapy(P = 0.476).Unexpected,15 of 24(62.5%) IBD patients without prior thiopurine treatment also showed increased FSP-specific immune responses(P = 0.001).CONCLUSION: These findings propose FSPs as potential novel class of inflammation-associated antigens and this in turn may have implications for screening,diagnosis as well as clinical management of patients suffering from IBD and other inflammatory conditions.

关键词： Microsatellite-instability Inflammatory bowel dise

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CONJUGATE-SYMPLECTICITY OF LINEAR MULTISTEP METHODS

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Journal of Computational Mathematics 2008年第5期26卷 657-659页

作者： ernst Hairer Section de Mathématiques Univ.de Genève

For the numerical treatment of Hamiltonian differential equations, symplectic integrators are the most suitable choice, and methods that are conjugate to a symplectic integrator share the same good long-time behavior. This note characterizes linear multistep methods whose underlying one-step method is conjugate to a symplectic integrator. The bounded- hess of parasitic solution components is not addressed.

关键词： Linear multistep method Underlying one-step method Conjugate-symplecticity,Symmetry.

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Establishment,functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line

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World Journal of Gastroenterology 2018年第33期24卷 3749-3759页

作者： Michael Gock Christina S Mullins Christine Harnack Friedrich Prall Robert Ramer anja Goder Oliver H Kramer ernst Klar Michael Linnebacher Department of General Surgery University of RostockRostock 18055Germany Department of General Surgery Section of Molecular Oncology and ImmunotherapyUniversity of RostockRostock 18055Germany Institute of Pathology University of RostockRostock 18055Germany Institute of Pharmacology University of RostockRostock 18055Germany Institute of Toxicology University Medical Center MainzMainz 55131Germany

AIM To establish cell line and patient-derived xenograft(PDX) models for neuroendocrine carcinomas(NEC) which is highly desirable for gaining insight into tumor development as well as preclinical research includingbiomarker testing and drug response *** Cell line establishment was conducted from direct in vitro culturing of colonic NEC tissue(HROC57). A PDX could also successfully be established from vitally frozen tumor samples. Morphological features, invasive and migratory behavior of the HROC57 cells as well as expression of neuroendocrine markers were vastly analyzed. Phenotypic analysis was done by microscopy and multicolor flow cytometry. The extensive molecular-pathological profiling included mutation analysis, assessment of chromosomal and microsatellite instability; and in addition, fingerprinting(i.e., STR analysis) was performed from the cell line in direct comparison to primary patient-derived tissues and the PDX model established. Drug responsiveness was examined for a panel of chemotherapeutics in clinical use for the treatment of solid *** The established cell line HROC57 showed distinct morphological and molecular features of a poorly differentiated large-cell NEC with KI-67 > 50%. Molecular-pathological analysis revealed a Cp G island promoter methylation positive cell line with microsatellite instability being absent. The following mutation profile was observed: KRAS(wt), BRAF(mut). A high sensitivity to etoposide, cisplatin and 5-FU could be demonstrated while it was more resistant towards rapamycin. CONCLUSION We successfully established and characterized a novel patient-derived NEC cell line in parallel to a PDX model as a useful tool for further analysis of the biological characteristics and for development of novel diagnostic and therapeutic options for NEC.

关键词： Patient-derived tumor model Large cell neuroendocrine carcinoma Individualized medicine

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Insensitive high explosives:Ⅳ. Nitroguanidine-Initiation & detonation

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Defence Technology（防务技术） 2019年第4期15卷 467-487页

作者： ernst-Christian Koch Lutradyn-Energetic Materials

This paper reviews the detonative properties of low bulk density(LBD),high bulk density(HBD)Nitroguanidine(NGu)(1),CAS-No:[556-88-7]and 82 explosive formulations based on NGu reported in the public *** rank the performance of those formulations they are compared with 15 reference compositions containing both standard high explosives such as octogen(HMX)(2),hexogen(RDX)(3),pentaerythritol tetranitrate(PETN)(4),2,4,6-trinitrotoluene(TNT)(5)as well as insensitive high explosives such as 3-nitro-1,2,4-triazolone(NTO)(6),1,3,5-triamino-2,4,6-trinitrobenzene(TATB)(7),1,1-diamino-2,2-dinitroethylene(FOX-7)(8)and N-Guanylurea dinitramide(FOX 12)(9).NGu based formulations are superior to those based on FOX-12 or TATB and are a close match with FOX-7 based explosives,the latter just having higher Gurney Energies(-10%)and slightly higher detonation pressure(+2%).NGu based explosives even reach up to 78% of the detonation pressure,82% Gurney energy and up to 95% of detonation velocity of ***-NGu dissolves in many melt cast eutectics forming dense charges thereby eliminating the need for costly High Bulk Density *** based formulations are at the rock bottom of sensitiveness among all the above-mentioned explosives which contributes to the safety of these *** review gives 132 references to the public *** a review on the synthesis spectroscopy and sensitiveness of Nitroguanidine see Ref.[1].

关键词： Cook-off Detonation Insensitive munitions Nitroguanidine Shock sensitvity

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Special materials in pyrotechnics Ⅶ: Pyrotechnics used in thermal batteries

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Defence Technology（防务技术） 2019年第3期15卷 254-263页

作者： ernst-Christian Koch Lutradyn Energetic Materials Science & Technology

Thermal batteries are unique direct current(DC) electrical power sources with long shelf live, high reliability and higher power density than classical alkaline batteries. This paper gives a brief overview into the working principle of thermal batteries and reviews the properties of zirconium/barium chromate(Zr/BaCrO4) pyrolant previously used as first fire and iron/potassium perchlorate(Fe/KClO4) pyrolant(Heat), commonly applied as heating pellet in thermal batteries and its hazard properties. The review gives 64 references to the public domain. CAS-Nos. Zr: [7440-67-7], BaCrO4: [10294-40-3], Fe: [7439-89-6], KClO4: [7778-74-7], Viton: [9011-17-0].CAS-Nos. Zr: [7440-67-7], BaCrO4: [10294-40-3], Fe: [7439-89-6], KClO4: [7778-74-7], Viton: [9011-17-0].

关键词： Barium chromate Heat-powder Iron Lithium Molten salt Potassium perchlorate Pyrotechnics Thermal battery Zirconium

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Using coalgebras and the Giry monad for interpreting game logics a tutorial

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Frontiers of Computer Science 2017年第6期11卷 948-970页

作者： ernst-Erich DOBERKAT Math++ Software Bochum 44879 Germany

The stochastic interpretation of Parikh＇s game logic should not follow the usual pattern of Kripke models, which in turn are based on the Kleisli morphisms for the Giry monad, rather, a specific and more general approach to proba- bilistic nondeterminism is required. We outline this approach together with its probabilistic and measure theoretic basis, in- troducing in a leisurely pace the Giry monad and its Kleisli morphisms together with important techniques for manipu- lating them. Proof establishing specific techniques are given, and pointers to the extant literature are provided. After working through this tutorial, the reader should find it easier to follow the original literature in this and related areas, and it should be possible for her or him to appreciate measure theoretic arguments for original work in the areas of Markov transition systems, and stochastic effectivity func- tions.

关键词： coalgebras modal logics monads Giry monad,upper closed monad composition of monads game logics

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Review of Late Jurassic-early Miocene sedimentation and plate-tectonic evolution of northern California:illuminating example of an accretionary margin

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Chinese Journal Of Geochemistry 2015年第2期34卷 123-142页

作者： W.G.ernst Department of Geological & Environmental Sciences Stanford University

Production of voluminous igneous arc rocks,high-pressure/low-temperature(HP/LT) metamafic rocks,westward relative migration of the Klamath Mountains province,and U-Pb ages of deposition,sediment sources,and spatial locations of Jurassic and younger,detrital zirconbearing clastic rocks constrain geologic development of the northern California continental edge as follows:(1) At~ 175 Ma,transpressive plate underflow began to generate an Andean-type Klamath-Sierran arc along the margin.(2)Oceanic crustal rocks were metamorphosed under HP/LT conditions in an inboard,east-inclined subduction zone from~ 170-155 *** for the Red Ant blueschists,such Ethologies remained stored at depth;most HP/LT mafic tectonic blocks returned surfaceward only during mid- and Late Cretaceous time,chiefly entrained in circulating,buoyant Franciscan mud-matrix melange.(3) By ~ 165 Ma and continuing to ~ 150-140 Ma,erosion supplied volcanogenic debris to proximal Mariposa-Galice ± Myrtle overlap strata.(4) At ~ 140,immediately prior to the onset of paired Franciscan and Great Valley Group(GVG) +Hornbrook deposition,the Klamath salient was deformed and displaced ~ 100-150 km westward relative to the Sierran arc,stranding pre-existing oceanic crust on the south as the Coast Range Ophiolite(CRO).(5) After the end-ofJurassic seaward step-out of the Farallon-North American convergent plate junction,terrigineous debris began to be deposited in the outboard Franciscan trench and intervening Great Valley forearc.(6) Voluminous sedimentation and accretion of Franciscan Eastern + Central belts and GVG detritus took place during paroxysmal igneous activity and rapid,nearly orthogonal plate convergence at^125-80 Ma.(7) Sierran arc volcanism-plutonism ceased by^80 Ma in northern California,signaling a transition to shallow,nearly subhorizontal eastward plate underflow attending Laramide orogeny far to the east.(8) Presently exposed Paleogenelower Miocene Franciscan Coastal Belt sedimentary strata were

关键词：板块构造早中新世加利福尼亚州晚侏罗世增生保证金 U-Pb年龄地层沉积

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The Mechanism of Ground Granulated Blastfurnace Slag Preventing Alkali Aggregate Reaction

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Journal of Wuhan University of Technology(Materials Science) 2010年第2期25卷 332-341页

作者： STARK Jochen FREYBURG ernst F A Finger-Institute for Building Material Science of Bauhaus-University Weimar

Three different methods were applied to study the alkali content of gelpores in cement. In the closed system, the concentration of K＋, Na＋ and OH - have not reduced with the increase of age. In the open system, the diffusion and transferring of K＋ and Na＋ towards free space leads to the de-crease of total alkali content. In the micro-analysis system, the contents of K＋ and Na＋ in the first hy- drated layer of ground granulated blastfurnace slag （GBFS） are very low, while the contents of calcium and magnesium are relatively high. This phenomenon shows that the mechanism of GBFS preventing alkali aggregate reaction （AAR） is： when GBFS is dissolved by alkali medium, SiO2 and Al2O3 are dissolved into the cement matrix, then around GBFS particles form reaction rings rich in Ca2＋ and Mg^2＋, and the C-S-H gel of positive charges formed in the area repulses K＋ and Na＋, which are forced to transfer to the mortar＇s matrix, pore or mortar sample surface. The transferred K ^＋ and Na^＋ form alkali gel products with other dissolved ions, then become evenly distributed in the mortar sample and react with Ca（OH）2 in pore solutions to form （Na,K）x-2z·zCa·（SiO2）y·（OH）x gel products; and thus changes the AAR gel products＇ structure. The gel products will not expand, and so they can delay expansion destruction.

关键词： granulated blastfurnace slag (GBFS) alkali aggregate reaction (AAR) alkali content preventing mechanism

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Superlubricity on the nanometer scale

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Friction 2014年第2期2卷 106-113页

作者： ernst MEYER Enrico GNECCO Department of Physics University of BaselKlingelbergstr.824056 BaselSwitzerland IMDEA Nanociencia Campus Universitario de CantoblancoCalle Faraday 928049 MadridSpain

The transition from atomic stick-slip to continuous sliding has been observed in a number of *** extended contacts are moved in different directions,so-called structural lubricity is observed when the two surface lattices are ***,a“superlubric”state of motion can be achieved if the normal force is reduced below a certain threshold,the temperature is increased,or the contact is actuated *** processes have been partially demonstrated using atomic force microscopy,and they can be theoretically understood by proper modifications of the Prandtl−Tomlinson model.

关键词： structural lubricity dynamic superlubricity atomic force microscopy friction force microscopy themolubricity Prandtl−Tomlinson model

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