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| 1 | Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy显示文摘AIM:To characterize development of diet-induced nonalcoholic steatohepatitis(NASH)by performing live biopsy in wild-type and genetically obese mice.METHODS:Male wild-type C57BL/6J(C57)mice(DIO NASH)and male Lep ob/Lep ob(ob/ob)mice(ob/ob-NASH were maintained on a diet high in trans-fat(40%)fructose(22%)and cholesterol(2%)for 26 and 12 wk respectively.A normal chow diet served as control in C57 mice(lean chow)and ob/ob mice(ob/ob chow)After the diet-induction period,mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted.Mice were then stratified into groups counterbalanced for steatosis score and fibrosi stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk.Global gene expression in liver tissue was assessed by RNA sequencing and bioin formatics.Metabolic parameters,plasma liver enzyme and lipids(total cholesterol,triglycerides)as well a hepatic lipids and collagen content were measured b biochemical analysis.Non-alcoholic fatty liver disease activity score(NAS)(steatosis/inflammation/ballooningdegeneration)and fibrosis were scored.Steatosis and fibrosis were also quantified using percent fractional area.RESULTS:Diet-induction for 26 and 12 wk in DIONASH and ob/ob-NASH mice,respectively,elicited progressive metabolic perturbations characterized by increased adiposity,total cholesterol and elevated plasma liver enzymes.The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis.Overall,the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice.During the eight week repeated vehicle dosing period,the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation.Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice(0 vs4.7±0.4,P<0.001 compared to lean chow)and ob/ob-NASH mice(2.4±0.3 vs 6.3±0.2,P<0.001compared to ob/ob chow),respectively.Furthermore,fibrosis stage was significantly elevated for DIO-NASH mice(0 vs 1.2±0.2,P<0.05 compared to lean chow)and ob/ob NASH(0.1±0.1 vs 3.0±0.2,P<0.001compared to ob/ob chow).Notably,fibrosis stage was significantly(P<0.001)increased in ob/ob-NASH mice,when compared to DIO-NASH mice.CONCLUSION:These data introduce the obese dietinduced DIO-NASH and ob/ob-NASH mouse models with biopsy-confirmed individual disease staging as a preclinical platform for evaluation of novel NASH therapeutics. | Maria Nicoline Baandrup Kristiansen Sanne Skovgard Veidal Kristoffer Tobias Gustav Rigbolt Kirstine Sloth Tolbol Jonathan David Roth Jacob Jelsing Niels Vrang Michael Feigh | 2016 | World Journal of Hepatology2016，8，16： | 10 |
| 2 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018，24，2： | 7 |
| 3 | Analytical formulation for the bend loss in single-ring hollow-core photonic crystal fibers显示文摘Understanding bend loss in single-ring hollow-core photonic crystal fibers(PCFs)is becoming of increasing importance as the fibers enter practical applications.While purely numerical approaches are useful,there is a need for a simpler analytical formalism that provides physical insight and can be directly used in the design of PCFs with low bend loss.We show theoretically and experimentally that a wavelength-dependent critical bend radius exists below which the bend loss reaches a maximum,and that this can be calculated from the structural parameters of a fiber using a simple analytical formula.This allows straightforward design of single-ring PCFs that are bend-insensitive for specified ranges of bend radius and wavelength.It also can be used to derive an expression for the bend radius that yields optimal higher-order mode suppression for a given fiber structure. | MICHAEL H.FROSZ PAUL ROTH MEHMET C.GüNENDI PHILIP ST.J.RUSSELL | 2017 | Photonics Research2017，5，2： | 5 |
| 4 | The shuttle radar topography mission—a new class of digital elevation models acquired by spaceborne radar显示文摘 | Bernhard Rabus Michael Eineder Achim Roth Richard Bamler | 2002 | ISPRS Journal of Photogrammetry and Remote Sensing2002，，4： | 3 |
| 5 | Interferon-Induced Gene Expression Is a Stronger Predictor of Treatment Response Than IL28B Genotype in Patients With Hepatitis C显示文摘 | Michael T. Dill Francois H.T. Duong Julia E. Vogt Stéphanie Bibert Pierre–Yves Bochud Luigi Terracciano Andreas Papassotiropoulos Volker Roth Markus H. Heim | 2011 | Gastroenterology2011，，3： | 2 |
| 6 | 用遗传算法联合反演高分辨率数据里的瑞利波和导波显示文摘瑞利波和导波是明显且普遍存在的震源产生的地震噪声。这些噪声对高分辨率地震成像造成严重问题。在泊松比较高的地区,导波可以当成是封闭在地表和地下第一主要地震不连续面之间的伪声波。瑞利波和导波在性质上都是频散的,而且分别对横波和纵波速度结构敏感,我们提出一种允许我们从这些波中提取地下最浅层速度信息的反演方法。在这些地区传统的地震反射技术效果很差。这种方法通过对瑞利波和导波的频散特性的联合反演,利用包含其中的补充信息。这种反演的可行性根据实际地震模型的合成数据进行测试和验证。 | Michael Roth Klaus Holliger 张玮璧 张小兵 郑爱敏 | 1999 | 国外油气勘探1999，11，6： | 2 |
| 7 | 航天飞机成像雷达地形测绘任务显示文摘1 介绍 2000年2月,装载于“奋进号”航天飞机的干涉成像雷达经过11天的全球性作业,获取了覆盖地表80%面积(北纬60°和南纬57°之间)的干涉雷达数据,生产出水平精度30m,高程精度16m的全球地形数据,远远优于现在能得到的1km网格的全球地图,成功地完成了航天飞机成像雷达地形测绘(SRTM)任务,显示了INSAR技术用于测绘地形图的无与伦比的潜力,被誉为是与“建立人类基因库相并列的伟大工程”。可以说。 | Bernhard Rabus Michael Eineder Achim Roth Richard Bamler 赵争 | 2003 | 导航定位学报2003，，3： | 2 |
| 8 | A Laboratory Model to Evaluate Cutout Resistance of Implants for Pertrochanteric Fracture Fixation显示文摘 | Mark B. Sommers Christoph Roth H. Hall Benjamin C. C. Kam Larry W. Ehmke James C. Krieg Steven M. Madey Michael Bottlang | 2004 | Journal of Orthopaedic Trauma2004，，6： | 2 |
| 9 | Salient Value Similarity, Social Trust, and Risk/Benefit Perception显示文摘 | Michael Siegrist George Cvetkovich Claudia Roth | 2002 | Risk Analysis2002，，3： | 2 |
| 10 | Automated seismic event location for hydrocarbon reservoirs显示文摘 | Volker Oye Michael Roth | | 0，，07： | 1 |
| 11 | Automated seismic event location for hydrocarbon reservoirs显示文摘 | Physics of the Earth Volker Oye Michael Roth | 2003 | Com- puters Geosciences2003，29，： | 1 |
| 12 | OCT4: A Novel Biomarker for Dysgerminoma of the Ovary显示文摘 | Liang Cheng Antoinette Thomas Lawrence M Roth Wenxin Zheng Helen Michael Fadi W. Abdul Karim | 2004 | The American Journal of Surgical Pathology2004，，10： | 1 |
| 13 | Quality Risk in Offshore Manufacturing: EvidenceFrom The Pharmaceutical Industry显示文摘 | JognV Gray Aleda V Roth Michael J Leiblein | 2011 | Journal ofOperations Management2011，29，7： | 1 |
| 14 | Fluorescence In Situ Hybridisation in the Diagnosis of Upper Urinary Tract Tumours显示文摘 | Christine Mian Guido Mazzoleni Silke Vikoler Thomas Martini Ruth Knüchel-Clark Dirk Zaak Alexander Lazica Stephan Roth Michael Mian Armin Pycha | 2010 | European Urology2010，，2： | 1 |
| 15 | BRAF Polymorphisms and Risk of Melanocytic Neoplasia显示文摘 | Michael R James Richard B Roth Michael M | | 0，，： | 1 |
| 16 | Automated seismic event location for hydrocarbon reservoirs显示文摘 | OYE Volker ROTH Michael | 2003 | Computers & Geosciences2003，29，： | 1 |
| 17 | Interferon-Induced Gene Expression Is a Stronger Predictor of Treatment Response Than IL28B Genotype in Patients With Hepatitis C显示文摘 | Michael T. Dill Francois H.T. Duong Julia E. Vogt Stéphanie Bibert Pierre–Yves Bochud Luigi Terracciano Andreas Papassotiropoulos Volker Roth Markus H. Heim | 2011 | Gastroenterology2011，，3： | 1 |
| 18 | A simplified method for the cultivation of extreme anaerobic Archaea based on the use of sodium sulfite as reducing agent 显示文摘 | Oliver Rothe Michael Thomm | 2000 | Extremophiles2000，4，： | 1 |
| 19 | Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation显示文摘 | Dirk Foell Michael Frosch Clemens Sorg Johannes Roth | 2004 | Clinica Chimica Acta2004，，1： | 1 |
| 20 | Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects显示文摘 | George Karakiulakis Michael Roth Fábio Santos Lira | 2012 | Mediators of Inflammation2012，，： | 1 |
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