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Aquaporin-8 expression is reduced in ileum and induced in colon of patients with ulcerative colitis

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World Journal of Gastroenterology 2007年第11期13卷 1687-1695页

作者： Alexandra Zahn Christoph Moehle Thomas Langmann robert ehehalt Frank Autschbach Wolfgang Stremmel Gerd Schmitz Department of Gastroenterology University Hospital Heidelberg Heidelberg 69120 Germany Institute of Clinical Chemistry University of Regensburg Regensburg 93042 Germany Institute of Pathology University of Heidelberg Heidelberg 69120 Germany

AIM： To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease （IBD）. METHODS： To identify potential susceptibility genes we performed global gene expression profiling in patients with IBD and control specimens. For determination of an intrinsic gene expression profile in ulcerative colitis （UC） and Crohn＇s disease （CD） compared to normal subjects, mucosal biopsies of non-inflamed regions of the colon and the terminal ileum were subjected to DNA microarray analysis. Real-time RT-PCR and immunohistochemistry were used for verification of selected regulated candidate genes and a genetic analysis was performed. RESULTS： We could show that aquaporin-8 （AQP8） mRNA and protein levels were significantly increased in the colon of UC patients compared to controls. Genetic analysis of the six exons and the promoter region of AQPS, however, revealed no mutations or polymorphisms in IBD patients. CONCLUSION： Our results suggest that upregulation of AQP8 in the colon of UC patients represents a secondary phenomenon which may, due to altered water exchange of the distal intestinal mucosa, disturb the physiologic colonic mucus barrier and thus lead to chronic inflao mmation and ulceration.

关键词： Aquaporin-8 Colonic mucus barrier DNA microarrays Expression profiling Ulcerative colitis

Increased basolateral sorting of carcinoembryonic antigen in a polarized colon carcinoma cell line after cholesterol depletion-Implications for treatment of inflammatory bowel disease

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World Journal of Gastroenterology 2008年第10期14卷 1528-1533页

作者： robert ehehalt Markus Krautter Martin Zorn Richard Sparla Joachim Füllekrug Hasan Kulaksiz Wolfgang Stremmel Department of Gastroenterology Hepatology and Infectious diseases University of Heidelberg INF 410 Heidelberg 69120 Germany Central Laboratory Unit University of Heidelberg INF 410 Heidelberg 69120 Germany

AIM: To investigate a possible increase of basolateral expression of carcinoembryonic antigen (CEA) by interfering with the apical transport machinery, we studied the effect of cholesterol depletion on CEA sorting and secretion. METHODS: Cholesterol depletion was performed in polarized Caco-2 cells using lovastatin and methyl-b- cyclodextrin. RESULTS: We show that CEA is predominantly expressed and secreted at the apical surface. Reduction of the cholesterol level of the cell by 40%-50% with lovastatin and methyl-b-cyclodextrin led to a significant change of the apical-to-basolateral transport ratio towards the basolateral membrane. CONCLUSION: As basolateral expression of CEA has been suggested to have anti-inflamatory properties, Cholesterol depletion of enterocytes might be a potential approach to influence the course of inflammatory bowel disease.

关键词： Inflammatory bowel disease Cholesterol Polarized secretion Carcinoembryonic antigen Caco-2

Real-life outcome of anti-tumor necrosis factor α in the ambulatory treatment of ulcerative colitis

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World Journal of Gastroenterology 2015年第11期21卷 3282-3290页

作者： Enayatullah Baki Philipp Zwickel Anna Zawierucha robert ehehalt Daniel Gotthardt Wolfgang Stremmel Annika Gauss Division of Gastroenterology University of Heidelberg Outpatient Clinic of Gastroenterology

AIM:To evaluate the outcome of anti-tumor necrosis factor alpha(anti-TNFα) therapy in outpatients with ulcerative colitis at a tertiary referral ***:All patients with a confirmed diagnosis of ulcerative colitis undergoing therapy with infliximab and/or adalimumab at the outpatient clinic for inflammatory bowel diseases at the University Hospital Heidelberg between January 2011 and February 2014 were retrospectively *** with a followup period of less than 6 mo from start of anti-TNFα therapy were *** records of all eligible individuals were carefully ***-free clinical remission of a duration of at least 3 mo,colectomy rate,duration of anti-TNFα therapy,need for anti-TNFα dose escalation,and the occurrence of adverse events were evaluated as the main outcome ***:Seventy-two patients were included(35 treated with infliximab,17 with adalimumab,20 with both consecutively).Median follow-up was 27 mo(range:6-87 mo).Steroid-free clinical remission was achieved by 22.2% of the patients(median duration:21 mo until end of follow-up; range:3-66 mo).Patients attaining steroid-free clinical remission displayed lower hemoglobin and albumin blood levels at the start of treatment than those who did not achieve *** overall colectomy rate was 20.8%.Nearly 50% of the patients underwent anti-TNFα dose escalation during the follow-up *** both the infliximab and the adalimumab treated patients,non-response to anti-TNFα therapy was the major reason for treatment discontinuation.18.2% of the infliximab-treated patients and 13.5% of the adalimumab-treated patients had to discontinue their therapy due to adverse ***:Real-life remission rates of ulcerative colitis under anti-TNFα are overall low,but some patients have a clear long-term benefit.

关键词： Inflammatory bowel disease Tumor necrosis factor α

Biliary phosphatidylcholine and lysophosphatidylcholine profiles in sclerosing cholangitis

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World Journal of Gastroenterology 2013年第33期19卷 5454-5463页

作者： Annika Gauss robert ehehalt Wolf-Dieter Lehmann Gerhard Erben Karl-Heinz Weiss Yvonne Schaefer Petra Kloeters-Plachky Adolf Stiehl Wolfgang Stremmel Peter Sauer Daniel Nils Gotthardt Gastroenterology and Hepatology Unit Department of Internal MedicineUniversity Hospital Heidelberg Department of Spectroscopy German Cancer Research Center

AIM:To analyze phospholipid profiles in intrahepatic bile from patients with primary sclerosing cholangitis(PSC)and secondary sclerosing cholangitis(SSC).METHODS:Intrahepatic bile specimens collected via endoscopic retrograde cholangiography from 41 patients were *** of these patients were diagnosed with PSC,10 with SSC,11 with choledocholithiasis or no identifiable biliary disease,and 6 with cholangiocellular carcinoma(CCC).Bile acid,cholesterol,protein,and bilirubin contents as well as pancreas lipase activity in bile were determined by biochemical ***(PC)and lysophosphatidylcholine(LPC)species were quantified using nanoelectrospray ionization tandem mass ***:Bile from all the examined patient groups showed a remarkably similar PC and LPC species composition,with only minor statistical *** biliary PC concentrations were highest in controls(8030±1843 mol/L)and lowest in patients with CCC(1969±981 mol/L)(P=0.005,controls vs SSC and CCC,respectively,P<0.05).LPC contents in bile were overall low(4.2%±1.8%).Biliary LPC/PC ratios and ratios of biliary PC to bilirubin,PC to cholesterol,PC to protein,and PC to bile acids showed no intergroup ***:PC and LPC profiles being similar in patients with or without sclerosing cholangitis,these phospholipids are likely not of major pathogenetic importance in this disease group.

关键词： Primary sclerosing cholangitis Secondary sclerosing cholangitis Cholangiocellular carcinoma Phosphatidylcholine Lysophosphatidylcholine Bile Mass spectrometry

Predicting the coefficient of friction in a sliding contact by applying machine learning to acoustic emission data

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Friction 2024年第6期12卷 1299-1321页

作者： robert GUTIERREZ Tianshi FANG robert MAINWARING Tom REDDYHOFF Tribology Group Department of Mechanical EngineeringImperial College LondonExhibition RoadLondon SW72AZUK Shell Global Solutions(US)Inc.Shell Technology Center Houston 3333 Highway 6 SouthHoustonTX 77082USA Shell International Petroleum Company Limited Shell CentreYork RoadLondon SE17NAUK

It is increasingly important to monitor sliding interfaces within machines,since this is where both energy is lost,and failures *** emission(AE)techniques offer a way to monitor contacts remotely without requiring transparent or electrically conductive ***,acoustic data from sliding contacts is notoriously complex and difficult to ***,we simultaneously measure coefficient of friction(with a conventional force transducer)and acoustic emission(with a piezoelectric sensor and high acquisition rate digitizer)produced by a steel‒steel rubbing *** data is then used to train machine learning(ML)algorithms(e.g.,Gaussian process regression(GPR)and support vector machine(SVM))to correlated acoustic emission with *** training requires the dense AE data to first be reduced in size and a range of processing techniques are assessed for this(e.g.,down-sampling,averaging,fast Fourier transforms(FFTs),histograms).Next,fresh,unseen AE data is given to the trained model and the resulting friction predictions are compared with the directly measured *** is excellent agreement between the measured and predicted friction when the GPR model is used on AE histogram data,with root mean square(RMS)errors as low as 0.03 and Pearson correlation coefficients reaching ***,predictions remain accurate despite changes in test conditions such as normal load,reciprocating frequency,and stroke *** paves the way for remote,acoustic measurements of friction in inaccessible locations within machinery to increase mechanical efficiency and avoid costly failure/needless maintenance.

关键词： acoustic emission condition monitoring friction machine learning Gaussian process regression support vector machine

A general mirror equivalence theorem for coset vertex operator algebras

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Science China Mathematics 2024年第10期67卷 2237-2282页

作者： robert McRae Yau Mathematical Sciences Center Tsinghua UniversityBeijing 100084China

We prove a general mirror duality theorem for a subalgebra U of a simple conformal vertex algebra A and its commutant V=ComA(U).Specifically,we assume that A≌■_(i∈I)U_(i)■V_(i) as a U■V-module,where the U-modules Uiare simple and distinct and are objects of a semisimple braided ribbon category of Umodules,and the V-modules Viare semisimple and contained in a(not necessarily rigid) braided tensor category of *** also assume U=ComA(V).Under these conditions,we construct a braid-reversed tensor equivalence τ:u_(A)→v_(A),where u_(A)is the semisimple category of U-modules with simple objects Ui,i∈I,and v_(A)is the category of V-modules whose objects are finite direct sums of *** particular,the V-modules Viare simple and distinct,and v_(A)is a rigid tensor *** an application,we find a rigid semisimple tensor subcategory of modules for the Virasoro algebra at central charge 13+6p+6p^(-1),p∈Z_(≥2), which is braided tensor equivalent to an abelian 3-cocycle twist of the category of finite-dimensional ***,the Virasoro vertex operator algebra at central charge 13+6p+6p^(-1)is the PSL_(2)(C)-fixed-point subalgebra of a simple conformal vertex algebra w(-p),analogous to the realization of the Virasoro vertex operator algebra at central charge 13-6p-6p^(-1)as the PSL_(2)(C)-fixed-point subalgebra of the triplet algebra W(p).

关键词： vertex operator algebras coset conformal eld theory braid-reversed tensor equivalence Virasoro algebra

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Necrotic enteritis and antibiotic-free production of broiler chickens:Challenges in testing and using alternative products

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Animal Nutrition 2024年第01期16卷 288-298页

作者： robert J.Moore School of Science RMIT University

The global trend towards raising broiler chickens without the use of in-feed antibiotics(IFAs) means that there is an ongoing need to develop alternative treatments capable of delivering the benefits that IFAs previously provided. IFAs supported the productivity performance of chickens and played a key role in maintaining their health. Necrotic enteritis(NE) is an important disease of broilers that affects health,productivity, and welfare, and was previously well controlled by IFAs. However, with the reduction in IFA use, NE is resurgent in some countries. Vaccines and various feed additives, including pre-, pro-, and postbiotics, phytobiotics, fatty acids, and phage therapies have been introduced as alternative methods of NE control. While some of these feed additives have specific activity against the NE pathogen, Clostridium perfringens, most have the more general goal of reinforcing gut health. Extensive reviews of the effects of many of these feed additives on gut health have been published recently. Hence, rather than cover previously well reviewed areas of research this review focuses on the challenges and pitfalls in undertaking experimental assessment of alternative NE treatments and translating laboratory research to real world commercial production settings. The review is based on the author's particular experience,reading, thoughts, and analysis of the available information and inevitably presents a particular understanding that is likely to be at odds with others thinking on these issues. It is put forward to stimulate thinking and discussion on the issues covered.

关键词： Necrotic enteritis Clostridium perfringens Vaccines Feed additive Farm management

A detailed rock density model of the Hong Kong territories

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Geodesy and Geodynamics 2024年第1期15卷 75-81页

作者： Albertini Nsiah Ababio robert Tenzer Department of Land Surveying and Geo-Informatics Hong Kong Polytechnic UniversityHong KongChina

We used the geological map and published rock density measurements to compile the digital rock density model for the Hong Kong *** then estimated the average density for the whole *** to our result,the rock density values in Hong Kong vary from 2101 to 2681 kg·m^(-3).These density values are typically smaller than the average density of 2670 kg·m^(-3),often adopted to represent the average density of the upper continental crust in physical geodesy and gravimetric geophysics *** finding reflects that the geological configuration in Hong Kong is mainly formed by light volcanic formations and lava flows with overlying sedimentary deposits at many locations,while the percentage of heavier metamorphic rocks is very low(less than 1%).This product will improve the accuracy of a detailed geoid model and orthometric heights.

关键词： Density model Rock types Gravimetric modeling Hong Kong

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The concept of gene therapy for glaucoma:the dream that has not come true yet

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Neural Regeneration Research 2024年第1期19卷 92-99页

作者： robert Sulak Xiaonan Liu Adrian Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland GlaucoTech Co. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in *** glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glaucoma IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

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