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Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inlammatory bowel disease

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World Journal of Gastroenterology 2009年第25期15卷 3134-3141页

作者： Carsten Gnewuch Gerhard Liebisch thomas Langmann Benjamin Dieplinger thomas mueller Meinhard Haltmayer Hans Dieplinger Alexandra Zahn Wolfgang Stremmel Gerhard Rogler Gerd Schmitz Institute of Clinical Chemistry and Laboratory Medicine Regensburg University Medical Center Institute of Human Genetics University of Regensburg Department of Laboratory Medicine Konventhospital Barmherzige Brueder Linz Division of Genetic Epidemiology Department of Medical GeneticsClinical and Molecular PharmacologyInnsbruck Medical University Department of Gastro-enterology University Hospital Heidelberg Department of Internal Medicine I Regensburg University Medical Center

AIM:To determine free and conjugated serum bile acid (BA) levels in in? ammatory bowel disease (IBD) subgroups with defi ned clinical ***: Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy controls by liquid chromatography coupled to electrospray ionization tandem mass ***: Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the secondary BA lithocholic acid (LCA), was increased significantly in Crohn's disease (CD) and ulcerative colitis (UC), while most other serum BA species were decreased significantly. Total BA, total BA conjugate, and total BA glycoconjugate levels were decreased only in CD, whereas total unconjugated BA levels were decreased only in UC. In UC patients with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were as significantly increased as the secondary BAs LCA, ursodeoxycholic acid, and tauroursodeoxycholic acid compared to UC patients without hepatobiliary manifestations. Finally, we found that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid and chenode-oxycholic acid, were increased significantly compared to controls and patients without surgical ***: Serum BA profiling in IBD patients that indicates impaired intestinal barrier function and increased detoxification is suitable for advanced diagnostic characterization and differentiation of IBD subgroups with defined clinical manifestations.

关键词：屏障功能胆汁酸炎症解毒血清肠肝

Salt Stress Triggers Phosphorylation of the Arabidopsis Vacuolar K＋ Channel TPK1 by Calcium-Dependent Protein Kinases （CDPKs）

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Molecular Plant 2013年第4期6卷 1274-1289页

作者： Andreas Latz Norbert Mehlmer Simone Zapf thomas D. mueller Bernhard Wurzinger Barbara Pfister Edina Csaszar Rainer Hedrich Markus Teige Dirk Becker Department of Molecular Plant Physiology and Biophysics Julius-von-Sachs-lnstitute University of Wurzburg Julius-von-Sachs-Platz 2 D-97082 Wurzburg Germany Department of Biochemistry and Cell Biology Max F. Perutz Laboratories University of Vienna Dr. Bohrgasse 9 A-1030 Vienna Austria Present address: Department of Biology I Botany Munich Center for Integrated Protein Science CiPSM Ludwig-Maximilians-Universitat Munchen D-82152 Planegg-Martinsried Germany College of Science King Saud University Riyadh 11451 Saudi Arabia

14-3-3 proteins play an important role in the regulation of many cellular processes. The Arabidopsis vacuolar two-pore K＋ channel 1 （TPK1） interacts with the 14-3-3 protein GRF6 （GF14-λ）. Upon phosphorylation of the putative binding motif in the N-terminus of TPK1, GRF6 binds to TPK1 and activates the potassium channel. In order to gain a deeper understanding of this 14-3-3-mediated signal transduction, we set out to identify the respective kinases, which regulate the phosphorylation status of the 14-3-3 binding motif in TPK1. Here, we report that the calcium-dependent protein kinases （CDPKs） can phosphorylate and thereby activate the 14-3-3 binding motif in TPK1. Focusing on the stress-activated kinase CPK3, we visualized direct and specific interaction of TPK1 with the kinase at the tonoplast in vivo. In line with its proposed role in K＋ homeostasis, TPK1 phosphorylation was found to be induced by salt stress in planta, and both cpk3 and tpkl mutants displayed salt-sensitive phenotypes. Molecular modeling of the TPK1-CPK3 interaction domain provided mechanistic insights into TPK1 stress-regulated phosphorylation responses and pinpointed two arginine residues in the N-terminal 14-3-3 binding motif in TPK1 critical for kinase interaction. Taken together, our studies provide evidence for an essential role of the vacuolar potassium channel TPK1 in salt-stress adaptation as a target of calcium-regulated stress signaling pathways involving Ca2＋, Ca2＋-dependent kinases, and 14-3-3 proteins.

关键词： potassium channel vacuole calcium calcium-dependent kinase 14-3-3 protein salt stress.

Topography Measurement for Monitoring Manufacturing Processes in Harsh Conditions

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Engineering（科研） 2016年第5期8卷 292-300页

作者： thomas mueller Andreas Poesch Eduard Reithmeier Institute of Measurement and Automatic Control Leibniz University Hannover Hannover Germany

High precision manufacturing, e.g. milling and grinding, which have manufacturing tolerances in the range of <10 μm require microscopic measurement techniques for the inspection of the manufactured components. These measurement techniques are very sensitive to cooling liquids and lubricants which are essential for many manufacturing processes. Therefore, the measurement of the components is usually conducted in separate and clean laboratories and not directly in the manufacturing machine. This approach has some major drawbacks, e.g. high time consumption and no possibility for online process monitoring. In this article, a novel concept for the integration of high precision optical topography measurement systems into the manufacturing machine is introduced and compared to other concepts. The introduced concept uses a reservoir with cooling liquid in which the measurement object is immersed during the measurement. Thereby, measurement disturbance by splashing cooling liquids and lubricants can effectively be avoided.

关键词： Optical Inspection Topography Measurement Laser Triangulation Precision Manufacturing

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高性能聚合物过滤器的清洁技术

产业用纺织品 2007年第7期25卷 42-44页

作者： thomas mueller FRG Filter Recycling公司

介绍了一种用于高性能聚合物纺丝溶液过滤器的清洁工艺。采用FilaTech公司的标准TEG过滤设备,附加一道引入微量氧气真空热解处理工序,可以从烧结非织造不锈钢过滤介质上清除像PSU或PES一类高性能聚合物的残留物,使过滤介质达到重复使用... 详细信息

介绍了一种用于高性能聚合物纺丝溶液过滤器的清洁工艺。采用FilaTech公司的标准TEG过滤设备,附加一道引入微量氧气真空热解处理工序,可以从烧结非织造不锈钢过滤介质上清除像PSU或PES一类高性能聚合物的残留物,使过滤介质达到重复使用的要求,并与新过滤器有相近的过滤时间。

关键词：高性能聚合物过滤器清洁工艺

Time-domain Dynamic State Estimation for Unbalanced Three-phase Power Systems

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Journal of Modern Power Systems and Clean Energy 2023年第2期11卷 446-454页

作者： Martin Pfeifer Felicitas mueller Steven de Jongh Frederik Gielnik thomas Leibfried Sören Hohmann Institute of Control Systems(IRS) KarlsruheGermany Institute of Electrical Energy Systems and High Voltage Technology(IEH)at the Karlsruhe Institute of Technology(KIT) 76131 KarlsruheGermany

In this paper,we present a time-domain dynamic state estimation for unbalanced three-phase power *** dynamic nature of the estimator stems from an explicit consideration of the electromagnetic dynamics of the network,i.e.,the dynamics of the electrical *** enables our approach to release the assumption of the network being in quasi-steady ***,based on the line dynamics,we derive a graphbased dynamic system *** handle the large number of interacting variables,we propose a port-Hamiltonian modeling *** on the port-Hamiltonian model,we then follow an observer-based approach to develop a dynamic *** estimator uses synchronized sampled value measurements to calculate asymptotic convergent estimates for the unknown bus voltages and *** design and implementation of the estimator are illustrated through the IEEE 33-bus *** simulations verify the estimator to produce asymptotic exact estimates,which are able to detect harmonic distortion and sub-second transients as arising from converterbased resources.

关键词： Dynamic state estimation power system harmonic observer port-Hamiltonian system static state estimation transient

The effects of tannins-containing ground pine bark diet upon nutrient digestion,nitrogen balance,and mineral retention in meat goats

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Journal of Animal Science and Biotechnology 2015年第3期6卷 347-354页

作者： Byeng Ryel Min Sandra Solaiman thomas Terrill Aina Ramsay Irene mueller-Harvey Department of Agricultural and Environmental Sciences Tuskegee University Agricultural Research Station Fort-Valley State University School of Agriculture Policy and DevelopmentUniversity of Reading

Background： Pine bark is a rich source of phytochemical compounds including tannins, phenolic acids, anthocyanins, and fatty acids. These phytochemicals have potential to significantly impact on animal health and animal production. The goal of this work is to measure the effects of tannins in ground pine bark as a partial feed replacement on feed intake, dietary apparent digestibility, nitrogen balance, and mineral retention in meat goats. Results： Eighteen Kiko cross goats （initial BW = 31.8 ± 1.49 kg） were randomly assigned to three treatment groups （n = 6）. Dietary treatments were tested： control （0 % pine bark powder （PB） and 30 % wheat straw （WS））; ] 5 % PB and 15 % WS, and 30 % PB and 0 % WS. Although dry matter （DM） intake and digestibility were not affected （P〉 0.10） by feeding PB, neutral detergent fiber （linear; P= 0.01）, acid detergent fiber （linear; P= 0.001） and lignin digestibility （linear; P= 0.01） decreased, and crude protein （CP） digestibility tended to decrease （P=0.09） as PB increased in the diet, apparent retention of Ca （P= 0.09）, P （P=0.03）, Mg （P= 0.01）, Mn （P= 0.01）, Zn （P= 0.01） and Fe （P= 0.09） also increased linearly. Nitrogen intake and fecal N excretion were not affected （P〉 0.05） by addition of PB in the diet, but N balance in the body was quadratically increased （P〈 0.01） in the 15 % PB diet compared to other diets. This may be due to more rumen escape protein and less excreted N in the urine with the 15 % PB diet. The study showed that a moderate level of tannin-containing pine bark supplementation could improve gastrointestinal nitrogen balance with the aim of improving animal performance. Conclusion： These results suggest that tannin-containing PB has negative impact on fiber, lignin, and protein digestibility, but positively impacted on N-balance.

关键词： Digestibility Goats Phytochemicals Tannins

Liver stiffness reversibly increases during pregnancy and independently predicts preeclampsia

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World Journal of Gastroenterology 2018年第38期24卷 4393-4402页

作者： Franziska J Ammon Anna Kohlhaas Omar Elshaarawy Johannes mueller thomas Bruckner Christof Sohn Gabriele Fluhr Herbert Fluhr Sebastian mueller Department of Obstetrics and Gynecology University of Heidelberg Department of Medicine and Center for Alcohol Research Liver Disease and NutritionSalem Medical CenterUniversity of Heidelberg Institute of Medical Biometry und Informatics University of Heidelberg

AIM To study liver stiffness(LS) during pregnancy and its association with complications during *** In this observational, diagnostic study, 537 pregnant women were prospectively enrolled at the Department of Obstetrics and Gynecology, University hospital Heidelberg and Salem Medical Center. LS was measured using the Fibroscan device(Echosens, Paris) in all women and in 41 cases 24 h after delivery. Clinical and morphological data were recorded and abdominal ultrasound and standard laboratory tests were performed. No complications were observed in 475 women(controls) while preeclampsia and intrahepatic cholestasis of pregnancy(ICP) developed in 22 and 40 women, *** In controls, LS increased significantly from initially 4.5 ± 1.2 kPa in the second trimester to 6.0 ± 2.3 kPa(P < 0.001) in the third trimester. In the third trimester, 41% of women had a LS higher than 6 kPa. Elevated LS in controls was significantly correlated with alkaline phosphatase, leukocytes, gestational age and an increase in body weight and body mass index(BMI). In women with pregnancy complications, LS was significantly higher as compared to controls(P < 0.0001). Moreover, in multivariate analysis, LS was an independent predictor for preeclampsia with an odds ratio of 2.05(1.27-3.31) and a cut-off value of 7.6 kPa. In contrast, ICP could not be predicted by LS. Finally, LS rapidly decreased in all women within 24 h after delivery from 7.2 ± 3.3 kPa down to 4.9 ± 2.2 kPa(P < 0.001).CONCLUSION During pregnancy, LS significantly and reversibly increases in the final trimester of pregnant women without complications. In women with preeclampsia, LS is significantly elevated and an independent noninvasive predictor.

关键词： Pregnancy Transient elastography Liver stiffness Pregnancy complications Hemolysis,elevated liver enzymes and low platelets syndrome Intrahepatic cholestasis of pregnancy Preeclampsia

Primary liver injury and delayed resolution of liver stiffness after alcohol detoxification in heavy drinkers with the PNPLA3 variant I148M

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World Journal of Hepatology 2016年第35期8卷 1547-1556页

作者： Vanessa Rausch Teresa Peccerella Carolin Lackner Eray Yagmur Helmut-Karl Seitz thomas Longerich Sebastian mueller Salem Medical Center and Center for Alcohol Research University of Heidelberg Institute for Pathology Medical University Graz Laboratory Diagnostics Center RWTH-University Hospital Aachen Aachen and Medical Care Center Institute of Pathology RWTH-University Hospital Aachen

AIM To investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness(LS) during alcohol withdrawal and its association with *** Caucasian heavy drinkers(n = 521) with a mean alcohol consumption of 192.1 g/d(median alcohol consumption: 169.0 g/d; 95%CI: 179.0-203.3) were enrolled at the Salem Medical Center, University of Heidelberg. LS was measured by transient elastography(Fibroscan, Echosens SA, Paris, France). LS and serum markers were prospectively studied in these patients with all stages of alcoholic liver disease(steatosis, steatohepatitis, fibrosis) prior and after alcohol detoxification with a mean observation interval of 6.2 ± 3.2 d. A liver biopsy with histological analysis including the Kleiner score was obtained in 80 *** The PNPLA3 rs738409 genotype distribution for CC, CG and GG was 39.2%, 52.6% and 8.2%. GG genotype primarily correlated with histological steatohepatitis(r = 0.404, P < 0.005), ballooning(r = 0.319, P < 0.005) and less with steatosis(r = 0.264, P < 0.05). Mean LS was lowest in CC carriers(13.1 k Pa) as compared to CG and GG carriers(17.6 and 17.2 kPa). Notably, LS primarily correlated with fibrosis stage(r = 0.828, P < 0.005), ballooning(r = 0.516, P < 0.005), steatohepatitis(r = 0.319, P < 0.005) but not with steatosis. After alcohol withdrawal, LS did not change in CC carriers, significantly decreased in CG-carriers from 17.6 to 12.7 kPa but to a lesser extent in GG carriers from 17.6 to 14.5 kPa. This was due to prolonged resolution of inflammation with significantly elevated aspartate transaminase levels after alcohol withdrawal in GG carriers. Non-invasive fibrosis assessment by LS in all patients showed a significantly higher F0 rate as compared to the biopsy cohort(47% vs 6%) with 3.8% more CC carriers while 3.7% less were seen in the F4 cirrhosis group. Thus, about 20% of patients with alcoholic liver cirrhosis would be attributable to PNPLA3 G variants. The OR to

关键词：肝僵硬含酒精的肝疾病 Adiponutrin PNPLA3 短暂 elastography 白酒退却发炎

Increased liver stiffness in alcoholic liver disease:Differentiating fibrosis from steatohepatitis

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World Journal of Gastroenterology 2010年第8期16卷 966-972页

作者： Sebastian mueller Gunda Millonig Lucie Sarovska Stefanie Friedrich Frank M Reimann Maria Pritsch Silke Eisele Felix Stickel thomas Longerich Peter Schirmacher Helmut Karl Seitz Department of Medicine and Center for Alcohol Research Salem Medical Center University of Heidelberg Institute of Medical Biometry and Informatics University of Heidelberg Institute of Clinical Pharmacology University of Bern Department of Pa-thology University of Heidelberg

AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of ***:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.

关键词： Alcoholic liver disease Alcoholic steatohep-atitis Liver cirrhosis Bilirubin Tissue elasticity imaging FibroScan