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Evaluation of acoustic radiation force impulse imaging for determination of liver stiffness using transient elastography as a reference

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World Journal of Gastroenterology 2012年第10期18卷 1077-1084页

作者： Gerald Kircheis Abdurrahman Sagir Christoph Vogt Stephan vom Dahl ralf kubitz Dieter Hussinger Department of Gastroenterology Hepatology and Infectious Diseases Heinrich-Heine-University Düsseldorf Moorenstrasse 5 Düsseldorf 40225 Germany Christoph Vogt St. Josef Hospital Moers Asberger Str. 4 Moers 47441 Germany St. Franziskus Hospital Schnsteinstraβe 63 Kln 50825 Germany

AIM: To evaluate cut-off values and performance of acoustic radiation force impulse imaging (ARFI) using transient elastography [FibroScan■ (FS)] as a reference. METHODS: Six hundred and six patients were enrolled in this *** patients underwent liver stiffness measurement with FS (FS-LS) and ARFI (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in comparison to FS was determined. Sixtyeight patients underwent liver biopsy. RESULTS: Significantly higher success rates for the determination of liver stiffness were found using ARFI as compared to FS [604/606 (99.7%) vs 482/606 (79.5%); P 13.0 kPa)). ARFI-SWV cut-off values were identified for no significant fibrosis (1.29 m/s; sensitivity 91.4% and specificity 92.6%) and for liver cirrhosis (1.60 m/s; sensitivity 92.3% and specificity 96.5%). The optimal cut-off value for predicting liver fibrosis (F ≥ 2) was 1.32 m/s (sensitivity 87.0% and specificity 80.0%) and for liver cirrhosis (F4) 1.62 m/s (sensitivity 100% and specificity 85.7%), for patients who underwent liver biopsy. An excellent inter-and intraobserver reproducibility was observed for ARFI-SWV determinations. CONCLUSION: An ARFI-SWV cut-off value of 1.29 m/s seems to be optimal for patients with no significant liver fibrosis and 1.60 m/s for patients with liver cirrhosis.

关键词： Acoustic radiation force impulse imaging Elastography Fibroscan Liver

Partial external biliary diversion in bile salt export pump deficiency: Association between outcome and mutation

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World Journal of Gastroenterology 2017年第29期23卷 5295-5303页

作者： Philipp Ellinger Jan Stindt Carola Droge Katharina Sattler Claudia Stross Stefanie Kluge Diran Herebian Sander HJ Smits Martin Burdelski Sebastian Schulz-Jürgensen Antje Ballauff Jan Schulte am Esch Ertan Mayatepek Dieter Haussinger ralf kubitz Lutz Schmitt In-stitute of Biochemistry Hein-rich-Hein-e-Un-iversity Düsseldorf Medical Faculty Departmen-t of Gastroen-terology Hepatology an-d In-fectious Diseases Hein-rich-Hein-e-Un-iversity Düsseldorf Departmen-t of Gen-eral Pediatrics Neon-atology an-d Pediatric Cardiology Medical Faculty Hein-rich-Hein-e-Un-iversity Düsseldorf Departmen-t of Paediatrics Un-iversity Hospital Schleswig Holstein- Departmen-t of Paediatrics Helios Clin-ic Departmen-t of Gen-eral Surgery Hein-rich-Hein-e-Un-iversity

To investigate the relation of two different mutations to the outcome of partial external biliary diversion (PEBD) in severe bile salt export pump (BSEP) deficiency. METHODSMutations in the gene encoding BSEP leading to severe BSEP deficiency in two unrelated patients were identified by genomic sequencing. Native liver biopsies and transiently transfected human embryonic kidney (HEK) 293 cells expressing either wild-type or mutated BSEP were subjected to immunofluorescence analysis to assess BSEP transporter localization. Bile acid profiles of patient and control bile samples were generated by ultra-performance liquid chromatography-tandem mass spectrometry. Wild-type and mutant BSEP transport of [3H]-labeled taurocholate (TC) and taurochenodeoxycholate (TCDC) was assessed by vesicular transport assays. RESULTSA girl (at 2 mo) presented with pruritus, jaundice and elevated serum bile salts (BS). PEBD stabilized liver function and prevented liver transplantation. She was heterozygous for the BSEP deletion p.T919del and the nonsense mutation p.R1235X. At the age of 17 years relative amounts of conjugated BS in her bile were normal, while total BS were less than 3% as compared to controls. An unrelated boy (age 1.5 years) presenting with severe pruritus and elevated serum BS was heterozygous for the same nonsense and another missense mutation, p.G1032R. PEBD failed to alleviate pruritus, eventually necessitating liver transplantation. BS concentration in bile was about 5% of controls. BS were mainly unconjugated with an unusual low amount of chenodeoxycholate derivatives (< 5%). The patients’ native liver biopsies showed canalicular BSEP expression. Both BSEP p.T919del and p.G1032R were localized in the plasma membrane in HEK293 cells. In vitro transport assays showed drastic reduction of transport by both mutations. Using purified recombinant BSEP as quantifiable reference, per-molecule transport rates for TC and TCDC were determined to be 3 and 2 BS molecu

关键词： Familial intrahepatic cholestasis type 2 Partial external biliary diversion Bile salt export pump ATP binding cassette transporter Intrahepatic cholestasis

Importance of hydrogenotrophic, aceticlastic and methylotrophic methanogenesis for methane production in terrestrial, aquatic and other anoxic environments: A mini review

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Pedosphere 2020年第1期30卷 25-39页

作者： ralf CONRAD Max Planck Institute for Terrestrial Microbiology Karl-von-Frisch-Str.10Marburg 35043(Germany)

Microbial methanogenesis is a major source of the greenhouse gas methane(CH4).It is the final step in the anaerobic degradation of organic matter when inorganic electron acceptors such as nitrate,ferric iron,or sulfate have been *** of this degradation pathway is important for the creation of mechanistic models,prediction of future CH4 emission scenarios,and development of mitigation *** most anoxic environments,CH4 is produced from either acetate(aceticlastic methanogenesis)or hydrogen(H2)plus carbon dioxide(CO2)(hydrogenotrophic methanogenesis).Hydrogen can be replaced by other CO2-type methanogenesis,using formate,carbon monoxide(CO),or alcohols as *** ratio of these two pathways is tightly constrained by the stoichiometry of conversion *** the degradation of organic matter is complete(e.g.,degradation of straw in rice paddies),then fermentation eventually results in production of acetate and H2 at a ratio of>67%aceticlastic and<33%hydrogenotrophic ***,acetate production can be favored when heterotrophic or chemolithotrophic acetogenesis is enhanced,and H2 production can be favored when syntrophic acetate oxidation is *** typically occurs at low and elevated temperatures,***,temperature can strongly influence the methanogenic pathway,which may range from 100%aceticlastic methanogenesis at low temperatures to 100%hydrogenotrophic methanogenesis at high ***,if the degradation of organic matter is not complete(e.g.,degradation of soil organic matter),the stoichiometry of fermentation is not tightly constrained,resulting,for example,in the preferential production of H2,followed by hydrogenotrophic *** production of CH4 by either aceticlastic or hydrogenotrophic methanogenesis can also happen if one of the methanogenic substrates is not consumed by methanogens but is,instead,accumulated,volatilized,or utilized *** methano

关键词： electron acceptor fermentation methanogenic pathway organic matter degradation pH soil microbial community temperature Wood-Ljungdahl pathway

Sperm preparation： state-of-the-art--physiological aspects and application of advanced sperm preparation methods

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Asian Journal of Andrology 2012年第2期14卷 260-269页

作者： ralf Henkel Department of Medical Biosciences University of the Western Cape Bellville 7535 South Africa

For assisted reproduction technologies （ART）, numerous techniques were developed to isolate spermatozoa capable of fertilizing oocytes. While early methodologies only focused on isolating viable, motile spermatozoa, with progress of ART, particularly intracytoplasmic sperm injection （ICSI）, it became clear that these parameters are insufficient for the identification of the most suitable spermatozoon for fertilization. Conventional sperm preparation techniques, namely, swim-up, density gradient centrifugation and glass wool filtration, are not efficient enough to produce sperm populations free of DNA damage, because these techniques are not physiological and not modeled on the stringent sperm selection processes taking place in the female genital tract. These processes only allow one male germ cell out of tens of millions to fuse with the oocyte. Sites of sperm selection in the female genital tract are the cervix, uterus, uterotubal junction, oviduct, cumulus oophorus and the zona pellucida. Newer strategies of sperm preparation are founded oni （i） morphological assessment by means of＇motile sperm organelle morphological examination （MSOM E）＇; （ii） electrical charge; and （ili） molecular binding characteristics of the sperm cell. Whereas separation methods based on electrical charge take advantage of the sperm＇s adherence to a test tube surface or separate in an electrophoresis, molecular binding techniques use Annexin V or hyaluronic acid （HA） as substrates. Techniques in this category are magnet-activated cell sorting, Annexin V-activated glass wool filtration, flow cytometry and picked spermatozoa for ICSI （PICSI） from HA-coated dishes and HA-containing media. Future developments may include Raman microspectrometry, confocal light absorption and scattering spectroscopic microscopy and polarization microscopy.

关键词： advanced sperm selection biomimetics conventional sperm selection female genital tract physiological sperm selection

Bottomonium suppression in heavy-ion collisions and the in-medium strong force

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Nuclear Science and Techniques 2023年第4期34卷 185-187页

作者： ralf Rapp Cyclotron Institute and Department of Physics and Astronomy Texas A&M UniversityCollege StationTX 77843-3366USA

A large suppression of various bottomonium states in ultra-relativistic heavy-ion collisions has been reported by the STAR collaboration at the Relativistic Heavy-Ion *** observation is consistent with the formation of a quark-gluon plasma,but similar findings in more energetic collisions at the Large Hadron Collider suggest that a consistent picture requires additional *** states of a heavy quark (charm or bottom) and its antiquark,commonly referred to as quarkonia,have long been recognized as excellent probes of quark-gluon plasma(QGP) formation in high-energy collisions of atomic *** the vacuum,most quarkonium states are dominantly bound by a linearly rising potential (the so-called Cornell potential,see Fig.1),as a direct manifestation of the confinement property of Quantum Chromodynamics (QCD).

关键词： quark linearly vacuum

Leukocytes and oxidative stress： dilemma for sperm Function and male fertility

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Asian Journal of Andrology 2011年第1期13卷 43-52页

作者： ralf R Henkel Department of Medical Biosciences University of the Western Cape Bellville 7535 South Africa

Spermatozoa are constantly exposed to the interphase between oxidation through high amounts of reactive oxygen species （ROS） and leukocytes, and reduction by means of scavengers and antioxidants. Considering the very special functions as being the only cells with such high polarization and exerting their functions outside the body, even in a different individual, the female genital tract, the membranes of these cells are chemically composed of an extraordinary high amount of polyunsaturated fatty acids. This in turn, renders them very susceptible to oxidative stress, which is defined as an imbalance between oxidation and reduction towards the oxidative status. As a result, ROS deriving from both leukocytes and the male germ cells themselves cause a process called ＇lipid peroxidation＇ and other damages to the sperm cell. On the other hand, a certain limited amount of ROS iS essential in order to trigger vital physiological reactions in cells, including capacitation or the acrosome reaction in sperm. The treatment of patients with antioxidants to compensate the oxidative status caused by oxidative stress is highly debated as uncontrolled antioxidative treatment might derail the system towards the reduced status, which is also unphysiological and can even induce cancer. This paradox is called the ＇antioxidant paradox＇. Therefore, a proper andrological diagnostic work-up, including the evaluation of ROS levels and the antioxidant capacity of the semen, has to he carried out beforehand, aimed at keeping the fine balance between oxidation and scavenging of vital amounts of ROS.

关键词： antioxidants balance beneficial effects detrimental effects leukocytes male infertility reactive oxygen species sperm functions

Targeting copper to combat macrophage-driven inflammation: a potential advanced therapeutic strategy

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4426-4427页

作者： ralf Weiskirchen Institute of Molecular Pathobiochemistry Experimental Gene Therapy and Clinical Chemistry(IFMPEGKC)RWTH University Hospital AachenPauwelsstr.30D-52074AachenGermany

In a recent paper published in Nature,Solier and coworkers showed that a rationally designed dimer of metformin targeting mitochondrial copper content can effectively oppose macrophage activation and plasticity.1 Since macrophages play critical roles in the initiation and maintenance of inflammation,this drug termed supformin holds promise to be a therapeutic effective in suppressing inflammation-related diseases related to macrophages.

关键词： inflammation therapeutic macrophage

Rainfall Algorithms Using Oceanic Satellite Observations from MWHS-2

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Advances in Atmospheric Sciences 2021年第8期38卷 1367-1378页

作者： Ruiyao CHEN ralf BENNARTZ Earth&Environmental Sciences Department Vanderbilt UniversityNashvilleTN 37235USA Space Science&Engineering Center University of Wisconsin-MadisonMadisonWI 53706USA

This paper describes three algorithms for retrieving precipitation over oceans from brightness temperatures (TBs) of the Micro-Wave Humidity Sounder-2 (MHWS-2) onboard Fengyun-3C (FY-3C). For algorithm development, scattering- induced TB depressions (ΔTBs) of MWHS-2 at channels between 89 and 190 GHz were collocated to rain rates derived from measurements of the Global Precipitation Measurement’s Dual-frequency Precipitation Radar (DPR) for the year 2017. ΔTBs were calculated by subtracting simulated cloud-free TBs from bias-corrected observed TBs for each channel. These ΔTBs were then related to rain rates from DPR using (1) multilinear regression (MLR);the other two algorithms, (2) range searches (RS) and (3) nearest neighbor searches (NNS), are based on k-dimensional trees. While all three algorithms produce instantaneous rain rates, the RS algorithm also provides the probability of precipitation and can be understood in a Bayesian framework. Different combinations of MWHS-2 channels were evaluated using MLR and results suggest that adding 118 GHz improves retrieval performance. The optimal combination of channels excludes high-peaking channels but includes 118 GHz channels peaking in the mid and high troposphere. MWHS-2 observations from another year were used for validation purposes. The annual mean 2.5° × 2.5° gridded rain rates from the three algorithms are consistent with those from the Global Precipitation Climatology Project (GPCP) and DPR. Their correlation coefficients with GPCP are 0.96 and their biases are less than 5%. The correlation coefficients with DPR are slightly lower and the maximum bias is ~8%, partly due to the lower sampling density of DPR compared to that of MWHS-2.

关键词： rainfall retrievals 118 GHz FY-3C MWHS-2 multilinear regression k-d tree

Advancements in personalized stem cell models for aging-related neurodegenerative disorders

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Neural Regeneration Research 2024年第11期19卷 2333-2334页

作者： Mingxi Weng ralf Jauch School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Translational Stem Cell Biology Hong Kong Special Administrative RegionChina

Neurodegenerative diseases(NDDs)are a class of disorders characterized by the gradual loss or malfunction of specific cell populations in the nervous system,which can be triggered by genetic or environmental *** a result,patients often experience a decline in mobility,sensation,memory,and cognition,which can ultimately lead to a fatal *** global incidence of NDDs,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,amyotrophic lateral sclerosis(ALS),and multiple sclerosis,is increasing.

关键词： degenerative Huntington sensation