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Induction of chronic cholestasis without liver cirrhosis-Creation of an animal model

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World Journal of Gastroenterology 2017年第23期23卷 4191-4199页

作者： Felix Dondorf RenéFahrner Michael Ardelt Eleonora Patsenker Felix Stickel Uta Dahmen Utz Settmacher falk Rauchfuβ Department of General Visceral and Vascular SurgeryJena University Hospital Division of Gastroenterology and Hepatology University Hospital Zürich

To analyze time intervals of inflammation and regeneration in a cholestatic rat liver *** 36 Lewis rats, divided into six groups of 6 animals (postoperative observation periods: 1, 2, 3, 4, 6, 8 wk), the main bile duct was ligated with two ligatures and observed for the periods mentioned above. For laboratory evaluation, cholestasis parameters (bilirubin, γ-GT), liver cell parameters (ASAT, ALAT) and liver synthesis parameters (quick, albumin) were determined. For histological analysis, HE, EvG, ASDCL and HMGB-1 stainings were performed. Furthermore, we used the mRNA of IL-33, GADD45a and p-21 for analyzing cellular stress and regeneration in cholestatic *** chemical laboratory and histological evaluation, a distinction between acute and chronic cholestatic liver injury with identification of inflammation and regeneration could be demonstrated by an increase in cholestasis (bilirubin: 1-wk group, 156.83 ± 34.12 μmol/L, P = 0.004) and liver cell parameters (ASAT: 2-wk group, 2.1 ± 2.19 μmol/L.s, P = 0.03; ALAT: 2-wk group, 1.03 ± 0.38 μmol/L.s, P = 0.03) after bile duct ligation (BDL). Histological evaluation showed an increase of bile ducts per portal field (3-wk group, 48 ± 6.13, P = 0.004) during the first four weeks after bile duct ligation. In addition to inflammation, which is an expression of acute cholestasis, there was an increase of necrotic areas in the histological sections (2-wk group, 1.38% ± 2.28% per slide, P = 0.002). Furthermore, the inflammation could be verified by ASDCL (4-wk group, 22 ± 5.93 positive cells per portal field, P = 0.041) and HMGB-1 [2-wk group, 13 ± 8.18 positive cells per field of view (FoV), P = 0.065] staining. Therefore, in summary of the laboratory evaluation and histological studies, acute cholestasis could be found during the first four weeks after bile duct ligation. Subsequently, the described parameters declined so that chronic cholestasis could be assumed. For quantification of secondary biliary ci

关键词： Rats Cholestasis Chronic cholestasis Rat liver model

Role of nuclear factor kappa B in central nervous system regeneration

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Neural Regeneration Research 2014年第7期9卷 707-711页

作者： Christian Engelmann falk Weih Ronny Haenold Leibniz Institute for Age Research-Fritz Lipmann Institute

Activation of nuclear factor kappa B （NF-κB） is a hallmark of various central nervous system （CNS） pathologies. Neuron-specific inhibition of its transcriptional activator subunit RelA, also referred to as p65, promotes neuronal survival under a range of conditions, i.e., for ischemic or excitotoxic insults. In macro- and microglial cells, post-lesional activation of NF-κB triggers a growth-permissive program which contributes to neural tissue inflammation, scar formation, and the expression of axonal growth inhibitors. Intriguingly, inhibition of such inducible NF-~B in the neuro-glial compartment, i.e., by genetic ablation of RelA or overexpression of a trans- dominant negative mutant of its upstream regulator IκBa, significantly enhances functional recovery and promotes axonal regeneration in the mature CNS. By contrast, depletion of the NF-κB subunit p50, which lacks transcriptional activator function and acts as a transcriptional repressor on its own, causes precocious neuronal loss and exacerbates axonal degeneration in the lesioned brain. Collectively, the data imply that NF-κB orchestrates a multicellular pro- gram in which κB-dependent gene expression establishes a growth-repulsive terrain within the post-lesioned brain that limits structural regeneration of neuronal circuits. Considering these subunit-specific functions, interference with the NF-κB pathway might hold clinical potentials to improve functional restoration following traumatic CNS injury.

关键词： nuclear factor kappa B RelA p65 p50 central nervous system injury axonal regeneration neural regeneration

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类固体非晶态材料的变形与失效

力学进展 2021年第2期51卷 406-426页

作者： falk M L Langer J S 陈艳(译) 王云江(校) 约翰霍普金斯大学材料科学与工程系、机械工程系、物理与天文系马里兰州巴尔的摩21218 加州大学物理系加利福尼亚州圣巴巴拉93106-9530 中国科学院力学研究所

自20世纪70年代以来,类固体非晶态材料变形与失效的理论模型相继出现,这些模型基于应力驱动分子重排从而在局部流动缺陷处发生剪切转变这一物理图像.该图像是现代剪切转变区理论的基础,也是本综述的焦点.我们将首先概述该理论框架并给... 详细信息

自20世纪70年代以来,类固体非晶态材料变形与失效的理论模型相继出现,这些模型基于应力驱动分子重排从而在局部流动缺陷处发生剪切转变这一物理图像.该图像是现代剪切转变区理论的基础,也是本综述的焦点.我们将首先概述该理论框架并给出一些应用案例,特别是块体金属玻璃应力−应变测量结果的阐释,剪切带数值模拟分析和剪切转变区运动方程在自由边界计算中的应用.在本综述的第二部分,为简单起见,将关注非晶塑性的非热模型,并基于该模型说明剪切转变区理论是如何从非平衡热力学的系统描述中发展起来的.

关键词：塑性非平衡热力学剪切转变区

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Burn injury prevention in low-and middleincome countries:scoping systematic review

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Burns & Trauma 2021年第1期9卷 123-144页

作者： Kate Price Kwang Chear Lee Katherine E.Woolley Henry falk Michael Peck Richard Lilford Naiem Moiemen College of Medical and Dental Sciences University of BirminghamEdgbastonBirminghamB152TTUK University Hospital Birmingham NHS Foundation Trust Queen Elizabeth Hospital BirminghamMindelsohn WayEdgbastonBirminghamB152WBUK Institute of Applied Health Research University of BirminghamEdgbastonBirminghamB152TTUK Adjunct Professor of Environmental Health Emory UniversityRollins School of Public HealthAtlantaGA 30322US Clinical Professor of Surgery University of Arizona College of MedicinePhoenixAZ 85004US

Background:Burn injuries are a leading cause of morbidity and disability,with the burden of disease being disproportionately higher in low-and middle-income countries(LMIC).Burn prevention programmes have led to significant reductions in the incidence of burns in high-income ***,a previous systematic review published in 2015 highlighted that implementation and evaluation of similar programmes has been limited in *** objective of this scoping review and narrative synthesis was to summarise and understand the initiatives that have been carried out to reduce burn injuries in LMIC and their ***:We aimed to identify publications that described studies of effectiveness of burn prevention interventions applied to any population within a LMIC and measured burn incidence or burns-related *** publications were identified from three ***,data was extracted from manuscripts identified in the systematic review published by Rybarczyk et *** then performed a search for manuscripts on burn prevention interventions published between January 2015 and September ***,we extracted data from two systematic reviews where burn evidence was not the primary outcome,which were identified by senior authors.A quality assessment and narrative synthesis of included manuscripts were ***:In total,24 manuscripts were identified and categorized according to intervention *** majority of manuscripts(n=16)described education-based *** manuscripts focused on environmental modification interventions and four adopted a mixedmethods *** of the education-based initiatives demonstrated improvements in knowledge relating to burn safety or first aid,however few measured the impact of their intervention on burn *** manuscripts described population-based educational interventions and noted reductions in burn *** one of the four manuscripts describing environmental modification i

关键词： Burns Prevention Low-and-middle income countries Systematic review

Muscle RING-finger protein-1 (MuRFl) functions and cellular localization are regulated by SUMOl post-translational modification

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Journal of Molecular Cell Biology 2019年第5期11卷 356-370页

作者： Gabriel Heras Arvind Venkat Namuduri Leonardo Traini Ganna Shevchenko Alexander falk Sara Bergstrom Lind Mi Jia Geng Tian Stefano Gastaldello Department of Physiology and Pharmacology Karolinska Institutet Solnavagen 9 Quarter B5 Stockholm SE-17177 Sweden Department of Chemistry-BMC Analytical Chemistry Uppsala University Box 599 Uppsala SE-75124 Sweden Precision Medicine and Pharmacy Research Center Binzhou Medical University Yantai 264003 China

The muscle RING-finger protein-1 (MuRFl) is an E3 ubiquitin ligase expressed in skeletal and cardiac muscle tissues and it plays important roles in muscle remodeling. Upregulation of MuRFl gene transcription participates in skeletal muscle atrophy, on contrary downregulation of protein expression leads to cardiac hypertrophy. MuRFl gene point mutations have been found to generate protein aggregate myopathies defined as muscle disorder characterized by protein accumulation in muscle fibers. We have discovered that MuRFl turned out to be also a target for a new post-translational modification arbitrated by conjugation of SUM01 and it is mediated by the SUMO ligases E2 UBC9 and the E3 PIASy/4. SUMOylation takes place at lysine 238 localized at the second coiled-coil protein domain that is required for efficient substrate interaction for polyubiquitination. We provided evidence that SUMOylation is essential for MuRFl nuclear translocation and its mitochondria accumulation is enhanced in hyper? glycemic conditions delivering a stabilization of the overall SUMOylated proteins in cultured myocytes. Thus, our findings add this SUM01 post-translational modification as a new concept to understand muscle disorders related to the defect in MuRFl activity.

关键词： TRIM63/MuRFl muscle remodeling SUMO protein degradation hyperglycemia

Recirculating IL-1R2^(+) Tregs fine-tune intrathymic Treg development under inflammatory conditions

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Cellular & Molecular Immunology 2021年第1期18卷 182-193页

作者： Eirini Nikolouli Yassin Elfaki Susanne Herppich Carsten Schelmbauer Michael Delacher Christine falk Ilgiz A.Mufazalov Ari Waisman Markus Feuerer Jochen Huehn Department of Experimental Immunology Helmholtz Centre for Infection ResearchBraunschweigGermany Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-University MainzMainzGermany Regensburg Center for Interventional Immunology(RCI) Chair for ImmunologyUniversity Regensburg and University Hospital RegensburgRegensburgGermany Institute of Transplant Immunology Integrated Research and Treatment Center TransplantationIFB-TxHannover Medical SchoolHannoverGermany Hannover Medical School HannoverGermany

The vast majority of Foxp3^(+)regulatory T cells(Tregs)are generated in the thymus,and several factors,such as cytokines and unique thymic antigen-presenting cells,are known to contribute to the development of these thymus-derived Tregs(tTregs).Here,we report the existence of a specific subset of Foxp3^(+)Tregs within the thymus that is characterized by the expression of IL-1R2,which is a decoy receptor for the inflammatory cytokine *** flow cytometric analysis of the thymocytes from Foxp3^(hCD2)xRAG1^(GFP) reporter mice revealed that the IL-1R2^(+)Tregs are mainly RAG1^(GFP-)and CCR6^(+)CCR7^(-),demonstrating that these Tregs are recirculating cells entering the thymus from the periphery and that they have an activated *** the spleen,the majority of IL-1R2^(+)Tregs express neuropilin-1(Nrp-1)and Helios,suggesting a thymic origin for these ***,among all tissues studied,the highest frequency of IL-1R2^(+)Tregs was observed in the thymus,indicating preferential recruitment of this Treg subset by the *** fetal thymic organ cultures(FTOCs),we demonstrated that increased concentrations of exogenous IL-1β blocked intrathymic Treg development resulting in a decreased frequency of CD25^(+)Foxp3^(+)tTregs and an accumulation of CD25^(+)Foxp3^(-)Treg ***,the addition of IL-1R2^(+)Tregs,but not IL-1R2^(+)Tregs,to reaggregated thymic organ cultures(RTOCs)abrogated the IL-1β-mediated blockade,demonstrating that these recirculating IL-1R2^(+)Tregs can quench IL-1 signaling in the thymus and thereby maintain thymic Treg development even under inflammatory conditions.

关键词： Thymus Treg development Inflammation IL-1 system

California Simulation of Evapotranspiration of Applied Water and Agricultural Energy Use in California

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Journal of Integrative Agriculture 2013年第8期12卷 1371-1388页

作者： Morteza N Orang Richard L Snyder Shu Geng Quinn J Hart Sara Sarreshteh Matthias falk Dylan Beaudette Scott Hayes Simon Eching California Department of Water Resources Department of Land Air and Water ResourcesUniversity of California School of Environment and Energy Shenzhen Graduate SchoolPeking University

The California Simulation of Evapotranspiration of Applied Water （CaI-SIMETAW） model is a new tool developed by the California Department of Water Resources and the University of California, Davis to perform daily soil water balance and determine crop evapotranspiration （ETo）, evapotranspiration of applied water （ETaw）, and applied water （AW） for use in California water resources planning. ETaw is a seasonal estimate of the water needed to irrigate a crop assuming 100% irrigation efficiency. The model accounts for soils, crop coefficients, rooting depths, seepage, etc. that influence crop water balance. It provides spatial soil and climate information and it uses historical crop and land-use category information to provide seasonal water balance estimates by combinations of detailed analysis unit and county （DAU/County） over Califomia. The result is a large data base of ETc and ETaw that will be used to update information in the new California Water Plan （CWP）. The application uses the daily climate data, i.e., maximum （Tx） and minimum （Tn） temperature and precipitation （Pcp）, which were derived from monthly USDA-NRCS PRISM data （PRISM Group 2011） and daily US National Climate Data Center （NCDC） climate station data to cover California on a 4 kmx4 km change grid spacing. The application uses daily weather data to determine reference evapotranspiration （ETo）, using the Hargreaves-Samani （HS） equation （Hargreaves and Samani 1982, 1985）. Because the HS equation is based on temperature only, ETo from the HS equation were compared with CIMIS ETo at the same locations using available CIMIS data to determine correction factors to estimate CIMIS ETo from the HS ETo to account for spatial climate differences. CaI-SIMETAW also employs near real-time reference evapotranspiration （ETo） information from Spatial CIMIS, which is a model that combines weather station data and remote sensing to provide a grid of ETo information. A second database containing the available soil water

关键词： soil water balance crop water requirements weather generator water resource planning crop coefficient energy use

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Soybean Root System Architecture Trait Study through Genotypic,Phenotypic,and Shape-Based Clusters

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Plant Phenomics 2020年第1期2卷 149-171页

作者： Kevin G.falk Talukder Zaki Jubery Jamie A.O’Rourke Arti Singh Soumik Sarkar Baskar Ganapathysubramanian Asheesh K.Singh Department of Agronomy Iowa State UniversityAmesIowaUSA Department of Mechanical Engineering Iowa State UniversityAmesIowaUSA USDA-Agricultural Research Service Corn Insects and Crop Genetics Research UnitAmesIowaUSA

We report a root system architecture(RSA)traits examination of a larger scale soybean accession set to study trait genetic *** from the limitation of scale,scope,and susceptibility to measurement variation,RSA traits are tedious to *** 35,448 SNPs with an imaging phenotyping platform,292 accessions(replications=14)were studied for RSA traits to decipher the genetic *** on literature search for root shape and morphology parameters,we used an ideotypebased approach to develop informative root(iRoot)categories using root *** RSA traits displayed genetic variability for root shape,length,number,mass,and *** accessions clustered into eight genotype-and phenotype-based clusters and displayed ***-based clusters correlated with geographical *** profiles indicated that much of US origin genotypes lack genetic diversity for RSA traits,while diverse accession could infuse useful genetic variation for these ***-based clusters were created by integrating convolution neural net and Fourier transformation methods,enabling trait cataloging for breeding and research *** combination of genetic and phenotypic analyses in conjunction with machine learning and mathematical models provides opportunities for targeted root trait breeding efforts to maximize the beneficial genetic diversity for future genetic gains.

关键词： neural breeding Root

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黄体期高催乳素血症

实用妇产科杂志 1995年第3期 180-181页

作者： falk RJ

在月经周期中任何时期,正常妇女的血催乳素(PRL)水平可以暂时升高,称为黄体期高催乳素血症(LPH)。本文的目的在于了解:①月经周期正常的不孕妇女偶发及反复的 LPH 发生率。②LPH 与孕酮缺乏的关系。③通过比较 LPH 妇女及 PRL 正常的对... 详细信息

在月经周期中任何时期,正常妇女的血催乳素(PRL)水平可以暂时升高,称为黄体期高催乳素血症(LPH)。本文的目的在于了解:①月经周期正常的不孕妇女偶发及反复的 LPH 发生率。②LPH 与孕酮缺乏的关系。③通过比较 LPH 妇女及 PRL 正常的对照组妇女对促甲状腺素释放激素(TRH)

关键词： OH