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Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma:results from a retrospective multicenter trial

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Frontiers of Medicine 2023年第5期17卷 878-888页

作者： Elias A.T.Koch Anne Petzold Anja Wessely Edgar Dippel markus Eckstein Anja Gesierich Ralf Gutzmer Jessica C.Hassel Harald Knorr Nicole Kreuzberg Ulrike Leiter Carmen Loquai Friedegund Meier markus meissner Peter Mohr Claudia Pföhler Farnaz Rahimi Dirk Schadendorf Max Schlaak Kai-Martin Thoms Selma Ugurel Jochen Utikal Michael Weichenthal Beatrice Schuler-Thurner Carola Berking markus V.Heppt Department of Dermatology Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg(FAU)91054ErlangenGermany Comprehensive Cancer Center Erlangen—European Metropolitan Area of Nürnberg(CCC ER-EMN) 91054ErlangenGermany Deutsches Zentrum Immuntherapie(DZI) Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg(FAU)91054ErlangenGermany Bavarian Cancer Research Center(BZKF) Uniklinikum ErlangenÖstliche Stadtmauerstraße 3091054ErlangenGermany Department of Dermatology Ludwigshafen Medical Center67059LudwigshafenGermany Institute of Pathology Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg91054ErlangenGermany Department of Dermatology University Hospital Würzburg97080WürzburgGermany Skin Cancer Center Minden Department of DermatologyMühlenkreiskliniken AöRRuhr UniversityBochum Campus Minden32423MindenGermany Skin Cancer Center Department of Dermatology and National Center for Tumor Diseases(NCT)University Hospital Heidelberg69120HeidelbergGermany Department of Ophthalmology Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg(FAU)91054ErlangenGermany Department of Dermatology and Venereology Skin Cancer Center at the Center of Integrated Oncology(CIO)Köln BonnUniversity Hospital of Cologne50937CologneGermany Department of Dermatology Center for DermatooncologyUniversity Hospital Tübingen72056TübingenGermany Department of Dermatology University Medical Center Mainz55131MainzGermany Skin Cancer Center at the University Cancer Center Dresden and National Center for Tumor Diseases&Department of Dermatology University Hospital Carl Gustav Carus01307DresdenGermany Department of Dermatology Venereology and AllergologyGoethe University60590Frankfurt am MainGermany Department of Dermatology Elbeklinikum21614BuxtehudeGermany Department of Dermatology Saarland University Medical School66421Homburg/SaarGermany Department of Dermatology and Allergy Munich University Hospital(LMU)81377MunichGermany Departmen

Metastases of uveal melanoma(UM)spread predominantly to the *** to low response rates to systemic therapies,liver-directed therapies(LDT)are commonly used for tumor *** impact of LDT on the response to systemic treatment is unknown.A total of 182 patients with metastatic UM treated with immune checkpoint blockade(ICB)were included in this *** were recruited from prospective skin cancer centers and the German national skin cancer registry(ADOReg)of the German Dermatologic Cooperative Oncology Group(DeCOG).Two cohorts were compared:patients with LDT(cohort A,n=78)versus those without LDT(cohort B,n=104).Data were analyzed for response to treatment,progression-free survival(PFS),and overall survival(OS).The median OS was significantly longer in cohort A than in cohort B(20.1 vs.13.8 months;P=0.0016)and a trend towards improved PFS was observed for cohort A(3.0 vs.2.5 months;P=0.054).The objective response rate to any ICB(16.7%vs.3.8%,P=0.0073)and combined ICB(14.1%vs.4.5%,P=0.017)was more favorable in cohort *** data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.

关键词： uveal melanoma liver-directed therapy immune checkpoint blockade SIRT anti-PD-1 anti-CTLA-4

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Current humanized mouse models for studying human immunology and HIV-1 immuno-pathogenesis

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Science China(Life Sciences) 2010年第2期53卷 195-203页

作者： meissner Eric Lineberger Comprehensive Cancer Center Department of Microbiology and ImmunologySchool of MedicineUniversity of North Carolina at Chapel Hill

A robust animal model for "hypothesis-testing/mechanistic" research in human immunology and immuno-pathology should meet the following ***,it has well-studied hemato-lymphoid organs and target cells similar to those of ***,the human pathogens establish infection and lead to relevant ***,it is genetically inbred and can be manipulated via genetic,immunological and pharmacological *** human-tropic pathogens such as HIV-1 fail to infect murine cells due to the blocks at multiple steps of their life *** mouse with a reconstituted human immune system and other human target organs is a good candidate.A number of human-mouse chimeric models with human immune cells have been developed in the past 20 years,but most with only limited success due to the selective engraftment of xeno-reactive human T cells in hu-PBL-SCID mice or the lack of significant human immune responses in the SCID-hu Thy/Liv *** review summarizes the current understanding of HIV-1 immuno-pathogenesis in human patients and in SIV-infected primate *** also reviews the recent progress in the development of humanized mouse models with a functional human immune system,especially the recent progress in the immunodeficient mice that carry a defective gammaC ***/SCID/gammaC-/(NOG or NSG) or the Rag2-/-/gammaC-/double knockout (DKO) mice,which lack NK as well as T and B cells (NTB-null mice),have been used to reconstitute a functional human immune system in central and peripheral lymphoid organs with human CD34+ *** NTB-hu HSC humanized models have been used to investigate HIV-1 infection,immuno-pathogenesis and therapeutic *** models,with further improvements,will contribute to study human immunology,human-tropic pathogens as well as human stem cell biology in the tissue development and function in vivo.

关键词： Humanized mouse models HIV-1 NOD/SCID/gammaC-/- Rag2-/-/gammaC-/-

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Sex and age-specific differences in wing pointedness and wing length in blackcaps Sylvia atricapilla migrating through the southern Baltic coast

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Current Zoology 2021年第3期67卷 271-277页

作者： Agnieszka Ozarowska Grzegorz Zaniewicz Wtodzimierz meissner Department of Vertebrate Ecology and Zoology Avian Ecophysiology UnitUniversity of GdanskGdansk80-308Poland Bird Migration Research Station University of GdanskGdansk80-308Poland

The blackcap Sylvia atricapilla shows a complex migratory pattern and is a suitable species for the studies of morphological migratory syndrome,including adaptations of wing shape to different migratory *** migrants of this species that breed in northern,central,and Eastern Europe differ by migration distance and some cover shorter distance to the wintering grounds in the southern part of Europe/North Africa or the British Isles,although others migrate to sub-Saharan *** on>40years of ringing data on blackcaps captured during autumn migration in the Southern Baltic region,we studied age-and sex-related correlations in wing pointedness and wing length of obligate blackcap migrants to understand the differences in migratory behavior of this *** though the recoveries of blackcaps were scarce,we reported some evidence that individuals which differ in migration distance differed also in wing *** found that wing pointedness significantly increased with an increasing wing length of migrating birds,and adults had longer and more pointed wings than juvenile *** indicates stronger antipredator adaptation in juvenile blackcaps than selection on flight efficiency,which is particularly important during ***,we documented more pronounced differences in wing length between adult and juvenile males and *** differences in wing length may enhance a faster speed of adult male blackcaps along the spring migration route and may be adaptive when taking into account climatic effects,which favor earlier arrival from migration to the breeding grounds.

关键词： blackcap migration population wing shape

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Predicting erosion and sediment yield in a mesoscale basin in the semiarid monsoon region Miyun/China

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Ecological Processes 2014年第1期3卷 214-224页

作者： Michael Gebel Mario Uhlig Stefan Halbfass Ralph meissner Shuhuai Duan Gesellschaft für Angewandte Landschaftsforschung(GALF)bR Am Ende 1401277 DresdenGermany Department of Soil Physics Helmholtz Centre for Environmental Research–UFZLysimeter StationDorfstraße 5539615 FalkenbergGermany Beijing Soil and Water Conservation Center(BWA) No.5 Yunuantan South RoadBeijing 100038Haidian DistrictChina

Introduction:Changes in land use and agricultural management have caused a strong increase in sediment and particulate phosphorus input into the Miyun *** simulation of the relevant runoff and sediment fluxes at the mesoscale needs adequate procedures,adapted to a semiarid monsoon climate and regional land-use ***:The modified Universal Soil Loss Equation(USLE-M)was integrated into the STOFFBILANZ model to calculate daily soil losses in the entire Miyun catchment *** results are well within the range of monitoring data from Wischmeier plots that are located inside the investigation *** the reference year 2009,soil erosion was estimated at an average of 952 kg ha^(-1) year^(-1).Daily based simulation of sediment input into surface waters was done in the next step,taking into account the likeliness of sediment input and sediment delivery *** sediment inputs are by 113 kg ha^(-1) year^(-1).Critical source areas are located on cropland and are particularly relevant on the former lakebed of the Miyun reservoir which has recently been used for corn ***:Compared with observation data from the Bai and Chao rivers,the simulation of sediment loads showed a satisfying agreement that underlines the suitability of the selected approach to substitute recently used one-year balances based on the Universal Soil Loss Equation(USLE)*** tillage was selected as a possible mitigation option to reduce soil erosion and sediment *** to the limited availability of spatial and monitoring data,the simulations are approximate and only a first step in contributing to an integrated river basin management that should be improved in future.

关键词： Direct runoff Mesoscale Miyun Model Sediment input Soil erosion STOFFBILANZ

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DISTRIBUTIONS OF TEMPERATURE, VELOCITY AND VISCOSITY AT SYMMETRICAL AXIS OF CYLINDRICAL PLUME IN EARTH'S MANTLE WITH VARIABLE VISCOSITY

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Science China Chemistry 1983年第12期26卷 1342-1348页

作者：李荫亭,R.O.meissner,薛恩 Institute of Mechanics Academia Sinica Beijing Institute of Geophysics Kiel University D-2300 Kiel Germany Mathematical Division Medical College of Beijing

The parameters at the symmetrical axis of a cylindrical plume characterize the strength of this plume and provide a boundary condition which must be given to investigate the structure of a plume. For Newtonian fluid with a temperature-and pressure-dependence viscosity, an asymptotical solution of hydrodynamic equations at the symmetrical axis of the plume is found in the present paper. The temperature, upward velocity and viscosity at the symmetrical axis have been obtained as functions of depth, The calculated results have been given for two typical sets of Newtonian rheological parameters. The results obtained show that the temperature distribution along the symmetrical axis is nearly independent of the theological parameters. The upward velocity at the symmetrical axis, however, is strongly dependent on the rheological parameters.

关键词： AT DISTRIBUTIONS OF TEMPERATURE VELOCITY AND VISCOSITY AT SYMMETRICAL AXIS OF CYLINDRICAL PLUME IN EARTH’S MANTLE WITH VARIABLE VISCOSITY

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循环荷载作用下饱和黏性土的弹塑性双面模型

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土木工程学报 2006年第1期39卷 92-97页

作者：李涛 H. meissner 北京交通大学北京100044 德国凯泽斯劳滕工业大学

基于作者新近提出的一种混合塑性硬化准则和临界状态土力学理论建立了一个三维形式表述的适于饱和黏性土的弹塑性双面模型,此硬化准则是著名的M asing方法在三维应力空间中的推广。该模型的二维形式已采用饱和黏性土样室内动态三轴不排... 详细信息

基于作者新近提出的一种混合塑性硬化准则和临界状态土力学理论建立了一个三维形式表述的适于饱和黏性土的弹塑性双面模型,此硬化准则是著名的M asing方法在三维应力空间中的推广。该模型的二维形式已采用饱和黏性土样室内动态三轴不排水剪切试验的结果进行了验证并已在另文发表。本文所建的三维弹塑性动本构模型与一个半经验的孔隙水压力增长模式相结合,通过有限元程序ABAQUS*对一个循环荷载作用下的条形基础下部地基土层内的位移、应力分布和超孔隙水压力随时间的变化进行了分析,计算结果表明模型预测的地基土的力学响应是符合实际的。

关键词：弹塑性本构模型循环加载黏性土有限元分析

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As bright as heaven

As bright as heaven

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作者： Susan meissner.

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MECHANICAL AND THERMAL STRUCTURE OF A CYLINDRICAL PLUME IN THE EARTH'S MANTLE

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Science China Chemistry 1985年第1期28卷 92-100页

作者：李荫亭,R. O. meissner,薛恩 Institute of Mechanics Academia Sinica Beijing Institute of Geophysics Kiel University D-2300 Kiel West Germany Mathematical Division Medical College of Beijing

A mantle plume is understood as a hot, narrow, upwelling flow in the earth's mantle and accompanied by an efficient transfer of mass and energy from deep to upper layer of the earth. The cylindrical plume in earth's mantle plays an important role in explaining the origin of the surface hot spots and linear island chains. From the basic hydrodynamical equations, the detailed mechanical and thermal structure of a cylindrical plume of Newtouian fluids with temperature and pressure-dependent viscosity are given in the present paper. For two sets of rheological parameters the radial profiles of upward velocity, temperature and viscosity in the plume and radiuses of the plume at various depths have been calculated.

关键词： viscosity rheological chains mantle narrow cylindrical understood spots radial island

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The intensity of supplementary feeding in an urban environment impacts overwintering Mallards(Anas platyrhynchos)as wintering conditions get harsher

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Avian Research 2024年第4期15卷 438-444页

作者： Marta Witkowska Wojciech Wesołowski Martyna Markiewicz Jonasz Pakizer Julia Neumann Agnieszka O˙zarowska Włodzimierz meissner Ornithology Unit Department of Vertebrate Ecology and ZoologyFaculty of BiologyUniversity of GdanskWita Stwosza 5980-308GdanskPoland Student’s Scientific Club KOS Department of Vertebrate Ecology and ZoologyFaculty of BiologyUniversity of GdanskWita Stwosza 5980-308GdanskPoland Department of Molecular Biology Faculty of BiologyUniversity of GdanskWita Stwosza 5980-308GdanskPoland Regional Directorate for Environmental Protection Chmielna 54/5780-748GdanskPoland

Although urbanization poses various threats to avifauna,some bird species,including Mallards(Anas platyrhynchos),choose towns and cities as their wintering habitats,possibly due to favourable temperatures and abundant anthropogenic *** this study,we investigated how population dynamics changed in relation to winter harshness and intensity of supplementary bird feeding in Mallard,a dabbing duck species well adapted to an urban *** surveyed 15 city ponds for five consecutive years,counting overwintering individuals and incidents of bird feeding conducted by the citizens of Gda′*** of Mallards observed in the studied area fluctuated both annually and within seasons,with on average 327(±SD=108.5)individuals and a malebiased sex ratio *** observed a gradient of feeding intensity on the surveyed ponds,with number of feeding incidents ranging from 0 to 30 in a *** results indicated that the number of Mallards increased with the bird feeding intensity,independently of the size of the studied ponds,and both males and females were similarly attracted by food *** severe wintering conditions,expressed by the percentage of the ice cover of studied ponds resulted in more birds wintering in the urban *** effect was more pronounced in females compared to males,possibly due to females having a lower ability to withstand severe wintering conditions,forcing them to relocate towards urban *** results confirm that urbanized areas may serve as wintering grounds for birds,due to additional food resources available there and milder wintering conditions compared to surrounding rural areas.

关键词： Anthropogenic food Duck Ecology of cities Human impact Urban ecology Waterbird

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Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation

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World Journal of Gastroenterology 2004年第6期10卷 864-870页

作者： RolfJ.Schauer SinanKalmuk Alexander L.Gerbes Rosemarie Leiderer Herbert meissner Friedrich W.Schildberg Konrad Messmer Manfred Bilzer Surgical Department Klinikum GrosshadernLudwig-Maximilians-University of MunichGermany Department Institute for Surgical Research Klinikum GrosshadernLudwig-Maximilians-University of MunichGermany Institute of Pathology Klinikum GrosshadernLudwig-Maximilians-University of MunichGermany

AIM:To investigate the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation. METHODS:Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic *** a 2-h reperfusion period either saline (controls,n=8) or GSH (50 or 100 μmol/(h·kg),n=5 each) was continuously administered via the jugular vein. RESULTS:Two hours after starting reperfusion plasma ALT increased to 1 457±281 U/L (mean±SE) in controls but to only 908±187 U/L (P<0.05) in animals treated with 100 μmol GSH/(h·kg).No protection was conveyed by 50μmol GSH/(h·kg).Cytoprotection was confirmed by morphological findings on electron microscopy:GSH treatment prevented detachment of sinusoidal endothelial cells (SECs) as well as loss of microvilli and mitochondrial swelling of ***,postischemic bile flow increased *** fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal *** infusion of 50μmol and 100 μmol GSH/(h·kg),plasma GSH increased to 65±7 mol/L and 97±18 mol/L,but to only 20±3 mol/L in untreated recipients. Furthermore,plasma glutathione disulfide (GSSG) increased to 7.5±1.0 mol/L in animals treated with 100μmol/(h·kg) GSH but infusion of 50μmol GSH/(h·kg) did not raise levels of untreated controls (1.8±0.5 mol/L vs 2.2±0.2 mol/L). CONCLUSION:Plasma GSH levels above a critical level may act as a “sink” for ROS produced in the hepatic vasculature during reperfusion of liver ***,GSH can be considered a candidate antioxidant for the Drevention of reperfusion injury after liver transplantation,in particular since it has a low toxicity in humans.

关键词： Liver Circulation Liver Transplantation Animals Glutathione dosage Hepatocytes Infusions, Intravenous Male Postoperative Period Rats Rats, Inbred Lew Reperfusion Injury control

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