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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 liver.Due to low response rates to systemic therapies,liver-directed therapies(LDT)are commonly used for tumor control.The 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 analysis.Patients 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 A.Our 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 criteria.First,it has well-studied hemato-lymphoid organs and target cells similar to those of humans.Second,the human pathogens establish infection and lead to relevant diseases.Third,it is genetically inbred and can be manipulated via genetic,immunological and pharmacological means.Many human-tropic pathogens such as HIV-1 fail to infect murine cells due to the blocks at multiple steps of their life cycle.The 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 mouse.This review summarizes the current understanding of HIV-1 immuno-pathogenesis in human patients and in SIV-infected primate models.It 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 gene.NOD/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+ HSC.These NTB-hu HSC humanized models have been used to investigate HIV-1 infection,immuno-pathogenesis and therapeutic interventions.Such 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 performance.Obligate 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 Africa.Based 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 species.Even though the recoveries of blackcaps were scarce,we reported some evidence that individuals which differ in migration distance differed also in wing length.We found that wing pointedness significantly increased with an increasing wing length of migrating birds,and adults had longer and more pointed wings than juvenile birds.This indicates stronger antipredator adaptation in juvenile blackcaps than selection on flight efficiency,which is particularly important during migration.Moreover,we documented more pronounced differences in wing length between adult and juvenile males and females.Such 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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Prognostic value of Doppler transmitral filling patterns in patients with chronic heart failure

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Chinese Medical Journal 2004年第2期17卷 176-182页

作者：郑哲岚 A.meissner B.Hausmann H.Alexander R.Simon Department of Ultrasonography First Affiliated Hospital Zhejiang University College of Medicine Hangzhou 310003 China Department of Cardiology Kiel University Hospital Germany

Background Chronic heart failure is a significant cause of cardiovascular morbidity and mortality. This study tested the hypothesis that restrictive filling pattern may provide useful prognostic data for identifying patients with chronic heart failure at high risk of all-cause cardiac death.Methods Ninety patients with chronic heart failure [ 70 men and 20 women, mean age (58.1 ± 11.6) years] were investigated and followed for (18. 8 ±7. 9) months. During this period, 14 patients died of progressive pump failure, 12 patients underwent heart transplantation, 5 patients died suddenly, and 2 patients died of acute myocardial infarction. A new criterion, the restrictive filling index (RFI), was designed to subgroup patients into a restrictive and a nonrestrictive group.Results Patients with restrictive filling pattern had a more severe left ventricular dysfunction and a higher cardiac mortality. Analysis by the Kaplan-Meier method revealed that patients in the RFI≥1 and RFI <1 groups had a cardiac events-free survival rate of 52% versus 94% at 1 year, and 27. 5% versus 92% at 2 years, respectively. The multivariate Cox proportional hazard model selected RFI as the most powerful prognostic factor (x2 =8. 8017, P=0. 0030) for all-cause cardiac death.Conclusion These results indicate that RFI is a simple, noninvasive, and specific clinical predictor for adult chronic heart failure patients who are at a high risk for all-cause cardiac death.

关键词： prognosis echocardiography Doppler heart failure congestive blood flow velocity

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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 reservoir.The simulation of the relevant runoff and sediment fluxes at the mesoscale needs adequate procedures,adapted to a semiarid monsoon climate and regional land-use pattern.Results:The modified Universal Soil Loss Equation(USLE-M)was integrated into the STOFFBILANZ model to calculate daily soil losses in the entire Miyun catchment area.The results are well within the range of monitoring data from Wischmeier plots that are located inside the investigation area.For 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 ratio.Average 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 cropping.Conclusions: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)approach.Conservation tillage was selected as a possible mitigation option to reduce soil erosion and sediment loads.Owing 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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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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PI 3-kinase pathway is responsible for antiapoptotic effects of atrial natriuretic peptide in rat liver transplantation

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World Journal of Gastroenterology 2006年第7期12卷 1049-1055页

作者： Uwe Grutzner Melanie Keller Michael Bach Alexandra K Kiemer Herbert meissner Manfred Bilzer Stefan Zahler Alexander L Gerbes Angelika M Vollmar Institute for Surgical Research Klinikum GroBhadernUniversity of MunichD-81377 MunichGermany Department of Pharmacy University of MunichD-81377 MunichGermany Department Institute of Pathology University of MunichD-81377 MunichGermany

AIM:To investigate the in vivo effect of atrial natriureticpeptide(ANP)and its signaling pathway during ortho-topic rat liver transplantation.METHODS:Rats were infused with NaCl,ANP(5 μg/kg),wortmannin(WM,16 μg/kg),or a combination ofboth for 20 min.Livers were stored in UW solution(4°C)for 24 h,transplanted and reperfused.Apoptosis wasexamined by caspase-3 activity and TUNEL staining.Phosphorylation of Akt and Bad was visualized by West-ern blotting and phospho-Akt-localization by confocalmicroscopy.RESULTS:ANP-pretreatment decreased caspase-3activity and TUNEL-positive cells after cold ischemia,indicating antiapoptotic effects of ANP in vivo.The an-tiapoptotic signaling of ANP was most likely caused byphosphorylation of Akt and Bad,since pretreatment withPI 3-kinase inhibitor WM abrogated the ANP-inducedreduction of caspase-3 activity.Interestingly,analysis ofliver tissue by confocal microscopy showed translocationof phosphorylated Akt to the plasma membrane of hepa-tocytes evoked by ANP.CONCLUSION:ANP activates the PI-3-kinase pathwayin the liver in vivo leading to phosphorylation of Bad, an event triggering antiapoptotic signaling cascade inischemic liver.

关键词： 3-激酶尿钠排泄肝移植细胞凋亡缺血损伤

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Remote sensing and analysis of tropical cyclones:Current and emerging satellite sensors

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Tropical Cyclone Research and Review 2023年第4期12卷 267-293页

作者： Lucrezia Ricciardulli Brian Howell Christopher R.Jackson Jeff Hawkins Joe Courtney Ad Stoffelen Sebastian Langlade Chris Fogarty Alexis Mouche William Blackwell Thomas meissner Julian Heming Brett Candy Tony McNally Masahiro Kazumori Chinmay Khadke Maria Ana Glaiza Escullar Remote Sensing Systems Santa RosaCAUSA Joint Typhoon Warning Center Pearl HarborHawaiiUSA Global Ocean Associates(supporting NOAA/NESDIS STAR) AlexandriaVAUSA University of Wisconsin Cooperative Institute for Meteorological Satellite StudiesMadisonWIUSA Bureau of Meteorology PerthAustralia Royal Netherlands Meteorological Institute(KNMI) De BiltNetherlands Tropical Cyclone/Regional Specialized Meteorological Center Meteo FranceReunionFrance Canadian Hurricane Center(CHC) DartmouthNova ScotiaCanada University Brest CNRSIRDIfremerLaboratoire d’Oceanographie Physique et Spatiale(LOPS)IUEMBrestFrance MIT Lincoln Laboratory LexingtonMAUSA Met Office ExeterUK European Centre for Medium-Range Weather Forecasts ReadingUK Japan Meteorological Agency(JMA) TokyoJapan India Meteorological Department(IMD) New DelhiIndia Philippine Atmospheric Geophysical and Astronomical Services Administration(PAGASA)Diliman Quezon CityPhilippines

This article describes recent advances in the capability of new satellite sensors for observing Tropical Cyclones(TC)fine structure,wind field,and temporal evolution.The article is based on a World Meteorological Organization(WMO)report prepared for the 10th International Workshop on Tropical Cyclones(IWTC),held in Bali in December 2022,and its objective is to present updates in TC research and operation every four years.Here we focus on updates regarding the most recent space-based TC observations,and we cover new methodologies and techniques using polar orbiting sensors,such as C-band synthetic aperture radars(SARs),L-band and combined C/X-band radiometers,scatterometers,and microwave imagers/sounders.We additionally address progress made with the new generation of geostationary and small satellites,and discuss future sensors planned to be launched in the next years.We then briefly describe some examples on how the newest sensors are used in operations and data assimilation for TC forecasting and research,and conclude the article with a discussion on the remaining challenges of TC space-based observations and possible ways to address them in the near future.

关键词： Tropical cyclones Surface wind Satellite sensors Operations

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1 + 1 = 3: Synergy Arithmetic in Economics

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Applied Mathematics 2017年第2期8卷 133-144页

作者： Mark Burgin Gunter meissner UCLA Department of Mathematics Marina Del Rey USA University of Hawaii Honolulu USA

Counting has always been one of the most important operations for human be-ings. Naturally, it is inherent in economics and business. We count with the unique arithmetic, which humans have used for millennia. However, over time, the most inquisitive thinkers have questioned the validity of standard arithmetic in certain settings. It started in ancient Greece with the famous philosopher Zeno of Elea, who elaborated a number of paradoxes questioning popular knowledge. Millennia later, the famous German researcher Herman Helmholtz (1821-1894) [1] expressed reservations about applicability of conventional arithmetic with respect to physical phenomena. In the 20th and 21st century, mathematicians such as Yesenin-Volpin (1960) [2], Van Bendegem (1994) [3], Rosinger (2008) [4] and others articulated similar concerns. In validation, in the 20th century expressions such as 1 + 1 = 3 or 1 + 1 = 1 occurred to reflect important characteristics of economic, business, and social processes. We call these expressions synergy arithmetic. It is common notion that synergy arithmetic has no meaning mathematically. However in this paper we mathematically ground and explicate synergy arithmetic.

关键词： Synergy Synergy Arithmetic Non-Diophantine Arithmetics Mergers and Acquisitions

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