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Pancreatic cancer cells render tumor-associated macrophages metabolically reprogrammed by a GARP and DNA methylation-mediated mechanism

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3348-3365页

作者： Mengwen Zhang Xingyi Pan Kenji Fujiwara Noelle Jurcak stephen muth Jiaojiao Zhou Qian Xiao Anqi Li Xu Che Zihai Li Lei Zheng Department of Oncology Johns Hopkins University School of MedicineBaltimoreMD21287USA The Sidney Kimmel Cancer Center Johns Hopkins University School of MedicineBaltimoreMD21287USA The Pancreatic Cancer Precision Medicine Center of Excellence Program Johns Hopkins University School of MedicineBaltimoreMD21287USA The Cellular and Molecular Medicine Graduate Program Johns Hopkins University School of MedicineBaltimoreMD21287USA Pelotonia Institute for Immune-Oncology The Ohio State University Comprehensive Cancer CenterColumbusOH43210USA Department of Surgery Johns Hopkins University School of MedicineBaltimoreMD21287USA The Second Affiliated Hospital Zhejiang University School of MedicineHangzhouChina Department of Surgery Sada HospitalFukuokaJapan Cancer Hospital Chinese Academy of Medical SciencesShenzhenChina

How tumor-associated macrophages transit from a predominant antitumor M1-like phenotype to a protumoral M2-like phenotype during the development of pancreatic ductal adenocarcinoma (PDA) remains to be elucidated. We thus conducted a study by employing a PDA-macrophage co-culture system, an “orthotopic” PDA syngeneic mouse model, and human PDA specimens, together with macrophages derived from GARP knockout mice and multiple analytic tools including whole-genome RNA sequencing, DNA methylation arrays, multiplex immunohistochemistry, metabolism measurement, and invasion/metastasis assessment. Our study showed that PDA tumor cells, through direct cell–cell contact, induce DNA methylation and downregulation of a panel of glucose metabolism and OXPHOS genes selectively in M1-like macrophages, leading to a suppressed glucose metabolic status in M1-like but not in M2-like macrophages. Following the interaction with PDA tumor cells, M1-like macrophages are reprogrammed phenotypically to M2-like macrophages. The interaction between M1-like macrophages and PDA cells is mediated by GARP and integrin αV/β8, respectively. Blocking either GARP or integrin would suppress tumor-induced DNA methylation in Nqo-1 gene and the reprogramming of M1-like macrophages. Glucose-response genes such as Il-10 are subsequently activated in tumor-educated M1-like macrophages. Partly through Il-10 and its receptor Il-10R on tumor cells, M1-like macrophages functionally acquire a pro-cancerous capability. Both exogenous M1-like and M2-like macrophages promote metastasis in a mouse model of PDA while such a role of M1-like macrophages is dependent on DNA methylation. Our results suggest that PDA cells are able to reprogram M1-like macrophages metabolically and functionally through a GARP-dependent and DNA methylation-mediated mechanism to adopt a pro-cancerous fate.

关键词： metabolism metastasis mediated

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Anisotropic deformation for local shape control

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Computational Visual Media 2017年第4期3卷 305-313页

作者： Matteo Colaianni Christian Siegl Jochen Süвmuth Frank Bauer Günther Greiner Computer Graphics Group University Erlangen-Nuremberg Adidas AG

We present a novel approach to mesh deformation that enables simple context sensitive manipulation of 3 D geometry. The method is based on locally anisotropic transformations and is extended to global control directions. This allows intuitive directional modeling within an easy to implement framework. The proposed method complements current sculpting paradigms by providing further possibilities for intuitive surface-based editing without the need for additional host geometries. We show the anisotropic deformation to be seamlessly transferable to free boundary parameterization methods, which allows us to solve the hard problem of flattening compression garments in the domain of apparel design.

关键词： anisotropy modeling as-rigid-aspossible(ARAP) deformation parameterization

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Blessing and a curse of outpatient management of delayed graft function

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World Journal of Transplantation 2019年第4期9卷 58-61页

作者： Justin W Blazel Jennifer A Turk Brenda L muth Sandesh Parajuli Division of Nephrology Department of Medicine University of Wisconsin School of Medicine and Public Health

Delayed graft function (DGF) is a common complication occurring most often after deceased donor kidney transplant with several donor characteristics as well as immunologic factors that lead to its development *** patients require dialysis and close kidney function monitoring until sufficient allograft function is *** has resulted in limited options for DGF management,either prolonged hospitalization until graft function improves to the point where dialysis is no longer needed or discharge back to their home dialysis unit with periodic follow up in the transplant *** is associated with a higher risk for acute rejection,premature graft failure,and 30-d readmission;therefore,these patients need close monitoring,immunosuppression management,and prompt allograft biopsy if prolonged DGF is *** may not occur if these patients are discharged back to their home dialysis *** address this issue,the University of Wisconsin-Madison created a clinic in 2011 specialized in outpatient DGF *** clinic was able to successfully reduce hospital length of stay without an increase in 30-d readmission,graft loss,and patient death.

关键词： Delayed graft function Kidney transplantation Immunosuppression Acute rejection Kidney donor profile index Kidney donor risk index Dialysis

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Heart Rate Variability from Underwater Spiroergometry:How Meaningful?

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Journal of Science in Sport and Exercise 2023年第2期5卷 116-122页

作者： Andreas Koch Fabian Möller Elena Jacobi Thomas muth Clark Pepper Uwe Hoffmann Jochen D.Schipke German Naval Medical Institute Maritime MedicineKronshagenGermany Department of Exercise Physiology Institute of Exercise Training and Sport InformaticsGerman Sport University CologneCologneGermany Institute of Occupational Social and Environmental MedicineHeinrich-Heine-UniversityDüsseldorfGermany Department of Neurology Johanna Etienne HospitalNeussGermany Forschungsgruppe Experimentelle Chirurgie Universitäts-Klinikum DüsseldorfMoorenstrasse 540225 DüsseldorfGermany

Cardiovascular fitness of divers is overwhelmingly performed using bicycle ergometry.A more sport-specific alternative presents fit2dive,an underwater spiroergometry *** of this exploratory study:using fit2dive to investigate the diagnostic value of measures of heart rate variability(HRV)after markedly increasing physical *** scuba divers employed the fit2dive system and increased fin-swimming speed until *** gas consumption(VE)and heart rate(HR)were measured.A three-lead ECG was recorded to analyze for time and frequency domain *** increased from 16.5±6.5 to 68.3±26.6 L/*** increased from 96±13 beats/min(mean±SD)at rest to 170±14 beats/min before *** variability(SDNN:132±42 vs.54±17 ms)decreased along with two measures of parasympathetic activity(RMSSD:59±31 vs.24±16 ms;pNN50:22%±12%vs.3%±3%).Measures from the frequency domain decreased[low frequency(LF):3167±2651 vs.778±705 ms_(2)]or remained unaltered[high frequency(HF):885±652 vs.431±463 ms^(2)].Thus,LF/HF decreased from 4.3±2.3 to 2.5±*** sports-specific fit2dive can help assessing diving fitness by employing HRV ***,this study supports the view that these measures much depend on ***,HRV measures regarding altered autonomic control during exercise will lead to serious misinterpretation:as HR increases,variability decreases.

关键词： Scuba diving Physical fitness Heart rate Heart rate variability Autonomic nervous system

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电子提单权利凭证功能研究

电子提单权利凭证功能研究

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作者： KANYUGO muth 大连海事大学

学位级别：硕士

本文以电子提单为中心,专门研究其作为物权凭证的功能。该研究认为,纸质提单被誉为国际贸易中最重要的运输单证,是全球供应链的支柱,从原产地到目的地,对清关、融资和货物所有权至关重要。本研究探讨了纸质提单与电子提单相比作为物权... 详细信息

本文以电子提单为中心,专门研究其作为物权凭证的功能。该研究认为,纸质提单被誉为国际贸易中最重要的运输单证,是全球供应链的支柱,从原产地到目的地,对清关、融资和货物所有权至关重要。本研究探讨了纸质提单与电子提单相比作为物权凭证的具体功能。通常情况下,电子提单是为了取代传统的纸质提单,应该具有相同的功能以及相同的法律地位,然而,本文表明,电子提单作为物权凭证的功能面临着诸多障碍。本研究旨在探讨电子提单作为所有权凭证这一功能的现状、其可转让性要素、面临的挑战以及对其的批判。毫无疑问,由于电子商务在不同司法管辖区的法律差异,作为所有权凭证的电子提单与纸质提单不具有相同的统一适用性。本研究旨在客观地研究和分析现代航运世界中的电子提单,将其作为所有权凭证的功能与传统提单中的相同功能相比较;审查并强调电子提单作为所有权凭证的优势和劣势,并进一步探讨其在海上贸易实践中的适用性;具体而言,分析作为所有权凭证的电子提单在执行过程中面临的各种法律和技术挑战,并探索和分析电子提单作为所有权凭证的功能性所面临问题的可能解决方案。这项研究的结论是,随着世界贸易全面迈向数字空间,电子提单作为所有权凭证的全部功能以及法律的统一性在海上贸易中至关重要。

关键词：电子提单提单非物质化所有权文件

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术前腰椎间盘损伤的磁共振诊断的质量分析

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放射学实践 1996年第4期11卷 155-158页

作者： muth.,CP 樊友武南京军区总医院

术前腰椎间盘损伤的磁共振诊断的质量分析ＡｎａｌｙｓｅｚｕｒＱｕａｌｉｔａｔｄｅｒｐｒｏｐｅｒａｔｉｖｅｎＫｅｒｎｓｐｉｎｄｉａｇｎｏｓｔｉｋｖｏｎＢａｎｄｓｃｈｅｉｂｅｎｌａｓｉｏｎｅｎｄｅｒＬｅｎｄｅｎｗｉｒｂｅｌ... 详细信息

术前腰椎间盘损伤的磁共振诊断的质量分析ＡｎａｌｙｓｅｚｕｒＱｕａｌｉｔａｔｄｅｒｐｒｏｐｅｒａｔｉｖｅｎＫｅｒｎｓｐｉｎｄｉａｇｎｏｓｔｉｋｖｏｎＢａｎｄｓｃｈｅｉｂｅｎｌａｓｉｏｎｅｎｄｅｒＬｅｎｄｅｎｗｉｒｂｅｌｓａｕｌｅ￥Ｃ．－Ｐ．Ｍｕｔｈ，Ｆ...

关键词：椎间盘突出腰椎 NMR 诊断

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重防腐涂料用新型附着力促进剂

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电镀与涂饰 2011年第12期30卷 53-57页

作者：谢林 Andreas Freytag Martin muth Enduse Specialist Protective Coatings BYK-Chemie GmbHGermany

环氧涂料由于其优良的抗腐蚀性能和机械性能,被广泛应用于海洋涂料和重防腐涂料。在这些应用中,环氧涂料通常作为底漆直接施工在各种不同的金属底材上。当金属底材的表面处理、施工条件不一样时,要使涂料与底材获得良好的附着力并不容... 详细信息

环氧涂料由于其优良的抗腐蚀性能和机械性能,被广泛应用于海洋涂料和重防腐涂料。在这些应用中,环氧涂料通常作为底漆直接施工在各种不同的金属底材上。当金属底材的表面处理、施工条件不一样时,要使涂料与底材获得良好的附着力并不容易。使用附着力促进助剂能有效地改善涂料对金属底材的附着力,从而提高涂层的抗腐蚀性能。本文介绍了为改善海洋和重防腐涂料性能而开发的新型附着力促进剂。该附着力促进剂可应用于典型的环氧底漆中,能改善涂料对不同底材的附着力,增进涂料的抗腐蚀性能,同时增加漆膜的柔软性和机械性能。

关键词：重防腐涂料环氧底漆附着力促进剂盐雾试验

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应用题中无关信息处理的研究

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心理科学通讯 1989年第4期12卷 29-32,67页

作者：叶仁敏王初宪 K.Denise muth 上海师范大学 Georgia大学

本研究由中美两国教育心理研究工作者合作进行。研究对在应用题中加入了无关信息后对小学生解题产生的影响,从时间、正确列式、正确答案三项指标进行了分析。结果表明,中国学生无论是哪个年级、性别或地区,无关信息的加入对解题的影响... 详细信息

本研究由中美两国教育心理研究工作者合作进行。研究对在应用题中加入了无关信息后对小学生解题产生的影响,从时间、正确列式、正确答案三项指标进行了分析。结果表明,中国学生无论是哪个年级、性别或地区,无关信息的加入对解题的影响非常显著。此外,本文还对中国学生解题中各年级、男女、城乡学生之间的数据作了比较,以及应用题的列式与语文、算术成绩的关系进行了分析与讨论。

关键词：算术应用题城乡学生正确答案试卷阅读分析能力阅读能力语文成绩研究工作数学应用题教学内容

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颜值爆表终成绝配

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科学之友 2014年第12期 62-63页

作者： Felicity muth

很多雄性动物在求偶时都会给雌性送礼物。这听起来似乎太过简单,不过事实就是这样,比如雄性翠鸟在求偶时会捕鱼送给雌鸟。然而,这种送礼行为中却不乏有一些耍小聪明的动物。如果能找到一份廉价的山寨货骗雌性交配,那为什么还要费心找一... 详细信息

很多雄性动物在求偶时都会给雌性送礼物。这听起来似乎太过简单,不过事实就是这样,比如雄性翠鸟在求偶时会捕鱼送给雌鸟。然而,这种送礼行为中却不乏有一些耍小聪明的动物。如果能找到一份廉价的山寨货骗雌性交配,那为什么还要费心找一份真正的礼物呢?的确,很多雄性动物都选择送没有什么价值的礼物。一些狡猾的雄性还会重复利用它们已经送出去的礼物,甚至还有些雄性会用不能吃的东西冒充食物送给雌性。

关键词：雄性动物雌鸟重复利用瘦骨伶仃人工饲养蛛丝营养状况强体最后的胜利令人

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Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression

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World Journal of Transplantation 2019年第6期9卷 123-133页

作者： Sandesh Parajuli Fahad Aziz Neetika Garg Sarah E Panzer Emily Joachim Brenda muth Maha Mohamed Justin Blazel Weixiong Zhong Brad C Astor Didier A Mandelbrot Arjang Djamali Division of Nephrology Department of MedicineUniversity of WisconsinMadisonWI 53705United States Department of Pathology University of WisconsinMadisonWI 53705United States Department of Population Health Sciences University of WisconsinMadisonWI 53705United States Division of Transplantation Department of SurgeryUniversity of WisconsinMadisonWI 53705United States

BACKGROUND The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the *** To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive *** In a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the *** We identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. The three most common biopsy findings were interstitial fibrosis and tubular atrophy(IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy(TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR(40%),TG(17%), and IFTA(13%). Most grafts failed within two years of post-transplant(36%). Subsequently, approximately 10%-15% of grafts failed every two years: >2-4 years(16%), > 4-6 years(13%), > 6-8 years(11%), > 8-10 years(9%) and > 10 years(16%). AR was the most common cause of graft failure in the first six years(48%), whereas TG was the most prevalent cause of graft failure after 6 years(32%) of *** In the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.

关键词： Kidney biopsy Acute rejection Graft failure Transplant glomerulopathy Interstitial fibrosis and tubular atrophy

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