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First-line anti-VEGF plus EGFR-TKI in EGFR-mutant NSCLC: adding the ARTEMIS trial to the puzzle of current evidence

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Signal Transduction and Targeted Therapy 2022年第1期7卷 4-6页

作者： Susanne hafner Institute of Pharmacology of Natural Products and Clinical Pharmacology Ulm UniversityD-89081 UlmGermany

In the ARTEMIS-CTONG1509 multicenter phase 3 study recently published in Cancer Cell,Zhou et *** the combination of the EGFR tyrosine kinase inhibitor(TKI)erlotinib and anti-angiogenic bevacizumab in treatmentnaive Chinese patients with advanced EGFR-mutant non-small cell lung cancer(NSCLC).^(1) The primary endpoint of progression-free survival(PFS)was significantly exte nded from 11.2 months with erloti nib mono therapy to 17.9 mon ths with the combination.

关键词： NSCLC TKI EGFR

Driver Intent Prediction and Collision Avoidance With Barrier Functions

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IEEE/CAA Journal of Automatica Sinica 2023年第2期10卷 365-375页

作者： Yousaf Rahman Abhishek Sharma Mrdjan Jankovic Mario Santillo Michael hafner the Ford Motor Company DearbornMichigan 48121 USA IEEE

For autonomous vehicles and driver assist systems,path planning and collision avoidance algorithms benefit from accurate predictions of future location of other vehicles and intent of their *** the literature,the algorithms that provide driver intent belong to two categories:those that use physics based models with some type of filtering,and machine learning based *** this paper we employ barrier functions(BF)to decide driver *** are typically used to prove safety by establishing forward invariance of an admissible ***,we decide if the“target”vehicle is violating one or more possibly fictitious(i.e.,non-physical)barrier constraints determined based on the context provided by the road *** algorithm has a very small computational footprint and better false positive and negative rates than some of the *** predicted intent is then used by a control barrier function(CBF)based collision avoidance system to prevent unnecessary interventions,for either an autonomous or human-driven vehicle.

关键词： Driver Intent Prediction and Collision Avoidance With Barrier Functions Intent

Combined VEGF/PDGF improves olfactory regeneration after unilateral bulbectomy in mice

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Neural Regeneration Research 2018年第10期13卷 1820-1826页

作者： Kate Beecher Louise M.hafner Jenny Ekberg James A.St.John Fatemeh Chehrehasa School of Biomedical Sciences Queensland University of Technology Clem Jones Centre for Neurobiology and Stem Cell Research Griffith Institute for Drug DiscoveryGriffith University Institute of Health and Biomedical Innovation Queensland University of Technology Menzies Health Institute Queensland Griffith University

The olfactory receptor neurons lining the nasal cavity have a remarkable capacity to regenerate throughout life. They are replenished continuously and their axons make new connections within the olfactory bulb. However, some factors such as head trauma and skull base surgery damage the olfactory nerve which lead to olfactory dysfunction. Losing the sense of smell has considerable effects on quality of life and life-expectancy. Therefore, there is a clear need to find a treatment for olfactory dysfunction. One such potential treatment is growth factor therapy which showed promising results in the spinal cord and brain injuries. The aim of the present study was to investigate whether combined delivery of two growth factors, vascular endothelial growth factor and platelet-derived growth factor treatment can improve the olfactory neurons regeneration in mice. The degeneration of the olfactory neurons was induced by unilateral bulbectomy. The treatment group received 1.5 μg of the combined growth factors intranasally, while the control injured group received saline. Growth factor treatment significantly increased the number of immature neurons at 5 and 7 days post injury and also the number of mature olfactory neurons at 10 and 14 days post bulbectomy. Regenerating axons extended over a larger volume in the operated cavity in the treatment group compared to control group at 14 days post bulbectomy. The growth factor treatment also significantly reduced astrocytic glia scar in the operated cavity. The results indicate that the combined delivery of the growth factors has the potential to improve olfactory dysfunction.

关键词： astrocytes olfactory bulb glial scar axon growth factors neuron

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两级R744超市中央制冷系统节能特性

化工学报 2018年第A2期69卷 394-401页

作者：林励冠代彦军 hafner Armin 上海交通大学制冷与低温研究所上海200240 挪威科技大学

比较了以二氧化碳(R744)为工质的超市中央制冷系统制冷技术方案,包括普通两级制冷(CB)、旁通压缩两级制冷(PC)和多引射器-旁通压缩耦合两级制冷(EJ),讨论了配置空调系统(AC)之后的功耗变化。根据计算得到,在环境温度20℃以上,相较于CB系... 详细信息

比较了以二氧化碳(R744)为工质的超市中央制冷系统制冷技术方案,包括普通两级制冷(CB)、旁通压缩两级制冷(PC)和多引射器-旁通压缩耦合两级制冷(EJ),讨论了配置空调系统(AC)之后的功耗变化。根据计算得到,在环境温度20℃以上,相较于CB系统,PC系统的功耗减少了6.8%～12.3%;EJ系统功耗降低了6.3%～17.5%。在耦合了AC系统之后,相较于PC-AC系统,EJ-AC系统的功耗降低了4.9%～6.5%。与R404a系统相比,超市两级R744系统都有明显的节能效果。

关键词：旁通压缩引射器二氧化碳跨临界制冷循环中央制冷系统

Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

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World Journal of Gastroenterology 2005年第29期11卷 4511-4518页

作者： Christian hafner Stefanie Meyer Ilja Hagen Bernd Becker Alexander Roesch Michael Landthaler Thomas Vogt Department of Dermatology University Hospital of Regensburg Regensburg D-93042 Germany

AIM： Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells. METHODS： Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase （FAK） activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy. RESULTS： Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair- related genes is also accompanied by activation of the ERKI/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION： Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

关键词： Ephrin-B IEC-6 Wound healing Gene expression c-Fos Egr-1/2 COX-2

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不同参数对有机颜料在涂料中分散性的影响

涂料工业 1994年第4期24卷 42-47页

作者： O. hafner

对某些有机颜料而言，在确定其最佳研磨料组成时，诸如丹尼尔所提出的流动点方法并不适用。在此情况下，必须进行有效的研磨试验。本文描述了用实验室砂磨机进行的研磨试验，并以通常认为难分散的两种有机颜料为例，测定了研磨料组成变... 详细信息

对某些有机颜料而言，在确定其最佳研磨料组成时，诸如丹尼尔所提出的流动点方法并不适用。在此情况下，必须进行有效的研磨试验。本文描述了用实验室砂磨机进行的研磨试验，并以通常认为难分散的两种有机颜料为例，测定了研磨料组成变化对展色性和流变性的影响。

关键词：涂料有机颜料分散性颜料

Human induced pluripotent stem cells: A new source for brown and white adipocytes

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World Journal of Stem Cells 2014年第4期6卷 467-472页

作者： Anne-Laure hafner Christian Dani Faculté de Médecine UMR CNRS/INSERMUniversité Nice Sophia AntipolisiBV06107 Nice Cedex 2France

Mesenchymal stem cells(MSCs) derived from human induced pluripotent stem cells(hiPSCs) provide a novel source for generating adipocytes, thus opening new avenues for fundamental research and clinical medicine. We present the adipogenic potential of hiPSCs and the various methods to derive hiPSC-MSCs. We discuss the main characteristic of hiPSC-MSCs, which is their low adipogenic capacity as compared to adult-MSCs. Finally, we propose several hypotheses to explanation this feature, underlying a potential critical role of the micro-environment. We favour the hypothesis that the range of factors or culture conditions required to induce adipocyte differentiation of MSCs derived from adult tissues and from embryonic-like cells could differ.

关键词： Human induced pluripotent stem cells Mesenchymal stem cells Brown adipocytes White adipocytes Obesity Lipodystrophy

Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro

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World Journal of Gastroenterology 2005年第26期11卷 4024-4031页

作者： Christian hafner Stefanie Meyer Thomas Langmann Gerd Schmitz Frauke Bataille Ilja Hagen Bernd Becker Alexander Roesch Gerhard Rogler Michael Landthaler Thomas Vogt Department of Dermatology University Hospital of Regensburg D-93042 Regensburg Germany Department of Clinical Chemistry University Hospital of Regensburg D-93042 Regensburg Germany Institute of Pathology University Hospital of Regensburg D-93042 Regensburg Germany Department of Internal Medicine University Hospital of Regensburg D-93042 Regensburg Germany

AIM:Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD). METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinAl, we found abundantly co-expressed EphB2 and ephrin-B1/2. Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrin- B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge. CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD.

关键词： Ephrin-B2 Crohn's disease IBD IEC-6 Wound healing Epithelial restitution

Artificial Intelligence in the Game of Go

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当代外语研究 2006年第12期 9-11页

作者： Katie hafner 夏廷芳

编程人员认为,围棋比象棋更能精确地反映人类的思维方式。这是因为国际象棋虽然错综复杂,但仍可简化成强力运算。而围棋却不同,无论是人还是电脑,必须经过多年探索,运用积累的知识和逻辑,综合自己的模式匹配能力,才有可能掌握精湛的棋... 详细信息

编程人员认为,围棋比象棋更能精确地反映人类的思维方式。这是因为国际象棋虽然错综复杂,但仍可简化成强力运算。而围棋却不同,无论是人还是电脑,必须经过多年探索,运用积累的知识和逻辑,综合自己的模式匹配能力,才有可能掌握精湛的棋艺。至今仍没有电脑能够超出业余围棋手的水平。鉴于此,大卫·福兰指出,“编写一套好的围棋程序比编写一套好的象棋程序更具挑战性,它能让电脑更接近人的思维方式”。电脑围棋与人工智能究竟有何渊源?近几年来,专攻人工智能的科学家们有望在电脑模拟人类思考这一人工智能的核心技术中有所突破。

关键词：思维方式围棋人工智能电脑模拟国际象棋人类匹配能力核心技术程序编程