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Journal of Hydrodynamics 2006年第6期18卷 727-735页

作者： ZHAO Gai-ping wU Jie XU Shi-xiong collins m.w. JIANG Yu-ping wANG Jian Department of mechanics and Engineering Science Fudan University Shanghai 200433 China Brunel Institute for Bioengineering School of Engineering and Design Brunel University Uxbridge MiddlesexUB8 3PH UK Department of Neurology Huashan Hospital Fudan University Shanghai 200040 China

Numerical simulation of hemodynamics under the combined effects of both the host blood vessel and the microvascular network, which is based on a 2-D tumor inside and outside vascular network generated from a discrete mathematical model of tumor-induced angiogenesis, is performed systemically. And a ＂microvascular network-- transport across microvascular network--flow in interstitium＂ model is developed to study the flow in solid tumor. Simulations are carried out to examine the effects of the variations of the inlet Reynolds number in the host blood vessel, the hydraulic conductivity of the microvascular wall, and interstitial hydraulic conductivity coefficient on the fluid flow in tumor microcirculation. The results are consistent with data obtained in terms of physiology. These results may provide some theoretical references and the bases for further clinical experimental research.

关键词： solid tumors host blood vessel microvascular network hemodynamics numerical simulation

生理参数及药物注射方式对球形实体肿瘤中药物输运的影响

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医用生物力学 2006年第1期21卷 20-26页

作者：浏丹许世雄 collins m.w. 蒋雨平王坚林原复旦大学力学与工程科学系上海200433 School of Engineering Systems and Design South Bank UniversityLondonUK 复旦大学附属华山医院上海200040 复旦大学附属肿瘤医院上海200032

目的研究球形实体肿瘤中生理参数对药物输运的影响,以及探讨有较好效果的药物注射方式。方法设肿瘤中毛细血管网成球对称分布,肿瘤中的毛细血管表面积和肿瘤体积之比为半径的函数。肿瘤间质为多孔介质,化学药物透过毛细血管壁进入肿瘤间... 详细信息

目的研究球形实体肿瘤中生理参数对药物输运的影响,以及探讨有较好效果的药物注射方式。方法设肿瘤中毛细血管网成球对称分布,肿瘤中的毛细血管表面积和肿瘤体积之比为半径的函数。肿瘤间质为多孔介质,化学药物透过毛细血管壁进入肿瘤间质,在肿瘤间质中输运满足扩散方程。肿瘤外正常组织富含血管和淋巴,药物能被淋巴管吸收,药物输运采用改进的药代动力学模型。用肿瘤中各部位药物浓度维持在最小药物浓度mEC水平以上的时间曲线面积(AUC)来衡量药物的效果。结果增大肿瘤间质中毛细血管对药物的通透性P,提高药物在肿瘤间质的扩散系数D,AUC的值均增大。在给出的六种给药方式中,分时段连续滴注和等时间间隔一次性注射的给药方式,它们的AUC值最大。结论增大肿瘤间质中毛细血管对药物的通透性,提高药物在肿瘤间质的扩散系数,以及采用分时段连续滴注和等时间间隔一次性注射的给药方式,有利于肿瘤的治疗。

关键词：实体肿瘤药物输运药物注射方式最小有效药物浓度

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实体肿瘤血管生成、血液动力学及应用

实体肿瘤血管生成、血液动力学及应用

注射方式对二维实体肿瘤中药物输运影响的数值研究

庆祝中国力学学会成立50周年暨中国力学学会学术大会’2007

作者：许世雄吴洁赵改平 LONG Quan collins m.w. 复旦大学力学与工程科学系 Brunel Institute for Bioengineering Brunel University

肿瘤是严重危害人类健康与生命的常见病和多发病,探索和研究新的治疗策略、方法、途径对解决这一难题至关重要。数值模拟手段在理解肿瘤生理学及探索新的治疗策略中起重要作用。介绍作者研究小组近年来在实体肿瘤血管数值生成、肿瘤血...

肿瘤是严重危害人类健康与生命的常见病和多发病,探索和研究新的治疗策略、方法、途径对解决这一难题至关重要。数值模拟手段在理解肿瘤生理学及探索新的治疗策略中起重要作用。介绍作者研究小组近年来在实体肿瘤血管数值生成、肿瘤血液动力学及抗肿瘤血管生成中应用的工作。

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医用生物力学 2006年第4期21卷 309-316页

作者：浏丹许世雄吴洁卫晶晶 Long Quan collins mw Carola Koenig 蒋雨平 Padhani AR 复旦大学力学与工程科学系上海200433 Brunel Institute for Bioengineering School of Engineering and Design Brunel University UxBridge Middlesex UK 复旦大学附属华山医院上海200040 Paul Strickland Scanner Centre Mount Vernon Hospital Middlesex HA6 2RN UK

目的研究药物注射方式对二维实体肿瘤中药物输运的影响,确定较适当的注射方式。方法根据数值生成的肿瘤二维血管网,研究药物的输运。采用肿瘤中各部位药物浓度维持在最小药物浓度mEC水平以上的时间曲面下体积VUS来衡量药物的效果。对不... 详细信息

目的研究药物注射方式对二维实体肿瘤中药物输运的影响,确定较适当的注射方式。方法根据数值生成的肿瘤二维血管网,研究药物的输运。采用肿瘤中各部位药物浓度维持在最小药物浓度mEC水平以上的时间曲面下体积VUS来衡量药物的效果。对不同的施药注射方式进行了探讨。结果mEC较小时各种注射方式效果接近;mEC较大时,比较适合采用短时间集中注射方式。结论对肿瘤进行药物注射策略选取时,应根据肿瘤具体特性,以及药物施加方式对肿瘤细胞产生的不同作用来组合设计相应的优化施药方案。

关键词：二维实体肿瘤药物输运注射方式数值研究

Two-dimensional discrete mathematical model of tumor-induced angiogenesis

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Applied mathematics and mechanics(English Edition) 2009年第4期30卷 455-462页

作者：赵改平陈二云吴洁许世雄 m.w.collins 龙泉 School of medical Instrument and Food Engineering University of Shanghai for Scienceand Technology School of Energy and Power Engineering University of Shanghai for Science and Technology Department of mechanics and Engineering Science Fudan University Brunel Institute for Bioengineering School of Engineering and DesignBrunel University

A 2D discrete mathematical model of a nine-point finite difference scheme is built to simulate tumor-induced angiogenesis. Nine motion directions of an individual endothelial cell and two parent vessels are extended in the present model. The process of tumor-induced angiogenesis is performed by coupling random motility, chemotaxis, and haptotaxis of endothelial cell in different mechanical environments inside and outside the tumor. The results show that nearly realistic tumor microvascular networks with neoplastic pathophysiological characteristics can be generated from the present model. moreover, the theoretical capillary networks generated in numerical simulations of the discrete model may provide useful information for further clinical research.

关键词： tumor angiogenesis discrete mathematical model nine-point scheme nu-merical simulation

The potential of bone morphogenetic protein 2 as a neurotrophic factor for Parkinson’s disease

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Neural Regeneration Research 2020年第8期15卷 1432-1436页

作者： Susan R.Goulding Aideen m.Sullivan Gerard w.O’Keeffe Louise m.collins Department of Biological Sciences Cork Institute of TechnologyCorkIreland Department of Anatomy and Neuroscience and Cork Neuroscience Centre University College CorkCorkIreland Department of Physiology University College CorkCorkIreland

Parkinson’s disease is the second most common neurodegenerative disorder;it affects 1%of the population over the age of *** number of people with Parkinson’s disease is set to rapidly increase due to changing demographics and there is an unmet clinical need for disease-modifying *** pathological hallmarks of Parkinson’s disease are the progressive degeneration of dopaminergic neurons in the substantia nigra and their axons which project to the striatum,and the aggregation ofα-synuclein;these result in a range of debilitating motor and non-motor *** application of neurotrophic factors to protect and potentially regenerate the remaining dopaminergic neurons is a major area of research ***,this strategy has had limited success to *** trials of two well-known neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have reported limited efficacy in Parkinson’s disease patients,despite these factors showing potent neurotrophic actions in animal *** is therefore a need to identify other neurotrophic factors that can protect againstα-synuclein-induced degeneration of dopaminergic *** bone morphogenetic protein(BmP)family is the largest subgroup of the transforming growth factor-βsuperfamily of *** are naturally secreted proteins that play crucial roles throughout the developing nervous ***,many BmPs have been shown to be potent neurotrophic factors for dopaminergic *** we discuss recent work showing that transcripts for the BmP receptors and BmP2 are co-expressed with several key markers of dopaminergic neurons in the human substantia nigra,and evidence for downregulation of BmP2 expression at distinct stages of Parkinson’s *** also discuss studies that explored the effects of BmP2 treatment,in in vitro and in vivo models of Parkinson’s *** studies found potent effects of BmP2 on dopaminergic neurites,which is important given that axon deg

关键词： axon growth BmP2 dopaminergic neurons neuroprotection neurotrophic factor neuroregeneration Parkinson’s disease α-synuclein

Growth differentiation factor 5:a neurotrophic factor with neuroprotective potential in Parkinson’s disease

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Neural Regeneration Research 2022年第1期17卷 38-44页

作者： Susan R.Goulding Jayanth Anantha Louise m.collins Aideen m.Sullivan Gerard w.O’Keeffe Department of Anatomy and Neuroscience and Cork Neuroscience CentreUniversity College CorkCorkIreland Department of Physiology University College CorkCorkIreland

Parkinson’s disease is the most common movement disorder worldwide,affecting over 6 million *** is an age-related disease,occurring in 1%of people over the age of 60,and 3%of the population over 80 *** disease is characterized by the progressive loss of midbrain dopaminergic neurons from the substantia nigra,and their axons,which innervate the striatum,resulting in the characteristic motor and non-motor symptoms of Parkinson’s *** is paralleled by the intracellular accumulation ofα-synuclein in several regions of the nervous *** therapies are solely symptomatic and do not stop or slow disease *** promising disease-modifying strategy to arrest the loss of dopaminergic neurons is the targeted delivery of neurotrophic factors to the substantia nigra or striatum,to protect the remaining dopaminergic neurons of the nigrostriatal ***,clinical trials of two well-established neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have failed to meet their primary *** failure is thought to be at least partly due to the downregulation byα-synuclein of Ret,the common co-receptor of glial cell line-derived neurorophic factor and ***/differentiation factor 5 is a member of the bone morphogenetic protein family of neurotrophic factors,that signals through the Ret-independent canonical Smad signaling ***,we review the evidence for the neurotrophic potential of growth/differentiation factor 5 in in vitro and in vivo models of Parkinson’s *** discuss new work on growth/differentiation factor 5’s mechanisms of action,as well as data showing that viral delivery of growth/differentiation factor 5 to the substantia nigra is neuroprotective in theα-synuclein rat model of Parkinson’s *** data highlight the potential for growth/differentiation factor 5 as a disease-modifying therapy for Parkinson’s disease.

关键词： adeno-associated virus bone morphogenetic protein dopaminergic neurons growth/differentiation factor 5 neurodegeneration neuroprotection neurotrophic factor Parkinson’s disease Smad signaling α-synuclein

An Efficient,Energy Stable Scheme for the Cahn-Hilliard-Brinkman System

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Communications in Computational Physics 2013年第4期13卷 929-957页

作者： Craig collins Jie Shen Steven m.w.se Department of mathematics University of TennesseeKnoxvilleTN 37912USA Department of mathematics Purdue UniversityWest LafayetteIN 47907USA

we present an unconditionally energy stable and uniquely solvable finite difference scheme for the Cahn-Hilliard-Brinkman(CHB)system.w.ich is comprised of a Cahn-Hilliard-type diffusion equation and a generalized Brinkman equation modeling fluid *** CHB system is a generalization of the Cahn-Hilliard-Stokes model and describes two phase very viscous flows in porous *** scheme is based on a convex splitting of the discrete CH energy and is *** equations at the implicit time level are nonlinear,but we prove that they represent the gradient of a strictly convex functional and are therefore uniquely solvable,regardless of time step *** to energy stability,we show that the scheme is stable in the time and space discrete ℓ^(∞)(0,T;H_(h)^(1))and ℓ^(2)(0,T;H_(h)^(2))*** also present an efficient,practical nonlinear multigrid method–comprised of a standard FAS method for the Cahn-Hilliard part,and a method based on the Vanka smoothing strategy for the Brinkman part-for solving these *** particular,we provide evidence that the solver has nearly optimal complexity in typical *** solver is applied to simulate spinodal decomposition of a viscous fluid in a porous medium,as well as to the more general problems of buoyancy-and boundary-driven flows.

关键词： Cahn-Hilliard equation Stokes equations Brinkman equation finite difference methods nonlinear multigrid convex splitting energy stability

Late Neoproterozoic adakitic magmatism of the eastern Arabian Nubian Shield

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Geoscience Frontiers 2019年第6期10卷 1981-1992页

作者： Grant m.Cox John Foden Alan S.collins Centre for Tectonics Resources and Exploration(TRaX) Dept of Earth SciencesThe University of Adelaide

Late Neoproterozoic adakitic magmatism.w.thin the Eastern Arabian Nubian Shield has been dated at633.2±9.0 ma(2σ).These magnas intrude the forearc Ad Dawadimi Basin,which is composed of metapelitic schists and greywacke along with ophiolitic melanges of boninitic affinity which underwent inversion and deformation by^620 *** adakitic magmatism.w.ile intruding parts of the Ad Dawadimi Basin,predates this deformation,but is possibly coincident with basin *** adakitic magmatism requires melting of an amphibolite or eclogitic source,empirical and experimental constraints require anomalously hot supra-subduction zone *** that this magmatism immediately predates basin inversion,these magmas possibly pinpoint the timing of the slab breaking,marking the terminal stages of arc magmatism,terrane accretion and the influx of hot oceanic asthenospheric *** influx of hot asthenospheric mantle may also be responsible for postcolltsional A-type magmatism.

关键词： Arabian Nubian Shield Adakites A-type magmatism

Numerical simulation of blood flow and interstitial fluid pressure in solid tumor microcirculation based on tumor-induced angiogenesis

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Acta mechanica Sinica 2007年第5期23卷 477-483页

作者： Gaiping Zhao Jie wu Shixiong Xu m. w. collins Quan Long Carola S. Konig Yuping Jiang Jian wang A. R. Padhani Department of mechanics and Engineering Science Fudan University Shanghai 200433 China Brunel Institute for Bioengineering School of Engineering and Design Brunel University Uxbridge Middlesex UK Department of Neurology Huashan Hospital Fudan University Shanghai 200040 China Paul Strickland Scanner Centre Mount Vernon Hospital Rickmansworth Road Northwood Middlesex HA6 2RN UK

A coupled intravascular-transvascular-interstitial fluid flow model is developed to study the distributions of blood flow and interstitial fluid pressure in solid tumor microcirculation based on a tumor-induced microvascular network. This is generated from a 2D nine-point discrete mathematical model of tumor angiogenesis and contains two parent vessels. Blood flow through the microvascular network and interstitial fluid flow in tumor tissues are performed by the extended Poiseuille＇s law and Darcy＇s law, respectively, transvascular flow is described by Starling＇s law; effects of the vascular permeability and the interstitial hydraulic conductivity are also considered. The simulation results predict the heterogeneous blood supply, interstitial hypertension and low convection on the inside of the tumor, which are consistent with physiological observed facts. These results may provide beneficial information for anti-angiogenesis treatment of tumor and further clinical research.

关键词： Solid tumor pressure-Angiogenesis Blood flow - Interstitial Numerical simulation