MIMS Workshop on
Modeling and Numerical Analysis
of Nonlinear Phenomena:
Fluid Dynamics,
Motion of Interfaces,
and Cell Biology
December 6–8, 2017
MIMS, Meiji University, Tokyo

Supported by
MIMS, Meiji University,
A3 Foresight Program,and JST PRESTO

Organizers:
Hirofumi Notsu,
Karel Švadlenka,
Hideki Murakawa,and Masayasu Mimura

Program2∗ All lectures are given by invited speakers.

∗ Each lecture consists of 40 minutes talk and 10 minutes discussion.

Wednesday, December 6
13:00 – 13:10

Opening

Session 1 (2 talks) Chair: H. Notsu
13:10 – 14:00 Mária Lukáčová-Medvid’ová (University of Mainz, Germany)
Energy stable linear schemes for viscoelastic phase separation
14:00 – 14:50 Shuji Ishihara (The University of Tokyo, Japan)
Continuum model for epithelial tissue
14:50 – 15:10

Coffee break

Session 2 (3 talks) Chair: X. Xu
15:10 – 16:00 Julien Dambrine (University of Poitiers, France)
Interface motion involving the Dirichlet-to-Neumann operator
16:00 – 16:50 Hideru Togashi (Kobe University, Japan)
Cellular tessellation in sensory epithelia
16:50 – 17:10

Coffee break

17:10 – 18:00 Amy Q. Shen (OIST-Okinawa Inst. Sci. Tech. Gr. Univ., Japan)
Elastic and inertial instabilities in microfluidic flows

2
3

Thursday, December 7
Session 3 (3 talks) Chair: M. Lukáčová-Medvid’ová
09:30 – 10:20 Cassio M. Oishi (UNESP-Universidade Estadual Paulista, Brazil)
Computational simulation in complex flows of non-Newtonian fluids
10:20 – 10:35

Coffee break

10:35 – 11:25 Yangjin Kim (Konkuk University, Korea)
Mathematical models of tumor invasion and OV/immune therapy
11:25 – 11:40

Coffee break

11:40 – 12:30 Catherine Kublik (University of Dayton, USA)
Integration over implicitly defined interfaces and extension to unstructured
point clouds
12:30 – 14:00

Lunch break

Session 4 (2 talks) Chair: J. Dambrine
14:00 – 14:50 Sungrim Seirin-Lee (Hiroshima University, Japan)
Pattern formation induced by a domain deformation: A mystery of remodelingprocess in nuclear architecture
14:50 – 15:40 Makoto Sato (Kanazawa University, Japan)
Mathematical modeling and genetic analysis of fly visual system development
15:40 – 16:00

Coffee break

Session 5 (2 talks) Chair: H. Murakawa
16:00 – 16:50 Eliot Fried (OIST-Okinawa Inst. Sci. Tech. Gr. Univ., Japan)
Isogeometric phase-field analysis
16:50 – 17:40 Danielle Hilhorst (Université de Paris-Sud / CNRS, France)
On a reaction-diffusion-ODE model for the neolithic dispersal of farmers andhunter-gatherers
18:30 – 21:00

Dinner3
4

Friday, December 8
Session 6 (3 talks) Chair: C. M. Oishi
09:30 – 10:20 Markus Schmidtchen (Imperial College London, UK)
Convergence of splitting schemes and segregation in reaction-(cross-)diffusion
systems
10:20 – 10:35

Coffee break

10:35 – 11:25 Natsuhiko Yoshinaga (Tohoku University, Japan)
Active soft materials: Self-propelled motion and its collective behaviours of
colloids and liquid drops
11:25 – 11:40

Coffee break

11:40 – 12:30 Xianmin Xu (Chinese Academy of Science, China)
Modelling and computations for wetting on rough surfaces
12:30 – 14:00

Lunch break

Session 7 (2 talks) Chair: H. Notsu
14:00 – 14:50 Hirofumi Izuhara (Miyazaki University, Japan)
Mathematical analysis on a nonlinear system for contact inhibition of cell
growth
14:50 – 15:40 Giulio G. Giusteri (OIST-Okinawa Inst. Sci. Tech. Gr. Univ., Japan)
Rheometric and modeling frameworks for complex fluids
15:40 – 16:00

Coffee break

Session 8 (3 talks) Chair: K. Švadlenka
16:00 – 16:50 Yana Di (Chinese Academy of Science, China)
Numerical methods for interfacial flows with surfactant
16:50 – 17:15 Akihisa Yamamoto (iCeMS / Gr. Sch. Med., Kyoto Univ., Japan)
Cancer progression alters morphological fluctuation and self-propelled motionof human gastric cells
17:15 – 17:40 Ryo Suzuki (iCeMS / Gr. Sch. Med., Kyoto Univ., Japan)
Active deformation and symmetry breaking in regenerating Hydra tissues
17:40 – 17:50

Closing

45

Abstracts

6

Energy stable linear schemes for viscoelastic phaseseparation
Mária Lukáčová-Medvid’ová1
1 Institute of Mathematics, University of Mainz, Mainz 55099, Germany

lukacova@uni-mainz.de
The mathematical modelling and simulation of complex polymer systems, such as multiphase
polymer fluids, is extremely challenging. One of the main reasons is the lack of time-scale separation
between the relaxation of macromolecules and the hydrodynamics of the surrounding solvent. In thepresent talk we concentrate on the macroscopic modelling of viscoelastic phase separation. We
follow the work of Zhou, Zhang and E (Physical Review E 73, 2006), where the mathematicalmodel has been proposed. It consists of the Cahn-Hilliard equation, which describes dynamics of
the interface that separates polymer and solvent and the Oldroyd-B equations for the hydrodynamics
of polymeric mixtures. The model is thermodynamically consistent and dissipates free energy. We
present newly derived linear numerical schemes for the polymer-solvent mixture model and prove
theoretically that the schemes are energy dissipative. This property is also illustrated on a series ofnumerical experiments. In future, our goal is to derive stable and consistent descriptions of complex
flow dynamics in phase-separating polymer systems on multiple scales by systematic calibration
strategies to determine unknown model parameters.
This is a joint work with Paul Strasser, Burkhard Dünweg (Mainz) and Giordano Tierra (Temple). This research has been supported by the German Science Foundation under the Collaborative
Research Center TRR146.

6
7

Continuum model for epithelial tissue
1

Shuji Ishihara1 , Philippe Marcq2, and Kaoru Sugimura3
Graduate school of Arts and Sciences, The University of Tokyo, Tokyo 153-8902, Japan
2
Institute Curie, Université Pierre et Marie Curie, Paris 75284, France3
WPI-iCeMS, Kyoto University, Kyoto 606-8501, Japan

Morphogenesis is composed of the collective and dynamic cell behaviors for which both the chemical
and mechanical interactions play an essential role for determining shape of tissue and bodies. Mathematicalmodels, such as cell vertex model (CVM) and cellular Potts model (CPM), have proven useful forunderstanding how the cellular behaviors result in the tissue deformation; however, the relationship between
cell morphogenetic processes and tissue scale deformation and rheology emerges from numerical simulations
without being directly tractable.
To make clearer insight on the connection between cellular and tissue scale, we develop a continuum
model for two-dimensional epithelial tissue. The model includes a field variable M(r) representing
coarse-grained cellular shape. By decomposing tissue deformation rate into those originated from cell shapechange and from topological change in cell position (cell rearrangement, cell division and death), as∇v = Ω + Ds + Dr ,we determine kinematic relationship between deformation rate and cell shape change. Employing free energy
and thermodynamics formalism, we derive a continuum model for the epithelial tissue [1]. Furthermore, by
including formalism developed in active gel theory [2], we introduce active terms into the model.
With the active terms, we studied contraction-elongation. In many morphogenetic systems tissue
deformation occurs perpendicularly to the direction of cell shape elongation, the mechanisms of which
remains unclear. We show that our model with active terms naturally provides the new mechanism for thisprocess. We also show spontaneous tissue flow with the active term.

M(r)cell shape change

cell rearrangement

Ω + Ds

Dr

e

tissu

FIG. 1: Cell shape variable M(r), and tissue deformation by cell shape change and cell rearrangement

REFERENCES
1. S. Ishihara, P. Marcq and K. Sugimura (2017) Phys Rev E 96: 022418
2. K. Kruse, J.F. Joanny, F. Jülicher, J. Prost, K. Sekimoto (2005) Eur Phys J E 16:5-16

78

Interface motion involving the Dirichlet-to-Neumann
operator
Julien Dambrine1
1 Laboratoire de Mathématiques et Applications, Université de Poitiers, France

julien.dambrine@univ-poitiers.fr
The motion of surfaces with a normal velocity depending on the Dirichlet-to-Neumann operator
for a given elliptic problem appear in various practical applications among which:• The motion of cells with a Hele-Shaw type model.
• Water-waves modelling through incompressible/irrotational Euler’s equations.
• Shape optimisation problems.
Using an implicit representation, the motion of the interface is described by the level-set equation:∂t f = Vn |—f | ,where f is the level-set function of the interface, and Vn the normal velocity. This method is wellknown for its ability to handle topological changes that might happen over time (for instance wavebreaking).
In this talk we focus on the numerical computation of the Dirichlet-to-Neumann operator for
the Laplace equation with a level-set representation on the interface, following the ideas that weredevelopped in [1] for the computation of the bulk solution.

References[1] Catherine Kublik, Nicolay M. Tanushev, Richard Tsai, An implicit interface boundary integral
method for Poisson‘s equation on arbitrary domains, JCP, 2013.

9

Cellular Tessellation in Sensory Epithelia
Hideru Togashi
Kobe University Graduate School of Medicine, Kobe 650-0017, Japanhtogashi@med.kobe-u.ac.jp

Animal tissues are composed of multiple cell types arranged in complex and elaborate patterns. In sensory
epithelia, including the auditory epithelium and olfactory epithelium, different types of cells are arranged inunique mosaic patterns. These mosaic patterns are evolutionarily conserved, and are thought to be important forhearing and olfaction. The complex patterns of cells in tissues often arise through self-organization of cells.
Differential adhesion has been proposed to promote selective aggregation or rearrangement of cells, and thesemechanisms could drive self-organized cell movements in the sensory epithelia. Recent progress has provided
accumulating evidence that the cellular pattern formation in sensory epithelia involves cell rearrangements,
movements, and shape changes. These morphogenetic processes are largely mediated by intercellular adhesion
systems. Many different types of cells in tissues express various types of cell adhesion molecules. Although
cooperative mechanisms between multiple adhesive systems are likely to contribute to the production of complex
cell shapes and patterns, our current understanding is insufficient to entirely explain the complex mechanisms.
Recent studies have revealed that nectins, in cooperation with cadherins, are crucial for the mosaic cellularpatterning in sensory organs. The nectin and cadherin systems are physically and functionally associated with
one another, and these associations provide cells with differential adhesive affinities for complex cellular patternformations in sensory epithelia. In this symposium, I will introduce and discuss recent progress of our studies on
cellular patterning and unique morphology of the cells in sensory organs.

References[1] Katsunuma, S., Honda, H., Shinoda, T., Ishimoto, Y., Miyata, T., Kiyonari, H., Abe, T., Nibu, K.,
Takai, Y., and Togashi, H. 2016. Synergistic action of nectins and cadherins generates the mosaic
cellular pattern of the olfactory epithelium. J. Cell Biol., 212: 561–575.
[2] Fukuda, T., Kominami, K., Wang, S., Togashi, H., Hirata, K., Mizoguchi, A., Rikitake, Y., and Takai,
Y. 2014. Aberrant cochlear hair cell attachments caused by Nectin-3 deficiency result in hair bundle
abnormalities. Development, 141: 399-409.
[3] Togashi, H., Kominami, K., Waseda, M., Komura, H., Miyoshi, J., Takeichi, M., and Takai, Y. 2011.
Nectins Establish a Checkerboard-like Cellular Pattern in the Auditory Epithelium. Science, 333: 1144–
1147.

10

Elastic and inertial instabilities in microfluidic flows
Amy Q. Shen1
1 Micro/Bio/Nanofluidics Unit, Okinawa Institute of Science and Technology Graduate University,

1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan
amy.shen@oist.jp

Microfluidics has emerged in recent years as a versatile platform of manipulating fluids at small
length-scales, and in particular, offers a large range of deformation rates and direct visualization of
resulting flow fields, providing unique opportunities for capturing the flow instabilities of viscoelastic fluids in real time. Two simple microfluidic platforms are used to highlight the intricate balance
between viscoelastic and inertial instabilities of complex fluids.
(1) Micro-cross-slot devices: studies of flow instabilities in stagnation point flow geometries havefocused mostly on either Newtonian fluids, in which the instabilities are driven entirely byinertia, or on highly elastic fluids where inertia plays a negligible role. However, weak fluid
elasticity can modify the flow response remarkably, giving rise to important effects such as
turbulent drag reduction in macroscale pipe flows. Here we examine fluid flow through microcross-slot devices with various aspect ratios, and investigate how weakly elastic fluids caninfluence an inertially-driven flow instability. Our experimental configuration allows direct
examination of a single steady vortex, shedding new insight into the competing effects ofinertial and elastic instabilities on vortex formation and dynamics at small length scales.
(2) Confined microfluidic cylinders: Wormlike micellar (WLM) solutions are frequently used as
fracture and proppant-carrying fluids in enhanced oil and gas recovery applications in porousrock beds where complex microscopic geometries result in mixed flow kinematics with strong
shear and extensional components. To gain understanding of WLM fluids flowing throughporous media, we examine the flow of WLM fluids around a single micro-scale cylinderaligned on the flow axis. The WLM solution is strongly viscoelastic and exhibit shear banding
behaviour. Flow of WLM solutions around confined cylinders results in the onset of a sequence of low Re flow instabilities, which depend on both Wi (as high as 105 ) and the blockage ratio. Interestingly the flow instabilities first emerged upstream of the cylinder, which areassociated with high stresses in fluid that accelerates into the narrow gap between the cylinder and the channel wall, while instabilities downstream of the cylinder are associated withstresses generated at the trailing stagnation point and the resulting flow modification in thewake, coupled with the onset of time-dependent flow upstream and the asymmetric divisionof flow around the cylinder.

10
11

Computational simulation in complex flows of
non-Newtonian fluids
Cassio M. Oishi1 ,1 Departamento de Matemática e Computacão, São Paulo State University (UNESP),

Presidente Prudente, Brazil
oishi@fct.unesp.br; cassiooishi@gmail.com

In this work we will present computational simulations of some nonlinear and peculiar phenomena observed in non-Newtonian fluid flows. In particular, we will discuss some recent progress in thedevelopment of numerical schemes for solving incompressible Navier-Stokes equations in complex
flows combined with complex fluids. In the context of complex flows, we will describe numericalstrategies for dealing with moving interface (two-phase or free surface) problems [1] and flows withgeometric singularities (or sharp corners) [2]. Moreover, we will explore finite difference formulations for stabilizing the constitutive equations used to represent the non-Newtonian effects. Finally,
we will present some computational results of complex fluids which can exhibit different properties,
such as viscoelasticity, plasticity and thixotropy [3].

References[1] R.A. Figueiredo, C.M. Oishi, A.M. Afonso, I.V.M. Tasso and J.A. Cuminato. A two-phase solver
for complex fluids: studies on the Weissenberg effect, International Journal of Multiphase Flow,
Vol. 84, pp. 98-115, 2016.
[2] J.D. Evans and C.M. Oishi, Transient computations using the natural stress formulation forsolving sharp corner flows, Journal of Non-Newtonian Fluid Mechanics, Vol. 249, pp. 48-52,
2017.
[3] C.M. Oishi, R.L. Thompson and F.P. Martins, Transient motions of elasto-viscoplastic
thixotropic materials subjected to an imposed stress field and to stress-based free-surface boundary conditions, International Journal of Engineering Science, Vol. 109, pp. 165-201, 2016.

12

Mathematical models of tumor invasion and OV/immune
therapy
Yangjin Kim1,2 , Avner Friedman2 , Hans Othmer3 , Hyejin Jeon4 ,Ji Young Yoo5 , Michael A Caligiuri6 , and Balveen Kaur5
1 Department of Mathematics, Konkuk University, Seoul, 05029, Republic of Korea

2 Mathematical Biosciences Institute, Ohio State University, Columbus, OH 43210, USA
3 School of Mathematics, University of Minnesota, Minneapolis, MN 55455, USA

4 Dept of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea

5 Dept of Neurosurgery, University of Texas Health Science Center at Houston, TX 77030, USA

6 Dept of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH,

43210, USA

Malignant gliomas are the most common type of brain cancer, which arise from glial cells,
and in their most aggressive form are called GBMs. GBMs are highly invasive and difficult to treat
because cells migrate into surrounding healthy brain tissue rapidly, and thus these tumors are difficult
to completely remove surgically. GIMs, which can comprise up to one third of the total tumor
mass, are present in both intact glioma tissue and necrotic areas. They apparently originate fromboth resident brain macrophages (microglia) and newly recruited monocyte-derived macrophages
from the circulation. Activated GIMs exhibit several phenotypes: one called M1 for classically
activated, tumor suppressive, and another called M2 for alternatively activated, tumor promoting,and immunosuppressive. Within a tumor the balance between these phenotypes is typically shiftedto the M2 form. Numerous factors secreted by glioma cells can influence GIM recruitment andphenotypic switching, including growth factors, chemokines, cytokines and matrix proteins. In thiswork, we focus on mutual interaction between a glioma and M1/M2 microglia mediated by CSF-1,
TGFbeta, and EGF. Up-regulated TGFbeta leads to up-regulation of Smad within the tumor cells andsecretion of MMPs, leading to proteolysis for EMT process and cell infiltration. The mathematicalmodel consists of densities of glioma cells, M1 type cells, M2 type cells, and concentrations of
CSF-1, EGF, TGFbeta, Extracellular matrix, and MMPs. We developed the model to investigate themutual interactions between tumor cells in the upper chamber and microglia in the lower chamber. In
the experiments, Boyden invasion assay was used to show that this mutual interaction induces glioma
infiltration in vitro and in vivo. We show that our simulation results are in good agreement with theexperimental data and we generate several hypotheses that should be tested in future experiments invivo. We also apply the role of M1/M2 macrophages in OV therapy in glioma.
As a second part of the talk, we investigated the role of natural killer (NK) cells in combination
therapy with oncolytic virus (OV) and bortezomib. NK cells display rapid and potent immunity
to metastasis and hematological cancers, and they overcome immunosuppressive effects of tumor
microenvironment. We developed a mathematical model in order to address the question of how thedensity of NK cells affects the growth of the tumor. We found that the anti-tumor efficacy increases
when the endogenous NKs are depleted, and also when exogenous NK cells are injected into thetumor. These predictions were validated by our in vivo and in vitro experiments.

References[1] Yangjin Kim, Hyejin Jeon, and Hans Othmer, The role of the tumor microenvironment inglioblastoma: A mathematical model, IEEE Trans Biomed Eng (IF 2.347), 64(3):519-527,
March 2017[2] Yangjin Kim, Ji Young Yoo, Tae Jin Lee, Joseph Liu, Jianhua Yu, Michael A Caligiuri, Balveen
Kaur, and Avner Friedman, Complex Role of NK cells in regulation of OV-Bortezomib therapy,
under revision.
[3] Yoo et al, Bortezomib-induced unfolded protein response increases oncolytic HSV-1 replication
resulting in synergistic antitumor effects. Clin Cancer Res. 2014 Jul 15;20(14):3787-98. doi:
10.1158/1078-0432.CCR-14-0553. Epub 2014 May 9.
13

Integration over implicitly defined interfaces andextension to unstructured point clouds
Catherine Kublik1 ,1 Department of Mathematics, University of Dayton, USA. ckublik1@udayton.edu

We discuss related approaches for integrating over interfaces that are defined implicitly througha level set function or by their closest point representation. The idea behind these methods is torewrite the integral over the interface as an integral over the embedding space, thus making the lattereasy to discretize on a uniform Cartesian grid. These integral formulations over the embedding space
use specific kernels supported on a tubular neighborhood around the interface, and approximate theDirac delta function. We show numerical examples demonstrating the capability of these approaches,
especially the most recent approach which allows accurate numerical integration over curves andsurfaces with singularities such as corners. We finish with a discussion of the application of oneof these formulations to integration over unstructured point sets. Joint work with Richard Tsai (UT
Austin, USA and KTH, Royal Institute of Technology, Sweden).

14Pattern formation induced by a domain deformation: A
mystery of remodeling process in nuclear architecture
Sungrim Seirin-Lee1,2,4,∗ , Fumitaka Osakada 3,4 and Hiroshi Ochiai2,4,∗
1 Department of Mathematics, Hiroshima University ,Kagamiyama 1-3-1, Higashi-hiroshima

739-0046, Japanseirin@hiroshima-u.ac.jp
2 Department of Mathematical and Life Sciences, Hiroshima University ,Kagamiyama 1-3-1,
Higashi-hiroshima 739-0046, Japan
3 Graduate School of Pharmaceutical Sciences & Laboratory of Neural Information Processing
Institute for Advanced Research Nagoya University, Japan
4 Japan Science and Technology Agency, PRESTO, Kawaguchi 332-0012, Japan∗ These authors contributed equally
Nuclear architecture, which plays an important role in organizing the function of the nucleus,
is composed of heterochromatin and euchromatin. Conventional nuclear architecture is found when
the distribution of heterochromatin is enriched in the periphery of the nucleus. Conventional architecture is the primary structure in the majority of eukaryotic cells, and the rod cells of diurnal
mammals contain this structure. In contrast, inverted nuclear architecture occurs when the heterochromatin is distributed in the center of the nucleus; this occurs in the rod cells of nocturnal
mammals. Surprisingly, the inverted architecture found in the rod cells of the adult mouse is formed
through reorganization of the conventional architecture during terminal differentiation. Although anexperimental approach has shown the relationship between these two types of nuclear architecture
at the molecular level, the mechanisms mediating the long-range reorganization processes remain
unknown. Here, we suggest a new mathematical approach to understanding the dynamics of nuclear
architecture, by which we found that the deformation of nucleus can play a critical role in the process of chromatin remodeling. With the interdisciplinary work, we also succeeded in developing an
in vitro experiment and found that the dynamical deformation of nucleus promotes the clustering ofchromocenters. With the basis of theoretical observation, we prove that the deformation of nucleus issufficient condition to induce the remodeling of chromatin architecture. This interdisciplinary work
has been started from the theoretical hypothesis and we suggest a new framework of interdisciplinary
research in life sciences.

14
15

Mathematical modeling and genetic analysisof the fly visual system
Makoto Sato
Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-8640, Japan
makotos@staff.kanazawa-u.ac.jp

During development of multicellular organisms, multiple signaling systems play important roles. However, it isvery hard to understand the interplays between many signaling pathways using conventional methods ofmolecular biology, biochemistry and genetics. Mathematical modeling should be combined with these biologicalmethods to solve this problem.
The waves of differentiation in visual system development are key examples of the complex
interplays between multiple signaling systems [1]. In this study, we focus on a wave of differentiation called theproneural wave, which occurs in the developing fly brain and accompanies Notch-mediated lateral inhibition and
EGF-mediated neural differentiation. During proneural wave progression, the sheet-like neuroepithelial cells(NEs) sequentially differentiate to neural stem cells called neuroblasts (NBs). The proneural wave is an ideal
model system to investigate the roles and dynamics of the interplay between important signaling pathways suchas Notch and EGF.
Notch-mediated lateral inhibition regulates binary cell-fate choice, resulting in salt-and-pepper
patterns during various developmental processes. The proneural wave accompanies Notch activity that is
propagated without the formation of a salt-and-pepper pattern. However, mathematical modeling and genetic
analysis clearly demonstrated that Notch-mediated lateral inhibition is implemented within the proneural wave[2]. Because partial reduction in EGF signaling causes the formation of salt-and-pepper pattern, it is most likelythat EGF diffusion cancels salt-and-pepper pattern formation in silico and in vivo. Moreover, the combination of
Notch-mediated lateral inhibition and EGF-mediated reaction diffusion enables a novel function of Notch
signaling that regulates propagation of the wave of differentiation.
In our previous results, Notch signaling is activated only once at the wave front. However, Notch
signaling is actually activated again behind the wave front forming twin peaks in vivo. The results of ourparameter search show that the twin peaks of Notch activity can be reproduced by elevating the coefficient of
cis-inhibition, by which Notch activity is autonomously repressed by Delta ligand. Moreover, the formation of
the twin peaks could be stabilized by introducing strong non-linearity to cis-inhibition. The possible effects of
non-linearity in cis-inhibition will be discussed.

References[1] Sato, M., Suzuki, T. and Nakai, T. Developmental Biology 380, 1-11 (2013).
[2] Sato, M., Yasugi, T., Minami, Y., Miura, T. and Nagayama, M. Proceedings of the National Academy of
Sciences 113, E5153-E5162 (2016).

15
16

Isogeometric phase-field analysis
Eliot Fried1
1 Mathematics, Mechanics, and Materials Unit, Okinawa Institute of Science and Technology

Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa 904-0495, Japaneliot.fried@oist.jp

Many processes in engineering and sciences involve the evolution of interfaces. A mathematicalframework that describes these types of problems is the phase-field method. Cahn and Hilliard proposed a popular phase-field description for phenomena associated with spontaneous phase separationof immiscible fluids. These processes occur below a critical temperature, where phase separation
allows for the formation of spatial domains rich in each component. Phase-fields lead to initialboundary-value problems for complex nonlinear, high-order partial differential equations, whose
solutions pose many mathematical and computational challenges.
To illustrate the robustness of the methodology, we report multi-dimensional simulations of the
Allen–Cahn, Cahn–Hilliard, Swift–Hohenberg, and phase-field crystal models. We also discuss
droplet dynamics, as modeled by the Navier–Stokes–Cahn–Hilliard equations. These simulations
use PetIGA and PetIGA-MF, high-performance isogeometric analysis frameworks that are specifically designed to handle nonlinear, time-dependent problems.

16
17

On a reaction-diffusion-ODE model for the neolithic
dispersal of farmers and hunter-gatherers
Jan Elias1 , Danielle Hilhorst2 , Masayasu Mimura 3 , and Yoshihisa Morita 4
1 Institute for Mathematics and Scientific Computing, University of Graz, 8010 Graz, Austria
2 CNRS and Laboratoire de Mathématiques, Université Paris-Sud, 91405 Orsay Cedex, France
3 Meiji Institute for Advanced Study of Mathematical Sciences, Meiji University, and Departmentof Mathematical Engineering, Musashino University, Tokyo, Japan

4 Department of Applied Mathematics and Informatics, Ryukoku University, Otsu, JapanThe Neolithic migration of farmers in regions previously inhabited by hunter-gatherers has beenstudied for a long time [1, 2]. In particular the Lotka-Volterra type system(
Ft = dF DF + rF F(1 F + aH),(1)
Ht = dH DH + rH H(1 H bH),
has been studied by [3]. In this model, the populations of farmers F and hunter-gatherers H are
assumed to diffuse freely and randomly by linear diffusion with constant diffusion rates dF and dH
throughout the region. Recently, [4] have proposed a new three component reaction-diffusion system
8F1 (1 F1 F2 ) + sF1 H k (p(F1 + F2 )F1 (1 p(F1 + F2 ))F2 ) ,>< F1,t =k(P ) F2,t = dDF2 + F2 (1 F1 F2 ) + sF2 H + k (p(F1 + F2 )F1 (1 p(F1 + F2 ))F2 ) ,>:Ht = DH + rH(1 H) g(F1 + F2 )H,allowing to monitor the expanding farming population in terms of the sedentary and migrating farmers denoted by F1 and F2 , respectively. In Problem (P k ), p = p(F) is the probability density function which is included in the switching mechanism betwen the sedentary and migrating farmers andwhich depends on the total density of the farmers F = F1 + F2 . We assume that p satisfies
8(i) p(0) = 0,><(ii) p(F) is increasing in F,>: (iii) lim p(F) = 1.
F!•

A simple example is given by p(F) = F/(F + Fc ), where Fc is the switching value of the conversion
between F1 and F2 ; more precisely, the probabilities of remaining sedentary and migrating are equal
when F = Fc . Finally the parameter k > 0 is the rate of conversion between F1 and F2 . In view of(i)-(iii), the model (P k ) implies that whenever the total density of farmers is low, the farmers prefera sedentary lifestyle. On the other hand, if the total density of farmers is high, then some of the
farmers start migrating and searching for new places favourable for sedentary life.
In this talk, we consider Problem (P k ) together with homogeneous Neumann boundary conditions for the populations F2 and H, and prescribed initial conditions, and study the singular limit of
the solution as the conversion rate k tends to •. We will show that (Fk,1 + Fk,2 , Hk ) converges to(F, H) as k ! •, where (Fk,1 , Fk,2 , Hk ) saisfies Problem (P k ) and (F, H) satisfies the system(
Ft = dF D(p(F)F) + rF F(1 F) + sFH,
(2)
Ht = dH DH + rH H(1 H) gFH.
together with homogeneous Neumann boundary conditions and suitable initial conditions. Unlikein the system (1), the diffusion of farmers may degenerate if p = 0. In this model, the Neolithic
dispersal of farming in Europe takes into account the population density pressure due to limited
space and the advanced lifestyle resulting in farmer overcrowding.
18

References[1] A.J. Ammerman, and L.L. Cavalli-Sforza, Measuring the rate of spread of early farming inEurope, Man , 6 (4) : 674-688, 1971.
[2] A.J. Ammerman, and L.L. Cavalli-Sforza, The Neolithic Transition and the Genetics of Populations in Europe, Princeton University Press, Princeton, 1984.
[3] K. Aoki, M. Shida, and N. Shigesada, Travelling wave solutions for the spread of farmers intoa region occupied by hunter-gatherers, Theoretical Population Biology, 50 (1) : 1-17, 1986.
[4] J. Elias, K. Humayun, and M. Mimura, On the well-posedness of a dispersal model for farmers
and hunter-gatherers in the Neolothic transition, preprint.

19

Convergence of Splitting Schemes and Segregation In
Reaction-(Cross-)Diffusion Systems
Markus Schmidtchen1
1 Imperial College London

m.schmidtchen15@imperial.ac.uk
One of the most fascinating phenomena observed in reaction-diffusion systems is the emergenceof segregated solutions, i.e. population densities with disjoint supports. We analyse such a reaction
cross-diffusion system. In order to prove existence of weak solutions for a wide class of initial data
without restriction about their supports or their positivity, we propose a variational splitting scheme
combining ODEs with methods from optimal transport. In addition, this approach allows us to proveconservation of segregation for initially segregated data even in the presence of vacuum.

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Active Soft Materials: Self-propelled motion and its
collective behaviours of colloids and liquid drops
Natsuhiko Yoshinaga1,2
1 WPI - Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan
2 MathAM-OIL, AIST, Sendai 980-8577, JapanOne of the striking phenomena in biology is the ability of a cell to move without an external force.
This is distinct from passive systems. Such active materials consumes energy obtained from internalenergy sources and simultaneously dissipates the energy to its environment[1]. Aiming for a genericunderstanding in this field, we have been working on spontaneous motion, which has attracted lotsof attention in the last decades in fluid dynamics for its potential application to biological problems
such as cell motility.
Recently, several model experiments showing spontaneous motion driven by chemical reactions
have been proposed and revealed the underlying mechanism of the motion. Inspired by these experiments, several simple theoretical models such as active Brownian particles, squirmers, selfthermophoretic swimmers have been proposed and extensively analysed. We have theoreticallyderived a set of nonlinear equations showing a transition between stationary and motile states driven
away from an equilibrium state due to chemical reactions[4, 5, 6]. A particular focus is on howhydrodynamic flow destabilizes an isotropic distribution of a concentration field. It is of interest that
due to self-propulsive motion and flow around the droplet, a spherical shape becomes unstable andit elongates perpendicular to the direction of motion. This implies that the self-propulsion driven bychemical reaction is characterized as a pusher in terms of a flow field.
A next step is to understand interactions between self-propelled particles and drops. Even forthe simple models, non-trivial collective patterns such as motility-induced phase separation, global
polar state, and clustering have been reported. Nevertheless, it is still not clear how hydrodynamic
interactions and the interaction mediated by a concentration field give rise to collective behaviors.
I shall discuss these issues based on our recent results of theoretical calculations of interactions
between chemically driven self-propelled particles[3] and collective behaviours of squirmers[2].

References[1] Natsuhiko Yoshinaga, J. Phys. Soc. Japan, 86 101009 (2017).
[2] Natsuhiko Yoshinaga and Tanniemola B. Liverpool, Phys. Rev. E Rapid Communications, 96020603 (2017).
[3] Shunsuke Yabunaka and Natsuhiko Yoshinaga, J. Fluid. Mech., 806 205-233 (2016).
[4] Natsuhiko Yoshinaga, Phys. Rev. E, 89 012913 (2014).
[5] Shunsuke Yabunaka, Takao Ohta, and Natsuhiko Yoshinaga, J. Chem. Phys., 136 074904 (2012).
[6] Natsuhiko Yoshinaga, Ken H. Nagai, Yutaka Sumino, and Hiroyuki Kitahata, Phys. Rev. E, 86
016108 (2012).

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Modelling and computations for wetting on roughsurfaces
Xianmin Xu1,2 and Xiaoping Wang3
1 LSEC, ICMSEC, Academy of Mathematics and Systems Science, Chinese Academy of Sciences,

Beijing 100190, China

2 School of Mathematical Sciences, University of Chinese Academy of Sciences, Beijing 100049,

China
xmxu@lsec.cc.ac.cn
3 Department of Mathematics, Hong Kong University of Science and Technology, Hong Kong,
China
mawang@ust.hk

Wetting on rough surfaces is common in nature and some industry applications. It is a twophase ow problem with complicated boundary conditions. Mathematically, it can be modeled bya free interface problem in a domain with rough boundaries. In this talk, we will introduce somerecent analysis and computations for this problem. We first show some multi-scale analysis for the
problem. Basically, we derive a homogenized equation to describe the macroscopic contact angle
on rough surface. The equation describes the local minimizers in the system and thus can be used todescribe the contact angle hysteresis phenomena. Then we introduce a volume preserving threshold
dynamics method for this problem. The method is simple, stable and very efficient. In each iteration,
only one or two convolution operations for functions defined in a regular domain are needed. Thiscan be done by fast methods. We also show analysis and simulation results for interesting contact
angle hysteresis phenomena.

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Mathematical analysis on a nonlinear systemfor contact inhibition of cell growth
Hirofumi Izuhara
Faculty of Engineering, University of Miyazaki, Miyazaki 889-2192, Japanizuhara@cc.miyazaki-u.ac.jp
We consider a cell growth model involving a nonlinear system of partial differential equations
which describes the growth of two types of cell populations, say normal and abnormal cells, withcontact inhibition. Numerical experiments show that there is a parameter regime where, for a large
class of initial data, the large time behavior of the solutions is described by a segregated travelingwave solution with positive wave speed c. Here, the word segregated expresses the fact that thedifferent types of cells are spatially segregated, and that the single densities are discontinuous at themoving interface which separates the two populations. Here, we have the following question. Whenabnormal cells appear by a mutation, is the expanding speed of abnormal cell density determined bya segregated traveling wave solution? In this talk, we discuss this problem from the viewpoint ofanalysis of the model.

References[1] Chaplain M., Graziano L. and Preziosi L., Mathematical modelling of the loss of tissue compression responsiveness and its role in solid tumour development, Math. Med. Biol., 23 (2006)
197–229.
[2] Bertsch M., Dal Passo R. and Mimura M., A free boundary problem arising in a simplified
tumour growth model of contact inhibition, Interfaces Free Boundaries 12 (2010) 235–250.
[3] Bertsch M., Mimura M. and Wakasa T., Modeling contact inhibition of grwoth: Traveling waves,
Netw. Heterogeneous Media 8 (2012) 131–147.
[4] Bertsch M, Hilhorst D., Izuhara H., Mimura M. and Wakasa T., Travelling wave solutions of aparabolic-hyperbolic system for contact inhibition of cell-growth, Euro. Jnl of Applied Mathematics 26 (2015) 297–323.

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Rheometric and modeling frameworks for complex fluids
Giulio G. Giusteri1 and Ryohei Seto1
1 Mathematics, Mechanics, and Materials Unit, Okinawa Institute of Science and Technology

Graduate University, Onna 904-0495, Japan
giulio.giusteri@gmail.com, setoryohei@me.com

The objective of rheology is to figure out reasonable constitutive prescriptions for complex materials, based on standardized experimental investigations [1, 2]. The development of rheologicalmodels requires a flexible continuum mechanical framework, a clear way to connect observations
with model parameters, and reliable simulation techniques to compare predictions with experiments.
The great success of continuum mechanics in describing linearly elastic solids and viscous fluids invited researchers to develop more complicated models by mixing those effective theories. Nevertheless, materials that combine solid and fluid behaviors, such as viscoelastic fluids, remain difficult to
describe in a satisfactory way. To keep up with the significant evolution of experimental techniques
and results, it is necessary to improve the theoretical framework of continuum mechanics and give a
unified picture in which elastic, plastic, and viscous effects are all present.
The first step in understanding the material response is to have a clear framework to compare andinterpret data retrieved in different situations [3, 4]. In the first part of the talk, we introduce a generaldecomposition of the stress tensor for incompressible fluids in terms of its components on a tensorial
basis adapted to the local flow conditions, which include extensional flows, simple shear flows, andany type of mixed flows. Such a basis is determined solely by the symmetric part of the velocity
gradient and allows for a straightforward interpretation of the non-Newtonian response in any local
flow conditions. In steady flows, the material response functions that represent the components ofthe stress on the adapted basis generalize and complete the classical set of viscometric functions
used to characterize the response in simple shear flows.
In the second part of the talk, we discuss frameworks for constitutive modeling analyzing therole of local geometric and topological evolution in continuum mechanics. These concepts canprovide useful insight regarding the physical mechanisms that are captured by different continuum
mechanical frameworks. The evolution of local geometries plays an important role in modelingvisco-elasto-plastic phenomena and we wish to highlight the potential usefulness of a perspective inwhich the evolution of the observed geometry is clearly distinct from that of the intrinsic geometry
favored by the material microstructure.

References[1] C. W. Macosko. Rheology. Wiley-VCH, New York, 1994.
[2] R. G. Larson. The Structure and Rheology of Complex Fluids. Oxford University Press, NewYork & Oxford, 1999.
[3] G. G. Giusteri, R. Seto. A theoretical framework for steady-state rheometry in generic flow
conditions. ArXiv:1702.02745.
[4] R. Seto, G. G. Giusteri, A. Martiniello. Microstructure and thickening of dense suspensions
under extensional and shear flows. J. Fluid Mech. 825, R3, 2017, doi:10.1017/jfm.2017.469.

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Numerical methods for interfacial flows with surfactant
Yana Di1
1 LSEC, ICMSEC, Chinese Academy of Sciences, Beijing 100190, China

yndi@lsec.cc.ac.cn
The research of surfactant systems is one of the important areas in soft condensed matter physics.
The surfactant behaviors result in various kinds of interface/surface phenomena and also effectgreatly on the physical characters of complex fluid systems. Here, we treat these problems in aphysical way, and simulate the interface wetting and spreading phenomena of polydimethylsiloxane
oil/ surfactant solution systems. We try to understand how the electrostatic/volume effect related tosurface change the wetting status.

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Cancer Progression Alters Morphological Fluctuationand Self-Propelled Motion of Human Gastric Cells
Akihisa Yamamoto1,2 , Yusuke Sakamaki2 , Tatsuaki Tsuruyama1,3 and Motomu Tanaka2,4
1 Center for Anatomical, Pathological and Forensic Medical Researches, Graduate School of

Medicine, Kyoto University, Kyoto 606-8501, Japan
yamamoto.akihisa.6w@kyoto-u.ac.jp
2 Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8501, Japan
3 Department of Drug Discovery Medicine, Graduate School of Medicine, Kyoto University, Kyoto
606-8507, Japan
4 Institute for Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany
The structure of multicellular tissues becomes disordered according to the cancer progression,and single cells become to show a wider variety in size and shape (atypism). Although these static,
phenomenological features are utilized as an important indicator of cancer staging in the field of
pathology, little is known about the mechanism how the collective ordering in tissues and the morphological fluctuation and dynamics of single cells are correlated during the cancer progression. In
this research we describe human gastric cells at different cancer grades as self-propelled, deformableparticles, and aim to reveal the correlation between their active deformation, adhesion (frictional
coupling to the environment), and migratory motion.
To model the interactions between gastric cells and extracellular environments, we functionalized
the surface of supported membranes with laminin, which is the main component of basal lamina.
Human gastric cells from four different cancer stages were seeded, and the active deformation of theadhesion zone was recorded with label-free, reflection interference contrast microscopy (RICM) over
2 d. We found that well differentiated, "healthy" cancer cells hardly migrate nor deform, while poorly
differentiated, "sick" cancer cells actively deform and migrate in a directional manner. Moreover,
we found that metastatic (invasive) cancer cells showed a remarkable deformation and migrationin the presence of naturally occurring chemokine CXCL12. Our data unraveled that active shapefluctuation and migration are clearly correlated with cancer progression.

References[1] T. Tsuruyama, et al., Transpl. Int. 25, 537 (2012)[2] M. Tanaka and E. Sackmann, Nature 437, 656 (2005)[3] T. Kaindl, et al., PLoS ONE 7, e42991 (2012)26

Active deformation and symmetry breaking inregenerating Hydra tissues
Ryo Suzuki1,2,† , Mariam Veschgini3 , Thomas W. Holstein4 and Motomu Tanaka2,3
1 Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan

2 Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, Japan
3 Institute of Physical Chemistry, University of Heidelberg, Heidelberg 69120, Germany
4 Centre for Organismal Studies, University of Heidelberg, Heidelberg 69120, Germany† Email: suzuki.ryo.8z@kyoto-u.ac.jp

The freshwater polyp Hydra is a paradigm for unlimited regenerative capacity, where wholeorganisms regenerate from a broad range of initial conditions. During the initial phase of regeneration, Hydra tissues form their major body axis from a spherical configuration —- termed “symmetry
breaking” —- which is accompanied by extremely dynamic fluctuations both in size and shape, indicating active force generation. Although it is currently understood that Wnt signaling is responsible
for the molecular patterning [1, 2] and mechano-genetic/chemical coupling is possibly an importantfactor for regeneration processes in Hydra [3, 4], how active tissue fluctuation leads to the regeneration over time still remains elusive. Therefore, we investigate the “physics of regenerating tissue”
via a non-invasive, full mode analysis of actively fluctuating Hydra regenerates.
To understand the body axis formation of regenerating Hydra, morphological dynamics are studied using mode analysis. To minimize the loss of information regarding translational and rotationalmotion of the regenerating tissue in a non-invasive manner, Hydra tissues on dish surface were allowed to undergo active deformation without contact to side walls [5].
During the regeneration process, the Hydra spheres show continuous inflation / burst cycles. Ourdata unravelled (a) the moment of symmetry break can be characterized by the anti-phasing of mode
0 and 2, and (b) the translational and rotational motions are strongly suppressed after the symmetry
break. Interestingly, the regeneration process of cell reaggregates — dissociation into single cells
and reaggregating them — showed similar mode behaviour but lost motion, both translational androtational. This can well be due to the loss of intrinsic cell polarity in the cell reaggregates.
Moreover, mode analysis of regenerates (i.e., tissue fragments) that over-express b -catenin —which enhances head organisation via the Wnt signaling pathway — displayed similar features tothat of cell reaggregates which produced multiple heads. This infers the important relation between
the head organisers and the active tissue deformation.
Here, we would like to focus mainly on outlining the vast colourful features observed in experiments and to ask questions into how such phenomena can eventually be fully understood by aid oftheoretical inputs.

References[1] B. Hobmayer, F. Rentzsch, K. Kuhn, C. M. Happel, C. C. v. Laue, P. Snyder, U. Rothbächer and
T. W. Holstein, Nature 407, 186 (2000).
[2] U. Technau, C. C. v. Laue, F. Rentzsch, S. Luft, B. Hobmayer, H. R. Bode and T. W. Holstein,
Proc. Natl. Acad. Sci. 97, 12127 (2000).
[3] J. Soriano, S. Rüdiger, P. Pullarkat and A. Ott, Biophys. J. 96, 1649 (2009).
[4] A. Gamba, M. Nicodemi, J. Soriano and A. Ott, Phys. Rev. Lett. 108, 158103 (2012).
[5] C. Fütterer, C. Colombo, F. Jülicher and A. Ott, Europhys. Lett. 64, 137 (2003).

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Dinner28

Dinner information
Date: Thursday, December 7, 2017
Time: 18:30
Place: Kamadoka
http://www.kamadoka.com/kodawari.html (in Japanese)
https://goo.gl/Ugy9sr (in English)
Address: 2-25-3, Nakano, Nakano-ku, Tokyo
Fee: 3,500 JPY

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