© iStock.com/BlackJack3D

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TABLEOF
CONTENTS

Guided by its motto “Always aim higher,” CHIBA UNIVERSITY strives to nurture

globally minded students who have broad outlooks. The university values academic diversity
and actively conducts leading-edge fundamental and applied research.

Top Research Program
Chiba University was founded as a national university in Japan in 1949, when Chiba Normal School,
established in 1874, merged with Chiba Medical College and several other educational institutions.
Currently composed of 10 faculties and 13 graduate schools, Chiba University is one of Japan’s largest
national universities, having about 11,000 undergraduate students, 3,500 graduate students and 3,500
faculty members on 4 campuses located near Tokyo. The main campus at Nishi-Chiba occupies an area ofalmost 400,000 square meters (100 acres) and is conveniently located between Tokyo Station (about
40 minutes by train) and Narita International Airport. The 850-bed University Hospital, a core hospital

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08

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MUCOSAL IMMUNOLOGY AND
THERAPEUTICSINTERNATIONAL CENTER FOR
HADRON ASTROPHYSICSCHIRAL
MATERIALS SCIENCEFighting Pathogens at Their
Point of Entry

Revealing Hidden Messages fromthe Cosmos

Using Light to Establish a New
Field of Chiral Materials

for the region, is adjacent to the School of Medicine on the lnohana campus.

Research Incubator Program

25

PHYTOCHEMICAL PLANT
MOLECULAR SCIENCES

26

CANCER EPIGENOME CENTER

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A Different Approach to Fighting Cancer

TRANSLATIONAL RESEARCH PROGRAM OFPSYCHIATRY AND PSYCHOLOGY
Cognitive Behavioural Theraphy
Comes of Age in JapanINTEGRATED RESEARCH CENTER ON
REGENERATIVE SYSTEMS AND DISEASESSteeped in Stem Cells

Science and Engineering

17

MEDICAL MYCOLOGY RESEARCH CENTER

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MEDICINE FOR IMMUNE RELATEDRARE DISEASES

Manipulating Microbes for Human HealthInnovative Approach Offers Hopefor Intractable Problems
19

CENTER OF EXCELLENCE FOREND OF LIFE CARE

Putting the Care Back into End-Of-Life Care
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GLYCOMEDICINE RESEARCH CENTER

21

LABORATORY OF DDS DESIGN AND
DRUG DISPOSITION

Humanities and Social Sciences
24

CHIBA STUDIES ON GLOBAL FAIR SOCIETY
Forging a Fairer World

NEXT-GENERATION THREE-DIMENSIONALDISPLAY AND MEASUREMENT
Future Images —More than Meets the Eye

31

MULTIMODAL MEDICAL ENGINEERING

32

HIGH-EFFICIENCY ENERGY CONVERSION33

CENTER FOR INNOVATIVE MICROWAVE

Toward Image-Based Disease Diagnostics

Toward a Zero-Emission Society

REMOTE SENSING

The Next Wave in Remote Sensing

Sugar Science’s Immunotheraphy PlayBig Hopes for Nanotechnology Based
Drug Delivery Systems

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MULTI-PERSPECTIVE UNDERSTANDING
COGNITIVE BEHAVIOUR GROUP
Predicting Human Behaviour

Unlocking the Potential of Phytochemicals
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AND ITS APPLICATION

Improving Datasets Using Small Area Estimation

Medical and Pharmaceutical Sciences
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SMALL AREA ESTIMATION34

IMAGING SCIENCE AND TECHNOLOGYFOR MATERIAL APPEARANCE
Realness in Digital Images

35

INSECTS-INSPIRED BIG INNOVATION

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SOFT MOLECULAR ACTIVATIONFOR INTELLIGENT MATERIALS

Looking to Nature to Revolutionize Flight

Catalyzing the Future of Smart Materials

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Top Research Program
MUCOSAL IMMUNOLOGY AND THERAPEUTICSFighting Pathogens at Their Point of Entry

INTERNATIONAL CENTER FOR HADRON AS TROPHYSICS

Revealing Hidden Messages From the Cosmos

CHIRAL MATERIALS SCIENCE USING LIGHT TO ESTABLISH

Using Light to Establish a New Field of Chiral Materials© iStock.com/gremlin

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MUCOSAL IMMUNOLOGY AND THERAPEUTICS

FIGHTING PATHOGENSAT THEIR POINT OF ENTRY-Vaccines that induce immune responses at mucosal

membranes of the intestines, lungs and other organs could
help prevent deadly infections.

Research Keywords: Immunology, Mucosal Immunity, Allergy

The mucous membranes that line manyof the tracts and structures in the body are
the first lines of defense against foreign
invaders. Equipped with a powerful andhighly specialized immune system, thesemucosal sentinels protect the surfaces and,by extension, the body interior, against thethreat of gastrointestinal, respiratory andsexually transmitted infections, as well ascancer, allergies and more.
If these immune cells let their guard
down, pathogens such as bacteria andviruses can invade. On the other hand,
if they are overly vigilant, hyper-reactive
conditions like asthma or autoimmune
inflammatory bowel disease can take hold.
Getting the balance right is the goal of
the International Center of Excellencein Mucosal Immunology and Innovative
Allergy Therapeutics.
Launched as a joint initiative between
Chiba University and the University ofCalifornia, San Diego, in 2016, the center
aims to harness the power of the mucosal immune system to develop the next
generation of preventive vaccines against
infectious, allergic and inflammatory
diseases.
Most vaccines in use today are administered by injection. But since most infectious agents enter the body at mucosal
surfaces, vaccinating through the nose,
mouth, or some other mucosal route
could provide more protection. Sincetransmission often occurs at these sites,
boosting the body’s ability to block thattransmission could stop an infection or
autoimmune reaction at its source.
“While existing injectable vaccines areable to prevent serious conditions fromdeveloping, they are not effective enoughto defend against infection,” notes program director, Toshinori Nakayama.

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FROM BASIC RESEARCH TO
CLINICAL APPLICATIONSBefore new treatments can be developed,
however, much more needs to be learned
about the molecular architecture of themucosal immune system. That is why theInternational Center of Excellence is focusing on basic research while simultaneously advancing clinical applications. It isalso strengthening ties between researchers and industry in the hope of translating
its discoveries into therapies for patients.
To this end, Nakayama is building a robust
pipeline of talented scientists who canmove research findings seamlessly fromthe lab bench to the hospital bedside.
“The research system we are creating isunprecedented,” says Nakayama, who isalso vice president of Chiba Universityand dean of the Graduate School of Medicine and the Faculty of Medicine.
Projects at the International Center of
Excellence fall into three categories:
Hiroshi Kiyono is studying the basic
mechanisms of mucosal immunology inresponse to microbial infections and assorted diseases; Nakayama and colleagues,
including Atsushi Onodera, Motoko
Kimura and Osamu Ohara, are focusing
on allergic reactions and novel treatmentsthat target the mucosa; and Hiroshi
Nakajima, Yoshitaka Okamoto and Naoki
Shimojo belong to the clinical researchteam that is developing new vaccines andadjuvants for pathogens endemic to Japanand around the world.
Chiba has initially committed US$2
million over five years to this alliance.
Together with a matching contribution
from UC San Diego, the project will facilitate joint research and exchanges between
investigators and students on both sidesof the Pacific.

MUCOUS MEMBRANE
IN THE AIRWAY

Mucous coat layered
with tiny hairlike cila.

Immune cells in the
mucous membraneprotect the bodyagainst invasion bypathogens such asbacteria and viruses,
but they are too vigilant
they can cause disease.

Vaccines that directly
target the mucosal surface
could provide more protection
than a typical injection.

Members
Toshinori NAKAYAMA
Professor, Graduate School of Medicine

Yoshitaka OKAMOTO

Naoki SHIMOJO

Hiroshi NAKAJIMA

Hiroshi KIYONO

Osamu OHARA

Motoko KIMURA

Atsushi ONODERA

Akira SUTO

Yosuke KURASHIMA

Ryo NASU© Science Photo Library / Alamy Stock Photo

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INTERNATIONAL CENTER FOR HADRON ASTROPHYSICSREVEALING
HIDDEN MESSAGESFROM THE COSMOS

Two towers receive informationfrom 5,160 light-detecting
sensors buried 2,500 metersbeneath the South Pole.

The IceCube Neutrino Observatory, at theSouth Pole's Amundsen-Scott station. The International
Center for Hadron Astrophysics is part of the
global collaboration constructing IceCube.

Research Keywords:
Neutrino Astronomy, Cosmic Rays, South Pole, Elementary Particle Experiment-From a remarkable observatory buried deepin the south polar ice, Chiba University astrophysicists
are helping to explore the origins of the Universe.

Humans have been observing the stars
for tens of thousands of years, first with
our eyes, then with optical telescopes,
and more recently using devices that can
detect light at the extremes of the electromagnetic spectrum far beyond the visible
range. Yet despite phenomenal progressin astronomy over the past half century,
much of the Universe remains completely hidden from view, obscured by othermatter, other radiation sources, and light’sinteraction with the interstellar medium.
Now, scientists are on the verge of being
able to peer into some of the most mysterious corners of the cosmos using not lightbut neutrinos — near-massless subatomic
particles that travel close to the speed oflight across the Universe without being
deflected by magnetic fields or absorbed
by matter.
The International Center for Hadron
Astrophysics (ICEHAP) led by Shigeru
Yoshida is part of the global collaboration
responsible for managing the IceCube
Neutrino Observatory deep in the ice at
the South Pole’s Amundsen–Scott station.
“One of the longest standing puzzles inastrophysics is the origin of high-energy
cosmic rays and neutrinos,” says Yoshida. “The new windows to our Universe
opened by neutrino observations, combined with powerful computer simulations

8of cosmic plasma, have great potential to
finally resolve this mystery.”THE ICECUBE COLLABORATION

Neutrinos are the most abundant particles
in the Universe after photons (light particles). They originate in some of the mostviolent and least understood cosmologicalphenomena like supernovas, galactic coresand black holes. After their birth, they
travel in straight lines from their sourcewith almost no deflection or absorption,
making them ideal messengers from theheart of these mysterious astronomical
objects. But these same properties also
make them exceedingly difficult to detect.
The IceCube collaboration, involving 300
physicists from 48 institutions in 12 countries, has gone to extreme lengths to detect
these ghost-like, high-energy particles.
The IceCube observatory is a cubic
kilometer of crystal-clear ice, deep below
South Pole Station — the only place on
Earth where such large volumes of clear,pure and stable ice can be found alongwith the infrastructure needed to supportscientific research. By suspending thousands of delicate photodetectors on strings
in a network of vertical holes drilled
through the ice, physicists can capture
the rare explosion of energy that occurs
when a neutrino collides with an oxygenor hydrogen nucleus. Of the trillion, trillion
neutrinos that pass through IceCube every
day, the facility records just a few hundred
collisions from high-energy neutrinos— a minute fraction of the neutrino flux
but more than enough to stimulate somevery exciting research. “We are proud of
having been key players in the discoveryof high-energy cosmic neutrinos, which
astrophysicists have been dreaming
about for more than 30 years,” says
Yoshida talking about his team members in ICEHAP.
Another important contribution of ICEHAP to understanding the high-energy
Universe is its supercomputer-based massive numerical simulation programfor deep investigation of the physical mechanisms behind high neutrino production.
“Through our simulations we are helping
to uncover the hidden messages carried bythese neutrinos and to reveal the physicalmechanism by which high-energy cosmic
rays are accelerated
at their source,” says Yoshida.
In 2018, the IceCube collaboration has
finally discovered that a special type ofgalaxy, TXS 0506+056, is a birthplaceof cosmic neutrinos. This achievement
was selected as one of the top breakthroughs by Science. It clearly shows thesteps being taken forward.

Neutrinos are subatomic
particles that typicallypass freely through matter.
Other particles cannot
penetrate the Earth, so
below the 'Dark Sector'
near the South Pole,
free from every otherinterference, it is quiet
enough for the neutrinos
to be detected.

Members
Shigeru YOSHIDA
Professor, Graduate School of Science

Aya ISHIHARA

Keiicih MASE

Ryo NAGAILu LU

Simon ARCHAMBAULT

Yuya MAKINO

Ryoji MATSUMOTO

Yosuke MATSUMOTO

Tomoyuki HANAWA

Tomoaki ISHIYAMA

Hideyuki HOTTA

9CHIRAL MATERIALS SCIENCE

USING LIGHT TO ESTABLISH
A NEW FIELD OF
CHIRAL MATERIALS
Research Keywords: Applied Optics, Optical Vortex, Chirality-Understanding theuniversal property of chirality
could lead to new materials
and technologies for photonics
and other applications.

Members
Takashige OMATSU
Professor, Graduate School of Engineering

Hisao ISHII

Masami SAKAMOTO

Takeshi MURATA

Peter KRÜGER

Kazuyuki SAKAMOTO

Hiroyuki YOSHIDA

Kenichi OTO

Toyokazu YAMADA

Nobuyuki AOKIKazuki NAKAMURA

Takayoshi ARAI

Atsushi NISHIDA

Akira YANAGISAWA

Midori ARAI

Shiki YAGAI

Kazuhiro YOSHIDA

Tetsuhiro NEMOTO

Motohiro AKAZOME

Akira MATSUURA

Yoshihiro NISHIDA

Kohji ITO

Hiroki TAKAHASHI

Daisuke UMENO

Naohiko ANZAI

Keisuke IIDA

Satoshi OGASAWARA

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Of the many mysteries still to be unraveled in the natural sciences, one of themost compelling is the origin and powerof chirality — the property of a moleculeor object that has two mirror-image forms— like our left and right hands.
Chirality is universal in biology, chemistry
and physics. It critically affects the biochemical processes underpinning life, is avital aspect of drug discovery, and crops up
in particle physics. Light can have chiralproperties that affect how it interacts withmatter. But how can the power of chirality
be harnessed and controlled? And what
new discoveries and technologies might
this give rise to? These are some of thequestions Takashige Omatsu and his teamare asking.
Light beams can be chiral when they are
imparted with so-called helical wavefronts, that is, polarity that rotates either
left or right. “We can use ‘optical vortices’to twist the physical properties of metals,
semiconductors and organic materials on
the nanoscale to create chiral nanostructures with unique features,” says Omatsu.
“Our goal is to establish chiral photonic
materials as an original research field andto pioneer new technologies such as chiralplasmonics and metasurfaces for nanoscalechiral chemical reactors, chiral-selective
imagers and chiral sensors,” he explains.
LIGHT CORKSCREWS

Omatsu’s team focuses on the interaction
between helical light and materials, andthe physical properties and potential usesof such modified materials. The electromagnetic field of helical light rotates as
the light moves through space. When thisfield interacts with conductive materials
like metals, nanoscale corkscrew-likevariations in physical properties can be

inscribed on the material’s surface. The
modified surface can then react differently
to left- and right-handed chiral molecules
or helical light, giving rise to a range ofinteresting possibilities for chemical sensing, synthesis and imaging.
“We can use helical light to create nanostructures such as twisted needles, twisted
reliefs and twisted fibers,” says Omatsu.
“We have also found that the same process
can polymerize fullerene — a well-known
functional organic molecule that is normally not conductive. This causes fullerene
to form a novel conductive metallic phase,
which could be used as the basis for fabricating electronic devices without metals
and semiconductors.”
Omatsu believes ‘nanovortices’ will one
day be used for nanoscale precisioncontrol of light polarization, electron
orbital motion and the aggregation ofchiral molecules. “Our research will leadto materials for next-generation photonics
and electronics, and new applications inchemical synthesis, pharmacy, biology andmedicine,” he says. “It might also allow us
one day to answer the scientific mystery:‘Why does handedness exist in nature?’”Omatsu has collaborated with many
Japanese and international researchers,
and is always looking for students andearly career researchers. “Our research
center brings together physicists, chemists,biologists and even medical doctors, andwe frequently have brainstorming meetings to think up ideas for new projects,”
he says. “Several international researchers
work here. There is a wonderful diversityof backgrounds and expertise.”© iStock.com/loops7

11Medical andPharmaceutical
Sciences
PHYTOCHEMICAL PLANT MOLECULAR SCIENCES

Unlocking the Potential of Phytochemicals

CANCER EPIGENOME CENTER

A Different Approach to Fighting Cancer
INTEGRATED RESEARCH CENTER ON
REGENERATIVE SYSTEMS AND DISEASESSteeped in Stem Cells

MEDICAL MYCOLOGY RESEARCH CENTER

Manipulating Microbes for Human Health

MEDICINE FOR IMMUNE RELATED RARE DISEASES

Innovative Approach Offers Hopefor Intractable Problems

CENTER OF EXCELLENCE FOR END OF LIFE CARE

Putting the Care Back into End-Of-Life Care

GLYCOMEDICINE RESEARCH CENTER

Sugar Science’s Immunotheraphy PlayLABORATORY OF DDS DESIGN AND
DRUG DISPOSITION

Big Hopes for Nanotechnology Based
Drug Delivery Systems© iStock.com/BlackJack3D

PHYTOCHEMICAL PLANT MOLECULAR SCIENCES

CANCER EPIGENOME CENTERUNLOCKING THE POTENTIAL
OF PHYTOCHEMICALSA DIFFERENT APPROACH
TO FIGHTING CANCER

Research Keywords: Plant Molecular Science, Phytochemical, Gene

Research Keywords: Cancer, Epigenome, Inhibitor

Members
Atsushi KANEDA
Professor, Graduate School of Medicine-Advanced genetic and genomic techniques
are transforming our understanding of how
phytochemicals can improve human health.

-A new center aims to combat cancer by rewriting
the epigenetic modifications harbored by tumor cells.

Yuzuru IKEHARA

Tetsuhiro NEMOTO

Kiyoe URA

Hisahiro MATSUBARA

Ichiro YOSHINO

Chiaki NAKASEKO

Yoshitaka OKAMOTO

Hideki HANAOKA

Yukihisa HOTTA© iStock.com/mashuk

ENLISTING PHYTOCHEMICALSTO FIGHT DISEASE

Members
Kazuki SAITO
Professor, Graduate School of Pharmaceutical Sciences

Mami YAMAZAKI

Naoko YOSHIMOTO

Amit RAI

Hiroki TAKAHASHI

Hideyuki SUZUKI

Daisuke UMENO

Takashi TSUCHIMATSU

Hajime SATO

Hiromitsu TAKAYAMA

Masami ISHIBASHI

Mariko KITAJIMA

Midori ARAI

Noriyuki KOGURE

Tomoko IGAWA

Mitsumasa HANAOKA

Eiji GOTO

Natsuko KAGAWA

Takashi SHIMADA

Hidenori SASSA

Since ancient times, people have used thenatural compounds in plants, known as
phytochemicals, for medicinal and nutritional use. Now, scientists at Chiba University
are using advanced genetic and genomic
techniques to verify how phytochemicals are
generated in plants, how they can be manipulated to optimize certain plant groups,
and how they may help tackle lifestyle- andaging-related diseases.
Plants naturally generate chemicals forvarious purposes, including for attracting
pollinators and defending themselves. These
specialized metabolites allow plants to colonize specific niches in the food chain, adapt
to new environments and evolve to survive
potential stressors. Crucially, phytochemicals also exhibit properties that can help
treat human diseases. Examples in modern
medicine include morphine, the antimalarial
drug artemisinin and chemotherapy agents
derived from taxanes.

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Kazuki Saito, who leads the Phytochemical
Plant Molecular Sciences program, says that
because phytochemicals display considerable
natural diversity, they have huge potential
to fight disease. “Although phytochemicals
have been used in pharmaceuticals andancient remedies for many years, it is only
now, with the advent of next-generation
DNA sequencing, that we can really begin
to understand how they work and unlock
their full potential,” says Saito.
The program consists of three collaborative research groups, each working on a
specific theme.
One group is focusing on the genomics of
medicinal plants and food crops with the
key aim of revealing the genomic principles
of phytochemical production. Employing
state-of-the-art technologies, the researchers
identify and clarify the roles of unknown
genes, as well as investigate plant metabolism.
In 2016, Saito’s team assembled a draft
genome for licorice (Glycyrrhiza uralensis),which is used worldwide as a natural sweetener and a medicinal component.
They identified several components known
to play a positive role in human healthwithin the plant, while pinpointing key
genes, the manipulation of which could leadto crop improvements.
The second team is identifying novel phytochemicals and active products in a wide
variety of plants, searching for drug components to tackle diseases such as cancer,
dementia and diabetes. As well as isolating
and analyzing promising molecules, thegroup conducts animal trials to assess thepharmaceutical potential of molecules. In
particular, they have extensively investigatedLycopodium alkaloids (LAs), molecules
found in the vascular plant Lycopodiaceae,
which may help to treat Alzheimer’s disease
and schizophrenia.
The third group is investigating how
plants respond to different environmental
stresses by growing plants in different artificial environments and monitoring their
responses to change.
“Our aim is to optimize plants so that they
produce high-quality phytochemicals that we
can harvest for use in medicines and functional foods,” explains Saito. “Our insights
will enable us to grow rare plants more
successfully and will also inform agricultural
practices for commercial crops in the future.”
While the group is focusing on phytochemicals, it also conducts wide-ranging interdisciplinary studies and hence welcomes
researchers and students with backgrounds
in chemistry, horticulture, genetics andpharmacy who are interested in this exciting
and rapidly developing area of research.

Cancer is thought of as a genetic disease,with mutations to a cell’s DNA causing
a normal cell to give birth to a malignant
tumor. Yet epigenetic alterations, whichleave the DNA sequence intact, can be justas important in a cell’s transformation tocancer. Even though epigenetic regulation
through mechanisms such as methyl tags
and histone modifications does not alter the
DNA sequence, it can chemically modify
the genome to signal which genes should beturned on and off. When tumor-suppressor
genes are silenced or oncogenes are activatedin this way, many different forms of cancer
can result.
Fortunately for medicine, epigenetic
alterations are not permanent. They can beundone to prevent or reverse cancer, leaving
a cell with its entire complement of normal
DNA intact.
This is exactly what researchers at theCancer Epigenome Center are striving to
do. Led by Atsushi Kaneda, the center isseeking to understand the various epigenetic
drivers that contribute to different typesof cancer and then develop new drugs that
overturn these effects.
“We will explain key epigenomic aberrations
and their molecular causes,” says Kaneda.
“And then, taking advantage of small molecules that bind to DNA in a sequence-specific manner, we will develop drugs thatcan rewrite the accumulated epigenomic
aberrations or prevent them accumulating intargeted genomic regions.”

UNRAVELING MOLECULARMECHANISMS
Kaneda points to ongoing investigations ofgastric cancer as an example of this strategy
in action. Patients with this cancer exhibit
different levels of DNA methylation in theirtumor cells, depending on the pathogen responsible for the disease. The cancer-causing
bacterium Helicobacter pylori is one sourceof irregular methylation, infection with Epstein Barr virus is another. Both seem to haveprofound epigenetic impacts on stomach
cells, leading to the silencing of many tumor
suppressors.
Kaneda and his colleagues are using clinicalsamples and cell experiments to unravel themolecular mechanisms that induce hyperactive methylation patterns following infection
with these pathogenic agents. They ultimately
hope to stop the process in its tracks. Similar
projects are ongoing to combat colorectal
cancers — which Chiba researchers haveshown can be categorized into three types,
depending on methylation levels — as well as
blood cancers and other types of tumor.
With an eye to developing novel therapeutics, chemists at the Cancer Epigenome
Center are working on new methods toefficiently synthesize molecules that can act
on epigenetic aberrations. One such groupof molecules is the pyrroleimidazole polyamides. These molecules can bind to DNA
at specific sites in the genome, and whencoupled to an epigenetic inhibitor they can
prevent methylation-based gene silencing.
Kaneda hopes to deploy the molecules toedit the epigenome at targeted regions toregulate tumor formation.

The Cancer Epigenome Center includes researchers from a wide range of backgrounds
and specialties. This multidisciplinary teamapproach, says Kaneda, is essential for turning the center’s discoveries into clinicallymeaningful treatments and diagnostic tools.
“We will help determine the mechanismsof cancers and develop new cancer drugs
through collaborating with experts in medicine, physics and pharmacy,” he says.

© iStock.com/vitanovski

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INTEGRATED RESEARCH CENTER ON
REGENERATIVE SYSTEMS AND DISEASESMEDICAL MYCOLOGY RESEARCH CENTER

MANIPULATING MICROBESFOR HUMAN HEALTHSTEEPED IN STEM CELLSMembers
Research Keywords: Hematopoietic Stem Cells, iPS Cells, Platelets

Research Keywords: Infection and Immunity, Microbiota, Superorganism

1)

Atsushi IWAMA

Professor, Graduate School of Medicine-New cell therapies, drugs and disease insights
should flow from a coordinated approach tostem cell research.

Stem cells have the remarkable capacity toboth self-renew and give rise to many typesof more specialized cells in the body, which
explains their great therapeutic potential inregenerative medicine. But that is not the
only reason stem cells have become such ahotbed of scientific inquiry — these cellulartransformers are also an invaluable researchtool for probing the disease mechanismsthat underpin cancer, aging and a host ofother health problems.
At the Integrated Research Center on
Regenerative Systems and Diseases, Chiba
University scientists are advancing boththese avenues of stem cell research. Some
researchers are focused on developing new
kinds of therapies based on stem cells, whileothers are gaining important insights intodisease biology. However, they all share thecommon goal of improving the lives ofpatients using stem cells as their tool.
The center, which opened in 2016,is divided into three main
research groups. The first isdedicated to using stem

Koji ETO

Goro MATSUMIYA

Koutaro YOKOTE

Takashi MIKI

Tomoaki TANAKA

Naoya TAKAYAMA

Tomomi FURIHATA

cells found in the blood and brain to better
understand disease and normal development; the second focuses on reprogramming
tissue biopsies taken from patients to makedisease-specific stem cells for drug screening; and the third is developing stem celltherapies for treating diabetes, heart disease
and other disorders.
Center director, Atsushi Iwama, says theirwork covers a wide spectrum, from basic
to clinical research. Yet despite different
researchers adopting different approaches,
they all work in a collaborative manner,
holding regular group meetings and retreats
where new data are discussed and newalliances forged.
COLLABORATIVE PARTNERSHIPSAROUND THE WORLDThe Integrated Research Center is also
looking further afield to create across-disciplinary research networkthat spans the globe. It has
already formed partnerships

with other leading stem cell research groups
in Japan, Singapore and the United States,
and it hopes to build more international
connections in the future.
One of those partnerships is with Kyoto
University’s Center for iPS Cell Researchand Application, where Koji Eto has worked
for years developing a protocol for making
platelets from reprogrammed stem cells.
Last year, Chiba University recruited Eto
to join its new center. And while Eto will
maintain a lab in Kyoto, where he plans to
run the first human trial of platelets derived
from stem cells, he hopes to expand thestudy to include patients needing transfusions at Chiba University Hospital.
Other notable members of the Integrated
Research Center on Regenerative Systems
and Diseases include Koutaro Yokote, aleading expert on a form of progeria known
as Werner syndrome, and Chiaki Nakaseko,
a world leader on a rare plasma cell disordercalled POEMS syndrome.
Yokote is making stem cells from patientswith Werner syndrome to better understand the disease and find new drugs, while
Nakaseko is focused on developing new kindsof transplantation therapies from stem cells
derived from bone marrow.
These and many other world-renowned investigators make the new Chiba center an ideal
place to work and train the next generationof scientists. “We hope to recruit many young
people interested in stem cell research andclinical translation,” Iwama says.

1)© Akiko Sato

16

Prof. Iwama has moved from
Chiba Universiy on October 1st, 2018.

Members
Mitsutoshi YONEYAMA
Professor, Medical Mycology Research Center-Detailed investigations of host–microbe interactions
could yield new therapies against infectious agentsand
autoimmune diseases.

The human body is made up of a staggering
30 trillion cells or so. But just as numerous, if
not more so, are the several hundred trillionsof microbial co-inhabitants that teem in andon us. These commensal bacteria and fungi
are essential to our well-being, and a distortion in the microbial balance can trigger awide range of disorders, from acne to obesity.
Only recently, however, have scientists
come to appreciate just how critical thiscollection of microbiota is for determining
human health and disease. They are also
becoming excited about the prospect of
how manipulating this microbial ecosystem
could form the basis for the next generationof life-saving therapeutics. Led by Mitsutoshi Yoneyama, researchers at the Medical
Mycology Research Center have launched acomprehensive research effort to dissect the
intricacies of host–microbe interactions inthe skin, lung, intestines and bone marrow.
“Dysregulation of host–microbe interactions
can give rise to a wide variety of humandisorders, including opportunistic infections,allergies and autoimmune disease,” explains

Yoneyama. “It is hence crucial to understandhow hosts and commensal microbes communicate as a superorganism.”
Creating a superorganism is an apt metaphor for what Yoneyama is trying to achieve
because, through the melding of minds fromacross Chiba and around the world, the center can make a far greater impact than any
individual scientist working independently.
At Chiba University, the investigators comefrom the Graduate School of Medicine and
the Graduate School of Pharmaceutical
Sciences, while external collaborators are
based in the United States, Germany andelsewhere in Japan. These scholars, together
with others from around the world, convene
each November at the Medical Mycology
Research Center for the annual Global
Network Forum on Infection and Immunity.

Shinobu SAIJO

Koichi HIROSE

Tomohiro TAMACHI

Akiko TAKAYA

Hiroki TAKAHASHI

Yoshiyuki GOTO

Yumi MATSUOKA

studying molecular interactions in different host–microbial systems. One, led by
Shinobu Saijo and Yuumi Nakamura-Matsuoka, is focused on fungal infections in theskin of mice and humans; another, led by
Koichi Hirose and Tomohiro Tamachi, isinvestigating the microbes — both good andbad — that reside in the respiratory tract. A
third group, which includes Yoshiyuki Goto,is concentrating on the gut microbiome
and how opportunistic intestinal infections
gain a foothold; while the fourth, led by
Akiko Takaya, is working on more basic
mechanisms of immunological memory in
response to microbial invaders.
“Results obtained from our projects will
help efforts to create innovative newtherapeutics against infectious diseases
and will eventually lead to improvements
in human health,” says Yoneyama, whose
own research focuses on the mechanisms ofinnate antiviral immunity.
To assist all these research projects,
investigators from each group have accessto the Japanese government’s networkof core facilities — a resource known as
the Joint Usage/Research Center, whichis staffed by specialized researchers andtechnicians who can run state-of-the-art
experiments, including with fungi andother microbes. A bioinformatics unit
at Chiba led by Hiroki Takahashi helps
with computational analyses.

EXPLORING HOST–MICROBE
INTERACTIONS
The team that Yoneyama has put together
is roughly divided into four groups, each17

MEDICINE FOR IMMUNE RELATED RARE DISEASESCENTER OF EXCELLENCE FOR END OF LIFE CAREINNOVATIVE APPROACH
OFFERS HOPE FORINTRACTABLE PROBLEMS

PUTTING THE CAREBACK INTO
END-OF-LIFE CARE

Research Keywords: Rare Disease, Intractable Cancer, iPS Cell

Research Keywords: Clinical Nursing Science, End of life care, Super-aged Death-ridden Era-The ReDenim network is developing therapies totreat rare and intractable diseases.

TWO-PRONGED APPROACH

Members
Shinichiro MOTOHASHI
Professor, Graduate School of Medicine

Hideki HANAOKA

Itsuko ISHII

Masayuki KURODA

Kiyoshi HIRAHARA

Daiju SAKURAI

Sonoko MISAWA

Kotaro SUZUKI

Scientists at Chiba University have along track record of excellence in clinicalresearch, particularly for investigations inpatients with immune-related diseases.
And Chiba University researchers havemade a number of important breakthroughs
in basic immunology and disease biology.
However, connecting these two areas, afield known as translational research, hasoften been less successful.
That is a problem that Shinichiro Motohashi wants to fix. Motohashi leads Chiba’s
Research and Development Network of
Innovative Medicine for Immune Related
Rare and Intractable Diseases — ReDenim.
The network is aiming to provide the clinical support and resources needed to takediscoveries from the lab to the clinic.
In particular, ReDenim has singled out two
disease areas for which there are currently
no good treatment options — deadly formsof cancer, such as head and neck tumors;and rare diseases that each afflict fewer than
50,000 people in Japan, but collectively
affect about 10 percent of the population.

18-A new research program recognizes that care for the dying
is an important issue for both public and professionals alikein a rapidly aging society like Japan .

Motohashi and Daiju Sakurai belong to thetumor immunity team, which intends tocapitalize on Chiba University’s expertisein developing cell-based immunotherapies.
Their approach uses tumor-destroying
natural killer T-cells to search for combination therapies that can further modulate
the tumor immune microenvironment in afavorable way. They also intend to identify
biomarkers that can predict how individual
patients will respond to these treatments.
Led by Sonoko Misawa, the rare-diseaseteam, including Masayuki Kuroda, Kotaro
Suzuki and Kiyoshi Hirahara, is using immunemodulating drugs and gene therapies
to address neurological syndromes, enzyme
deficiencies, inflammatory conditions andrecalcitrant fungal infections. Kuroda is also
working with the cancer team to develop atransgenic fat cell technology that has therapeutic applications for both tumors and therare metabolism disorders he is studying.
Importantly, both teams will share researchexperiences, technology platforms and manufacturing facilities. “Sharing the know-how
to treat each disease within the network will
accelerate drug development,” says Motohashi. And the two teams will also haveaccess to support units at the university’sCore Clinical Research Hospital, a designation granted to Chiba University underJapan’s Medical Care Act in recognitionof its ability to apply basic science toward
therapeutic applications.
This support includes consultation services
on issues such as intellectual property,
project management, clinical trial designand other steps needed to fulfill the promiseof translational medicine. “Our ultimate goal
is to form a therapeutic cluster that can beapplied to a wide variety of rare and intractable diseases,” Motohashi says. He can evenforesee a day when the infrastructure createdthrough ReDenim could be used to develop
new therapies for common diseases, such as
diabetes or lung cancer.
Judging by the progress they have made sofar, Motohashi and his coworkers are well on
their way to fulfilling their dream, and theirpotential is widely recognized. ReDenim has
already forged collaborations with some of
the world’s leading experts in cancer immunotherapy and rare diseases, and is working
with Japanese drug companies to partner on
additional research projects.

Japan is teetering on the precipice of ademographic crisis. Already, people over
the age of 65 make up more than one quarter of the country’s population. And thefraction of elderly people is only expected
to rise in the years ahead — it is predictedthat in 2060 two out of every five people
in Japan will be senior citizens, putting
huge logistical and financial strains on the
country’s long-term care systems.
The Center of Excellence for End of Life
Care is trying to ease the impact of thisskewed demographic by fostering cooperation between the public and the professionals who assist the elderly. The goal,says Center Director Mariko Masujima, isto develop a coordinated research strategy
that ensures all older Japanese people canlive out their final years in a comfortableand dignified manner with their wishes andaims fulfilled.
“We have to encourage people in oursociety to talk more openly about their own
end-of-life care,” she says. Only then willthose facing imminent or distant death
have the best quality of life in the time they
have left — regardless of diagnosis, healthcondition or age.
The new center is housed within the Chiba
Graduate School of Nursing, the oldest
school of its kind in the country. It includes
members from a wide range of interdisciplinary backgrounds, such as ethicists,
engineers, health economists and doctors.
These scientists are working together infour large research groups.

Members
Mariko MASUJIMA
Associate Professor, Graduate School of Nursing

Ikuko SAKAI

Miyuki ISHIBASHI

Sumie IKEZAKI

Mina ISHIMARU

Naho SATO

Mayuko TSUJIMURA

Miwa WATANABE

Zaiya TAKAHASHI

Narumi IDE

Takahiro ISHIKAWA

Mia KOBAYASHI

Shingo KUROIWA

Takeshi UMEZAWA

Noriko AKITA

Noboru SEKIYATakayuki KAWASE

Shiro ISONO

Natsuko TAGUCHI

Ayumi AMEMIYA

Yuko SEKINE

PREPARING FOR LATER LIFE
The first group is focusing on helping theelderly prepare for what lies ahead. In one
project, they have developed a web-based
education tool, which uses a range of animated scenarios to make users think aboutcommon end-of life problems, such as ahealth emergency or the loss of cognitive
functions. A prototype of the tool received
favorable reviews in a small feasibility
study and the team is now adding newfeatures and functionality to make it moreuser-friendly.
A second group at the new Center of
Excellence is developing a technologicalsurveillance system that deploys remotesensors to detect physical activity amongolder residents in long-term care facilities.
“By tracking changes of vital signs andphysical activity in the elderly, the sensors
serve as a tool both for research and for
end-of-life care,” explains Masujima.
“They can help nurses and care workers
pick up on discomfort that frail, older residents might not be able to express themselves.” The system will soon be deployedfor pilot testing.
The third research group is focusing on
global outreach and has already established links with researchers in Thailand,
Taiwan, South Korea, Northern Irelandand elsewhere in Japan, while the fourthgroup is developing educational materials — for both the public and for other
healthcare professionals.

“Students need a chance to think more
about end-of-life issues,” Masujima says.
“Unfortunately, our healthcare education
focuses almost entirely on treating the living,
but we also need to care for the dying.” The
new center hopes to make that a priority inthe face of such a rapidly aging society.

19

GLYCOMEDICINE RESEARCH CENTERLABORATORY OF DDS DESIGN AND DRUG DISPOSITION

SUGAR SCIENCE'S
IMMUNOTHERAPHY PLAY
-By bridging the gap between glycoscience and medicine,major advances in immunology and drug development
are imminent.
glycans produced by two enzymes —N-acetylglucosamine-6-O-sulfotransferase
1 (GlcNAc6ST-1) and GlcNAc6ST-2 —are essential for the binding of lymphocytes,
and consequently play a vital role in controlling lymphocyte homing in mice.
After working on this study at California’s
Burnham Institute, Kawashima returned
to Japan in 2005, bringing with him the‘knockout’ mice (deficient in the two key
enzymes) he had developed. At Chiba hehas used these to continue hunting for new
antibodies that target glycans.
GLYCOMEDICINE TAKES OFF
Today, the expanding fields of glycoscience(the study of glycans) and glycomedicine(combining glycoscience and medicine) areleading to breakthroughs in drug development and diagnostics for autoimmune
diseases.
Chiba University’s Glycomedicine ResearchCenter, which opened in August 2017, marksa shift towards accelerating such breakthroughs in Japan.
“Many researchers here at Chiba University have been working independently on© Akiko Sato

20

Hiroto KAWASHIMA
Professor, Graduate School of Pharmaceutical Sciences

Research Keywords: Immunology, Biochemistry, Glycobiology

Lymphocytes are the body’s warrior cells.
They circulate through the bloodstream
and arrive at sites in the body such as thespleen and lymph nodes, where they combat
harmful bacteria, viruses and even cancer
cells. Sugars, or glycans, are integral to thismigratory process called lymphocyte
homing, which is of intense interest to
researchers. These scientists hope to target
glycans to find new immunotherapies anddrugs for autoimmune diseases.
“We now know that glycans — chains ofsugar molecules that have diverse functions in our bodies — play an essential
role in lymphocyte homing,” says Hiroto
Kawashima, a professor at Chiba University’s Graduate School of Pharmaceutical
Sciences, Laboratory of Microbiology and
Immunology.
“These glycans are found on the surfaceof endothelial cells in lymph nodes,” heexplains. “Thanks to glycans, lymphocytes
recognize and bind to the surface of thosecells.” Lymph nodes activate lymphocytes
to fight disease.
In a study published in Nature Immunology
in 2005, Kawashima and his colleagues inJapan and the United States showed that

Members

Motoyuki ITOH

Yuzuru IKEHARA

Hirofumi DOHI

Tomomi FURIHATA

glycans,” Kawashima says. “Some specialize
in biological functions, while others focus onsynthesis or analyze glycan structures. The
idea is to bring all of these researchers together, build new collaborations and understandthe function of glycans across many
biological phenomena.”
The new centre has plans to collaborate
with teams both nationally, for example, at
the Glycomedicine Technology ResearchCenter and the National Institute of Advanced Industrial Science and Technology(AIST), and internationally.
Already, Kawashima has developed antibodies that will specifically bind to the building
blocks of glycans and disable them in studies
published in The Journal of Biological
Chemistry in 2010 and 2015. This could halt
the dysfunctions involved in autoimmune
disease, in which the immune system isoverreacting.
“Usually, it’s very difficult to generate monoclonal antibodies against carbohydrates,”says Kawashima. This difficulty in producing
clones of these antibodies is because carbohydrate antigens are not generally very antigenic. “To get around this problem, we immunized knockout mice with cells expressing themissing sugar chains, which are highly prone
to stimulating the production of antibodies.”
The next step will be to further investigate andidentify new ideas for drug development andto collaborate with pharmaceutical companies
to bring them to market.
“Right now, there are lots of antibody drugs,”
says Kawashima. These immunotherapies
target issues such as rheumatoid arthritis andcancer, but, he says, new advances are limited
by a shortage of molecules to target. “Glycans
have unexplored potential, so this is an exciting time to be looking into developing new
candidate drugs based on glycoscience.”

BIG HOPES FOR
NANOTECHNOLOGY BASEDDRUG DELIVERY SYSYEMSMembers
Hidetaka AKITA
Professor, Graduate School of Pharmaceutical Sciences

Akihiro HISAKA

Naohiko ANZAI

Kousei ITO

Takeshi MURATA

Kunikazu MORIBE

Research Keywords: Drug Delivery, Nanobio, Vaccine-Drug delivery systems that nanocarriers could enhance theeffectiveness of therapies ranging from genetics-based cancer
treatments Alzheimer's medicines.

© iStock.com/Dr_Microbe

Drug delivery systems that nanocarriers could
enhance the effectiveness of therapies ranging
from genetics-based cancer treatments to
Alzheimer’s medicines.
Personalised medicine — tailoring medical
treatments to individual needs — may nolonger be far-off.
Developments in nanocarriers have progressed
rapidly, promising targeted delivery andrelease of nucleic acid-based drugs (NABDs),an emerging class of therapeutics designed totarget diseases at the genetic level.
A BREAKTHROUGH MOLECULE
In 2013, Akita’s group reported on SS-cleavable Proton-Activated Lipid-like Material(ssPalm), a molecule designed and tested
over five years that showed promise fordrug delivery.
The molecule itself consists of two main
components: One, tertiary amines, are activated in response to an acidic environment,such as the endosome compartment inside
the cells of plants and animals. These activat-

ed amines enable membrane destabilisation.
The other, a disulfide bond (SS) that can becleaved in a reducing environment such as in
the cytoplasmic material inside cells, triggers
the release of NABDs in specific cells.
In proof-of-concept studies in mice in 2016,
the researchers showed that lipid-based
nanoparticles, formed using ssPalm, enabled
efficient delivery to the liver of a genetic
treatment that uses small interfering RNA.
They have since gone on to develop second-generation ssPalm, which uses Vitamin
E as a waterproofing scaffold (ssPalmE).
One of the biggest challenges for cancer
therapeutics researchers, Akita explains,
will be “to develop DNA- and RNA-based
vaccines that could target unique genetic
changes in individual cancers.”
The hope is that the versatility of ssPalm
could help maximise drug efficacy while
reducing side effects. For example, in mousestudies performed in 2018, Akita’s groupdemonstrated that a plasmid DNAencapsulating lipid nanoparticle (ssPalmE-LNP) induced anti-tumour effects. They

also showed that ssPalmE-LNP enhanced
the therapeutic effect of an antibody used
to combat immune system supressing
programmed cell death protein 1 (PD-1),
raising hopes for combination therapies tocombat cancer.
Brain disorder treatments also stand tobenefit from nanocarriers. Recent studies
suggest that using ssPalm as an alternative
to viruses that deliver genetic material
could improve treatments.
In experiments with Hokkaido University
in 2018, Akita’s team used ssPalm in thedelivery of messenger RNA (mRNA) toneurons and astrocytes — star-shaped cells
found in the brain and spinal cord increasingly implicated in neurodevelopment anddisease.
By surpassing the limitations of other forms
of delivery (such as DNA-based artificial
gene carriers), mRNA therapeutics could
be used to treat many conditions, including Alzheimer’s, Parkinson’s, Huntington’sdisease and other neurological disorders.
“Our strengths at the Faculty of Pharmaceutical Science include our expertise incharacterizing physicochemical properties,
and evaluation of pharmacokinetics andpharmacodynamics, as well as safety,” Akita
explains. These skills could potentiallycontribute to a wide range of fields he says,
including immunology and cancer research.
“We need to keep our eyes open to societal
needs,” Akita adds. “Until now, we havebeen concentrating on materials science.
We have only just begun to enter the arenaof nucleic acid-based therapeutics. I believe
innovations arise when you can look beyond
your own particular filed, and apply originaltechnologies in unexpected ways.”21

Humanities andSocial Sciences
CHIBA STUDIES ON GLOBAL FAIR SOCIETY

Forging a Fairer WorldSMALL AREA ESTIMATION AND
ITS APPLICATION

Improving Datasets Using
Small Area Estimation
MULTI-PERSPECTIVE UNDERSTANDING
COGNITIVE BEHAVIOUR GROUP

Predicting Human Behaviour
TRANSLATIONAL RESEARCH PROGRAM
OF PSYCHIATRY AND PSYCHOLOGY

Cognitive Behavioural Theraphy
Comes of Age in Japan22© piick/Shutterstock.com

23

CHIBA STUDIES ON GLOBAL FAIR SOCIETY

SMALL AREA ESTIMATION AND ITS APPLICATIONFORGING A
FAIRER WORLD

IMPROVING DATASETSUSING SMALL AREA
ESTIMATION

Research Keywords: Global Welfare Society, Multidisciplinary Social Science, Fairness

Research Keywords: Economic Statistics, Baysian Statistics, Small Area Estimation-A multidisciplinary team of researchers looks at
how to create a fair society — on a global scale.

With globalization comes the need toensure that people from all cultures,countries and backgrounds are treatedfairly and equally. The drive to create a justglobal society requires solid foundations in
all countries, backed by informed government policies and strong support networks
at local, regional and national levels.
Much previous research into justice andsocial change has been dominated bystudies of Western societies, but the rapidchanges experienced by Asian countries inrecent decades have spawned a growing
field of research focused on building fairsocieties in Asia.
Researchers in law, politics, economics andsocial sciences have recently established
the Chiba Studies on Global Fair Society
project, with the aim of creating an interdisciplinary research base to inform future
local, national and international policies.
Lead researcher on the project, Jiro
Mizushima, says the key concept is fairness.
“We define fairness as the basic element ofjustice,” he explains. “In fact, we argue thatit exceeds justice in most cases. At the sametime, we embrace values such as equality
and liberty.”
Mizushima, whose research interests lie
in welfare state reform in Europe, says the
project aims to go beyond the traditional
discussion of equality — it seeks to construct new principles that value diversity
among people in a global society.

24-Statistical techniques can improve the accuracy andscope of limited information, saving time and money.

HOW DO WE ACHIEVEA FAIR SOCIETY?
The project consists of four interrelated
research groups and a further six teams
working to publicize the findings to a wide
audience. Their focus is on challenging andovercoming unfair practices on all scales, investigating issues such as gender inequality,
widening income gaps, migration, and thecollapse of regional and marginal communities, both in Japan and around the world.
The key aims of the project are to investigate
the development, transformation and limitations of existing welfare state models andto provide empirical evidence for how a fairsociety can be achieved in the 21st century.
Mizushima has spent considerable time
researching aspects of the welfare state in the
Netherlands, including how it has responded
to social challenges such as global economic
fluctuations and an aging population.
“Fairness has been the core of legal and political philosophy since ancient times, and soanother of our teams is examining equality
and fairness from a historical perspective,
comparing political, economic and legal
standpoints over time,” he says. “Anothergroup will analyze the meaning of fairness
in the 21st century, providing us with fundamental guidelines to underpin our program.”
The team plans to form networks of academics across the globe. To this end, they havehosted five highly successful international
symposiums. “Many of our members are
involved in local and national policymaking
committees, and they are key to informing
policy makers of our work,” says Mizushima.

The project welcomes those interested
in all aspects of social science, from law
and politics to sociology and economics.
Students and researchers alike will receive
training from scholars in their own field andother program members, allowing them tobroaden their research interests.

Collecting comprehensive data on populations is not always possible, or even the bestuse of resources. Surveys can be expensive
and time-consuming, so improving theaccuracy of data with “small area problems”
can stretch data resources further.
“Small area problems happen when an
estimator, such as sample mean for a smallarea, becomes very unstable because of small
sample sizes,” explains Associate Professor
Genya Kobayashi, who is part of a new Chiba project called Small Area Estimation and
Its Application to the Analyses of Poverty,
Public Health and Disaster.
His group is focused on overcoming such
issues by developing small area estimation(SAE) techniques that borrow statisticalstrength from supplementary data.
OVERCOMING INEQUITY AND
PUBLIC HEALTH INSIGHTS

Members
Jiro MIZUSHIMA
Professor, Graduate School of Humanities and Studies
on Public Affiars

Masaya KOBAYASHI

Akiko OISHI

Hikari ISHIDO

Masahiro OGIYAMA

Hiroyuki MINAGAWA

Tetsuo OGAWA

Seiichi IGARASHI

Iwao FUJISAWA

Kentaro SATO

Michihiro YAMAGUCHI

Takayuki KAWASE

Chiyo YONEMURA

Reiko OGAWA

While the applications of SAE are broad,“small area problems arise particularly within
official statistics on which governments makeimportant political decisions. Hence, small
area estimation techniques could lead to more
effective policy making,” notes Kobayashi.
An example crops up in the monthly Family
Income and Expenditure Survey (FIES)
conducted by Japan’s Statistics Bureau.
Although FIES provides the latest information on household income and expenditure,
at a small area level, such as a city level, thesample size of FIES becomes so small that
direct estimators are unstable and can’t grasp
detailed trends.
But FIES, says Kobayashi, can borrow
statistical strength from data in the National

Survey of Family Income and Expenditure(NSFIE). The sample sizes in the NSFIE
are much larger than in the FIES and thus
more reliable, but because the survey is time
consuming and costly, it’s only carried out
every five years.
The FIES and the NSFIE collect area-level
aggregated data, so Kobayashi’s group used
the Fay-Herriot, a mixed regression model
routinely used in SAE.
However, when data is in other formats
more appropriate SAE models must be developed. Recently, for example, Kobayashi’sgroup has been working to improve an
income map of Japan based on the Statistic
Bureau’s Housing and Land Survey (HLS).
Using a new statistical model that accounts
for the grouped data format of the HLS andadditional data from the Population Census,
they measurably reduced the uncertainty of
the HLS’s income estimates.
SAE’s scope isn’t limited to stabilizing data,
adds Kobayashi. SAE techniques can add
information. For example, the HLS model could also infer income in areas wheredata is missing. Using a mixture modelingapproach, the team recently estimated the
distribution of land prices around train
stations in and around Tokyo by making
inferences across areas.
Contributing to public health discussions, in2018 Kobayashi collaborated on a paper thatused a spatial Poisson regression model tolook the links between access to clean waterand dropping mortality rates in the early
1900s. Kobayashi and collaborators at theTokyo Institute of Technology and Duke
University in the United States looked
at death rates in Tokyo in 1930 against a

Members
Genya KOBAYASHI
Associate Professor, Graduate School of Social Science

Yuki KAWAKUBO

Eisaku SATO

Kota OGASAWARA

Shimpei SANO

Hiromi SAITO

dataset of taps. The group found that accessto clean water accounted for 41.3 percent of
the improvement in Tokyo’s crude death rate
between 1921 and 1937. This paper adds
to discussions on the relative importanceof nutrition and clean water on mortality.
Kobayashi hopes that everyone from policy
makers to businesses will soon come to
the group to add a finer resolution to theirdatasets.

25

MULTI-PERSPECTIVE UNDERSTANDING COGNITIVE BEHAVIOUR GROUP

PREDICTINGHUMAN BEHAVIOUR
Research Keywords: Experimental Psychology, Cognitive Science, Data Mining-Understanding the mind’s influence on what weperceive may help researchers model human behaviour
to create better smart devices.

© iStock.com/spfdigital

As computers become more powerful,
nuanced modelling of human decisions is
becoming possible. At the same time, newtechnologies are also bringing fresh tools
and disciplines to researchers at Chiba
University studying the hidden relationships
between behaviour and phenomena, ranging
from the physiological to the physical.
“With the help of environmental engineers
and using deep learning and virtual reality
techniques we can expect big developmentsin the cognitive sciences,” says Professor
Makoto Ichikawa, part a diverse groupknown as the Multiperspective Understanding of Cognitive Behaviour (MUCB)Group.
Ichikawa and his colleagues have been examining the reactions of individuals during
a digitally created fire event in a virtual
reality environment. While psychologists
often use methods such as questionnaires
to understand reactions and decisions,
Ichikawa’s colleagues are also able to use
virtual reality scenarios to study biologicalparameters – such as blood pressure, heart
rate and pupil dilation – in real-time. At thesame time, they can also record reactions

26

related to changes in room temperature andhumidity. Virtual reality, says Ichikawa, canreveal the effects of situational elements
such as illumination, luminance, noise andspace on physiological reactions, ranging
from metabolism to circadian rhythm.
These developments, he says, are not only
exciting to psychologists, but will also provide the basis for creating more believable
digital worlds.
Ichikawa’s work is being complemented bymathematicians, such as findings publishedin 2016 by Chiba University computer scientists. In their paper, they proposed a new
method for predicting pedestrian dynamics.
Using a technique from geostatistics called‘kriging’ the researchers were able to predict
trajectories up to 10 steps ahead more than
80 per cent of the time. This, they say, could
lead to exciting developments in navigation,group-behaviour analysis and abnormal-behaviour detection.
THE COMMON FATE INFLUENCE
To accurately model human behaviour, it’salso important to also understand the mind’s

TRANSLATIONAL RESEARCH PROGRAM OF PSYCHIATRY AND PSYCHOLOGYMembers
Makoto ICHIKAWA
Professor, Graduate School of Humanities and Studies
on Public Affiars

Tomokazu USHITANI

Eiji KIMURA

Rumi TOKUNAGA

Midori TANAKA

Yasuharu DEN

Toshihiko MATSUKA

Kazuhiko KAWAMOTO

Yoko MIZOKAMI

Noriko YATA

Akinori ABE

Sachiyo ARAI

Hiroo SEKIYA

Yoshitsugu MANABE

Takahiko HORIUCHI

Keita HIRAI

Nobuyoshi KOMURO

Shoko IMAIZUMISatoru SHIMIZU

effect on perception. For example, while
sitting in a stationary car, some may havefelt like they have moved backwards if aneighbouring vehicle creeps forward. Thissense of ‘induced motion’ is an optical illusion created in the mind.
In a recent paper published in the journal
Perception, Ichikawa and his colleagues
examined why one part of a visual illusion(concentric circles) appeared to be moving
with or against another part of the illusion.
They found that whether the parts of theimage appeared to moved together or in
opposition is linked to a person’s thoughtson the connection between the parts.
In some configurations, the two parts appeared to be moving in opposite directions.
As in the car example, if one object appears
to be accelerating away from another, thestationary or slower parts may seem to bemoving in the opposite direction.
However, a recognition of a common fate,
which is an appreciation for the linked
nature of the parts, may encourage participants to see the elements move together.
The researchers suggest this stems from a
principle from the German Gestalt schoolof psychology that seeks to explain how
our brains create order in the world.
The common fate principle suggests that
because logical patterns tend to take precedence over individual elements in how we
see the world, a flock of birds, for example,
may seem to be moving as one.
All of these findings, Ichikawa says, will
have important ramifications for how wedisplay motion, and group and individual
dynamics, on digital devices, in cinematography and in virtual reality.

COGNITIVE
BEHAVIOURAL THERAPHYCOMES OF AGE IN JAPAN-Better access to mental health care in schools, at workand online could help people of all age groups sufferingfrom anxiety, depression and other related conditions.
THOUGHTS
What we think affects
how we feel and act

What we feel affects
how we think and act

CBT
CHANGING PERCEPTIONSBEHAVIOURS
What we do affects
how we think and feel© www.betterhelp.com

Major efforts are underway to help treat andprevent anxiety-related disorders in Japan—where as many as one in four people
experience mental health problems during
their lifetime.
Social Anxiety Disorder (social phobia), oneof the most prevalent, is characterised byan intense fear of social situations. In somecases, social phobia can lead to addiction,
depression or suicidal behaviour.
Many doctors, legislators and patients now
recognise cognitive behavioural therapy(CBT) as an effective treatment for social
phobia. By changing negative patternsof thinking and behavior, CBT can help
children overcome anxiety and the fear of
uncertainty, adolescents better manage depression and irritability, and adults deal witha host of stressful life experiences.
A LEADING CENTRE FOR CBTRESEARCH AND EDUCATION
We are now actively trying to increase thenumber of CBT experts in Japan,” says Eiji

Eiji SHIMIZU
Director and Professor, Research Center forChild Mental Development

Research Keywords: Psychiatry, Psychology, Cognitive Behavioral Therapy

EMOTIONS

Members

Shimizu of Chiba University’s ResearchCenter for Child Mental Development
and Chiba University Hospital’s Cognitive
Behavioral Therapy Center. “However, CBT
resources in Japan are still relatively scarce.”
Chiba University and its affiliated hospitalare spearheading efforts to address this.
The Chiba Improving Access to Psychological Therapies (Chiba-IAPT) program,
adapted from a UK model, became the firstpost-qualification training course of its
kind in 2010.
“It’s important to tailor treatments toreflect not only cultural differences, but also
personal differences,” Shimizu adds. His
team are developing new tailored interventions, such as internet-based CBT (iCBT),
which are low-cost, easy to use, and provide
optional anonymity.
In 2017, his group released a study protocol
for iCBT on patients with persistent insomnia. They have also produced a simplified,
five-minute program that can be used tohelp reduce depressive symptoms.
As part of his wider research, Shimizu

Eiji KIMURA

Makoto ICHIKAWA

Chikae ISOBE

Miho IWATA

Fumiko SUNAGAMI

Keito NAKAMICHITomihisa NIITSU

Aika TOMOTO

Yoshiyuki HIRANO

Toshiyuki OTANIKenichiro SHIMAI

Kensuke YOSHIMURA

contributed to the first study that visualised changes in brain activity during
psychotherapy in 2015. Using functional
magnetic resonance imaging (fMRI), theresults indicated that the left posteriorparietal cortex plays a vital role in cognitive restructuring — a process used in
CBT that enables people to challenge
existing beliefs.
In 2016, Shimizu and his colleagues showedthat CBT can help reduce social anxiety for patients ineffectively treated with antidepressants.
In recognition of the growing need for
professional CBT care, at the end of 2018
the Japanese government began to certify
licensed psychologists. The national healthinsurance system has been updated to cover
doctor-administered CBT for patients withdepressive disorders, anxiety disorders andbulimia nervosa.
There are also moves to introduce CBTbased anxiety prevention programs inJapanese elementary schools.
A 2018 study, designed by Yuko Urao andsupervised by Shimizu, examined the effectiveness of an anxiety prevention program
named Journey of the Brave, targeted atchildren aged 10–12 years. Consisting often 45-minute sessions held during school
hours, the program involved deepening understandings of anxiety, monitoring feelings,
and developing assertiveness skills to reducesocial stress.
While further follow-up studies are planned,
preliminary results indicate that the program
can help children manage their anxiety levels.
“Our hope is that in ten years’ time, allchildren in Japan will have access to thisprogram,” Shimizu says.

27

Science andEngineering
NEXT-GENERATION THREE-DIMENSIONALDISPLAY AND MEASUREMENT

Future Images —More than Meets the Eye
MULTIMODAL MEDICAL ENGINEERING

Toward Image-Based Disease Diagnostics
HIGH-EFFICIENCY ENERGY CONVERSION

Toward a Zero-Emission Society
CENTER FOR INNOVATIVE MICROWAVEREMOTE SENSING

The Next Wave in Remote Sensing
IMAGING SCIENCE AND TECHNOLOGYFOR MATERIAL APPEARANCE

Realness in Digital Images
INSECTS-INSPIRED BIG INNOVATION

Looking to Nature to Revolutionize Flight
SOFT MOLECULAR ACTIVATIONFOR INTELLIGENT MATERIALS

Catalyzing the Future of Smart Materials© iStock.com/Nongkran_ch28

29

NEXT-GENERATION THREE-DIMENSIONAL DISPLAY AND MEASUREMENTMULTIMODAL MEDICAL ENGINEERING

FUTURE IMAGES
MORE THAN MEETS THE EYETOWARD IMAGE-BASEDDISEASE DIAGNOSTICS

Research Keywords: Computer Holography, Volumetric Display, High Performance Computing

Research Keywords: Medical Engineering, Physical Measurement, Multimodality-Advances in three-dimensional image display andmeasurement techniques have applications in multiple fields,from medicine to communication and entertainment.

Members
Tomoyoshi SHIMOBABA
Associate Professor, Graduate School of Engineering

Takashi KAKUETakashige SUGIE

Atsushi SHIRAKI

Takashi OKAMOTO

Tomoyoshi ITO

Technologies based on three-dimensional(3D) image displays and holography may
conjure up visions of science fiction, but the
Next-generation Three-dimensional Display
and Measurement program aims to makethese advanced tools part of everyday life.
Holograms create true three-dimensional
images, which allow the viewer to see an
object from all angles. They are created using
coherent light sources such as lasers, which
can store the complex light interference patterns required to accurately recreate an entire
3D object in full color. However, the maindrawback of holography is the immense computational burden of producing high-quality
holograms, not to mention creating moving
3D video images in real time.
Leader of the 3D program, Tomoyoshi Shimobaba says his team is developing ultrafast
algorithms and dedicated computers for holography to create the world’s first real-time
holographic 3D display system.
“These dedicated computers will have a computational speed three or four orders of magnitude higher than the household computersof today,” adds Tomoyoshi Ito, advisor on the
project. “Based on this dedicated technology,
we will investigate holographic projection,
digital holographic microscopy and ultrarapid

30

holographic imaging techniques.”
Among the team’s recent successes is a small,
inexpensive, zoomable holographic projection system, suitable for use in classrooms,
medical applications and entertainment
products. Shimobaba’s team refined mathematical image manipulation techniques toensure a high-resolution, non-grainy holographic image even when zooming in andout. The researchers are further developing
algorithms that can reduce ‘speckle noise’ inreconstructed images to avoid degradationin image quality.
ONE IMAGE, MULTIPLE VIEWS
Another aim is to reconstruct large 3D
images with a large viewing angle —something that is difficult to realize using
current technologies.
“We are also developing accurate holographic
measurement systems, which will be invaluable in medical science because they allow
researchers to image and measure samples in
3D alongside visualizing moving phenomena
in real time,” explains Shimobaba.
In another exciting field of research, theteam is exploring a form of 3D image
creation called volumetric displays — thedifference being that, while holograms canonly be seen clearly by a few people at atime, volumetric displays can be viewed bymultiple people from different viewpoints.
And, in an even more challenging concept,
they are trying to create multi-viewpoint
images with plural information appearing
in specific directions. In other words, one
person standing at one place will see one
piece of information, while another standing-Novel, high-precision imaging techniques are being
used to provide non-invasive disease diagnosis and guide
future treatments.

somewhere else will see completely different
information.
“Our volumetric display simultaneously
provides several observers with different
information,” explains Shimobaba. “Thisvery exciting feature is quite new, and weare considering new applications for using
it, such as developing multi-language
signage for the Tokyo Olympics in 2020,”
he says. Such 3D displays may benefit fromadvanced aerial projection techniques, also
under development by Shimobaba’s team.
“Networking is the key to our success,”says Shimobaba. “Many students who have
graduated from our laboratory move on to
conduct research in academia or in privatecompanies, and we continue to work withthem. In this way, we expand our project andbuild fruitful working relationships acrossacademia and industry.”

Non-invasive, precise diagnosis of diseases
using advanced medical imaging technologies could one day replace traditional
techniques based on biopsy and dissection.
With this prospect in mind, researchers at
the Multimodal Medical Engineering program are combining medical and engineering expertise to create novel, noninvasive
imaging-based methods for diagnosing andtreating disease.
The program uses various scanning techniques, or ‘modalities’, including computerized tomography, magnetic resonanceimaging (MRI) and ultrasound, to analyze
cellular and organ variations caused bydifferent diseases.
The program’s goal is to develop highly
precise, non-invasive imaging methods,
while boosting existing imaging techniques
to improve resolution and enable more-detailed tissue analysis, says program leader
Hideaki Haneishi.
“Many current disease diagnostics, particularly for cancer, involve highly invasive,
unpleasant procedures to clarify the type andstage of the disease,” explains Haneishi. “We
are investigating, for example, the development of a system to diagnose breast cancer
using very-high-frequency ultrasound.”Rather than physically sampling and dissecting lymph nodes from potentially cancerous
tissue, his team has shown that it is possible
to analyse cell characteristics of lymph nodes
using ultrasound. Their technique highlights
metastasis positive and negative cells in lymph
nodes, enabling rapid, painless diagnosis.
Haneishi and his team are also devising ways
to combine data from two or more modalities.
For example, in 2016 they developed an image

registration method that transforms two data
sets into one coordinated system using MRI
and pathological images of brain tumors.
“If we can establish the technology forregistering two kinds of images, then MRI
features that are strongly related to the pathological features of tumors can be highlighted.
This may eventually allow us to diagnose using only MRI,” says Haneishi. “Determining
the relationships between different data setshelps us build up detailed pictures of what isgoing on inside the body, not only for diagnosis but also to improve our understandingof disease development,” he adds.

Members
Hideaki HANEISHI
Professor, Center for Frontier Medical Engineer

Tadashi YAMAGUCHI

Hideki HAYASHI

Hitoshi MARUYAMA

Kenji YOSHIDA

Kazuyuki SAITO

Kazuya KAWAMURA

Takashi UNO

Toshiya NAKAGUCHI

Mikio SUGA

Takashi ONISHI

Yuzuru IKEHARA

Yasuo IWADATE

Koichi HAYANO

Hao LIU

Ken-ichi TSUBOTA

WenWei YU

Ryoichi NAKAMURA

Hiroki SUYARI

standing of different diseases,” says Haneishi.
The Multimodal Medical Engineering
program has access to highly specialized
equipment and technologies that can help
realize researchers’ ideas.
“We welcome engineers and medical
researchers who wish to work at the cutting-edge of research and development withdirect clinical applications,” says Haneishi.

NOVEL OPTICAL PROBES
Alongside conventional imaging techniques,
the researchers are also exploring novel optical probes. One example involves a method
for monitoring microcirculation — the flowof red blood cells — in the body. The probe
comprises multicolored light-emitting diodes (LEDs). As the LED light is scatteredthrough the tissue, it is partly absorbed bymolecules in the red blood cells, generating
a clear, detailed picture of the cells and theirmicrocirculatory network.
Building on previous work, the team hopes
to use this probe to estimate features such as
the oxygen saturation of each blood vesselin areas around suspected tumors in realtime. This could aid diagnosis and further our
understanding of vascular behavior in andaround tumors. “Ultimately, we would like tobuild on these imaging techniques and use
machine learning and artificial intelligence
technologies to relate measured signals anddiagnoses, to develop a comprehensive under31

HIGH-EFFICIENCY ENERGY CONVERSIONCENTER FOR INNOVATIVE MICROWAVE REMOTE SENSING

THE NEXT WAVEIN REMOTE SENSINGTOWARD A
ZERO-EMISSION SOCIETY
Research Keywords: Fuel Cell, Photocatalyst for Water Splitting, Organic Nanoarchitecture

Research Keywords: Microwave Remote Sensing, Synthetic Aperture Radar,

Members

Environment and Disaster Monitoring

Nagahiro HOSHI-The future of clean energy production lies in perfecting
the nanoscale details of fuel cell components to create aninnovative carbon-neutral energy system.

Professor, Graduate School of Engineering

Masashi NAKAMURA

Yasuo IZUMIShiki YAGAI

Takashi KOJIMA-Microsatellites and remote imaging technology are
revolutionizing the way we predict earthquakes andmonitor disaster zones.

Members
Jasaphat Tetuko SRI SUMANTYO
Professor, Center for Environmental Remote Sensing

Kazuteru NAMBA

Fumio YAMAZAKI

Wen LIU

Katsumi HATTORI

Hiroyuki NAKATA

Chiharu HONGO

Akira KATO

The race is on to find ways to replace ourreliance on fossil fuels with clean, sustainable methods of generating power. Current
solar and hydrogen technologies are not yet
efficient enough to produce energy on a large
scale. With this in mind, researchers from theHigh-Efficiency Energy Conversion program
aim to improve current solar and hydrogenfuel cells, while finding ways to reduce thepollutants already in the environment.
“We hope to develop efficient energy conversion systems that don’t emit carbon dioxide and pollutants,” says Nagahiro Hoshi,
lead researcher on the program. “We will
create a system that generates power fueledby sunlight and water. To do this, we must
perfect the structures of the nanomaterials
used to make solar and hydrogen fuel cells
to optimize their ability to harness energy.”
Hoshi’s team works with various nanostructures, including nanoparticles, single-crystal
surfaces and organic nanoassemblies, tobuild devices that can capture as muchenergy as possible without wastage.

ENHANCING ENERGY CONVERSION
The surface structures of catalysts used insolar cells and hydrogen fuel cells can have aremarkable impact on conversion efficiency.
For example, the orientation of atoms on asolar cell’s surface significantly affects the
distribution of light across the cell.
One way of enhancing a solar cell is tocoat its surface with a dye. The dye’s atomic
make-up contributes to the cell’s ability
to generate electric current when exposed
to light, providing it is adsorbed onto an
appropriate surface. The researchers recently
explored the effects of using a zinc porphyrin (ZnP) dye on single-crystal titanium dioxide (TiO2) substrate surfaces. They trialed
three different TiO2 substrates and foundthat their surface structures significantly altered the ability of the ZnP dye to generate
an electric current efficiently. In fact, one of
the ZnP TiO2 substrates had an incident
photon-to-current conversion efficiency 13
times higher than one of the others.

© Akiko Sato

32

Hoshi attributes the high conversion efficiency on this substrate to the bent configuration of the adsorbed porphyrin ring,which results in a shorter distance between
the ring and surface. Such attention to detailin terms of nanoscale surface structures will
generate the breakthroughs needed to create
highly efficient, scalable and cost-effective
solar power.
At present, hydrogen is mainly manufactured by using heat and pressure to separate
it from natural gases. But since this manufacturing process also creates large amountsof carbon dioxide, scientists are exploring
ways to generate hydrogen from water instead. When burned, hydrogen releases only
water and steam, and it has the potential tofuel all kinds of systems. Hoshi’s team hasdeveloped a hydrogen-based method that
could transform excess carbon dioxide into
usable fuel.
“We are researching photocatalysts capableof decomposing pollutants such as carbon
oxides, ammonia and waste oil,” says Hoshi.
“We have had recent success in investigating
the photocatalytic conversion of carbon dioxide into methane — the reaction pressure
needed to reduce the carbon dioxide wascreated using hydrogen gas.”
To help realize this vision of a zero-emission society, Hoshi and his team welcome
collaborations with researchers and privatecompanies interested in this burgeoning
field of nanotechnology.

© iStock.com/Sirintra_Pumsopa

The Microwave Remote Sensing Laboratory is far more than a laboratory. It is anexperimental aerospace workshop whereworld experts in remote sensing collaborate
with mechanical and aerospace engineers
to construct state-of-the-art microsatellites
and airborne sensors. The research teamspecializes in microwave-radar technology
for detecting ground movements and earthquake predictors as part of a new generationof remote sensing technologies.
“Microwave radiation is particularly useful for
remote sensing because it penetrates cloud,haze and fog, allowing us to observe the Earth’s
surface from space,” explains Josaphat Tetuko
Sri Sumantyo who leads this research project.
The core area in this research project is thedevelopment of synthetic aperture radars(SARs) for microwave remote sensing tomonitor land deformation. SAR emits a
microwave signal in the direction of thetarget and then detects microwaves scatteredfrom the target. By comparing SAR images
obtained before and after a change such as

an earthquake or a landslide, researchers candetermine how much the land has moved.
The research team has a well-developed
research-and-development program with
15 researchers, 25 students and facilities fordesigning, manufacturing, calibrating andoperating SAR for both aircraft and microsatellite applications.
ADVANCED AEROSPACE FACILITIES“Our facilities include an anechoic chamber
for calibrating sensors, a satellite–groundcommunication system, and microsatellite
calibration and measurement systems. We
also have a simulator for designing microwave circuits and antennas, along with asuite of manufacturing equipment,” says Sri
Sumantyo. “We even have our own 6-meter
experimental unmanned aerial vehicle, theJX-1, which we developed in this laboratory.”
They have already developed SAR sensors
for circularly polarized (CP) microwave
radiation in the L, C and X bands, whichhave been deployed on both large and small
aircraft, as well as on the JX-1. The CPSAR sensor is the first of its kind, utilizing
interference between left- and right-handed
circularly polarized light to obtain precise
information about the Earth’s surface in acompact, lightweight and inexpensive sensor.
We have developed several techniques basedon SAR imaging to monitor infrastructure
and areas affected by disasters such as forest
fires, landslides, subsidence and volcanic
eruptions,” says Sri Sumantyo.
Engineers in this team are developing
two novel microsatellites. One is equippedwith radio occultation and electron density
temperature probe sensors for measuring theatmospheric signatures thought to precede
earthquakes, while the other is a CP-SAR
satellite with lightweight gold-coated meshantenna. These satellites are poised to take thelab’s research beyond the stratosphere.
“Our microsatellite program is very exciting
for future SAR sensor applications and planetary exploration,” says Sri Sumantyo. “Weeventually aim to have five microsatellites inorbit, which will provide real-time monitoring
for global disaster mitigation and research.”
The team has strong collaborations withJapanese and overseas research institutions and industry — it has more than 50
agreements with research and industry
partners throughout the world. The groupalso encourages short- and long-stay programs under various government programs,
through which more than 500 students andresearchers from many different countries
have worked at the lab.

33

IMAGING SCIENCE AND TECHNOLOGY FOR MATERIAL APPEARANCEINSECTS-INSPIRED BIG INNOVATIONREALNESSIN DIGITAL IMAGESLOOKING TO NATURE TO
REVOLUTIONIZE FLIGHT

Members
Hao LIU
Professor, Graduate School of Engineering

Research Keywords: Texture Engineering, Environmental Texture, Real-Time Processing

Research Keywords: Bioinspired Engineering, Biological flight, Drone-Understanding how the human brain interprets images
could underpin the future of internet shopping, cosmetics,
digital fabrication and even non-invasive medicine.

When internet purchases arrive and seemnothing like their picture, it can be a disappointing experience for shoppers. So, while
big e-commerce players are increasingly
investing in technologies to help personalize
products or shop via phone or virtual reality
headset, a significant stumbling block is rendering realistic, digitally produced images.
“To achieve a realistic rendering of something, we also need to deeply consider
human perception,” explains Keita Hirai,
a member of the Imaging Science andTechnology for Material Appearance groupat Chiba University’s Graduate School ofEngineering. How we perceive a material,
he says, can also be linked to cognition, notjust physical phenomena.
To examine the complex effect of the mind’seye, Chiba University have drawn froma diverse range of researchers, including
engineers, psychologists, and medical andcognitive scientists.
Recently, Hirai’s team developed a new
system for texture evaluation, and throughparticipant feedback have devised a set ofalgorithms that can produce more realistic
digital representations of patinas and colours
overlaid onto textured fabrics in digital
images. The aim, he says, is to one day digitally simulate photo-real fabric appearance via
a smart device. Hirai points out that this will
not only be helpful to internet shoppers, butthat these algorithms could also find applications in rapidly advancing digital fabrication
techniques, such as printing digital patinas
onto fabrics or objects, and manufacturing
representative digitally-designed 3D products.
In fact, the group aims to contribute to industries as diverse as cosmetics and medicine.

34© iStock.com/wacomka

Filtered through the brain
Among the work done by the diverse groupis a study examining texture. Viewers,
suggest the researchers, often see the broad
design of patinas printed on fabric, but some
textures contribute to a blurring out of finer
details. In contrast, high-resolution digital
images with very accurate representations of
the same material seem unnaturally sharp.
To explore this, the researchers developed
different ‘blurriness’ filters linked to material
qualities and fine-tuned them by asking
participants in their experiment to rate thenaturalness of the images.
Another group found that our perception ofcolour is affected by our understanding of
its dimensionality. The same viewer looking
at the same image saw colours differently
depending on whether they interpreted theimage as two dimensional or three dimensional. Viewing images with one eye orboth, and whether the image or the viewer’s
head was moving, also affected how natural
the image seemed. This work, says Hirai, is
important for better smart device production. “A more informed colour management
system, for example, may help realize moreaccurate colour reproduction between different devices: displays, cameras and printers,”
he explains.
Hirai says the group’s work will influence
the most cutting-edge imaging technology,
such as the omni-directional 3D camera
systems and virtual reality headsets coming from technology giants such as Sony,
Panasonic, Canon and Nikon. While healso mentions cosmetics and automotive
painting, one team have already had some

remarkable success in one crucial, but quite
unique area — medical diagnostics.
These researchers have carefully studied
the optical properties of haemoglobin inskin using images taken on a simple DSLR
camera. Incredibly, they found they could
measure both the heart rate and its variability with 99 percent accuracy. This opens
the door to everything from non-invasive
medical diagnosis to a better understanding of physical exertion using a simple
smartphone app.

Akio NAMIKI

Kazuya OKAWA

Toshiyuki NAKATA

Michinari KOHRI-The beating wings of insects hold the secrets
to controlled low-speed flight and Micro Aerial Vehicles.

Toshihiko MATSUKA

Tomokazu USHITANI

Arii WATANABE

Yuma TAKAHASHI

Hiroyuki ISHIKAWA

Akira KATO

Inspired by the fascinating flying ability of
insects and humming birds, Chiba University’s Biomechanical Engineering Laboratory
has been conducting pioneering research on
beating-wing flight for more than 20 years.
Headed by Professor Hao Liu, the lab is on
the verge of revolutionizing the very conceptof flight itself.
“Insects have this amazing ability to hoverand execute highly controlled flight in bothstill air and turbulent wind gusts,” says Liu.
“Scientists once knew very little about how
insects generate aerodynamic force in turbulent environments, and even less about
how they are able to maintain such agile
control in flight.”

more reliable and agile than anything based
on today’s rotor-based technology. We hopethat this will also lead to a new mechanismof flight with potentially much broader applications. In the meantime, we continue tocollaborate on the development of advanced,
flapping MAVs, as well as help improve thereliability of rotor-based drones by introducing flexible wing technology.”

BIOLOGY INSPIRES MICROAIR VEHICLESMembers
Norimichi TSUMURA
Associate Professor, Graduate School of Engineering

Takahiko HORIUCHI

Keita HIRAI

Yoko MIZOKAMI

Shoko IMAIZUMIMichinari KOHRI

Noriko YATA

Toshihiko MATSUKA

Conventional flight is based on the uninterrupted flow of air over the curved upperand lower surfaces of a wing, which causes a‘suction’ effect that lifts the wing upward.
“Fixed wings need smooth airflow to generate lift,” explains Liu. “Turbulence over thewing can lead to disaster. Our first major
breakthrough in unravelling the mysteryof insect flight was that most flying insects
in fact generate most of their lift force by
creating a vortex on the leading edge of the
flapping wing. It’s a completely different
principle of flight to conventional flight.”
It all started in 1996 with Liu’s developmentof the first computational fluid dynamics
simulation for insect flight, which led tothe discovery of the universal leading-edge
vortex mechanism in insect and bird flight.
To delve deeper, the laboratory installed anultra-low-speed wind tunnel capable of airflow as slow as half a metre a second. Theyuse it to observe and analyse the flight oflive birds and insects such as moths, beetles
and dragonflies, as well as micro air vehicles(MAVs), very small drones with potential
uses in disaster relief and covert operations.
“Using high-speed imaging and particle
image velocimetry data, we were able tocreate a computer model of an insect andits flight mechanism, and from there we
made an experimental robot insect that
actually flew. That was another pioneering
breakthrough,” says Liu.
“Our research brings together biology, engineering, computational physics, biorobotics
and neuroscience, and we collaborate withthe likes of Cambridge and the University of London on some really interesting
international, cooperative projects. Chiba
is definitely a world leader in this area witha strong interdisciplinary team and worldclass facilities.”
The lab’s research now focuses on developing insect-inspired flight systems, which heexpects to lead to big developments in thedesign of insect- and bird-size MAVs.
“For example, we think it’s wing flexibility
that gives insects much of their resilience
to wind gusts, but we are also seeing that
insects use their body much more than wethought to control direction and movement,
both actively and passively. This is completely different to the conventional wingbased control used by planes today and has
the potential to revolutionize flight control
strategies in general,” says Liu.
“Ultimately we want to develop an insect-inspired autonomous drone that is far

35

SOFT MOLECULAR ACTIVATION FOR INTELLIGENT MATERIALSMembers

CATALYZING THE FUTURE OF
SMART MATERIALS
Research Keywords: Synthetic Chemistry, Catalytic Reaction, Iodine Bond

-Catalysts developed from soft iodine, graphene
and metal complexes could transform smart material
technologies.

Takayoshi ARAI
Professor, Graduate School of Science

INSTITUTE FOR
GLOBAL PROMINENT RESEARCH

Hirofumi KANOH

Shoji MATSUMOTO

Katsuhiko MORIYAMA

Yasushi YOSHIDA

Akira YANAGISAWA

Tetsuhiro NEMOTO

Shigeru ARAI

Kazuhiro YOSHIDA

Takashi MINO

Katsuyoshi HOSHINO

Nobuyuki ICHIKUNITomonori OHBA

Yasuhiro YAMADA

Shoichi KATSUTA

Hideaki SHIROTA

Takeshi MORITA

IGPR was founded as a core institution at Chiba University in 2016. Aiming at fos-Hyuma MASU

Fumio SAKANE

Yasushi ARANO

Takeshi MURATA

tering seeds and delivering the fruits to the world, IGPR has been actively support-

Masami ISHIBASHI

Midori ARAI

To accelerate innovative research beyond the borders of academic disciplines, theing research projects with potential impact as a global hub for top-class research.

Takuya HASHIMOTO

The institute is also focused on developing young human resources who will lead
The very idea of materials that change theirshape or function as required sparks theimagination. Smart materials are impressive artificial molecules, often inspired bynaturally occurring chemicals, which have thepotential to revolutionize design. They undergo changes that are reversible and repeatable,
meaning they can function as molecularswitches, valves and sensors. Other smart
materials include shape-memory alloys that
return to their original shape after bending,metal-bearing polymers that can switch frominsulator to conductor and drug-delivery
systems that slowly release pharmaceuticals
where and when they are needed.
Researchers at the Soft Molecular Activation for Intelligent Materials program areleading investigations into catalysts madefrom soft molecules that could one day
transform smart material design.
Lead researcher Takayoshi Arai says the
program is focused on developing powerful
catalysts to create novel smart materials using three catalyst types. “Firstly, soft halogen

catalysts, predominantly using iodine, canbe used to develop highly targeted medications,” he explains. “A second type is ‘soft
Π-electron’ using carbon nanotubes andgraphene, which would provide a uniquereaction sphere for catalysis. The third type,‘soft metal’ catalysts allow us to introduce
soft elements such as gold and copper into
target molecules.”NEW CATALYST DESIGN
Arai says one of the main goals of the program is to create new asymmetric catalysts,
which are used to generate large numbersof very specific molecules. Most biologicalmolecules are chiral, meaning they exist in
one of two mirror-image forms called enantiomers. Many drugs and smart materials use
just one specific enantiomer, and so catalysts
are needed to direct the chemical reactions
toward forming the correct enantiomer.
For example, iodine has been used to help
synthesize specific enantiomers of cyclic© Akiko Sato36

and ring-shaped molecules. “We are luckythat Chiba prefecture in Japan is one of theworld’s leading producers of iodine,” says
Arai. “In fact, the Chiba Iodine Resource
Innovation Center (CIRIC) has opened at
Chiba University in July, 2018. A key goal of
our program is to perfect iodine-based soft
molecular activation.”
Recent success for Arai’s team includes
the development of an aminoiminophenoxy-copper carboxylate catalyst that can
trigger high yields of O-cyclized molecules.
These can, in turn, be used to generate aparticular chiral compound that is invaluable
for use in antimicrobial and antiosteoporotic
compounds.
“A crucial part of our research is designing
catalysts that can be reused multiple times,
thereby creating cost-effective, sustainable
methods for generating useful compounds,”
says Arai. His team recently designed arecyclable catalyst made from a zinc-polymeric ligand complex. The polymeric ligand
allows the catalyst to be separated from thefinal product by a simple filtration process,meaning it can be reused — indeed, poly-Zn
remained a stable and active catalyst for
creating iodine-based ring-shaped molecules
more than five times.
“By introducing soft elements to target molecules, our research will facilitate the development of smart materials with smooth andrapid responses,” says Arai. “We welcome
anyone interested in research at the forefrontof iodine-related soft molecular activation
chemistry to come and work in this diverseand challenging field at Chiba.”

new research fields in the next generation. Currently, IGPR is supporting more than
20 research projects in diverse areas such as neutrino astronomy and the interdisciplinary science for the End-of-Life Care.

Mail : gp-office@chiba-u.jp
URL : igpr.chiba-u.jp/global© iStock.com/farakos

37

MESSAGE FROM
THE DIRECTOR OF IGPR...to enhanceprominentinternational research
projects of Chiba
University
andsupport young

researchers who leadthe fields in the next
generation.

ABOUT
THIS MAGAZINE
Copyright © 2019 Chiba University.

It is my great pleasure to have the third

In November, Professor Tomoyoshi Itoissue of CHIBA RESEARCH available

and his team succeeded in developing

here for you. All of the research proj-a special purpose computer for holog-

ects introduced in this issue have been

raphy. This was a result of over 25 years

carried out with the support from theof study in high-speed computer for 3D

was correct at the time of going

Institute for Global Prominent Research

holography and our press release gained(IGPR), a university-wide organization ofbroader attention from the media bothto press in March 2019. The views

Chiba University. The IGPR was estab-in Japan and overseas.

lished in 2016, with the goal to enhanceprominent international research proj-

In December, the international scienceects of Chiba University and support

magazine Science selected the researchyoung researchers who lead the fields

outcome of the International Center forin the next generation. This is an orig-

Hadron Astrophysics led by Professor

inal attempt in that research resources

Shigeru Yoshida as a Breakthrough ofare brought together from all sources

the Year 2018. The Japanese scientists

throughout the university, and a variety

whose studies were selected for thisof research fields are comprehensively

honor include Dr. Shinya Yamanaka

supported. This approach is possible(2007 for iPS cell research) and JAXA’s

because Chiba University is a multidisci-

Hayabusa team (2011). We can see how

plinary university and cannot be foundhonorable this selection is.

All rights reserved.
The information in this publication

expressed by contributors in thispublication are not necessarily
those of Chiba University.

in any of the colleges or universities inJapan.

In the last year, the research projects
were covered by a total of about 90 me-

The year 2018 was the third year for thedia in and outside of Japan. The number

support programs by the IGPR, and itof symposiums by the research projects

was also a time for us to recognize thatreached about 20. As a measure to de-each project “seed” had been germi-

velop the next generation of researcher,nated and grown enough to bear somethe IGPR also organized a symposium

fruits.

for young researchers from a wide rangeof fields. It served as an opportunity for

In June 2018, Professor Toshinori

about 80 researchers to brush up skills

Nakayama and his team elucidated thefor communicating their studies quickly

mechanism of “tissue fibrosis”, harden-

and effectively to the people having

ing of tissues around trachea that occurs

different majors.

1-33 Yayoi-cho, Inage-ku,

ing a new immune cell population. As

Through the IGPR to promote the world

inhaled steroid therapy is ineffective toprominent research projects, Chiba

263-8522 Japan

Takeshi Tokuhisa

fibrotic tissues, Professor Nakayama’s

University continues our efforts to further

Director, IGPR andachievement is expected to lead to acontribute to society. I strongly hope thatPresident of Chiba University

new treatment for intractable respiratory

this issue of CHIBA RESEARCH can help

diseases for which no radical treatment

you to have deeper appreciation of Chiba

has been developed so far.

University’s front edge research activities.

in severe cases of asthma, by identify-

38

Chiba-shi, Chiba,www.chiba-u.jp/eWHERE IS
CHIBA UNIVERSITY?

PUBLIC TRANSPORTTO CHIBAŌmiya
Fuchuhonmachi

CHIBA Prefecture is located at the east edge of the South Kanto

HOKKAIDO

region. It has a population of approximately 6 million, the 6th largest

Kashiwanoha Campus

among the 47 prefectures in Japan. Chiba is the center of Keiyo Indus-

Minami-Nagareyama

trial Area and has the well-developed industry. The three sides ofthe prefecture are surrounded by the sea, which helps Chiba's

Kita-Senju

MatsudoKASHIWA-NO-HACAMPUS

Tsukuba

Abiko

Suido

growth in the seafood industry as well.

MATSUDOCAMPUS

Nippori

Chiba University has 4 campuses in Chiba Prefecture.
Nishichiba Campus (Main Campus) is located between Narita Interna-

Uenotional Airport and Tokyo Station. It takes about 30 to 40 minutes by

Mitakatrain to Tokyo Station and also Narita International Airport.

Shinjuku

Ichikawa

Akihabara

Shin Kamagawa
Nishi-Funabashi

Tokyo

Narita Airport
Hamamatsu Cho
Minami-Funabashi

TOHOKU

Shinagawa

Funabashi
NaritaHaneda Airport

Tsudanuma

Keisei Tsudanuma
Inage

Kurihama

SakuraMidoridai
Nishi-chiba

Keisei Chiba

Chiba

KANTO
CHUBU

CHUGOKU

Chiba

1. KASHIWA-NO-HA CAMPUS
5-min walk from the Tsukuba Express Kashiwanoha-campus Station.

KANSAI

ChōshiNISHI-CHIBACAMPUSINOHANACAMPUS

Chiharadai

Take the Tobu buses bound for National Cancer Center or Kashiwanoha Park frombus stop No2 at JR Kashiwa Station or near the east exit of Tobu Kashiwa Station.

Kimitsu

Kazusa-Ichinomiya

2. MATSUDO CAMPUS

SHIKOKU

10-min walk from Matsudo Station(JR Joban line, Tokyo Metro Chiyoda Line, Shin-Keisei Line)KYUSHU
Narita Airport
Tokyo

Chiba
University

3. NISHI-CHIBA CAMPUS

Tsukuba Express Line2-min walk from JR Nishi-Chiba Station to the South Gate of Nishi-Chiba Campus

Sōbu Line [Local Train]

7-min walk from Keisei Midoridai Station to the Center Gate of Nishi-Chiba- Campus
10-min walk from Chiba Monorail Tendai Station to the North Gate

Yamanote Line
Sōbu Line [Rapid Service]
Keisei Line
Yamanote Line

4. INOHANA CAMPUS
After arriving Chiba Station (JR) a bus stop can be found in front of east exit 7 (this bus
can also be taken if you get off at Keisei Chiba Station). Take buses bound for Chiba

University Hospital or Minami-Yahagi and get off at the School of Medicine Entrance
bus stop, or, to get to the university hospital, get off the bus at the Chiba University
Hospital stop.

Joban Line [Rapid Service] Narita LineMusashino Line
Keiyo Line
Tokyo Monorail
Keikyu Airport Line
Uchibo/Sotobo Line
Tobu Urban Park Line