実学 | Sci e n ce | サイヤンス

Issue 1
September 2015

JITSUGAKU
Showcasing the best research from Keio University

Inaugural Issue
Research highlights
Discover the groundbreaking research
produced at Keio

Features
Immerse yourself in the stories behind
Keio’s creativity and excellence

Inside Keio
Explore Keio’s long history ofsocial innovation

ON THE COVER

The Boshin War from 1868
to 1869 between Imperial
forces and Tokugawa
loyalists threw Edo, present-day
Tokyo, into a state of chaos. On
May 15, 1868, despite the battle
raging just five miles from his
school, Yukichi Fukuzawa remained calm and delivered a lecture from a text by the American

p olit i c a l e c onomist Franc is
Wayland. In doing so, Fukuzawa
demonstrated to his students thatwhen it came to pursuing education and research, there was not a
moment to be lost. The scene was
depicted in 1910 by traditional
Japanese painter Yasuda Yukihiko.
Every year, Keio University commemorates the day with a special
lecture at Mita Enzetsu-kan (Mita
Public Speaking Hall). 

Mita Enzetsu-kan (Mita
Public Speaking Hall), one ofnine National Treasures andImportant Cultural Properties
at Keio University.
(cover): “FUKUZAWA lecturing on
Wayland’s Elements of Political Economy”
by YASUDA Yukihiko1910 (Meiji 43)
Hanging-scroll, colors on silkL. 114.8 cm, W. 42.8 cm
Fukuzawa Memorial Center for Modern
Japanese Studios, Keio University.

Contents3

実学 | S c ie n c e | サイヤンス

JITSUGAKU
Editorial

Traditional yet innovative

Inside Keio

Igniting Japanese social innovation

6

Page 4

Research highlights
6

Enhanced X-ray imaging
Improved coherent X-ray diffraction imaging for intracellular analysis

7

Multi-tasking protein wires brain
One protein performs two roles to ensure correct brain network wiring

8

A quick spin unleashes waves of the future
Peering inside objects in just milliseconds using terahertz light9

Lab-grown uterus could reverse infertility
Tissue-engineered uteri produce successful pregnancies in rats
Page 6

Feature article

Lawyers in space

12

4Page 10

Research highlights
12

Door opened to novel nanomaterials
A simple route to immobilizing nanoclusters

13

Giving heart patients a breath of life
Hydrogen gas can minimize damage caused by cardiac arrest

14

Purer silicon promises perfection
A better basic unit for quantum computers using purer silicon

15

Bringing hard labor to accountRationalizing Japan’s infamous grueling work culture
Page 13

research-highlights.keio.ac.jp

10Contents

Page 16

18
Page 18

Faster, higher and more technologicalResearch highlights
18

A new degree of control for spintronics
Uncovering novel physics controlling spin-based electronics

19

A therapeutic lead for heart muscle disorder
Druggable hormone drives problems associated with hypertrophic cardiomyopathy

20

The not-so-symmetric Universe
Broken symmetries may provide a pathway to a unified theory of the Universe

21

Winning the super-enzyme lottery
A microfluidic instrument that can rapidly screen millions of enzymes

22

Preventing abnormal eye vessel growth
Uncovering a molecular process crucial to retina development

Feature article

24

Page 23

Reframing the language of dementia

23

Research highlights
24

Measuring the galactic center
Surveys of a huge gas disk orbiting the center of our Galaxy

25

An emerging new focus for heart disease
A critical regulatory protein offers potential for treating cardiac hypertrophy

26

Organic synthesis with light-coupled carbohydrates
A greener way to make carbohydrate-containing molecules

27

Combined therapy for breast cancer
A multi-pronged approach for an aggressive form of breast cancer

28

Quantum dots with temperature-dependent color
Nanometer-sized quantum dots whose color varies with temperature

実学 | S c i e n c e | サイヤンス

JITSUGAKUPage 25

Produced by:

Jitsugaku is a print publication of the online

Headquarters for Research Coordination

platform Keio Research Highlights, which offers

and Administration, Keio University

a taste of the important research and scientific2-15-45 Mita, Minato-ku,

developments from Keio University.

Tokyo 108-8345, Japan

www.keio.ac.jp@ 2015 Keio University. All Rights Reserved.

research-highlights.keio.ac.jp/

This publication may be reproduced in its original

Further information

form for personal use only. Modification or

Keio University is Japan’s oldest institute ofcommercial use without prior permission from thehigher education, founded in 1858 by educator andcopyright holder is prohibited.

intellectual leader Yukichi Fukuzawa.



16

Feature article

Jitsugaku | September 2015

Editorial
実学 | S c ie n c e | サイヤンス

JITSUGAKU
Traditional yet innovative
Keio has a legacy as Japan’s first modern institution of higher learningand continues to be one of Japan’s top research universities.

K

eio University has been selected as a Top Typeresearch university for the Japanese government’s Top Global University Project. Under thisproject, Keio is committed to further contributeto global society to bolster its position as a world-leading
research university.
Keio continues to follow in the footsteps of its founder,
Yukichi Fukuzawa, who aspired to contribute to society
through learning and who especially valued jitsugaku (science). Science has a particularly important role to play inJapan, which will be the first to face many societal challenges
requiring global attention. These challenges include anaging population and declining birth rate, increased risks toenvironmental, economic, and regional security, and a highdemand for innovation.
Keio is well prepared to address these important global
issues, drawing from research that extends across the humanities, social sciences, and natural sciences. And Keiois currently integrating its efforts through three transdisciplinary research and education initiatives focusing on
longevity, security, and creativity.
This inaugural issue of Jitsugaku includes three feature articles and a selection of eighteen shorter research highlights
covering a broad range of fields from biology and medicine,to physics, chemistry, law, and media studies. These articles
offer a taste of Keio’s groundbreaking discoveries and global
contributions to social change. The Inside Keio article
chronicles Keio’s long history of social innovation, which isgrounded on the principles of scientific realism, progressive
thinking, and wise leadership.
We hope that our global initiatives will contribute to asustainable, secure, and highly creative world where people
live better, longer lives.

research-highlights.keio.ac.jp

実学 | S ci en ce | サイヤンス

Issue 1
September 2015

JITSUGAKU
Showcasing the best research from Keio University

Inaugural Issue
Research highlights
Discover the groundbreaking research
produced at Keio

Features
Immerse yourself in the stories behind
Keio’s creativity and excellence

Inside Keio
Explore Keio’s long history ofsocial innovation

Issue 1, September 2015

WHAT IS JITSUGAKU?
Jitsugaku is a way of learning
about the world pursued by
Keio University’s founder
Yukichi Fukuzawa throughthe application of reason,
observation, and verification.
It is science in the true sense of
the word and a powerful tool in
Keio University’s never-ending
search for practical solutions toreal-life problems.

3

Inside Keio

IGNITING JAPANESESOCIAL INNOVATIONK

eio university is the oldest and one of the mostprestigious
universities
in Japan, with a history
that dates back more than 150 years.
Located in the heart of Tokyo, Keio is aforward-looking, progressive institution
founded on principles of scientific realism
and Western philosophy, and is focused onenhancing the globalization of educationin Japan.
Keio was founded by Yukichi Fukuzawa(1835–1901), an educator and intellectual
leader who is considered a pioneer ofmodern Japan. Fukuzawa was born to asamurai family during the final years of
the Edo period. He founded Keio Gijuku
in 1858, as a school for Western learningin Edo, today’s Tokyo. Keio Gijuku wascharacterized by its tenets of self-respect
and independence of mind combined with
an emphasis on jitsugaku (science). The
school began offering university education

Keio University Library is the
only library in Asia to own acopy of the Gutenberg Bible.
4

Handwritten manuscripts and letters
by Albert Einstein donated to
Keio University.

in 1890, setting up its first departments
in literature, economics and law, andhas since continued to establish a firm
reputation as a leading university in Japan.
Indeed, Keio has a long history of attracting some of the world’s brightest minds.
For example, in 1922, the year after he won
the Nobel Prize in Physics, Albert Einsteinvisited the university to deliver a five-hour
speech, his first in Japan, in front of an
audience of over 2,000 people.
Fukuzawa believed the best way forJapan to catch up with Western technology and social systems was to always strive
for progress and enlightenment, and provide the academic and moral educationneeded to create a generation of wise andcapable leaders. Graduates of Keio include
prominent leaders and historical figuresin all walks of life, including former prime
minister, Junichiro Koizumi, and highly
regarded people in the Japanese businessworld such as Toyota Motor Corp’s incumbent chief executive officer, Akio Toyoda.
Notable astronauts, writers, scientists, intellectuals, and artists also number among
Keio alumni.
This is also reflected by Keio’s 9th placeranking in the Times Higher Education
Alma Mater Index: Global Executives in
2013. The index ranks institutions by the
number of degrees they have awarded toCEOs of Fortune Global 500 companies.
Thinking for oneself, taking responsibility for one’s actions and jitsugaku (science)are basic principles held dear by Fukuzawathat Keio continues to uphold to this day.
Fukuzawa emphasized the importance of
freedom, equality, and lifelong learning.
Jitsugaku | September 2015

Inside Keio
He noted: “Heaven does not create one man
above or below another man.” Fukuzawa
is honored on the 10,000 yen note, Japan’shighest denomination.

“Today, Japan has the world’s highest longevity rate. If we can establish our country
as a model for a vibrant and prosperous
aging society, it means that we can set a
precedent for other countries that are also
Applying jitsugaku (science) tograying. Keio University continues to makesolve global problems
intellectual contributions to Japan and the
Keio is a comprehensive higher-education world to create such affluent aging societies,”
institution located on six campuses across the says Keio University President Atsushi Seike.
greater Tokyo area. It has 10 undergraduate
In recognition of its strengths in researchfaculties, 14 graduate schools and approxi- and education, Keio University was recently
mately 30 research centers and institutes, in- selected by Japan’s Ministry of Education,
cluding a university hospital. The institution’s Culture, Sports, Science and Technology asaffiliates include two primary schools, three one of the 13 top Japanese universities injunior high schools, and five high schools, the 2014 Top Global University Project. This
including one in New York. Keio is a unique 10-year grant will further strengthen Keio’s
academic entity that offers
capacity to promote research
lifelong education. Keio has
and education in various“Keio University
partnerships which include
important fields.
continues to
266 overseas institutions andUnder the Top Global
make intellectual
9 international organizations
University Project, Keio willcontributions toin 41 countries. Partner
set up three clusters focusing
Japan and theuniversities include Harvard
on Longevity, Security, andworld to create
Medical School, Columbia
Creativity, which will all consuch affluent
U n i v e r s i t y, S t a n f o r dtribute to its goal of attaining
aging societies.”
University, the University ofsustainable development of a
Oxford, and the University
super-mature society. Theseof London. International
three multidisciplinary clusorganization partnerships include the ters will draw on Keio’s unique heritage of inAsian Development Bank, the International novation and jitsugaku (science), and harness
Bank for Reconstruction and Development, the power of the university’s strong network
and UNESCO.
of collaborations with industry, academia,
Drawing on its vast research expertise, Keio and international organizations.
is now focused on solving challenges in order
For example, the Longevity Cluster will
to realize a prosperous super-mature society. focus on developing innovative solutions toThis includes finding ways to promote a the problems posed by aging societies. It willsustainable society while nurturing the next adopt a three-pronged holistic approach thatgeneration and maintaining the health of will involve considering health matters, sociothose in the prime of life and beyond.
political issues, and technological solutions;

The Pen Mark has been an official symbolof Keio University for more than ahundred years.
research-highlights.keio.ac.jp

The Old University Library on Keio’s
Mita campus.

Keio Founder Yukichi Fukuzawa.

examples of each of these aspects include thedevelopment of regenerative medicine basedon stem cell technology, research into thepolitics of aging societies, and the use of robots to undertake nursing duties, respectively.
In the Security Cluster, Keio researchers
will explore security issues relating to social,economic, and geopolitical risks. Such security issues include global pollution, cybersecurity in financial markets, and regional
security in East Asia.
Meanwhile, researchers in the Creativity
Cluster will investigate telecommunication
and analytical technologies as well as new
materials such as plastic optical fibers.
In addition, they will investigate newforms of expression in new media andparticipate in inter-university consortia
such as the Global Innovation Design
program. Finally, Keio Business School,
the first in Japan to be accredited by the
Association to Advance Collegiate Schoolsof Business, will undertake research on
topics that include value creation throughoutstanding marketing and humanresource management.
By consistently emphasizing the philosophy of jitsugaku (science), Keio will continue
to provide leadership for the future throughits commitment to education, research, andmedicine. Its progressive environment helps
students and researchers in their pursuit ofexcellence, both as researchers and as individuals, and enriches global society.
5Research highlights

Enhanced X-ray imaging
Improved coherent X-ray diffraction imaging makes it possible toanalyze the internal parts of cellsBy employing a ring-shaped mask
and appropriate signal processing, scientists in Japan havefound a way to overcome a common limitation of coherent X-ray diffraction
imaging and dramatically improve the qualityof analysis1. As a result, they have succeededin using the imaging technique to analyze
the internal structures of biological cells anda collection of metallic nanoparticles.
Masayoshi Nakasako from the
Department of Physics at Keio University
and the RIKEN SPring-8 Center and his
co-workers have been using the X-ray freeelectron laser at the SACLA facility in Japanfor their experiments.
6

Imaging the diffraction patterns that result
when X-rays interact with a sample is a very
powerful approach for visualizing the structure of materials. Indeed, the discovery of the
double-helix structure of DNA was based on
analysis of an X-ray diffraction image, thefamous ‘photo 51’ in 1952.
X - r ay s c a n d e e p l y p e n e t r at e i nt omaterials beyond the reach of electron
microscopy and their short wavelength
yields an imaging resolution of just a few
tens of nanometers, far better than optical
microscopy. Applying phase-retrieval
algorithms to the two-dimensional X-ray
diffraction pattern captured on an image
sensor with an array of pixels allows theelectron density map of the sample tobe reconstructed.
However, there is a problem that hinders
coherent X-ray diffraction imaging experiments based on X-ray free electron lasers,
especially those experiments involving
clusters of metal particles with large scattering cross-sections or cellular organelles. At
small diffraction angles, the image sensor
receives such an intense X-ray signal that it
saturates the detector, resulting in missing
data. Nakasako’s team solved the problem by
employing an annular mask (see image) anddark-field phase retrieval.
“ Through developing a diffraction
apparatus called KOTOBUKI-1 and data
Jitsugaku | September 2015

© 2015 Masayoshi Nakasako, Keio University

X-ray diffraction pattern from a cube-shaped copper oxide particle, approximately 500 nanometers in size.

Research highlights

processing software, we have succeeded in
the structure analyses of bacterial cells andorganelles in biology and the determinationof the size distribution and the structuresof synthesized metal nanoparticles fromindustry,” explains Nakasako. “Recently wehave succeeded in visualizing the structure of chloroplasts with the dimensionof approximately 1 micron at effective

resolutions of 70 nanometers, better than
the resolution limit of optical microscopy.”
The capabilities of this new form of coherent X-ray diffraction imaging are said tobe a valuable addition to the other forms ofimaging such as fluorescence and electron microscopy, for example. “The complementary
use of [coherent X-ray diffraction imaging]
together with other imaging techniques willbridge the resolution gap between cellular andstructural biology,” concludes Nakasako.
Reference
1.

Kobayashi, A., Sekiguchi, Y., Takayama, Y.,
Oroguchi, T. & Nakasako, M. Dark-field
phase retrieval under the constraint of
the Friedel symmetry in coherent X-ray
diffraction imaging. Optics Express 22,27892–27909 (2014).

Multi-tasking protein wires brain
Two roles are performed by one protein to ensure the correct wiring

Reproduced from Ref. 1 and licensed under CC BY-NC-ND 3.0 (creativecommons.org/licenses/by-nc-nd/3.0/legalcode) © K. Kuwako et al.

of brain networksAsingle cell-surface protein is
crucial for the precise wiringof a specific brain network,
according to work by Keio
University researchers1. The discovery
might reveal a general mechanism bywhich a family of proteins controls development of the nervous system.
During development, neurons extend
projections called axons, which makeconnections called synapses with otherneurons to bui ld sp e ci a lize d neura l
networks. For accurate wiring of these
networks, axons must stop growing when
they reach the right place and form synapses with the correct neurons. To identify
the molecular mechanisms underlying
this process, Ken-ichiro Kuwako from
Keio University’s School of Medicine andcolleagues focused on an area of the brain
called the cerebellum.
“The cerebellum is an excellent model
for studying circuit connectivity because it
has a well-characterized simple structurethat consists of a small number of neuronalcell types,” explains Kuwako.
Previous studies showed that two ofthese cell types — mossy fiber neurons andclimbing fiber neurons — make different
research-highlights.keio.ac.jp

connections during development. Kuwako
and colleagues aimed to determine whichmolecules underlie these differences byanalyzing the proteins expressed in the twocell types at specific developmental stages“This in vivo screening was a time-consuming step,” says Kuwako. “It to ok
us almost a year to complete.” But the
team’s patience paid off: they showedthat Cadherin-7 (Cdh7) — a cell-surface
protein that mediates interactions between
cells by binding to itself — is expressedat the developing synapses of mossy fiber
neurons but not of climbing fiber neurons.
They also discovered Cdh7 expression in
the neurons with which mossy fiber neurons form specific synapses.
To examine how Cdh7 affects axon
growth, the res earchers gre w a typ eof mossy fiber neurons called pontine
nucleus (PN) neurons alongside cells
that either did or did not express Cdh7.
They obser ved reduced axon growthwhen PN neurons were surrounded by

Sections of the cerebellum in mice show that when the cell-surface protein Cadherin-7 (Cdh7) is expressed (left),pontine nucleus (PN) neurons (green) do not connect to Purkinje cells (red). However, reducing levels of Cdh7 in
PN neurons (right) causes abundant connection of PN axons to Purkinje cells.

7Research highlights

receptor orchestrates precise wiring byregulating axonal growth termination andsynaptic specificity,” says Kuwako. “Over
100 members of the same protein superfamily are expressed in a circuit-specificmanner and may also play a dual role toestablish precise wiring.”
Reference
1.

Kuwako, K., Nishimoto, Y., Kawase, S.,
Okano, H. J. & Okano, H. Cadherin-7 regulates
mossy fiber connectivity in the cerebellum.
Cell Reports 9, 311–323 (2014).

A quick spin unleashes
waves of the future
Spinning crystals allow researchers to peer inside
objects in just milliseconds using terahertz lightA

new imaging device developed
at Keio University1 dramaticallyshortens the time needed toperform ‘terahertz electric-field
vector sensing’ — a technique of interest
to art historians and materials scientists
alike for examining molecular-scale surface
properties using low-power radiation. The
high-speed optical probing characteristicsof this device may find use in real-time
manufacturing monitors or hidden-object
detectors at security checkpoints.
Situated b etween the inf rared andmicrowave regions of the electromagnetic
spectrum, terahertz radiation has uniquecharacteristics ideal for high-tech applications. For example, it has an intrinsic
low energy, making it is less damaging
than X-rays but penetrating enough to see
through opaque materials such as plastics or
paper. However, it has proved challenging tofind ways to controllably generate terahertz
light and detect how the amplitude, phase,8

and polarization of these beams change
after interacting with a sample — data thatcan precisely identify material compositionand properties.
Since 2012, Shinichi Watanabe and his
team from Keio University’s Department of
Physics have been working to advance thisexperimental technology through ‘terahertz
time-domain spectroscopy’. In this approach,terahertz light is mixed with pulses ofshort-wavelength, near-infrared light insidea special electro-optic crystal before hitting
the target. By varying the timing of thenear-infrared light pulses, the researchers
can monitor the amplitudes and phases of
the terahertz waves on a video screen, similar
to an oscilloscope.
Now, the Keio researchers have improved
upon their concept by developing a way toprobe time-dependent changes to the terahertz beam polarization. Watanabe explainsthat traditional devices for tracking how lightbehaves in different planes, such as wire-gridpolarizers, limit the bandwidth of collected
data. Fortunately, the team found a superior
solution — the electro-optic crystal they used
to mix terahertz and near-infrared light pulses
had a natural symmetry that could detectpolarization changes with extreme precision.
By shining terahertz light onto a mechanically spinning electro-optic crystal,
the researchers used the polarized beams
and high-speed cameras to capture theterahertz electric-field vectors (see image).
These images provide real-time informationof the magnitude and spatial distributionsof the terahertz radiation passing througha substance — data that Watanabe says canimprove understanding of materials such as
birefringent polymer optical components
and light-harvesting biomolecules.

Rotating crystal
45 0
Rotating crystal-45 0

Researchers have used light, naturally polarized by a rotating crystal, to generate two-dimensional, real-time
snapshots of terahertz electric-field vectors (colored arrows in panels on right) for high-tech, subsurface
imaging applications.

Jitsugaku | September 2015

© 2015 Shinichi Watanabe, Keio University

Cdh7-expressing cells, indicating thatinteractions between Cdh7 molecules on
the two types of cells impede axon growth.
Cdh7 also proved important for theformation of specific synapses. In mice,
reduced Cdh7 expression in PN neurons
led to the formation of fewer synapses with
granule cells, which are normally specifictargets, and more with Purkinje cells,
which are not (see image).
“This study provides the first evidence
that a single bifunctional cell-surface

Research highlights“Seeing the amplitude, phases, and polarization of terahertz light gives us triple theamount of possible information,” explains
Watanabe. “And since the technology utilizes

the natural symmetry of the electro-optic
nonlinear crystal, it is versatile, precise,and suitable for real-time video mapping ofterahertz electric-field vectors.”

Reference
1.

Takai, M., Takeda, M., Sasaki, M., Tachizaki,T., Yasumatsu, N. & Watanabe, S. Video-rate
terahertz electric-field vector imaging.
Applied Physics Letters 105, 151103 (2014).

Lab-grown uterus could
reverse infertility
Tissue-engineered uteri produce successful and healthy pregnancies in rats

Reproduced, with permission, from Ref. 1 © 2014 ElsevierR

ats with bioengineered uteri
can achieve normal pregnancies, show researchers at Keio
University in Japan1. This work
could lead to novel treatments for women who
have abnormalities of the uterus that interferewith embryo implantation and fetal growth.
“The techniques might be clinicallyapplicable for treating partial defects of theuterus and, in the future, perhaps for thereconstruction of the whole uterus,” says
Tetsuo Maruyama, a reproductive medicine
specialist at Keio’s School of Medicine.
Uterine-related infertility can sometimes
be corrected surgically, but for most womenwith severely damaged or misshapen uteri
the only way to genetically mother a child isthrough uterine transplantation or throughthe services of a surrogate — a woman who
carries the baby to term and delivers it. Bothof these approaches are fraught with ethical,
legal and societal issues.
Tissue engineering offers a potential alternative. The technique involves fabricatingorgans from an individual’s own body cells
and then implanting these tailor-made organs into patients. So far, doctors have only
tested the approach in people who need relatively simple, hollow organs, such as bladders
and windpipes. But bioengineers aroundthe world are using similar techniques tobuild more complex organs, including livers,
research-highlights.keio.ac.jp

A recellularized uterine graft being cultured in the laboratory.

kidneys, lungs and even hearts. Perhaps theuterus would be possible, too.
Maruyama and his colleague Kaoru
Miyazaki set out to test that idea in a rodent
model. They surgically removed the uterus
from rats and used detergents to strip theorgans of all their cells. This procedure left
only the underlying matrix of collagen andother structural proteins, together with thecell-free architecture of the blood vessels thatsurround the uterus. The researchers thenreseeded this scaffold with tens of millions ofprimary uterine cells and mesenchymal stem
cells (see image). After three days in a bioreactor, tissue analyses showed that the lab-grownorgans had uterine-specific structural integrity.
The bioengineered uteri could also
yield healthy pregnancies. Maruyama andMiyazaki showed that pregnancy rates andaverage fetal weights in rats implanted withthe uterine scaffold were comparable with
control rats.
Many technical obstacles remain before
the same method can be applied to humans.
For example, scientists will need to figureout the best ways to surgically remove uteri
from donors, safely strip all the cellularremnants to avoid immune rejection, andreconstruct the organs in the lab. Once thesetechniques have been optimized, however,bioengineered uterine grafts could offer arevolutionary new fertility treatment.
Reference
1.

Miyazaki, K. & Maruyama, T. Partial
regeneration and reconstruction of the
rat uterus through recellularization of adecellularized uterine matrix. Biomaterials
35, 8791–8800 (2014).

9

Feature article

Lawyers in spaceT10

raffic police are not issuing
speeding tickets in space,but the long arm of the law
is far from absent in the‘final frontier’. A fast-growing bodyof national and international laws,
known as space law, is now being used
to regulate human activities in outerspace, and Keio University is at theforefront of this young but increasingly
important field.
In January 2012, the university, incollaboration with the Japan Aerospace
Exploration Agency (JAXA), established
the Center for Space Law (Institute ofSpace Law), which aims to examine andoffer legal solutions to issues arisingfrom space activities, as well as to fosterand enhance research in the field ofspace law in Japan and countries acrossAsia. The center also runs a space
law master’s program. “It is the only
institute of its kind in Japan and one of
only about a dozen in the world,” says
Setsuko Aoki, a professor at the center.

many of the problems we face today,”says Aoki, who became enamored withthe field while studying law in Canada.
Examples of the benefits of space include the use of satellite data to combat
infectious diseases and predict ozone
depletion, she says. But legislation isneeded to manage these inherently
dangerous activities. “Space law canact as a vital facilitator for reducing
risk and to cover compensation issues
that arise when accidents do occur,”
Aoki explains.
For Aoki, the field offers an appealing
mix of international relations andscience, such as calculating satellite
orbits. Space law covers the financing
of off-planet enterprises, insurance,
navigation, export control, security,
intellectual property protection, andmore. It also encompasses international
politics, as typified by the Outer Space
Treaty brokered by the United Nations.
About 100 countries are parties to thistreaty, which was produced in 1967.

Space exploration
Space activities have grown rapidly
through large international space missions and satellites for communication,scientific research, espionage and remotesensing. Technology that relies on these
activities is fast becoming a normal partof life — we use it every time we checkour position on a navigation device orview a sports event screened on satellite
television. Even space tourism is close to
becoming a reality.
“Space is potentially very beneficial tohumankind and can help us overcome

Debris damage and militarization
Keio is researching aspects of space
law that particularly affect Japan,such as the problem of space debris.
NASA tracks over half a million
pieces of debris orbiting the Earth,of which more than 2,000 are larger
than a softball. According to Aoki, theJapanese satellite operator SKY Perfect
JSAT Corporation has to adjust theorbits of its 16 satellites almost daily
to dodge space debris hurtling toward
them. Regulations are now in place thatassign responsibility for damage caused© koto_feja/iStock/Thinkstock

A new legal field has sprung up to regulate humanity’s
ever-growing activities in outer space

Space has great
potential to benefit
humankind, but
judicious regulation isneeded to facilitate theutilization of space.

Jitsugaku | September 2015

Feature article

by debris whose source is known, while
non-legally binding guidelines stipulate
ways to minimize the generation of
new debris.
A more sinister aspect of space law is
the militarization of space, particularly
anti-satellite attacks. This area has become
especially urgent since the anti-satellite
missile tests conducted in 2007 by China,
which involved the physical destructionof a Chinese satellite and generated
research-highlights.keio.ac.jp

thousands of pieces of trackable spacedebris. International treaties such as theOuter Space Treaty limit the deploymentof weapons of mass destruction in space,and are expected to become increasingly
important in preventing an arms race inspace as technology advances.
The year 2015 is particularly importantfor space science in Japan as the Japanese
government will begin to adopt national
space laws in compliance with the Outer

Space Treaty. “About 20 countries havealready created such laws, and now it isJapan’s turn,” explains Aoki. She and othermembers of the Center for Space Law will
be contributing to this process throughtheir participation in various guiding
committees. Thus, the center will beplaying a major role in shaping space law
policy in Japan. “This is a really excitingtime to be active in this developing field,”says Aoki.
11

Research highlights

Nanoclusters of caged structures (blue and red) and sandwich structures (blue and green) synthesized in the gas phase can be deposited
onto designer surfaces such as buckyball-functionalized conductive surfaces (center left) and alkanethiolate self-assembled monolayers(center right) as well as naked metal surfaces (bottom), with a range of possible applications in materials chemistry.

Door opened to novel nanomaterials

Researchers have developed atechnique for assembling novel
nanomaterials from clusters ofgaseous ions, with potential implications for solar energy, energy storage,
and high-performance catalysis1.
Small clusters of silicon cages holding
single metal atoms or ions have long been
identified as potential building blocks fornanomaterials. Before they can be used,however, these gaseous nanoclusters need to
be immobilized on a solid surface. Previous
attempts have resulted in undesirable
changes to the shape and electronic charge ofthe clusters.
Atsushi Nakajima from the Keio Instituteof Pure and Applied Sciences and colleagues
at Keio University have immobilized tantalum cations trapped inside cages comprised12

of 16 silicon atoms (Ta@Si16+) onto a conductive surface while retaining their vital
original properties.
The team selected a conductive surfacefunctionalized with buckyballs (C60) that areable to act as electron acceptors, theorizingthat the Ta@Si 16+ cations and buckyballs
would form charge-transfer complexes(Ta@Si16+-C60−). “The immobilization process
consists of two steps,” explains Nakajima.
First the Ta@Si16+ is neutralized, and then it
transfers an electron to the buckyball andbecomes cationic again. This transfer ofan electron between each cluster and the
buckyball it lands on is “a crucial factor inmaintaining its symmetric cage shape andcationic state,” he explains.
The researchers experimentally verified
their theory by vaporizing tantalum andsilicon atoms in a vacuum chamber to makethe Ta@Si16+ cations. They then used mass
spectrometry to identify the desired ionsfrom the range of differently sized nanoclusters that had formed. The selected ionswere fired onto the buckyball-functionalizedgraphite surface at a tightly controlled rate toensure a gentle landing.
The researchers used scanning tunneling microscopy and scanning tunnelingspectroscopy to study the structure of theresulting nanomaterial. A charge-transfer
complex had indeed formed, creating amonolayer of the Ta@Si16+ cations on top of
the anionic buckyballs attached to the conductive surface.
“This fabrication approach can be used tomake a range of nanomaterials comprisedof both different nanoclusters and different
Jitsugaku | September 2015

© 2015 Atsushi Nakajima, Keio University

A simple route to immobilizing nanoclusters opens up new
possibilities in materials chemistry

Research highlights

surfaces,” explains Nakajima. Such nanomaterials made of monolayers of cations next tomonolayers of anions could act as electricaljunctions in a range of devices such as solar
cells and supercapacitors. The technique could
also lead to the design of high-performance
catalysts. It has been predicted that the cationic state of supported nanoclusters is a key
factor for controlling their catalytic reactivity,

says Nakajima. “A novel avenue for developing nanocluster-based material scienceand technology has opened to us.”
Reference
1.

Nakaya, M., Iwasa, T., Tsunoyama, H.,
Eguchi, T. & Nakajima, A. Formationof a superatom monolayer using
gas-phase-synthesized Ta@Si16 nanocluster
ions. Nanoscale 6, 14702 (2014).

Giving heart patientsa breath of life
Animal studies show that hydrogen gas can minimize
damage caused by the production of potentially lethal
compounds following cardiac arrest© Mihajlo Maricic/iStock/ThinkstockInhalation treatment with hydrogengas protects against neurologicaldamage in a rat model of cardiac
arrest, increasing the likelihood ofsurvival and recovery, find researchers at
Keio University and Nippon Medical School
in Japan.
Many patients who sur vive cardiac
arrest remain at increased risk of death.
“Ne u ro l o g i c a l d y s f u n c t i on , c ard i a cdamage, and systemic inflammation cancontribute to their ultimate demise,”
explains Motoaki Sano, a cardiologist
at Keio University. The stress from the
one-two punch of oxygen deprivation andsubsequent sudden restoration of blood
stimulates the production of damaging
molecules known as reactive oxygen
species. These trigger inflammation andcreate regions of damaged tissue known as
infarcts in the brain and other organs.
Sano’s group has obtained evidence
that this damage might be mitigated byresearch-highlights.keio.ac.jp

treating patients with hydrogen after
manually restoring blood circulation
through cardiopulmonary resuscitation(CPR) 1. “Hydrogen gas has antioxidant

and anti-inflammatory properties, andlimits infarct volume in the brain andheart,” he explains. His team previously
demonstrated that they could reduce
post-cardiac arrest mortality by treating
animals with hydrogen at the same time as
they initiated CPR, but their investigation
did not look at longer-term recovery orassess physical brain damage.
The researchers therefore embarked
on a more thorough assessment of thisapproach in a rat model of cardiac arrest.
To make their investigation more clinicallyrealistic, they mixed hydrogen gas withnormal air rather than pure oxygen, anddelivered it only after normal circulation
had been restored via CPR. They also
tested their treatment in parallel withtargeted temperature management (TTM),
where a patient’s body is cooled to minimize post-recovery tissue damage. “To
date, TTM is the only approach proven to
improve patient outcomes,” says Sano.
Hydrogen treatment greatly improved
survival and recovery, and even more soin combination with TTM. Of the rats thatreceived both interventions, 86 per centwere alive one week post-cardiac arrest,
compared with 38 per cent of control
animals. This combination also reducedn e u rol o g i c a l d am a ge an d i mprove dA dose of hydrogen gas following cardiopulmonary resuscitation could potentially improve outcomes in patients
who survive cardiac arrest.

13

cognitive performance post-recovery. Most
importantly, histological analysis showedthat hydrogen treatment greatly reduced
cell death and inflammation in vulnerable
regions of the brain.
“This shows that hydrogen could be used
as a brain resuscitation gas,” says Sano.
His team observed no adverse effects fromtreatment and has since initiated pilot
safety studies in humans in preparation forformal human trials. While differences inhuman and rodent physiology make it difficult to predict precisely how effective thistreatment will be, Sano sees a clear road tothe clinic.
Reference
1.

Hayashida, K. et al. Hydrogen inhalation
during normoxic resuscitation improvesneurological outcome in a rat model ofcardiac arrest independent of targeted
temperature management. Circulation 130,
2173–2180 (2014).

Purer silicon promises
perfection
An electronic circuit made from isotope-engineeredsilicon creates a better basic unit for aquantum computerA

fundamental element of aquantum computer that isscalable and retains its state
for much longer than comparable approaches has been demonstrated
by an international team of researchers1.
Quantum computers promise to solve
problems far beyond the capabilities ofmodern machines. Whereas conventional
computers store and process information
as a sequence of electrical pulses, thequantum equivalent uses a physical systemthat is small enough to exhibit its quantum properties.
These quantum equivalents of classicalbits, known as qubits, can come in many
forms, and each has its own advantages
and disadvantages. One approach is to use
atomic impurities in otherwise perfect
crystal structures, while quantum dots
are another type of qubit. Quantum dots
are larger than atomic impurities and14

are hence easier to connect to electricalcontacts for inserting and extracting data.

Atomic impurities, on the other hand, canmaintain their quantum properties formuch longer.
Kohei Itoh from Keio University, Japan,
and colleagues from Australia and theNetherlands have now created a qubit thatoffers the advantages of both approaches.
The team made their qubit from a thinfilm of silicon. Crucial to their success was
the high purity of their material. In addition
to the common silicon-28 atoms, standard
silicon often includes atoms of the isotope
silicon-29. The samples at Keio University
were carefully created to reduce the numberof these heavier atoms. “Our work showsthat isotope engineering of silicon has a
crucial role to play for quantum information applications,” says Itoh. He and his
co-workers fabricated quantum dots bylaying down electrical contacts. The electrical field between the contacts trapped anelectron in an area approximately 30 nanometers in diameter (see image). A nearby
transistor monitored the quantum state ofthis electron and the magnetic field createdby a microwave transmission line controlled
the properties of the quantum dot.
The researchers tested the operation of
the qubit by applying a sequence of pulsesthat created a device known as a Clifford

Electrical contacts (red) trap a single electron (blue sphere) that is monitored by a nearby transistor (gray). The
properties of this quantum-dot qubit are tuned using the magnetic field around a transmission line (blue).

Jitsugaku | September 2015

Reproduced, with permission, from Ref. 1 © 2014 M. Veldhorst et al.

Research highlights

Research highlights

gate. They measured a control accuracy,
or fidelity, of 99.59 per cent. The quantum
properties of their dot could remain stablefor 28 milliseconds — an order of magnitude longer than other types of semiconductor-based qubits.
“Moving on to two and more qubits isthe next step,” says Itoh. “We also intend todevelop materials that will allow qubits to beburied under the surface and thus reduce thenegative influence of interface defects.”
Reference
1.

Veldhorst, M. et al. An addressable
quantum dot qubit with fault-tolerant
control-fidelity. Nature Nanotechnology 9,
981–985 (2014).

Bringing hard laborto accountOne man’s effort to rationalize Japan’s infamous
grueling work culture has yielded some fascinating
insights into the Japanese work ethic

K© Kazzpix/iStock/Thinkstock

aroushi is a Japanese wordthat means ‘death by overwork’. In a country notorious
for its long working hours
and tradition of lifetime commitment
to a single company, this term is familiar to many. Isamu Yamamoto at theFaculty of Business and Commerce, Keio

research-highlights.keio.ac.jp

University, has been studying this characteristically Japanese work culture for thelast seven years with the aim of identifying
some of its underlying motivations andeffects on productivity.
Yamamoto developed an interest in thesubject prior to joining Keio University
during his years of working at a quintessential Japanese company — a Japanesebank. He explains, “ That is
A combination of peer
where I found my researchpressure and company
strategies to prevent
question: Why did so many oflayoffs drive Japanese
my colleagues regularly work
workers to overwork.
very long hours every day?”By analyzing the allocationof human resources and examining the relationshipbetween work–
life balance andthe mental healthand performanceof workers,
Ya m a m o t ohopes toc ont r i b -ute to the development of better laborsystems in Japan.
His research makes extensive use of government statistics and census data, but also
involves surveying hundreds of workers
and firms over time, a type of longitudinal
data called panel data — an area where
Yamamoto is assisted by Keio University’s
Panel Data Research Center.
Using a unique data set on managerial-level employees who were transferredfrom Japanese to European branches of thesame global firms, Yamamoto found thatthe daily hours worked by Japanese workers
dropped significantly when they were relocated to European offices that did not havea long working-hour culture1. This findingshows that Japanese workers are no more
inclined to work long hours than workers inother countries, but are instead influenced
primarily by the work habits of their peers.
Using another data set for Japanese maleworkers and their matched firms he also
discovered that long hours is a product of arational strategy by Japanese companies tomaintain a skilled workforce2. Companies
value and honor the lifetime commitment
and skill accumulation of their employees,
and to avoid the need for layoffs during
downturns, they tend to understaff, resulting in chronic overwork of incumbents— the downside of lifetime employment.
Yet with long hours comes an inevitable
drop in human productivity. “Japanese employees are now working so long that thelabor productivity is among the lowest of
the developed countries,” notes Yamamoto.
He hopes that his team’s research will one
day lead to these issues being addressed at
the level of national policy.
References1.

Kuroda, S. & Yamamoto, I. Do peers affectdetermination of work hours? Evidence
based on unique employee data fromglobal Japanese firms in Europe. Journal ofLabor Research 34, 359–388 (2013).

2.

Kuroda, S. & Yamamoto, I. Firms’ demand
for work hours: Evidence from matchedfirm-worker data in Japan. Journal of theJapanese and International Economies 29,
57–73 (2013).

15

© 2014 Keio University

Feature article

The Superhuman Sports Committee is developing technologies that can enable individuals of varying
physical ability, including the elderly, to compete in sports events.

Faster, higher andmore technologicalJapanese researchers are engineering the technology
and rules of superhuman sports, just in time
for the Tokyo Olympics

16

Jitsugaku | September 2015

Feature articleT

he famous victory of supercomputer Deep Blueover world chess champion Garry Kasparov in 1997
proved that machines were beginning to challenge theintellectual ability of humans. Kasparov soon turned
his digital adversaries into allies, introducing Advanced Chess inwhich human players compete with the assistance of computer
programs. These hybrid teams have defeated even the mostadvanced supercomputers.
At Keio University’s Graduate School of Media Design, humanaugmentation and virtual-reality researcher Masahiko Inami is
now applying this concept of transhumanism — using technology
to enhance the human condition — to the physical arena.
“Man–machine integrated systems will become the strongest
systems in the world,” asserts Inami. In 2014, soon after theannouncement of the Tokyo Olympics, he brought together a group of
researchers, sports psychologists, video game designers, and magicians
to form the Superhuman Sports Committee, which aims to encourage
the development of human–machine integrated systems to transformthe experience of sport for players, trainers, and audience alike.
In the lead-up to the 2020 Olympic Games, the committee plansto test the functionality, strength, and entertainment value of suchintegrated systems in a series of public annual competitions.

is developing tactile communication systems that can convey
to audiences what it feels like to hit a tennis ball traveling over
200 kilometers an hour back over the net. Using liquid-crystal
goggles, the crowd can get a clearer view of the ball’s fuzzy surface
as it speeds across the court. Inami’s team is also developing a way
to mimic the vision of spiders, to give players a 360-degree field ofview through head-mounted displays.
Another member of the committee, Jun Rekimoto at the
University of Tokyo has designed what he calls a Flying Head, inwhich a camera attached to a floating drone can follow athletes
across the court and send real-time footage of their movementsfrom a third-person perspective via a head-mounted device.
This device could be used to train basketball players the way thatwall-to-wall mirrors give dancers and gymnasts perspective.
Rekimoto’s team has also designed a drone-powered ball thatevokes scenes from quidditch matches in Harry Potter.

More accessible sports
These technologies will force sports engineers to modify therules of existing sports or invent entirely new sports, says Inami.
Exoskeleton suits that can make sprinters run several ordersof magnitude faster, for example, could make speed the lesser
challenge. “Running fast is not so hard, but stopping safely is
Spider vision and flying balls
difficult.” Perhaps the 100-meter dash could be
As a high school student, Inami was fascinatedmade into a start-and-stop test, where runners“World records inwith the technology culture embodied by techare required to end the race exactly on thethe Paralympics
nology-inspired anime and Tokyo’s electronics
finish line.
wonderland of Akihabara. “I visited Akihabara“Technology can also balance out differences
could soon
almost every day,” says Inami, who would goinphysical ability, for example due to age
surpass those of
exploring with his friends and sometimes
or disability,” adds Inami, who foresees thethe Olympics.”
purchase used computer parts or electronic
emergence of more athletes like the German
circuits. Later as an undergraduate, he built
champion long-jumper and amputee Markus
small robots and virtual reality equipment, including a mechanical
Rehm who beat able-bodied competitors at the German Athletics
arm that could serve beer perfectly. During his doctorate, inspired
Championships in Ulm last year with a leap of 8.24 meters. Officials
by the manga and film series Ghost in the Shell, Inami developed
from Germany’s track-and-field governing body raised questions asan ‘invisibility cloak’ that used projection-based technology and ato whether Rehm’s carbon-fiber prosthetic leg gave him an unfair
special retroreflective material to optically camouflage objects.
advantage. Superhuman sports are likely to see such situations
Now a professor at Keio University, Inami is continuing theseabound, says Inami. “World records in the Paralympics could soon
projects through the Superhuman Sports Committee. His teamsurpass those of the Olympics.”
research-highlights.keio.ac.jp

17Research highlights

A new degree of control
for spintronics
Scientists in Japan have uncovered novel physics controllingspin-based electronics

As successful as modern electronics has become, it cannot
overcome one fatal flaw:
pushing electrons down wires
dissipates a lot of power. A new generationof spintronic devices can achieve much-improved power efficiencies by encoding
information in electron spin, but they also
face a steep challenge — spin informationis quickly lost. Now, Hiroto Sakimura,
Takaharu Tashiro and Kazuya Ando of
the Department of Applied Physics andPhysico-Informatics at Keio University inJapan have uncovered physics that may help
make the long-distance transmission of spin
information a reality1.
18

The researchers focused on a spintronicsystem in which an electrical signal in a
metal contact induces a traveling spin wave
in a neighboring insulating wire (see image).
This wave is a collective excitation of thespins of many immobile electrons andcomes in discrete chunks (or quasiparticles)
called magnons. The wave can travel long
distances down the wire before creating a
readout current in a second metal contact,which makes the system suitable for transmitting spin information in realistic devices.
Various unconventional techniques exist
for controlling the size of the spin current
flowing through the insulating wire. Amongthese is the process of splitting a single

magnon into two magnons to increase thespin current. Interactions between magnons
have also been observed to increase themagnitude of the current. Researchers, however, have been unclear about the underlying physics driving these enhancements.
Ando and his colleagues used the inverse
spin Hall effect, in which a flow of spins
creates a constant voltage, to demonstratethat these spin-current enhancements result
from an increase in the average magnon
lifetime. In the case of a single magnon
splitting into two, the increase in steadystate spin current is not, as one might expect, directly the result of the two particles
carrying a greater total angular momentum.
Jitsugaku | September 2015

© 2015 Kazuya Ando, Keio University

Diffusing electrons in a metal (blue) establish a collective spin excitation in a neighboring insulator (beige) for the long-distancetransmission of spin information in spintronic devices.

Research highlights

Instead, magnons interact with each otherthrough a process called spin damping ina way that increases their average lifetime.
The researchers found that this process canincrease spin currents even in the absenceof magnon splitting.
By revealing the central role that magnon
lifetimes and magnon–magnon interactions
play in determining the magnitude of spincurrents, these results may allow for a new
way to control signal strengths — andtherefore signal encoding — in spintronic
devices. “The ability to create a spin current
is an essential component of any spin-based
technology,” says Ando. “Our discovery
therefore will be the basis for a new generation of spintronic devices.”
Reference
1.

Sakimura, H., Tashiro, T. & Ando, K. Nonlinear spin-current enhancement enabled byspin-damping tuning. Nature Communications 5, 5730 (2014).

A therapeutic lead forheart muscle disorder
Reprogrammed stem cells show how a druggable
hormone helps drive the problems associated withhypertrophic cardiomyopathy© 2015 Shinsuke Yuasa, Keio UniversityAn in vitro model of the hereditary heart disorder hypertrophic
cardiomyopathy has revealed
how genetic backgrounds interact with environmental factors to cause thehallmark phenotypes of the disease1.
In hypertrophic cardiomyopathy, heart
muscle cells increase in size, leading tothickening that makes it hard for blood
to flow. The alignment of the cells also
becomes disordered and irregular, causingchanges in electrical signals that can
trigger life-threatening abnormal heart
rhythms. The condition is the leading causeof sudden unexpected death in young
athletes and can cause debilitating cardiac
problems in any age group.
To better understand the root cause of
the disease, a team led by Keiichi Fukuda
and Shinsuke Yuasa from Keio University
School of Medicine took skin cells or
research-highlights.keio.ac.jp

blood cells from three unrelated patientswith hypertrophic cardiomyopathy andthree healthy controls. They introduced
a virus expressing four pluripotenc y
genes — the so-called Yamanaka factors,

named after the Japanese Nobel laureate
Shinya Yamanaka — and created embryonic-like ‘induced pluripotent stem cells’.
The researchers then coaxed these reprogrammed stem cells to form heart muscle
cells called cardiomyocytes.
Under normal culture conditions, themorphological features and cellular behaviors of the cardiomyocytes from the healthyand diseased subjects appeared largely thesame. However, when the researchers exposed the cells to endothelin-1, a hormone
known to trigger the constriction of bloodvessels, they observed large differences in
the architecture of rod-like muscle fibrils(see image).
High-speed imaging studies further
revealed that the heart muscle cells frompatients with the condition beat out ofsync when subjected to treatment withendothelin-1. This was true whether the
cardiomyocytes came from stem cells
derived from someone with a mutation in
MYBPC3, a gene that is often dysfunctionalin people with hypertrophic cardiomyopathy, or from patients with the disease but
no known causative mutation.
The researchers confirmed their findings
in a mouse model. Using cardiomyocytes
derived from newborn mice with a heterozygous mutation in the mouse version of
the MYBPC3 gene, they showed that endothelin-1 induced similar problems in muscle
fibrils to those seen in the human cells.

Cardiomyocytes derived from the reprogrammed cells of a patient with hypertrophic cardiomyopathy show
augmented disarray in the presence of the hormone endothelin-1.

19

Research highlights

Several drugs that block endothelin
receptors are already on the market to treat
another heart condition called pulmonary
arterial hypertension. The findings from
Fukuda, Yuasa and their colleagues suggestthat these same agents might help people
with hypertrophic cardiomyopathy as well.
“We are planning a clinical study to know
if an endothelin-1 blocker could be a standard therapy,” says Yuasa.

Reference
1.

Tanaka, A. et al. Endothelin-1 induces
myofibrillar disarray and contractile vector
variability in hypertrophic cardiomyopathy-induced pluripotent stem cell-derived
cardiomyocytes. Journal of the American
Heart Association 3, e001263 (2014).

The not-so-symmetric Universe

Symmetry is an important mathematical concept that forms thebasis of fundamental laws of the
Universe. Researchers in Japan
have now uncovered that imperfections
rather than perfect symmetry might hold the
key to understanding the forces that drive
the Universe.
The fundamental forces of the Universe
such as gravity, magnetism, and even space
and time itself are inherently symmetric,
which means that they exhibit the same
properties in all directions. Therefore,
physicists searching for a unified theory thatcan describe the Universe and all its forces
are looking for theories that are based on
perfect symmetries.
Their efforts, however, have run into adead end. While it has been possible tounify most fundamental forces based onsymmetry principles, adding gravity has
been impossible. Muneto Nitta from Keio
University and Michikazu Kobayashi from
Kyoto University have now discoveredthat looking for perfect symmetries might
be the wrong approach. “Our finding
suggests a possibility of unification ofgravity with other fundamental forces, if

Domains are regions in magnets where the magnetism points in different directions (blue arrows).
Separating these domains are domain walls, which can show dynamic wave motions of the magnetic
direction (green, red arrows).

20

the relativistic symmetry is spontaneously
broken,” says Nitta.
Rather than studying forces and theirsymmetries at the high energies that were
present in the cosmos right after the creationof the Universe, the researchers focused on
low energies, such as conventional magnets.
Magnets that are fully magnetized aresymmetric, meaning that their magnetic
components all point in the same direction.
However, at intermediate magnetizations
magnetic domains form, which are regionswith different magnetic orientations.
Separating these regions are domain walls,
across which the magnetic orientation of
atoms switches (see the arrows in the image).
Domain walls break the symmetry of magnets and this results in energetic excitations,like when a stone is thrown into a pond. Theenergy created by the stone breaking the perfect symmetry of the water’s surface createssmall ripples. Similarly, the magnetic fields
across a domain wall can also create ripples.
Applying a theoretical framework ofequations describing broken symmetries,
Kobayashi and Nitta showed that some ofthese ripples are the consequence of a coupling of the magnetic force and the space andtime symmetry of the material1.
Given the difficulties in unifying symmetries of fundamental forces with space andtime at high energies, this coupling was unexpected, and, says Nitta, “can provide somehints for unified high-energy theories.” While
Jitsugaku | September 2015

© 2015 Michikazu Kobayashi, Kyoto University, and Muneto Nitta, Keio University

Broken symmetries may provide a pathway to a unified theory of the Universe

Research highlights

the present findings apply only to low-energy
dynamics, the strategy of unifying fundamental forces through broken rather than perfectsymmetries could lead to an entirely new
understanding of the Universe.

Reference
1.

Kobayashi, M. & Nitta, M. Nonrelativistic
Nambu-Goldstone modes associated withspontaneously broken space-time and internal symmetries. Physical Review Letters 113,
120403 (2014).

Winning thesuper-enzyme lottery
A microfluidic instrument that can rapidly screen
millions of electron-transferring enzymes may
uncover the next biofuel device

Potentiostat

Reproduced, with permission, from Ref. 1 © 2014 American Chemical Society

BDD

Microchip devices containing boron-doped diamond (BDD) microelectrodes can screen enzymes for catalytic
activity with remarkably high throughput, measured using a potentiostat.

T

he power output and stabilityof biofuel cells that generate
cheap electricity with catalytic
enzymes can now be improved
thanks to an analytic instrument developed
at Keio University1. Nobuhide Doi from the
Department of Biosciences and Informatics
and colleagues have fabricated a device thatscreens libraries of potential enzyme catalysts
hundreds to thousands of times faster thanconventional methods using micro-sized
electrodes and microfluidic sample handling.
NAD(P)-dependent oxidoreductasesa r e e n z y m e s t h at c at a l y z e e l e c t r o n
research-highlights.keio.ac.jp

transfer between a broad range of biomolecules. This versatility has led researchers toinvestigate if the enzyme could replace heavy
metal catalysts in electricity-generating fuelcells. So far, however, the oxidoreductases
tested in biofuel cells have shown insufficient
activity and stability for practical applications.
One way to improve the properties ofexisting oxidoreductases is with a process
called directed enzyme evolution that mimics
natural evolution to build up massive libraries
of enzymes bearing slight mutations in theirstructures. Then, screening and selection experiments test the mutated enzymes’ catalytic

properties to help guide the evolution process.
Current screening techniques based on lightadsorption can assess thousands of clones
at once, but higher-throughput methods areneeded to advance fuel cell development.
Doi and his team explored whether thecatalytic ability of NAD(P)-dependent oxidoreductases could be detected by measuring their electrochemistry — a significantly
faster screening method that requires only
tiny sample volumes. Achieving this goal
required special ‘boron-doped diamond(BDD) microelectrodes’ developed by
Yasuaki Einaga at Keio University. Theserobust, needle-shaped devices can survey
a wide range of electrochemical conditions
while having very low background current,
making them ideal for ultra-sensitive detection of enzyme activity.
The team constructed a tube-shaped
microfluidic device that continuously
flows small volumes of enzymes past a
BDD microelectrode detector (see image).
After optimizing for pH and anti-protein
aggregation effects, they tested the activityof two important catalytic enzymes: glucose-6-phosphate dehydrogenase and alcohol dehydrogenase. Remarkably, the new
instrument needed only a millisecond to
detect part-per-trillion concentration levelsof the dehydrogenases, and required mere
nanoliters of sample volumes. “The cost andtime can be saved significantly comparedwith conventional methods,” says Doi.
The speed and accuracy of the microfluidic–BDD microelectrode device implies it
could handle much larger screening libraries
than current techniques — potentially up to
one million enzyme clones. Doi is confident
this approach can narrow the search for ‘super
enzymes’ appropriate for biofuel cells, likening it to a gambler improving his odds. “The
more lottery tickets you buy, the higher yourchance of winning,” he adds.
Reference
1.

Oyobiki, R. et al. Toward high-throughput
screening of NAD(P)-dependent oxidoreductases using boron-doped diamond microelectrodes and microfluidic devices. Analytical
Chemistry 86, 9570–9575 (2014).

21

Research highlights

Preventing abnormal
eye vessel growth
A molecular process crucial to the postnatal development of the retina is
uncovered by an international team of researchers

This unprecedented mode of
VEGF regulation may help touncover strategies for targeting
human diseases related toexcess vessel growth, such as
cancer and rheumatoid arthritis.
The growth, pattern, and distribution ofblood vessels in the body is regulated by asignaling protein called vascular endothelial
growth factor (VEGF). New blood vessels
emerge from pre-existing vessels when VEGF
activates receptors present in endothelial
cells that line all of the veins in the body — aprocess called angiogenesis.
Yoshiaki Kubota and co-workers at
Keio University, together with scientists
from across Japan, the United States, andAustralia, made a surprising discovery when
22

VEGF
VEGFR2
Tip cellStalk cell

VEGF
VEGFR2

Endocytosis

Wild-type neuron

VEGFR2-null neuron

A growth receptor called vascular endothelial growth factor receptor 2 (VEGFR2) prevents over-vascularization ofretinal neurons by binding excess VEGF. In mouse models that do not express the VEGFR2 receptor in their retinal
neurons, the vessels grow inward toward the neurons instead of outward.

they set out to investigate angiogenesis in thedevelopment of the eye, and in particular the
retina, after birth.
“Most researchers are focusing on thesignaling and function of a VEGF receptor
called VEGFR2 in endothelial cells,” says
Kubota. “However, to our surprise we discovered that VEGFR2 is much more abundantly
expressed in neurons than in endothelial
cells in mouse retinas.”
This initial discovery enticed the researchers to examine why VEGFR2 was so strongly
expressed in retinal neurons. The teampainstakingly generated multiple lines ofmice with the Vegfr2 gene deleted from theirretinal neurons. They found that the absenceof neuronal VEGFR2 in the retina led to misdirected angiogenesis — instead of sprouting
new vessels outward, the vessels began togrow inward toward the neurons themselves(see image). This caused unusually dense

vascular growth around the retinal neurons.
“VEGFR2 essentially acts as a barrier, binding VEGF and therefore preventing excess
vessel growth in the retina,” explains Kubota.
“This process ensures that the eye receives
the appropriate level of vascular supply andprevents over-vascularization.”
Further analysis is required to determine
if a lack of VEGFR2 receptors in the retina
could have an impact on eye diseases such as
diabetic retinopathy.
“We also hope that this unprecedented
mode of VEGF regulation may help to uncover strategies for targeting human diseases
related to excess vessel growth, such as cancer and rheumatoid arthritis,” says Kubota.
Reference
1.

Okabe, K. et al. Neurons limit angiogenesisby titrating VEGF in retina. Cell 159,
584–596 (2014).

Jitsugaku | September 2015

Reproduced, with permission, from Ref. 1 © 2014 ElsevierA

key molecular process governing the healthy developmentof the eye in mice has been
uncovered by researchers at
Keio University, along with international
collaborators. Their unexpected findings may
inform new treatments for eye diseases1.
The eyes are a good example of the essential role played by complex interactions
between the central nervous system and theblood and lymph vessel networks that ensure
the healthy development of the body after
birth. Without the correct development of
the retina, signals sent via neurons to thecentral nervous system would be disrupted,
potentially affecting our ability for sight.

Feature article

Reframing the language of dementia
A structured approach to language shows promise for improving the lives ofdementia patients and their familiesA© imtmphoto/iStock/Thinkstock

diagnosis of dementia is likely to instill something
akin to terror. But consider what could happen if
we stopped using the language of loss when talking
about the condition. This is the approach advocated by Takashi Iba from the Faculty of Policy Management
and the Graduate School of Media and Governance at
Keio University. In a booklet specifically designed to provide a
structured way to communicate about dementia, Iba describes
the onset of dementia as the beginning of a journey.

such a support system, especially in Japan, and also, of course,
around the world,” says Iba.
The work was fast-tracked. Iba initiated the project withhis students and several external collaborators in June 2014.
They interviewed dementia patients and their caregivers andthen organized the mined information into a pattern language.
But for the work to make an impact, they realized that theyneeded to find a way of sharing the new language with patients,
families, caregivers, doctors, and people for whom dementia is
not a current concern. To realize that goal, they published thebooklet Words for a Journey in Japanese and English in October
2014, a mere five months after commencing the project.

Words of care
The researchers constructed a pattern language for three
separate groups: people with dementia; families and friends;
and society as a whole. Accordingly, Words for a Journey is
divided into three sections: “Words for the cared”, “Words forthe caring”, and “Words for everyone”. Each section is divided
into a context, problem, solution, and name.
For example, “Words for the cared” describes how dementia
Words for a Journey provides a structured way for families and patients tend to spend less time outside the home — thecaregivers to communicate with loved ones living with dementia.
context. One problem that can arise from this is that patients
may become depressed staying indoors or feel lost if they venture out by themselves. A solution would be to find a place thatAn aging society
the cared can travel to by themselves and which their familyWith the global rise in average life expectancy, it is more likely
knows; this place is called their ‘favorite place’ (name). To makethan ever that we or someone close to us will be affected byliving with dementia more manageable, Iba and his collaboradementia. In Japan — the world’s first super-aged nation withmore than 25 per cent of its present population above the age of tors suggest reframing dementia as a ‘new journey’ and viewing
65 — the number of people with dementia is projected to reach it as an opportunity to learn more about one’s loved ones.
To date, 500 copies of the booklet have been distributed. “It
7 million by 2025.
is touching to see the booklet welcomed by people who are
Iba’s research involves developing ‘pattern languages’, foraffected by dementia,” Iba notes. “We hope that these patterns
which practical knowledge is mined from a variety of data
will help to solve their problems and improve their daily lives.”
sources and then organized into a pattern format. Pattern
As a firm believer in the capacity of pattern languages tolanguages are used in a range of fields, including architecture,
improve lives, Iba hopes that the approach will encourage asoftware design and creative activities.
social movement in which individuals share their experiences
Iba was giving a seminar on the creation of pattern
and mine information to establish a practical knowledge baselanguages in early 2014, when Makoto Okada of Fujitsu
for living well with dementia. His group plans to build on
Laboratories approached him and asked whether he wastheir work through community-centered dialogue workshops
interested in collaborating with him to create a new type of
pattern language that would help people living with dementia. to demonstrate that “everyone can use patterns as a source ofimagination and innovation.”
“I was immediately struck by the importance of developing
research-highlights.keio.ac.jp

23Research highlights

Measuring the galactic center
Surveys of a huge gas disk orbiting the center of our Galaxy can improve
our understanding of black holes and star formationO

ur Galaxy, the Milky Way,
rotates around a supermassive black hole at its center.
Spinning around this center
is a large disk of molecular gas, known as thecircumnuclear disk, which was likely formed
when the intense gravity of the black holecaptured surrounding molecular clouds.
Given its great size and density, the circumnuclear disk is believed to be a likely site forthe formation of stars, but little is known
about its composition.
Now, researchers at Keio University
have collected spectral data that reveal the24molecular make-up of the circumnuclear
disk in great detail 1. Tomoharu Oka andco-workers at Keio’s School of Fundamental
Science and Technology and Departmentof Physics used the radio telescope at the
Nobeyama Radio Observatory to measure
the intensity of radio waves from the disk,
and from two neighboring giant molecular
clouds that may be feeding it.
“The Nobeyama Radio Observatory
45-meter telescope is one of the world’s
best instruments for this work, having
the largest diameter dish, wide frequency
coverage, and high mapping efficiency,” says

Oka. He and his team sampled frequencies
from 81 to 116 gigahertz, and attained thefirst unbiased spectra, meaning they had
uniform quality over the frequency range.
The biggest challenge for the researchers
was to identify which spectral lines camefrom which source. This was only possible
because the circumnuclear disk rotatesmuch faster than the nearby giant molecular clouds, producing a greater so-called
Doppler shift in frequency.
“The spectral line shapes were highly
complicated, so it was difficult to analyze,”says Oka. “However, we believed that there
Jitsugaku | September 2015

© alex-mit/iStock/Thinkstock

The Milky Way has a supermassive black hole at its center. Telescope surveys can be used to identify the chemicals in ahuge gas disk around the center to learn how the black hole functions and how stars are formed.

Research highlights

must be some difference in nature between
the molecular gas in the circumnuclear
disk and giant molecular clouds.” The
team’s analysis revealed that these hugeastronomical features contain a mix of
30 molecular species, including some rareorganic molecules.
We cannot see black holes, of course,
and the main evidence that ours exists is
a very bright source of radio waves, called
Sagittarius A*. However, Sagittarius A* is
not as bright as theory predicts. Oka andco-workers hope that their observations of
the circumnuclear disk could help to solve

this mystery and reveal other secrets about
the center of our Galaxy and others.
“The circumnuclear disk is a potential
reservoir for material flowing into thecenter, and so it could determine the future
activity of the black hole,” he says. “Its physical conditions and chemical composition
must reflect the central activity.”
Reference
1.

Takekawa, S., Oka, T., Tanaka, K., Matsumura, S., Miura, K. & Sakai, D. Millimeter-wave
spectral line surveys toward the galactic circumnuclear disk and Sgr A*. The Astrophysical Journal Supplement Series 214, 2 (2014).

An emerging new
focus for heart disease

Modified from Ref. 1 © 2014 The American Society for Biochemistry and Molecular Biology

A critical regulatory protein offers a potential newopportunity for treating the frequently fatal heart
condition cardiac hypertrophyAteam of researchers from Keio
University has shown that a
key transcription factor protein plays a role in regulating
cardiac hypertrophy in mouse models of
the disease1. The condition is characterized
by thickening of the heart muscle and a reduction in the size of the heart’s chambers,
including the left and right ventricles. It is
commonly caused by high blood pressure
which, according to statistics by the World
Health Organization, afflicts an estimatedone billion people worldwide.
The transcription factor Krüppel-likefactor 4 (KLF4) plays a crucial role in reading and interpreting the coded messages
written in DNA. KLF4 binds directly to
DNA to influence the behavior of multiple
genes related to cellular differentiation,
research-highlights.keio.ac.jp

proliferation, and inflammation. The protein is known to function throughout the
body but has been shown to be particularly

active in the body’s cardiovascular system— the heart and blood vessels.
Physician and bio chemist Tadashi
Yo s h i d a an d h i s c o l l e a g u e s at Ke i o
University School of Medicine have beenworking on the intriguing protein foralmost a decade. Most notably, since 2008
they have been exploring and explaining
the critical role KLF4 plays in regulating
the tough fatty build-up that accrues
along the walls of arteries. This build-up
is known as atherosclerotic plaque, andit narrows arteries and restricts the flowof oxygen-rich blood, ultimately causing
potentially fatal heart attacks and strokes.
Yoshida and colleagues, in collaboration
with researchers from other institutes, hadpreviously shown in mice that removing
the genes responsible for expressing KLF4
accelerates the appearance of this plaque.
In their most recent investigation,
Yoshida’s team found that in mouse models
of cardiac hypertrophy that lacked theKlf4 gene in their cardiac muscle cells,
or cardiomyocytes, the heart condition
became worse (see image). The researchers
further showed that KLF4 plays a role inmediating the antihypertrophic activity of
a compound called trichostatin A (TSA)— TSA repressed the development of cardiac hypertrophy in control mice, but notin the Klf4-deficient mouse models.
These findings suggest that KLF4 is worthy of further investigation as a treatment

Control

Hypertrophic signals

Normal heart

KLF4 deficiency

The hearts of mouse models deficient in Krüppel-like factor 4 (KLF4) protein show enhanced development of cardiac
hypertrophy relative to control mice following stimulation by signaling molecules to induce the disease.

25

Research highlights

for cardiac hypertrophy. Moreover, the response of TSA to KLF4 suggests other lines
of inquiry. TSA is known to have epigenetic effects on cardiomyocytes, a processthat could provide useful insights into thefunction of KLF4 if further explored. “It isof significant interest to find out how a cardiomyocyte-specific epigenetic modulator
regulates cardiac hypertrophy through theregulation of KLF4,” says Yoshida.

Reference
1.

Yoshida, T., Yamashita, M., Horimai, C. &Hayashi, M. Kruppel-like factor 4 protein
regulates isoproterenol-induced cardiac
hypertrophy by modulating myocardin
expression and activity. The Journal of
Biological Chemistry 289, 26107–26118 (2014).

Organic synthesis withlight-coupled carbohydratesT

he synthesis of organic molecules
using methods that result inminimal waste and take advantage of renewable energy sources
has been a long-term goal for chemists.
Researchers at Keio University have shownthat certain organic acids can facilitate thecoupling reaction between carbohydrates andvarious alcohols, and then be recovered andreused without any loss of reaction efficiency1.
The glycosylation reaction, as well as benefiting from the recyclability of the acidic reagent,is triggered by light — a clean energy source.
“Our glycosylation reaction is highly

environmentally benign compared withconventional methods,” says study author
Kazunobu Toshima. “Moreover, it is thefirst example of a synthetic organic reaction
employing reusable organic acids, whichhave been activated by photo-irradiation.”
Glycosylation involves attaching acarbohydrate to other sugars or organic
molecules to yield oligosaccharides or glycosides. Carbohydrate-containing molecules such as glycoproteins and glycolipids
are vital participants in many biologicalprocesses. Glycosylation reactions are also
common steps in the synthesis of bioactive

Ultraviolet lightO(PO) n+CC | 3

O

R-OH

CN

(PO) n

O
OR

OH

NH
CN
The environmentally benign glycosylation reaction for the coupling of carbohydrates (yellow) and alcohols(blue) using organic acids (black).

26

and functional products, ranging fromantibiotics to biodegradable surfactants.
Given their widespread application, noveland environmentally benign routes to glycosylated products are highly sought after.
With this in mind, Toshima and colleagues identified several organic acids
that can act as photo-activated reagentsfor glycosylation (see image). The organic
acids comprise aromatic molecules withhydroxyl groups attached directly to thearomatic system — more specifically,
phenol or naphthol derivatives. Irradiation
with ultraviolet light increases the acidityof the organic acids, which causes a trichloroacetimidate group to leave the glycosyl
donor and creates an intermediate suitable
for reaction with various alcohols. The
electron-donating capability of the organic
acids was not sufficient to react with this intermediate, so no unwanted coupling withthe hydroxyl group of the acids occurred.
The researchers then removed theultraviolet light source to neutralize thereaction mixture and applied heat at a relatively low temperature to isolate the glycosylated product from the recyclable organic
solvent, ether. The organic acids could berecovered in greater than 90 per cent yield,
Jitsugaku | September 2015

© 2015 Kazunobu Toshima, Keio University

A reusable reagent offers a greener way to makecarbohydrate-containing molecules

Research highlights

after purification of the reaction mixture
using column chromatography, and reusedwith no loss of efficiency.
Toshima sees few hurdles in scaling up
the reaction. “A large-scale reaction would
only need a more powerful light source
and a larger reaction vessel,” he says.
“We envisage the development of different types of synthetic organic reactions

using these light-activated organic acids,
for example, carbon–carbon bond formation reactions, such as Mannich or
Strecker reactions,” he notes.
Reference1.

Iwata, R., Uda, K., Takahashi, D. & Toshima, K.
Photo-induced glycosylation using reusableorganophotoacids. Chemical Communications
50, 10695–10698 (2014).

Combined therapy forbreast cancer
A multi-pronged approach appears to be the mosteffective early treatment against a common andaggressive form of breast cancerW© Lighthaunter/iStock/Thinkstockomen suffering frombreast cancer fueledby the overexpressionof human epidermal
growth factor receptor-2 (HER2) havethe best chance of eliminating the disease

when receiving two presurgical treatments
in conjunction with chemotherapy, a Keio
University School of Medicine research teamhas discovered1.
Breast cancer — the most common cancer in women — kills about half a million

Combining two presurgical treatments with chemotherapy offers women with an aggressive form of breast cancer
the best chance of eliminating the disease.

research-highlights.keio.ac.jp

women each year worldwide. Of the morethan 1.5 million new cases diagnosed annually, about 20 per cent are HER2 positive — anaggressive form of the disease characterized
by elevated levels of the HER2 protein, which
promotes cancer cell growth and division.
Historically, HER2-positive breast
cancer has had a poor prognosis. This has
made it the focus of an expanding range ofneoadjuvant therapies — treatments administered prior to primary treatments such as
the surgical removal of cancerous tissue.
As a result, HER2-positive breast cancer
has become highly treatable, with four US
Food and Drug Administration-approved
anti-HER2 therapies now available. Of these,
the monoclonal antibody trastuzumab has
become the preferred therapy option for themetastatic form of the disease.
To identify the most effective treatment,
Tetsu Hayashida and his colleagues at Keio
University conducted a ‘network meta-analysis’ of the available relevant research on
neoadjuvant therapies. Unlike conventional
meta-analysis, which compares two subjects
and determines which is better, the network
meta-analysis approach compares and ranks
all available subjects, resulting in improved
decision making. “Network meta-analysis
synthesizes information from a networkof trials and combines direct and indirect
evidence on the relative effectiveness of thetreatments,” explains Hayashida.
By using an electronic database, the Keio
research team assessed 1,047 studies fromwhich they identified 10 studies that met
the eligibility criteria for their analysis,covering a total 2,247 patients in 7 different
treatment arms.
To measure the efficacy of the different
neoadjuvant therapies, the researchers
compared for each treatment the numberof patients with no residual histologicalevidence of a tumor at the time of surgery, ameasure known as the pathological complete
response. Patients who achieve this response
are at a reduced risk of disease recurrence,
which is associated with long-term survival— “one of the most important values incancer treatment,” says Hayashida.
27

Research highlights

treatment of HER2-postive breast cancer,
says Hayashida.
Reference
1.

Nagayama, A. et al. Comparative effectivenessof neoadjuvant therapy for HER2-positive
breast cancer: A network meta-analysis. Journalof the National Cancer Institute 106, dju203 (2014).

Quantum dotswith temperaturedependent color
Nanometer-sized quantum dots whose color varies
with temperature could be used for thermal sensing
and solar protection

R

esearchers in Japan have produced quantum dots with sizesof around 1 nanometer by using
the tiny pores in microporous
silica as a mold1. The color of these quantum dots can be reversibly changed fromThe color of quantum dots generally changes with theirsize (as shown here), but microporous silica can beused to produce nanometer-scale quantum dots whosecolor also varies with temperature.

28

pale blue to deep green by varying theirtemperature from 25 to 400 degrees Celsius(see image). This ability to change color
with temperature, known as thermochromism, is promising for use in a wide range ofapplications, including solar protection andthermal indicators.
“One-nanometer and sub-nanometer
quantum dots have been little exploredbecause of the difficulty of synthesis,” says
Hiroaki Imai who led the research withco-workers from Keio University andTokyo Metropolitan Industrial Technology
Research Institute. “Our findings provide
a versatile method for producing size-controlled quantum dots in this size range.”
Quantum dots are tiny particles of asemiconducting material with diameters
generally in the 2 to 10 nanometer range,
containing only a few tens of atoms. At
these small sizes, quantum mechanical ef fects b ecome signif icant. One
manifestation of this is that their bandgap— the energy gap between the valence
and conduction bands — increases withdecreasing size.
Various methods have been developed
to produce nanoscale quantum dots, but
the synthesis of sub-nanoscale quantum
dots has proven difficult. Such a method
is highly desirable as it is anticipated thatmost transition-metal oxides will exhibit
significant quantum effects only when
they are approximately one nanometeror smaller.
Imai’s team has demonstrated a versatileand controlled method to produce such
quantum dots. The researchers grew
copper oxide quantum dots in three porous
silica samples with pore diameters of 0.6,
0.9, and 1.7 nanometers. Scanning transmission electron microscopy confirmedthat this technique produced quantum dots
whose diameters corresponded closely tothe pore sizes of the silica templates.
The researchers found that the color of
the copper oxide quantum dots depends
on their size and varies reversibly withtemperature. They attribute the variationof color with temperature to a shift of the
bandgap and enhanced coupling between
electrons and phonons induced by theconfined volumes of the quantum dots.
This strong coupling came as a surprise to the researchers and suggeststhat quantum dots that are 1 nanometeror smaller in size may harb or otherunusual properties.
“Conventional thermochromic materials
are generally used at around room temperature due to their poor heat resistance,”
explains Imai. “The good thermal stabilityof these size-dependent thermochromic
quantum dots means that they could beapplied in durable temperature gauges inhigh-temperature systems.”
Reference
1.

Tamaki, H., Watanabe, H., Kamiyama, S.,
Oaki, Y. & Imai, H. Size-dependent
thermochromism through enhanced
electron–phonon coupling in 1 nm quantum
dots. Angewandte Chemie International
Edition 53, 10706–10709 (2014).

Jitsugaku | September 2015

© dmelnikau/iStock/Thinkstock

The researchers’ analysis identified thatthe most effective neoadjuvant treatment
for HER2-positive breast cancer is to combine chemotherapy with two anti-HER2
agents — trastuzumab plus lapatinib
and trastuzumab plus pertuzumab. Thisfinding will directly impact the clinical

The Keio Medical Science Prize
Objective
The 2014 Keio Medical
Science Prize Laureates“

It is a tremendous
honor to receive the2014 Keio Medical
Science Prize, in recognition of our efforts
to develop optogenetics, and to apply thistechnology to deepen
the understanding of
the brain in health and disease. This Prize isparticularly meaningful because optogenetics
originated as a tool to study the basic scienceof biology, not medical illness, and yet is enabling discovery of insights into disease states, aswell as into healthy brain function. From boththe neuroscience and psychiatry perspectives, I
hope that this story helps further encourage andstrengthen fundamental biology research.

“

Karl Deisseroth“

I am grateful tothe selection committee for awarding me the
Keio Medical Science
Prize, by which I was
greatly honored. Thisaward recognizes our
20 years of efforts
to understand how
morphological asymmetries develop in themouse embryo. I have been fortunate to sharea number of exciting findings with many talented colleagues in Tokyo Metropolitan Institute of Medical Science and Osaka University. Collaborations with many scientists allover the world were also essential. My thanks
go to those colleagues and collaborators.

“

Hiroshi Hamada

The Keio Medical Science Prize is an international prize that gives recognition tothe outstanding and creative achievements of researchers in the fields of medicine and life sciences, in particular those contributing to scientific developments
in medicine. It aims to promote worldwide advances in these fields to encourage
the expansion of researcher networks throughout the world and to contribute to
the well-being of humankind.

Prize

Laureates receive a certificate of merit, a medal, and a monetary award. The
award ceremony and commemorative lectures are held at Keio University.

Nomination and Selection

Nominees must have made an outstanding contribution in the fields of medicine
or life sciences closely related to medicine, and must be currently active in theirfield of research.
1.
2.

3.

An invitation is sent out to academics and researchers all over the world
each year, inviting them to nominate a candidate for the Prize.
The Keio Medical Science Prize Selection Committee reviews the nominations, selects laureates through a rigorous review process, and submits arecommendation to the Board.
The Board makes the final decision and the President of Keio University
formally announces the laureate(s).

Yearly Schedule (Subject to change)••••

Call for Nominations: Late January
Deadline for Nominations: Early March
Prize Announcement: Mid-SeptemberAward Ceremony: November or December at Keio University

www.ms-fund.keio.ac.jp/prize

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Coordination and Administration
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