│ 実学 │ SCIENCE │サイヤンス│

Issue 4
December
2018

JITSUGAKU
Showcasing the best research from Keio University

Global Outlook of a Hundred Years of Nursing Education

Molecular jostling affects
diffusion at cell membranes

Drug helps blood vessels but
leaves lurking cancer cells

Tardigrade genomes explain
life on the extremes

Happy Centennial Anniversary !
The Keio University Faculty of
Nursing and Medical Care

© Keio University

ON THE COVERI

n 1918, Keio University established one ofJapan’s earliest educational facilities to train
nurses under the leadership of the first deanof the Keio University School of Medicine,
Shibasaburo Kitasato, who foresaw the integralrole of nurses in modern medical care. Now, 100
years after the first 54 nursing students enrolled at
the Department of Medicine Nurse Training
Center, Dean Hiroko Komatsu is bringing nursing
education at the Faculty of Nursing and Medical
Care into the future under the mantra of “training
individuals who strive to build a healthful society.”© Keio University

Editorial

Global Outlook of a Hundred Years of
Nursing Education at Keio

│ 実学 │ SCIENCE │サイヤンス│

Issue 4
December
2018

JITSUGAKU
Showcasing the best research from Keio University

The evolution of nursing education at Keio University over the last 100 years has
been inspired by the spirit and philosophy of Keio University’s founder, Yukichi Fukuzawa. His belief in dokuritsu-jison—independence and self-respect—and jitsugaku—
empirical science—led to the advent of the Women’s School of Welfare, the Keio Junior College of Nursing, and in 2001, the Faculty of Nursing and Medical Care.
Nursing entails an exploration of the multifaceted and practical aspects of science,and necessitates judgment and practical skills based on a spirit of mutual respect,humaneness, deep intellect, and ethics. Furthermore, nursing requires a lifetime of

Global Outlook of a Hundred Years of Nursing Education

study and interaction with other academic disciplines to advance the development of
nursing care as an “empirical science.”

Molecular jostling affects
diffusion at cell membranes

Drug helps blood vessels but
leaves lurking cancer cells

Tardigrade genomes explain
life on the extremes

Utilizing its wide-ranging strengths as a comprehensive higher education institution,
Keio University has established curricula and courses that includes tuition from fac-

Issue 4, December 2018ulty members of other departments, enabling students to take lectures and practical
exercise classes in other disciplines. In particular, the Faculty of Nursing and Medical
Care collaborates with the Faculty of Pharmacy and the School of Medicine to inspire

WHAT IS JITSUGAKU ?
Jitsugaku is a way of learning about
the world pursued by Keio University’sfounder Yukichi Fukuzawa through theapplication of reason, observation,and verification. It is science in thetrue sense of the word and a powerfultool in Keio University’s never-ending
search for practical solutions toreal-life problems.

and nurture students in their pursuit of education in health and medical care.
Notably, the Inter-professional Education program offered by the three medicinerelated departments launched a compulsory course in 2011, where undergraduate
students participate in group discussions with students from the other departmentsin their own year. The aim of such interaction is to learn to cooperate and respect theviews of professionals from other areas of expertise in order to provide higher quality
medical care and treatment for patients.
Advances in pharmaceutical treatments, innovative healthcare programs, and pre-@ 2018 Keio University.
All Rights Reserved.
This publication may be reproduced in
its original form for personal use only.
Modiﬁcation or commercial use without
prior permission from the copyright holder
is prohibited.
Produced by:
Headquarters for Research Coordination
and Administration,
Keio University
2-15-45 Mita,
Minato-ku, Tokyo 108-8345, Japan
Further information
Keio University is Japan’s oldest instituteof higher education, founded in 1858 byeducator and intellectual leader Yukichi
Fukuzawa.
Jitsugaku is a print publication of theonline platform Keio Research Highlights,
which offers a taste of the importantresearch and scientiﬁc developmentsfrom Keio University.
Keio Research Highlights is published for
Keio University by the Partnership andCustom Media unit of Nature Research,
part of Springer Nature, and RTCorp.
www.keio.ac.jp
research-highlights.keio.ac.jp

ventative measures against the spread of disease have necessitated a global approachto nursing. Anticipating social changes in the future, defining and prioritizing potential
medical issues, and so on, require a global perspective on medical care. With suchglobal concerns in mind, Keio University has implemented programs for accepting
short-term international students and set up overseas training programs in the UnitedStates, the UK, and Laos.
Students at the Faculty of Nursing and Medical Care nurture a rich human sensitivity and acquire expertise and a broad outlook that enables them to play leading roles
in medical care once they graduate. Nursing education at Keio University is continuously evolving to foster practitioners in nursing and medical care suited for the challenges of the 21st century.
The articles in this issue of Jitsugaku reflect the pioneering, multidisciplinary, andglobal outlook of research and education at Keio University. Research highlights
include ‘Heavy coffee-drinking mice produce fewer fat cells, bringing broad healthbenefits’ by Megumi Funakoshi-Tago; ‘Economic researchers dismiss growing concerns about the negative impact of globalization’ by Toshiyuki Matsuura; ‘Innovative
3D-printed “caring-tools” to enhance the quality of life of elderly people’ by Shoko
Miyagawa; and ‘DNA analysis shows how water bears survive extreme conditions, yetleaves evolutionary origin unclear’ by Kazuharu Arakawa.
| December 2018 | JITSUGAKU | 001

Contents
001 Editorial
Global Outlook of a Hundred Years of Nursing Education at Keio

004 The best drop for lean beans *Heavy coffee-drinking mice produce fewer fat cells, bringing broad
health benefits

005 Taking the temperature of the tiniest things *Nanoscale thermometer takes precise heat readings of tiny spots,billionths of a meter wide006 How 7-month-olds make sense of adult babble *Japanese infants determine where words start and finish by employing
a neural circuit attuned to speech sounds

007 Space technology for a world of problems *The benefits of satellites are far-reaching and versatile. They can
improve productivity on farms, locate people stranded in disaster zones,
and even track sports performance

008 Molecular jostling affects diffusion at cell membranes *Dynamic interactions between proteins and lipids at cell membranes
result in complex changes in diffusion rates

009 Future tech will read everything in your eyes *Researchers are creating smart eyewear that will measure your reading
habits and will even tell you how much you understood

010 Born before their time *‘Stuck’ brain cells in extremely premature babies lead to impairment inlater life

011 Foreign investment boosts productivity at home *Economic researchers dismiss growing concerns about the negative
impact of globalization

012 Drug helps blood vessels but leaves lurking cancer cells *Drug cuts the supply lines to brain tumors but doesn’t eliminate cancer
stem cells, which could explain resistance to the drug

013 Chromosomal chaos gives cancer a survival advantage *Cancer cells adapt to genomic abnormalities by producing a proteinthat confers drug resistance

014 Tarantula toxin reveals channel function *Revelation of how a spider toxin binds to a membrane protein could
lead to new drug therapie

015 Shaking up cell culture *Mechanical vibrations offer a gentler way to detach cells from culture dishes
002| JITSUGAKU | December 2018 |016 Ancient antiviral response could help treat cancer *A class of drugs can harness the power of the body’s immune system
to fight diverse tumors

017 Digital 3D-fabrication technology for nursing andhealthcare #Innovative 3D-printed ‘caring-tools’ to enhance the quality of life ofelderly people

018 Robotic arms with a human-like sense of touch #Birth of innovative touch sensitive avatar robotic arm based on realhaptics

019 Health economics offers unique insights into modern
Japanese society #Fusing expertise in medicine and health economics sheds new light onhealthcare and gambling in Japan

020 Tardigrade genomes explain life on the extremes *DNA analysis shows how water bears survive extreme conditions, yetleaves evolutionary origin unclear

022 Tracing the origins of the Japanese with 3D technology *By using computed tomography to analyze hominin bones, researchersat Keio are revealing the history of Japan’s first inhabitants

023 Using iron to accelerate organic synthesis *A catalyst made from Earth-abundant iron can drive an important
reaction for making organic compounds

024 Politics of populism behind Putin’s 2016 victory *Keio analyst Atsushi Ogushi argues that rising populism contributed to
Putin’s definitive result in the 2016 Russian Duma election

025 Frontiers of haptics science: Uncovering the secrets of
the human body’s perception of touch #Insights into human touch and body perception and their utilization for
positive psychological and cognitive effects in our daily lives

027 Smart paper gives low-cost diagnostics in living color *Inkjet printing technology transforms ordinary filter paper into devices
that can spot kidney disease or contaminated water

028 Faulty transporter protein could underpin delayed labor *A protein in the placental lining helps synthesize a fetal hormone thatsignals to pregnant mothers to begin contractions

This article was made for Keio University by Nature Research Custom Media, part of Springer Nature.
*# Thisarticle was made for Keio University by RTCorp.

| December 2018 | JITSUGAKU | 003

The best drop
for lean beans
Heavy coffee-drinking mice produce fewer fat cells,
bringing broad health benefits

Coffee contains active compounds that can suppress obesity and its related health effects.

C

an’t begin the day with-given a diluted drip-filter cof fee ex-ing coffee on obesity would demand aout a coffee? A morning

tract, the team discovered.

serious coffee habit, says Funakoshi-

brew might have broader

These lean, coffee-fed mice had ac-

Tago. Weight gain was restricted inbenefits than just an en-

cumulated less of a fat form called

mice given the equivalent of 6 to 7

ergizing jolt, new research shows. Pre-

adipose tissue — the ver y tissue

cups of cof fee per day. “To prevent

vious health surveys have hinted thatassociated with obesity. “It is wellobesity, we would have to drink moreregular coffee drinkers have a signifi-

understood that obesity is caused bythan 9 cups a day,” she adds.

cantly reduced chance of developing

abnormal ‘adipogenesis’,” the process

A more efficient route, would be to

obesity and associated diseases suchby which immature fat cells become

identify the coffee molecule respon-as type-2 diabetes and heart disease.

fully functional, fat-laden cells called

sible for the beneficial effect, which

Researchers at Keio University haveadipocytes, Funakoshi-Tago says. The

could be a lengthy task. “Cof fee

taken a closer look at these claims, andteam homed in on coffee’s effects on

extract contains a large number of

discovered a molecular mechanism by

adipocyte formation, and confirmed

chemical components,” Funakoshi-

which coffee inhibits fat cell formation1.

that it inhibits the formation of mature

Tago says. “We tested the effects ofadipocyte fat cells.

caffeine, chlorogenic acid, and caffeic“Our results provided evidence that004

© jacqueline harriet, photographer/Moment/Getty

drinking cof fee has advantages forDrilling down into the cellular signal-acid, which are known to be abundant

reducing obesity and its associateding pathway known to trigger adipo-

in coffee extract, however, they had

diseases,” says Megumi Funakoshi-

genesis, the researchers traced cof-

no effect on adipogenesis.” The teamTago from the Keio University Faculty

fee’s effect to a molecule called insulin

is now grinding through coffee’s otherof Pharmacy, who led the work.

receptor substrate 1 (IRS1). In thecomponent molecules, looking for the

The team’s first step was a control

presence of coffee, a key phosphorus

elusive active compound.

experiment in mice. In a study involv-

tag on IRS1 is removed, consigning theing 36 animals, just as earlier surveys

molecule to the cellular recycling bin

had predicted, mice on a high-fat dietand switching off adipocyte formation.

gained significantly less weight when

But to realize the full effects of drink-| JITSUGAKU | December 2018 |Reference
1. Maki, C. et al. Coffee extract inhibits adipogenesis in 3T3-L1 preadipocyes by interrupting
insulin signaling through the downregulation of
IRS1. PLOS ONE 12, e0173264 (2017).

Taking the temperatureof the tiniest things
Nanoscale thermometer takes precise heat readings of tiny spots,billionths of a meter wideT

he temperature of tiny struc-

fluorescence to fade away depends on

temperature distribution in minuscule

tur es, thousands of times

the quantum dots’ temperature.

straw-like str uctures called carbon

smaller than a grain of sand,

The team coated a silicon surface

nanotubes (CNTs). An electrical cur-can now be measured accu-

with the quantum dots, and used arent causes some CNTs to heat up

rately, thanks to a technique devel-

conventional electrical thermometerand emit light, which could be used tooped by Keio University researchers1.

to monitor its temperature. They shot

generate pulses that carry information

The method could help to design

incredibly brief pulses of blue laser

in novel forms of computer chips. “Un-

more efficient electronic components,

light at the surface through a specially

derstanding the local temperature dis-or monitor the behavior of individual

modified optical fiber, its core tapered

tribution is important for controllingcells.

to a 70-nanometer-wide opening.

the response speed of light emission,

The technique is a form of nanoscale

The pulses made the quantum dots

thermometr y, able to measure thefluoresce red light, which travelled

The researchers also aim to study

temperature at a point just billionths

back up the optical fiber to a detector.

living cells with Fluor-NOTN. “Theof a meter wide, and it avoids someThis showed that the fluorescencetemperature distribution of a cell is

key problems of previous approaches.

lifetime was just over 13 nanoseconds

still unknown,” says Taguchi. “Weand the light spectrum,” says Taguchi.

Scanning thermal microscopy tech-at room temperature. But as the tem-

aim to map the local temperature of aniques, which come in direct contact

perature increased to 40 degrees Cel-

single cell, such as a neuron.”with a sample, have a spatial precision

sius, the lifetime decreased to aboutof less than 100 nanometers. But the

12 nanoseconds.

microscope’s probe tip can damage

By measuring the fluorescencethe sample, and heat exchange be-

lifetime of quantum dots in this way,

tween the sample and the equipment

the researchers hope to study the

Reference
1. Seto, D., Nikka, R., Nishio, S., Taguchi, Y., Saiki, T.
& Nagasaka, Y. Nanoscale optical thermometry
using a time-correlated single-photon counting in
an illumination-collection mode. Applied Physics
Letters 110, 033109 (2017).

can affect the temperature measurement. Meanwhile, non-contact methods using lasers have a spatial resolution that is usually limited to half the
wavelength of the incoming light,
which is typically several hundred
nanometers.
Yoshihiro Taguchi of Keio University, and colleagues, have invented a
non-contact technique called fluorescence near-field optics thermal nanoscopy (Fluor-NOTN), with a spatial
resolution of just 70 nanometers. It relies on nanoscale-sized ‘quantum dots’
made of cadmium selenide, which
fluoresce when light shines on them.
Crucially, the time it takes for thisAn optical fiber, its coretapered to an aperture just
70 nanometers wide, shines
light onto fluorescent quantum dots to measure theirtemperature.
Reproduced from Ref. 1 and licensed under CC BY 4.0 © 2017 D.
Seto et al.

| December 2018 | JITSUGAKU | 005

How 7-month-olds makesense of adult babble
Japanese infants determine where words start and finishby employing a neural circuit attuned to speech soundsTo newbor ns, adult speech

brain activity. In contrast, Yasuyo

Infants aged 9-10 months spent sig-

sounds like a constant stream

Minagawa and colleagues at Keionificantly more time looking at theof babble. But at some point

used functional near-infrared spec-

screen when sentences included the

between their first squeals

troscopy (fNIRS), which measurestarget words, indicating their ability

and first steps, babies begin to rec-the concentration of hemoglobin

to segment the words from the sen-ognize the beginning and end of

associated with neuronal behavior,tences.

words — an important development

to reveal the exact brain regions en-in the process of language acquisi-

gaged in word segmentation.

Neuroimaging using fNIRS, however, indicated that this skill develops

tion known as word segmentation.

The researchers separated a co-slightly earlier. During the training

Keio University researchers havehort of 54 Japanese infants into threetask, infants in the 7-8-month andfound that Japanese babies can seg-

age-groups (5-6 months, 7-8 months,

9-10-month age-groups showed sig-

ment wor ds at seven months —and 9-10 months) and introduced

nificant activation in brain regions

two months earlier than previously

them to simple Japanese words, suchthat play a role in encoding and stor-

thought — and have clearly identi-

as tanishi (mud snail) and zakuro

ing shor t-term phonetic memor y.

fied the brain regions that help in-(pomegranate).

The test session, in contrast, signifi-

1

In an initial training session, the re-cantly activated regions associatedPrevious studies into the neural ba-

searchers attracted the infants’ atten-

with retrieving the phonetic memor y.

sis of word segmentation have usedtion to a screen, where single target

These results cor roborate witha technique known as event-related

words were read aloud together withpr evious studies using ERP, but

potentials (ERP), which can measure

a lively animation. This was followed

reveal for the first time the exact re-electrical activity in the brain result-by behavioral testing, in which thegions that play a role in infant word

ing from specific stimuli, but usuallytarget words and control words weresegmentation. These regions seemof fers only a crude visualization ofrecited as part of a sentence.

to be a part of the early cerebral cir-fants do this .

cuit involved in ar ticulating sounds(dorsal pathway) as opposed to thecircuit that registers meaning (ventral pathway).
Furthermore, the study pinpoints
when Japanese babies begin to segment words in their native language,
which is around the same time as babies learning English and German,
but slightly earlier than French.
Minagawa hopes to further study
how Japanese babies learn the meaning of words; and to explore the roleof social interaction in language acquisition.

Reference
1. Minagawa, Y. et al. Infant word segmentation
The ability to recognize words by the age of seven months facilitates language acquisition in infants.
© PeopleImages/DigitalVision/Getty

006| JITSUGAKU | December 2018 |recruits the cerebral network of phonologicalshort-term memory. Brain and Language 170, 3949 (2017).

Space technology fora world of problems
The benefits of satellites are far-reaching and versatile. They can improve productivity on
farms, locate people stranded in disaster zones, and even track sports performanceNaohiko Kohtake’s re-dimensional maps, they developed an

search area of space once

app that enables a single person to cal-seemed among the least

culate the optimal planting position —practical realms. But his

far more efficient than the traditional

work solves real-world problems forteam method using long wires.

everyday people working on the land,

As well as rural settings, Kohtake islooking for safety, or scoring theirworking in the most densely populated

next try.
Kohtake is a system design scientist

Satellite technology is helping rugby players improve their sports performance.

areas of the world. The obstacle of tallbuildings can cause errors in naviga-

at Keio University, who thinks big© Keio University Rugby Football clubtion systems of several meters, which

about how satellites can collect, ana-

to get location information about des-could lead to disaster for driverless

lyze, and even send out data. “The key

ignated meeting points or safe routes

cars. Kohtake’s solution is to develop

is a holistic view,” says Kohtake, whoto people in disaster zones. Already,a navigation app that uses data fromis also an adjunct associate professor

the system has been successfully

multiple satellite networks — the Japa-

at the School of Engineering, Asian

trialed for bushfires in Australia andnese Quasi-Zenith Satellite System, theInstitute of Technology. “Many people

for tsunami warnings in several Asian

Chinese BeiDou and the United States

focus on specific areas, but we focus

countries.

Global Positioning System (GPS) —on optimization, system thinking, andThis example, like many of Kohtake’s

modeling to design a sophisticated,diverse research areas, grew out of his

Kohtake’s positioning system is somerged system.”passion to broaden the uses of satellite

precise that he is now using it to ben-data.

efit his favorite pastime, rugby. EachA striking example of this is

and is accurate to within a meter.

Kohtake’s disaster management sys-

“Nearly every university has a pro-player is equipped with a small track-

tems. He has used location data col-gram on how to build rockets anding device, enabling them to download

lected from mobile phones and taxi

satellites, but few have courses ona record of their every movement on

GPS to analyze how people behave

how to use satellite technology,” hethe field, to analyze and improve theirduring disasters across Asia, suchsays. To address this, Kohtake leads

performance.

as the 2011 Tohoku earthquake and

the Geospatial and Space Technology

This revolution in spor t science,

resulting tsunami. “Data is useful for

Consortium for Innovative Social Ser-believes Kohtake, who is an adviser at

finding social issues,” he says. “Wevices (GESTISS), a collaboration set

the Japan Sport Council, will also give

can understand the program under-

up in 2012 between several universities

professionals a career path when they

neath — the human mind.”in Asia, including Keio University’s

retire from sport.

While developing these systems,

Graduate School of System Design and“Top athletes interested in their

Kohtake realized that satellites could

Management. Ever y year, GESTISS

performance data develop analyticalalso help with communication in theorganizes tutorials, seminars and sum-skills, which are good not only for

confusion of a natural catastrophe. “Af-mer camps for 100 students across Asia

sport but also can help them move to

ter a disaster it is difficult to maintainand inspires them to think about how

other domains.”

contact and communicate messages toto employ satellites for social good.

people,” he says.

Kohtake’s GESTISS students, in col-Taking advantage of the fact thatlaboration with Malaysian researchers,

Japanese navigation satellites cantraveled to palm plantations in Malay-

broadcast messages directly to thesia, where they revolutionized the la-

GPS receiver built into mobile phones,

bor-intensive planting practices. Using

Kohtake and students designed an app

satellite and drone data to create three-

References
1. Choy, S. et al. Application of satellite navigation system for emergency warning and alerting.
Computers, Environment and Urban Systems. 58,
12-18 (2016).
2. Okami, S. & Kohtake, N. Fine-scale mappingby spatial risk distribution modeling for regionalmalaria endemicity and its implications under the
low-to-moderate transmission setting in western
Cambodia. 11, PLOS ONE e0158737 (2016).

| December 2018 | JITSUGAKU | 007

Molecular jostling affects
diffusion at cell membranes
Dynamic interactions between proteins and lipids at cell membranes result
in complex changes in diffusion rates

M

olecular dynamics sim-of biological processes.

ing of the detailed molecular dynam-

ulations have revealed

The cell membrane is a remarkable

ics of these processes could providethat the dif fusion of

biological structure that is selectively

important information on biological

key biomolecules atpermeable to cer tain ions and bio-mechanisms. However, conventional

cell membranes changes dramaticallymolecules while being impermeable

methods for modeling and analyzingover short time scales due to complex

to most water-soluble molecules. Pe-

the dif fusion of PMPs provide onlymolecular interactions, including

ripheral membrane proteins (PMPs)

general characteristics and are unableclustering1. This suggests that the ap-

temporarily bind to the cell membrane

to resolve the detailed motion con-parently steady diffusion of these mol-to provide a range of biological func-

tributing to overall diffusion over longecules over longer time scales hides

tions, including the regulation of cell

periods.

a much more complex mo-signaling and other important cellular

Kenji Yasuoka and colleagues fromlecular ‘walk’, which may

events. As many of these func-

Keio University, in collaboration withbe a critical com-

tions are determined byresearchers from the University ofponentthe speed at which PMPs

Oxford and University of Leeds in theapproach, attach andUK, have now used high-resolution

detach from themolecular dynamics simulations tomembrane, anshow that there is much more to theunderstand-story.
“We found that the diffusivity of theprotein fluctuates anomalously due
to dynamic interactions between theprotein and specific lipids,”
explains Yasuoka. “This‘short-time’ diffusivity
is intrinsically different from long-timemeasurements, andshows that the overall mobility of signaling proteins on thesurface of cell membranes is sensitive
to lipid interactions.”
The researchers
used a new method
to estimate theshor t-time dif fusivMolecular dynamics simulation snapshot showing
the binding of a Pleckstrin
homology domain (yellow) with lipids (red/blue)in the cell membrane(grey).
Reproduced from Ref. 1 and licensed under CC BY 4.0 © 2017 E.
Yamamoto et al.

008| JITSUGAKU | December 2018 |ity from a single molecular trajectorysurface over a period of just 10 micro-

impor tant proteins,” says Yasuoka.

without relying on knowledge of

seconds.

“We are also interested in investigat-

changes in diffusivity, looking specifi-

The results show that cell mem-ing the diffusion process in more com-

cally at the dynamic interactions of thebranes are complex spatially and tem-plex systems, such as the interaction

Pleckstrin homology (PH) domain —porally inhomogeneous environments

between transmembrane proteins andthe PMP lipid recognition module that

where crowding of lipids and proteins

PMPs.”

controls membrane binding. Their mo-

is common.

lecular dynamics simulations tracked“Determining the interactions of

the motion of a hundred Pleckstrin ho-

PMPs with the membrane at the mo-mology domains when placed within

lecular level is crucial for understand-a few nanometers of a cell membrane

ing the function of these biological

Reference
1. Yamamoto, E., Akimoto, T., Kalli, A. C., Yasuoka, K. & Sansom, M. S. P. Dynamic interactions
between a membrane binding protein and lipids
induce fluctuating diffusivity. Science Advances
3, e1601871 (2017).

Future tech will readeverything in your eyes
Researchers are creating smart eyewear that will measure your reading habits
and will even tell you how much you understoodFor the foreseeable future,It’s relatively cheap to implement,

making tech more intuitiveand you gain a lot from it in the VR

will be about analyzing eyeheadset space.”gaze and the delicate mus-Reading glasses thatmeasure fatigue

cles and skin around your eyes, says
Kai Kunze, a researcher at Keio University. “Eyes can tell you everythingfrom where you’re focused to yourlevel of expertise in a topic,” explains

Japan, says Kunze, is an amazing
Future virtual reality devices are likely to be fittedwith eye-tracking technology. © mikkelwilliam/Getty

Kunze, a German-born, Tokyo-based

place to work on this type of tech because of the low resistance to incorporating new technologies into dailyexpert in wearable computing, cogni-

says, is more advanced than otherlife. Some of his innovations havetion-aware computing, and smart eye-technologies and will be the firstalready hit the market.

wear. “If you understand somethingcab of f the rank in the race toward

For example, prescription glasses

well, for example, your gaze will usu-

VR headsets and wearable comput-

from Japanese eyewear company

ally flow nicely and you won’t fixate

ing devices, such as Google Glass.

J!NS look like retro hor n-rimmed

on unfamiliar words for very long.”“There’s technology that can mea-

glasses, but use electrooculography

Kunze’s doctoral students at Keio’s

sure brain activity, but it’s too hard

eye tracking to give wearers all sorts

Graduate School of Media Design are

to process that information in realof information about their physicaltweaking wearable headsets in ways

time. For real-time feedback, eyes

and mental state (see image). Usingthat could change our everyday lives.

can provide a lot more information

installable apps, the glasses can alert

One project is looking at how to allow

much faster.”tired drivers and monitor concentra-

the motion-sick to navigate virtual en-“We’ve already seen a couple ofvironments nausea-free while stand-start-ups and kick-starter campaigns

ing still — a key problem holding

doing similar work. Three years ago,

Kunze, who was a consultant in thevirtual reality (VR) technology back.

we implemented our own eye track-

design, says that electrooculography

Another is seeking to harness youring in VR headsets because nobody

is a promising form of eye tracking

natural squint to zoom in on hard-to-

had done it before. I suspect the next

because it is computationally light.

see objects.

Oculus or Second Life head-mounted

It involves measuring changes indisplays will come with eye tracking.

electric fields caused by eye move-

Eye-interpreting equipment, Kunze

tion levels at work using feedback
from blinks and eye movement.

| December 2018 | JITSUGAKU | 009

80 per cent of sensor y information

so Kunze and his colleagues havecomes to humans via the head, Kunze

been measuring facial temperaturepoints out that these devices arepatterns and electrodermal activity

green pastures for researchers.

(EDA). EDA technology uses
spectacle touch points in a similar

Are you in the right headspace
to read that report?

w a y t o e l e c t r o o c u l o g r a p h y, b u t

Glasses being retailed by the Japanese eyewear
company J!NS can monitor fatigue and concentration levels. © 2017 Keio University

Your glasses could soon reveal yourchanges in skin resistance to a

intellectual habits — good and bad —small electrical cur rent, or the

doubling as a fitness tracker for yourdifferences in the electrical potential

ment using electrodes positioned onbrain.

between dif ferent parts of the skin.

the skin around the eyes, which can

For example, research by Kunze

The advantage of EDA is there is abe inser ted into the nose pads andand colleagues in Ger many andwealth of information on what thesebridges of conventional glasses. “EyesOsaka Prefecture University has

measurements can tell you about

are basically like a dipole,” says Kun-

provided a basic proof of concept ofyour psychological state — EDA hasze. “The electric charge the sensors

Kunze's Wordometer, which uses the

been used in psychological researchdetect varies as you move your eyes

electrooculography technology insince Carl Jung used it to study

toward or away from a sensor.”

J!NS glasses to count the number ofpsychological arousal in the earlywords the wearer reads in a day.

1900s.

J!NS commercially released theseglasses in 2015. In many respects,

More-subtle mental processes

In shor t, says Kunze, smar t

they echo the roll out of physicalsuch as cognitive load, attention

eyewear could ver y soon tell you

activity trackers — like Fitbits for

distribution, and stress require awhether it's time to read that difficult

the mind. However, since more thanlot of psychological research, andreport or just go for a walk.

Born before their time
‘Stuck’ brain cells in extremely premature babies leadto impairment in later lifeUthen migrate outward through thewhite matter to the gray matter at thebrain’s extremities. “Neuronal migration is an essential, early stage ofdevelopment in mammalian brains,”
explains Kubo. “It needs to happen.

p to half of babies bor n

bir th. The first of these babies are

Cells can’t just pile up in the middle

before 28 weeks develop

now in their teens or early twenties —of the brain; they need to move tosignificant difficulties latergo back further than this and these

the brain’s surface for the brain to bein life: attention deficit hy-

children simply didn’t survive.”correctly wired and function appropri-

peractivity disorder, autism, and other

Separated from the umbilical cord,developmental disorders. Keio re-extremely preterm babies do not have

The team studied brain samples

searchers have discovered that suchthe functional lungs or circulatory sys-of infants born before 28 weeks andproblems occur because neurons in

tem they need to supply their brains

found that significant amounts of neu-

the developing brain never completewith oxygen and blood, hampering

their journey to the outer regions ofbrain development at a critical stage.

the brain1.

It is this, rather than the early birth,

Extremely preterm births (those be-010

measures sweat gland permeability,that often causes issues.

fore 28 weeks) are on the rise, but no-

Leading a team of 27 researchers

one knows why. “Improved medical

in Japan and the United States, Kubo

care increases survival, but the preva-

and his colleague Kimiko Deguchi hy-

lence of preterm babies [in ratio topothesized that this brain damage isnormal-term births] is increasing. It’s

caused by the impairment of ‘neuronala big problem,” says Ken-ichiro Kubo

migration’. In this process, neuronsof Keio University. “We’re now discov-in the growing brain are produced inering the impact of extremely preterm

the innermost part of the brain and| JITSUGAKU | December 2018 |ately.”

Many babies born before 28 weeks develop
significant difficulties later in life. Keio researchers have found that such problems are caused
because neurons in the developing brain do notreach the outer regions of the brain.
© BSIP/Contributor/Getty

rons, frozen in time, never reachedtion, their mice exhibited the same

Kubo and his team intend to re-their destination — the cells werelearning dif ficulties as their humansearch neuronal communication with‘stuck’ mid-migration. “The processcounterparts — failing to distinguisha view to rescuing the development ofapparently hasn’t been completed ina novel object from one they had pre-children already living with affected

these cases,” says Kubo.

viously been exposed to. Examination

brains.

To validate this suspicion, the teamrevealed that these mice too exhibitedcreated a ‘model’ of this brain injury

incomplete neuronal migration. “Ourusing mice. Having developed in themice model really mimics the diseasewomb under a period of blood starva-

presentation in humans,” says Kubo.

Reference
1. Kubo, K. et al. Association of impaired neuronal migration with cognitive deficits in extremely
preterm infants. JCI Insight 2, e88609 (2017).

Foreign investment boosts
productivity at home
Economic researchers dismiss growing concerns about the negative impact of globalizationT

here has been a backlash

previous studies. It was based on two

against globalization, as evi-sets of Japanese gover nment data

denced by the Brexit vote inabout overseas af filiates. The teamthe UK and the election of

looked at more than 2,700 plants ofDonald Trump as US president, both

2,100 manufacturers in the electricalin 2016. Increasingly, people are view-machiner y and electronics industr y

ing corporate investment abroad as afrom 1985 to 2003. They selected thisthreat to employment in their homeindustry because it has the most FDI

countries.

among all Japanese industries.

Many people view the globalization of production as a threat, but a recent study shows thatinvesting in foreign countries can actually boost
the domestic economy. © Philippe Roy/Cultura/Getty

A recent study shows that the op-

Matsuura and co-workers introduced

posite may be true — setting up or

new definitions for FDI. Conventional

acquiring companies in foreign coun-studies consider two types of FDI:

tries, known as foreign direct invest-

horizontal FDI (HFDI) for investment

The team also found that VFDI inment (FDI), “does not necessarily

in developed countries and ver tical

East Asia greatly improved produc-

hollow out the domestic economy, but

FDI (VFDI) for investment in develop-

tivity in Japan. “We had thought thatrather it could help raise productivity

ing countries. But Matsuura and col-most companies produced parts in Ja-

at home,” says Toshiyuki Matsuura,

leagues defined HFDI as producing

pan and assemble them abroad wherean econometric researcher at Keiothe same products both abroad and atlabor is cheaper, but we actually dis-

University1.

home and VFDI as relocating a part ofcovered that many companies do thethe production process (for example,

opposite and that many labor-intensive

assembly) to overseas.

upstream activities are still done in Ja-

Conventionally, econometric researchers have investigated how FDI

some firm-level analyses.

af fects domestic per formance at a

In their analysis, Matsuura’s teamcompany level. But such studies tend

added various variables to conven-

The study’s findings have important

to be too broad and have led to con-tional methodologies to minimize pos-

implications for Japan’s economic

flicting conclusions. Matsuura andsible biases and calculated a key index

strategy. “It is impor tant for policy-

his collaborators hoped that a morecalled the total factor productivity.

makers to encourage companies topan,” Matsuura says.

focused study based on appropriately

The outcome was consistent withinvest more abroad in order to raise

selected data would give more consis-

what the researchers had predictednational productivity,” notes Matsuura.

tent results.

— VFDI significantly raised produc-

By considering FDI at a plant level,

tivity in Japan, whereas HFDI had nothe study by Matsuura and colleagues

clear effect on productivity. This find-provided a more detailed analysis thaning differed significantly from those ofReference
1. Hayakawa, K., Matsuura, T. & Motohashi, K.
How does FDI affect productivity at home?: Evidence from a plant-level analysis. Journal of Industry, Competition and Trade 16, 403-422 (2016).

| December 2018 | JITSUGAKU | 011

Drug helps blood vessels but
leaves lurking cancer cells
Drug cuts the supply lines to brain tumors but doesn’t eliminate cancer stem cells,
which could explain resistance to the drugW

hen given topatients newly
diagnosed withaggressive brain

cancer, the drug bevacizumab reduces the density of blood vessels
in tumors but shunts cancer stem
cells to areas where blood vessels
are still functioning normally, findKeio researchers. This discovery,
from a first-of-its-kind investigation of bevacizumab’s microscopic
ef fects, should help cancer researchers better understand themechanisms of resistance to thedrug and so design combination
strategies that promote patient
survival.
Sold under the brand name
Avastin, bevacizumab works byblocking a protein involved in theformation of new blood vessels,
thereby choking off the blood supply that normally fuels the growthand spread of cancer cells. The
drug is approved in many par tsof the world for patients whose
glioblastoma brain tumors havereturned after initial treatment.
In Japan, it is also available as afront-line therapy.
In clinical studies, bevacizumabhas been shown to delay tumor
growth and improve patient function. However, the drug did notextend patients’ lives. When thecancer recurred after treatment,
it tended to come back with a
vengeance — and now Hikar u
Sasaki and Ryota Tamura, neurosurgeons at the Keio University
School of Medicine, have an idea012

| JITSUGAKU | December 2018 |A magnetic resonance imaging scan showing nerve pathways around a glioblastoma (red) in the brain.
Keio researchers have found how the drug bevacizumab improves blood vessels around such tumors but
fails to eliminate cancer stem cells. © SHERBROOKE CONNECTIVITY IMAGING LAB/SCIENCE PHOTO LIBRARY

why that is.
Sasaki, Tamura and their colleagues collected tumor samplessfrom six patients with glioblastomas who under went surger yshor tly after treatment with
bevacizumab. They also analyzed
tumor samples from eleven patients who did not receive thedrug. Across the treated tumors,
the researchers saw that bevaci-

Chromosomal chaos
gives cancer asurvival advantage
Cancer cells adapt to genomic abnormalities
by producing a protein that confers drug resistanceseparate study, Sasaki and hisRteam also found that blood vesselly from a given drug. A recent study

Noguchi and his colleagues there-

congestion might be involved2.

by Kohji Noguchi and colleagues

fore exposed colorectal cancer cells

zumab dramatically affected bloodvessels: they became less dense;
they no longer proliferated; and1

oxygen levels recovered . In aesistance is a vexing prob-

inhibitors are showing promise inlem in the world of cancer

cancer clinical trials. “However,therapy, with many pa-

we lack predictable biomarkers fortients either failing to re-these inhibitors to understand theirspond or benefiting only temporari-effectiveness,” says Noguchi.

However, the therapy neverat Keio University has uncovered

to increasing doses of an aurora

completely wiped out the cancer

a sur vival mechanism that tumor

kinase inhibitor, VX-680, in order

stem cells that seeded the recur-

cells use to elude destruction, and a

to isolate a variety of drug-resistantrence of the disease. While it did

potential avenue for designing moreclones for closer study. One effecteliminate one of the places where

effective cancer treatments1.

of aurora kinase inhibitors is thecancer stem cells are often found,

Drugs that sabotage cell division,accumulation of abnormal numbers

when the researchers looked foror mitosis, can help to slow downof chromosomes, a state known

nestin, a protein that indicatesand stop tumor growth. “Classicalas aneuploidy. Aneuploidy is often

the presence of cancer stem cells,

anticancer dr ugs, such as vinca

obser ved in cancer cells, but thisthey found it clustered around thealkaloids and taxanes, target mito-

condition typically triggers a self-

remaining blood vessels in a spotsis,” explains Noguchi. “And mitotic

destr uct mechanism in healthy

called the perivascular niche.

aurora kinases have also been con-cells. The researchers obser ved“Combination therapies that tar-sidered as a novel pharmacologicalthat their VX-680-resistant cells had

get the perivascular niche mighttarget.” These enzymes help man-become highly aneuploid, contain-

be a rational approach to treat

age the appropriate redistribution

ing 70-80 chromosomes rather the

glioblastomas more ef ficiently,”of genetic material during cellnormal complement of 46, but theysays Sasaki, noting that the persis-

division, and several aurora kinase

had clearly acquired a mechanism

tence of cancer stem cells “might
constitute one of the mechanismsof resistance to bevacizumab.”
Sasaki and his colleagues are
currently running a prospective
trial to clarify the mechanismsof resistance and to identify biomarkers that might predict likely
responders to bevacizumab.
References
1. Tamura, R., Tanaka, T., Miyake, K., Tabei, Y.,
Ohara, K. et al. Histopathological investigation of glioblastomas resected under bevacizumab treatment. Oncotarget 7, 5242352435 (2016).
2. Tokuda, Y., Tamura, R., Ohara, K., Yoshida,
K. & Sasaki, H. A case of glioblastoma resected immediately after administering bevacizumab: consideration on histopathologicalfindings and safety of surgery. Brain Tumor
Pathology 34, 98-102 (2017).

Fluorescence imaging of aurora kinase inhibitor-resistant cells reveals that aurora kinase B (green)and AKT3 (red) overlap at the center of the cell during cell division. The blue label indicates chromosomes. © 2017 The American Society for Biochemistry and Molecular Biology| December 2018 | JITSUGAKU | 013

that allowed them to sur vive despite

AKT family has multiple oncogenic

tant potential escape mechanism fortheir condition.

functions and is usually consideredtumors being treated with aurora

A closer examination revealed thatto work in cell survival mechanisms,

kinase inhibitors, but it also shows afour of these five drug-resistant cellwhich would provide resistance tovulnerability that could be exploited

lines were producing excessive levels

cytotoxic drugs,” he says. “However,in future treatments. “I hope to findof a signaling protein called AKT3.

there were no repor ts connecting

novel molecular targets for the selec-

A series of experiments in other cell

AKT with aneuploidy.”

tive killing of aneuploid cancer cells,”

lines subsequently provided compel-

Aneuploidy is not uncommon inling evidence that AKT3 prevents

malignant cells, and Noguchi believes

both the cell death and chromosomalthat these results reveal a connec-

abnor malities caused by aur ora

tion between this characteristic andkinase inhibition. According to No-

the emergence of dr ug resistanceguchi, this was unexpected. “Thevia AKT3. This highlights an impor-says Noguchi.
Reference
1. Noguchi, K., Hongama, K., Hariki, S., Nonomiya,Y., Katayama, K. & Sugimoto, Y. Functional effects
of AKT3 on aurora kinase inhibitor-induced aneuploidy. Journal of Biological Chemistry 292, 19101924 (2017).

Tarantula toxin reveals
channel function
Revelation of how a spider toxin binds to a membrane protein
could lead to new drug therapiesA

str uctural analysis of
how a toxin from tarantula venom disr upts
electrical signaling pro-teins could help pave the way for new
drugs to treat cancer, heart disease,neurological disorders, and otherconditions.
The human genome encodes 40
different voltage-gated potassium ion
channels (Kv), each of which allows
potassium ions to flow across the cell
membrane (see image). This generates electrical signals in cells that are
involved in ever ything from neurotransmission to muscle contraction.
The Kv proteins consist of two
domains that dif fer in function and© RAMON ANDRADE 3DCIENCIA/SCIENCE PHOTO LIBRARY

structure: a pore that conducts ionstial drug targets, but completely shut-“The VSD is a fascinating drug tar-and a sensor that reads the electricalting of f the channels causes major

get portion in Kv channels,” says Osa-

gradient across the membrane. Tox-

problems such as heart arrhythmias.

wa, a structural biologist at the Keioins used by poisonous animals act byConsequently, most researchers —University Faculty of Pharmacy, “buteither blocking the pore or modifying

including Keio University’s Masanori

no structural information had been

the sensor. These two mechanisms

Osawa — are tr ying to find ways toobtained on the interaction between

are also promising for developing

fine tune the activity of the voltage-

the VSD and a gating modifier toxin.”

new drugs.

sensing domain (VSD), which acts as

In theory, both domains offer poten014

Schematic image showing the molecular structure of a potassium channel in the cell membrane.

| JITSUGAKU | December 2018 |a gatekeeper for the ion pore.

To rectify this, Osawa teamed up
with scientists at the University ofTokyo to look at how a toxin foundstabilizes the VSD in a cer tain con-in the venom of the Chilean Rose

formation, locking it in that position.

“We are only just beginning to un-tarantula inhibits Kv channels by“This stabilization provides a possible

derstand the structural basis of how

binding to the VSD1. Using a nuclear

mechanism for a new drug targeting

gating modifier toxins bind the VSD,”

magnetic resonance method that thethe VSD,” says Osawa.

Osawa says.

2group had previously developed ,Other toxins known to bind thethe researchers identified the pre-domain — such as those found in thecise binding sites. They then used

venoms of scorpions, snakes, and sea

this information to build a structural

anemones — probably connect at dif-model of how the toxin docks onto

ferent sites to induce other conforma-the domain and blocks the protein’s

tions, Osawa notes. These too could

function.

provide a treasure trove of therapeu-

Their model indicates that the toxin

tic drug leads and warrant study ingreater structural detail, he says.

References
1. Ozawa, S., Kimura, T., Nozaki, T., Harada, H., Shimada, I. & Osawa, M. Structural basis for the inhibition of voltage-dependent K+ channel by gating
modifier toxin. Scientific Reports 5, 14226 (2015).
2. Igarashi, S., Osawa, M., Takeuchi, K., Ozawa, S.
& Shimada, I. Amino acid selective cross-saturation
method for identification of proximal residue pairs
in a protein-protein complex. Journal of the American Chemical Society 130, 12168-12176 (2008).

Shaking up cell culture
Mechanical vibrations offer a gentler way to detach cells from culture dishesA

gentler method for re-uses ultrasonic vibrations to releasevibrations are applied to shake themoving cultured cells

cells from culture dishes, which better

cells free.

from their dishes that

preserves their health and function.

An initial demonstration with mouse

enables har vesting of

Takemura is not a cell biologist,

muscle cells showed that this gentler

stronger and healthier cells has been

but Keio colleague Yuta Kurashina

treatment made a significant dif fer-developed by researchers at Keio Uni-thought his expertise in ultrasonics

ence. Although the relative number ofversity1.

could lead to a useful alternative todetached cells was about 23 per centScientists have been culturing cells

tr ypsin. “I’ve been working on ultra-

lower for this new approach, the cells

in dishes and flasks for more than asonic actuators for almost 20 years —were generally healthier than thosecentur y, but the emerging technolo-

since I was a student,” says Takemura.

that had been exposed to tr ypsin.

gies of tissue engineering and regen-

The two researchers conceived an

Their initial survival rate was nearly 20

erative medicine are producing new

approach in which the culture surface

per cent higher, and they had higher

challenges since they require a huge

is cooled, causing cells to loosen their

proliferation rates after several days

number of cells for a single treatment.

grip, and then controlled mechanicalof cultivation. The cells detached by

For example, about a billion cells need
to be grown to produce new hear t
muscle to treat a patient with weak
myocardial tissue.
Cells anchor themselves to thesurfaces of culture containers using
proteins in their outer membranes.
Researchers typically use an enzyme
called trypsin to cut those anchors andliberate the cells when they are readyto be transplanted into a recipient.
This enzyme, however, often damages
cells, especially the proteins on theirsurface.
Now, researchers led by Kenjiro
Takemura of Keio University havedevised a less disruptive method that

A scientist working with cultured cells in a clean room. Researchers at Keio have found a way to harvest
healthier cells using ultrasonic vibrations to gently remove them from their dishes. © E+/Getty| December 2018 | JITSUGAKU | 015

vibration also retained key structuralwhich may make the mass culture oftion should be smooth, making the ap-

features that were more likely to becells feasible,” he says.

proach more accessible to the broader

lost after detachment by trypsin.

His team’s top priority is moving

Takemura is optimistic that thisfrom the stainless-steel culture sur-method will improve the overall ef-

faces used in this proof-of-concept

ficiency of cell preparation for clinicalstudy to the plastic surfaces used inapplications. “Automation of cell cul-conventional cell-culture systems. Pre-

ture should be easier with our method,liminary data indicate that this transi-cell-biology community.
Reference
1. Kurashina, Y., Hirano, M., Imashiro, C., Totani,K., Komotori, J. & Takemura, K. Enzyme-free celldetachment mediated by resonance vibration
with temperature modulation. Biotechnology andBioengineering 114, 2279-2288 (2017).

Ancient antiviral response
could help treat cancer
A class of drugs can harness the power of the body’s immune system to fight diverse tumors
the drug cut the number of tumorsthat formed by roughly a third andthat animals that received the drug
tended to have smaller tumors thanthose that did not.
Having demonstrated that 5-azaCdR can act on such cancers, the researchers then cultured cells derived
from mouse intestinal tumors underconditions that promote the formation of three-dimensional ‘organoids’.
“Organoids are budding, cyst-likestructures that closely recapitulate
the proper ties of the original tumors,” explains Saito, “This makes
them a power ful tool for studying
Three-dimensional organoids derived from human cholangiosarcoma tumor cells.
© 2017 Yoshimasa Saito, Keio University

B016

how cancers respond to treatment.”
The researchers found that 5-aza-y stimulating a patient’s

growth and sur vival.

CdR strongly inhibited the growth ofimmune system, a drug al-Some studies have shown thattumor-derived organoids and wereready in use to treat a blood

methylation inhibitors such as 5-aza-minimally toxic to healthy intestinal

disorder can thwar t theCdR could be used to treat othercells.

growth of a variety of solid tumors,

cancers. These ef fects have gener-D e l v i n g d e e p e r, S a i t o ’ s t e a mfind a team at Keio University1.

ally been attributed to the drugs re-looked at which genes were turned

The drug 5-aza-CdR is currently ap-

activating tumor-suppressor genes,of f and on by this treatment andproved for treating a blood disorderbut the actual mechanism remains

noticed a striking pattern. “Our find-that can lead to leukemia. It inhibits

poorly understood.

ings indicated that DNA demethyl-the methylation of DNA, preventing

Yo s h i m a s a S a i t o a n d h i s c o -ation suppresses the proliferation

enzymes from chemically modifying

workers at Keio University set about

of intestinal tumor organoids by in-genomic DNA. Such modifications

figuring out how the dr ugs work.

ducing an anti-viral response,” says

can greatly alter the expression of

They began by assessing the effects

Saito. He and his colleagues suggest

genes that control a variety of criti-of 5-aza-CdR on a mouse model of in-that the methylation inhibitors arecal cellular functions, including cell

testinal cancer. The team found thatsomehow reactivating endogenous| JITSUGAKU | December 2018 |shift in our understanding of theas cholangiosarcoma and pancreaticsequences that have accumulated

anti-tumor mechanisms of DNA de-cancer. “We are tr ying to develop aover evolutionar y histor y and now

methylating agents,” says Saito.

personalized therapy for refractor yretrovir uses — ancient viral DNA

lie dormant throughout the genome.

The team believes the strategy

This initial antiviral response leads

could be effective for treating otherto immune activation and the shut-cancers, and it has already obtainedting down of tumor proliferation.

promising results with organoids de-“These findings represent a major

rived from challenging tumors suchcancers,” says Saito.
Reference
1. Saito, Y., Nakaoka, T., Sakai, K., Muramatsu,
T., Toshimitsu, K., Kimura, M., Kanai, T., Sato, T. &Saito, H. Inhibition of DNA methylation suppresses
intestinal tumor organoids by inducing an antiviral response. Scientific Reports 6, 25311 (2016).

Digital 3D-fabrication technology
for nursing and healthcare
Innovative 3D-printed ‘caring-tools’ to enhance the quality of life of elderly people

3

D printing technology has

three types.

important medical applica-

Firstly, are self-help devices en-

tions, such as manufactur-

abling individuals to carr y out spe-ing prosthetic par ts, im-cific tasks. For example, someone

plants, and models of human organs.

with paralyzed fingers who is unable

Here, researchers at Keio University

to pinch, is assisted by a customizedin Tokyo, describe the potentially

3D-printed penholder for signing im-impor tant role of 3D printing in

portant documents.

nursing and long-term care for theSecond, ‘caring tools’ facilitate

elderly. Given Japan’s rapidly ageinginteraction between care-givers andsociety, demand for terminal care

care-receivers. For instance, cutting

in hospitals or care facilities will ex-out plasters in fun shapes — such as

ceed capacity in the near future. Fur-animals — with a laser cutter helps

the researchers are currently devel-

thermore, there are insufficient visit-patients overcome negative percep-

oping an ‘internet-of-things’ sensing

ing nurses to provide in-house care.

tion of surgical tape.

system: a data logger that can collect

A 3D printer used by Keio researchers to digitally
fabricate objects such as a pen holder and cranial model for nursing and healthcare.
© Keio University Social Fabrication Lab.

information about an object’s use for

Therefore, strengthening in-house

Third, Miyagawa and colleagues

care is an urgent task for healthcare

identified educational objects asof the elderly. The introduction oftools to lear n how to per form

Having established the relevance

information technology (IT) is an es-

therapy actions. For example, a 3D-

of 3D printing techniques for im-

sential strategy from both aspects ofprinted semi-transparent cranial

proving the quality of life and the in-work ef ficiency and providing highmodel can be used for practicing

dependence of elderly people, Miya-quality care.

the inser tion of a tube for vacuum-

gawa and colleagues conclude that,

one month.

Specifically, Shoko Miyagawa anding phlegm from a patient’s throat“in order to make digital fabricationcolleagues at Keio University noticed

with light-emitting diodes acting as

more useful it is necessar y to further

the increased availability of 3D print-

guides to follow its position inside

reduce the cost of introduction anders in self-help community centersthe model. The researchers also ad-

operation and to develop technolo-

throughout Japan. Based on interac-dressed the question of safety, as thegies to do so.”tions with nurses, medical practitio-

proposed 3D-printed objects must

ners, engineers and material design-

be washable and not produce skiners, Miyagawa and her collaborators

irritation. Another important aspectestablished a benchmark for specificof the research project of the Keio

digitally fabricated objects neededscientists is an assessment of the us-

by patients and classified them into

age level of the objects. To this end,

Reference
1. Asano, Y., Tanaka, H., Miyagawa, S. & Yoshioka, J. 3D printing and IoT for personalized everyday objects in nursing and healthcare. Proceedings SPIE 10167, Nanosensors, Biosensors, Info-Tech
Sensors and 3D Systems advance online publication, 17 April 2017

| December 2018 | JITSUGAKU | 017

Robotic arms witha human-like
sense of touch
Birth of innovative touch sensitive avatar robotic arm
based on real-haptics

T

sense of touch without using touch
sensors.
The real haptics robot GPA can recognize shapes and compositions ofmaterials — soft or hard — positionof objects in 3D-space, and manipulatethem according to real-time instructions from a remotely located user,
where the arm acts as a real-time avatar. Historically, the technical breakthrough in motor control and robotics

he world’s first‘real haptics’avatar-robot arm

This is the world’s first high preci-that led to the successful development

sion ‘tactile force transmission tech-of the robotic-avatar developed by No-

nology’ that remembers human move-zaki and colleagues was first reported

Conventional haptic robots

ments, edits and reproduces them.

by Keio University’s Kouhei Ohnishi

communicate with humans by trans-

Notably, the GPA does not employ

in 1983 in his paper titled, “Torque-mitting the sense of touch to their op-

conventional touch sensors, thereby

speed regulation of DC motor based

erators through mechanical vibrations

making it cheaper, more compact andon load torque estimation method”

using touch sensors, which can berobust. The realization of the Keio(IPEC — Tokyo’83, page 1209). Ohni-

insensitive and prone to malfunction.

University touch sensitive avatar-

shi continued to develop his ideas inHence, this type of haptics technology

robotic arm based on real-haptics is

his 1993 paper on ‘sensorless torqueis useful for games and entertainment

a dream come true for Nozaki. “As acontrol’ (IEEE Transactions on Indus-

but has limited industrial applications.

high school student I wanted to study

trial Electronics, 40, 259, (1993)).

Takahiro Nozaki, an assistant profes-

robotics, and sur veying my options

This report was followed by his pro-sor at the Faculty of Science and Tech-enrolled at the Department of System

posals for ‘motion control in mecha-

nology, Keio University and colleagues

Design Engineering at Keio University

tronics’ (IEEE Transactions on Mecha-

have developed a ‘real haptics’ avatar-— the top department in Japan con-tronics, 1, 56, (1996)).

robot with a General Purpose Arm

ducting this type of research.”(GPA) that transmits sound, vision,
movement, and importantly, a highly
sensitive sense of touch, to remotelyCore technology for the realtime haptic avatar arm

Commercializationof ideas and future work
Nozaki has launched the company

located users in real time. “Our real-

The two innovative key components

Motion Lib to commercialize his ‘real-

haptics technology is an integral partof the Keio avatar-robot GPA are highhaptics technology’. The main productof the Internet of Actions (IoA) tech-

precision motors in the avatar arm

is the ‘ABC-CORE’ IC force/tactile

nology with potential applications inand algorithms to drive them. Impor-controller that uses two synchronizedmanufacturing, agriculture, medicine,tantly, the precise control of force andmotors to adjust the force of DC/AC

and nursing care,” says Nozaki.

position is critical for transmitting theservomotors and transmission of tactile forces.
Furthermore, Nozaki is collaborating with 30 companies to conduct
proof of concept projects for applications to Internet of Actions (IoA). “In
one of our projects, the assist-avatar
robotic GPA is being tested for reallife applications in supporting farmers
to pick fruit and other agricultural applications,” says Nozaki.
Reference
1. Fukushima, S., Sekiguchi, H., Saito, Y., Iida, W.,

Touch sensitive avatar-robotic arm based on real-haptics developed by Takahiro Nozaki andcolleagues at the Keio University Haptics Research Center.
© 2017 Keio University

018| JITSUGAKU | December 2018 |Nozaki, T., & Ohnishi, K., Artificial Replacement of
Human Sensation Using Haptic Transplant Technology IEEE Transactions on Industrial Electronics
advanced online publication 2 October 2017
(doi: 10.1109/TIE.2017.2758757).

Health economics offers
unique insights into modern
Japanese society
Fusing expertise in medicine and health economics sheds new lighton healthcare and gambling in Japan“M

2013 using the Japanese Diagnostic

ed casino resor ts. “In this research

medical prac-

Procedure Combination (DPC) data-

we wanted to clarify the actual level

titioners, so I

base,” explains Goto. “Our aim wasof pathological gambling in Japany family are allfollowed in theto elucidate the effects of increasing

and verify whether easy access to

tradition and studied medicine at

subsidies for outpatient care on hos-gaming facilities is a risk factor for

Kyoto University,” says Rei Goto, anpital admissions.”

pathological gambling,” says Goto.

associate professor at the Graduate

The researchers conducted an

School of Business Administration,internet-sur vey on ‘lifestyle and lei-

Keio University. “But ever since mysure’ covering the whole of Japan

schooldays, when healthcare was(excluding minors) from 17 to 22 No-

free for the elderly, I have been in-

vember 2014, with responses fromterested in government policy and6,576 people, and used the South

management of Japan’s healthcare

Oaks Gambling Screen to determine

system.”signs of gambling dependence.

During his final year at medical

Generally, the sur vey showed that

school Goto went to Newcastle, Eng-

gambling dependence was not relat-

land, for a shor t course in clinicaled to the ease of access to pachinko

training and “discovered the fieldof health economics” that was at
the hear t of healthcare management in the UK. “My visit to the UK

parlors. However, accessibility was a
Rei Goto is combining his expertise in medicine
and health economics to analyze social issues inJapan such as healthcare and gambling.
© 2017 Rei Goto Keio University

significant factor in gambling dependence for men, and people living in
low income areas. Also, accessibility

reignited my interest in healthcare

The sur vey showed that in generalof pachinko parlors was not a factor

management,” says Goto. “So after

decreasing cost sharing for outpa-

for women and people living in highcompleting my two year hospitaltient care did not significantly affectincome areas.

residency, I star ted on a doctoraladmissions to hospital. However,“I hope that our research on healthcourse in health economics at Kyoto

hospitals in low income r egions

and social issues in Japan, which

University to study social issues inshowed a decrease in admissions,has the world’s fastest aging popula-

Japan, including healthcare costs

and those high income areas, an in-tion, will be a useful reference forand gambling.”

crease. “These results are importantscientists and policy makers in otherbecause prior to our study we didcountries,” says Goto. “We will con-

not know the ef fect of income ontinue to publish and disseminate

hospital admissions,” says Goto. “Ininformation about this research for a

low income areas, the increase inglobal audience.”

Rationalizing costsof outpatient treatment
for children withhospital admissions
In this study Goto and colleagues
analyzed the effect of reducing medical care subsidies given to children
receiving outpatient treatment on

outpatient medical expenses may beoffset by decreases in hospital medical expenses due to admissions.

Gambling on the future

inpatient admissions in JapaneseGambling in Japan is undergoinghospitals. “We obtained inpatient

unprecedented changes as exempli-

data for 366,566 children in 1,390

fied by recent government proposals

municipalities in Japan from 2012 toto allow the construction of regulat-

References
1. Kato, H. & Goto, R. Effect of reducing cost
sharing for outpatient care on children’s inpatient services in Japan. Health Economics Review
advance online 15 August 2017 (doi: 10.1186/
s13561-017-0165-3).
2. Kato, H. & Goto, R. Geographical accessibility
to gambling venues and pathological gambling:an econometric analysis of pachinko parlours inJapan. International Gambling Studies advanceonline 12 October 2017 (doi: 10.1080/14459795.20
17.1383503).

| December 2018 | JITSUGAKU | 019

Tardigrade genomes explain
life on the extremes
DNA analysis shows how water bears survive extreme conditions,
yet leaves evolutionary origin unclearT

iny water-dwelling creatures known as tardigrades
can sur vive for years in theface of extreme tempera-

tures, radiation exposure, desiccation, and even the vacuum of space.
How these micr oscopic animals
evolved and why they are invincible
have long puzzled scientists.
A genomic study co-led by Keio
University researchers sheds lighton how these hardy beasties withstand rapid desiccation, freezing,and other environmental trials, andprovides new clues on the contested
evolutionar y histor y of tardigrades,
also known as water bears or moss
piglets1.
The findings hold relevance beyond this particular quirk of natural
histor y, says Kazuhar u Arakawa
from Keio’s Institute for Advanced
Biosciences. “These mechanisms
to withstand significant cell damage
may lead us to better understand theintegrity of human cells on stressand damage,” he says.
What’s more, insights about how
tardigrades endure dehydration may
help scientists develop more stable
enzymes, vaccines, and cell therapies
that can be freeze-dried and stored
at room temperature. “We foreseesignificant impact on the preser vation and logistics of these products,”
Arakawa says.

Reference
1. Yoshida, Y., Koutsovoulos, G., Laetsch, D. R.,
Stevens, L., Kumar, S., Horikawa, D. D. et al. Comparative genomics of the tardigrades Hypsibius
dujardini and Ramazzottius varieornatus. PLOS
Biology 15, e2002266 (2017).

020| JITSUGAKU | December 2018 |Arakawa’s team at Keio joined forces with Mark Blaxter and his groupat the University of Edinburgh, UK,
to decode the full genomes of two
tardigrade species, Hypsibius dujardini and Ramazzottius varieornatus.
Together, they analyzed their gene
expression patterns at various developmental stages, including the desiccated ‘tun’ stage, and identified anumber of genes related to extreme
sur vival abilities and other genes involved in stress responses that wereshared by both species. They also
found many genetic differences that
could explain why H. dujardini takes
about a day to become dor mant
while R. varieornatus can do so inless than 30 minutes.
The researchers then exploredwhether the genomes could resolve the place of tardigrades in theevolutionar y tree of life. For many
years, biologists debated whether
tardigrades are more closely related
to nematode worms or ar thropods.
Their four pairs of stubby legs, eachtipped with claw-like bristles (see image), indicated arthropods were thenearest kin, but molecular biology
suggested that they might be closer
to nematodes.
However, genomic comparisonswere not definitive. Analyses of genesequences supported the tardigrade−nematode link, whereas studies ofrare genomic changes supported thetardigrade−ar thropod one. “We still
have contrasting evidence for phylogeny, and it remains unresolved,”
Arakawa says.
“But our r esults clearly showthat the tardigrade−nematode relationship cannot be immediately
rejected,” he adds, noting that additional genomes from related crittersshould help resolve this evolutionar y
enigma.

The genomes of Ramazzottius varieornatus (pictured) and another tardigrade species reveal
how these hardy creatures persist in extreme environments.
© 2018 Hiroki Higashiyama and Kazuharu Arakawa, Keio University| December 2018 | JITSUGAKU | 021

Tracing the origins of theJapanese with 3D technology
By using computed tomography to analyze hominin bones,
researchers at Keio are revealing the history of Japan’s first inhabitants

other known hominins in Asia.
She is now applying her technique
to sites in Japan. “We know that hominins came to the Japanese archipelago
about 40,000 years ago, but we don’tknow much else about the time before the Jomon period, which started
roughly 16,000 years ago,” says Kono.
“The Shiraho remains will definitely
give us much more accurate insight.”
One of the Shiraho remains had
surfer’s ear, a bone growth inside theear induced by regular exposure towind and cold water. Two had heavily worn teeth on both the upper andlower jaws, although the teeth on theupper jaw were more worn than those
A half-size, three-dimensional printed restoration model of a Shiraho skull.

Uon the lower. These are just some ofthe details Kono and colleagues aretr ying to explain in order to under-

nbeknownst to the manyscanning and three-dimensional (3D)

tourists who flock to Ish-printing to virtually restore the bones“One thing we can say for sure isigaki Island in Okinawa,of hominins — modern humans andthat any information we obtain fromthe island harbors an

extinct human species.

the Shiraho bones will provide valu-

stand the Shiraho people’s lifestyle.

archaeological site where the stor y

Kono begins her 3D virtual restora-

able new insights and be of greatof Japan’s first people is being gradu-

tions with a CT scan. The bone frag-impor tance to the study of humanally revealed. A limestone cave set

ments are converted into digital dataremains in Japan,” Kono comments.

slightly back from Shiraho beach has

made up of tiny pixelated cubes andyielded an unprecedented number

triangular surfaces. Kono then usesof bone fragments, which date backthis data to determine how the frag-more than 20,000 years — some ofments should be pieced together.

the oldest found in Japan.

Analyzing ancient bones using
modern technology
We know much less about the first
Asians than the early humans of Af-

022© 2018 Reiko Kono, Keio University

Coming face-to-facewith the Shiraho people
In addition to illuminating charac-“It may be time consuming, but it’steristic differences with other humana non-invasive way of restoring re-remains in Japan, Kono has her eyes

mains,” says Kono. “Printing out andset on another ambitious goal: re-physically touching the restoration

constructing the faces of the Shiraho

model also helps verify that the frag-people.

ment connections make sense.”“The remains from Minatogawa onrica and Europe. Reiko Kono of Keio

Recently, Kono’s exper tise in 3D

Okinawa Main Island 4 had been the

University’s Faculty of Letters is tak-restoration has helped advance‘industr y standard’ of what the first1

2

ing advantage of the power of modern

research in Taiwan , China and In-

Japanese people looked like,” says

technology to improve the effective-

donesia 3. Her models have allowed

Kono. “The Shiraho bones are now

ness of excavations in Asia. She isresearchers to confirm that they had

telling us that our ancestors in Japan

using computed tomography (CT)found groups of people distinct fromwere also more diverse.”| JITSUGAKU | December 2018 |One challenge has been that faces,

References
1. Chang, C., Kaifu, Y., Takai, M., Kono, R. T., Grün,

with small, delicate parts, shatter easily. But this is where 3D scanning canhelp. “With digital data, it’s possible
to make mirror images of fragments,”
says Kono. “If there’s a part missing
on one side, we can complement it inthis way.”
The 3D digital restoration of the
Shiraho people is nearing completion.
In the process, Kono reaches backto the beginning, shedding light on aburied chapter.

Doing a three-dimensional computed tomography scan of a Shiraho skull.

R., Matsu’ura, S. et al. The first archaic Homo from
Taiwan. Nature Communications 6, 6037 (2015).
2. Liu, W., Martinón-Torres, M., Kaifu, Y., Wu, X.,
Kono, R. T., Chang, C.-H. et al. A mandible from
the Middle Pleistocene Hexian site and its significance in relation to the variability of Asian Homoerectus. American Journal of Physical Anthropology 162, 715-731 (2017).
3. van den Bergh, G. D., Kaifu, Y., Kurniawan, I.,
Kono, R. T., Brumm, A., Setiyabudi, E. et al. Homofloresiensis-like fossils from the early Middle Pleistocene of Flores. Nature 534, 245-248 (2016).
4. Kaifu, Y., Fujita, M., Kono, R. T. & Baba, H. Late
Pleistocene modern human mandibles from theMinatogawa Fissure site, Okinawa, Japan: morphological affinities and implications for modern
human dispersals in East Asia. Anthropological
Science 119, 137-157 (2011).

© 2018 Reiko Kono, Keio University

Using iron to accelerateorganic synthesis
A catalyst made from Earth-abundant iron can drive an important reaction
for making organic compoundsA

simple iron catalyst cancompounds, three researchers at
1

materials and therapeutic drugs.

replace costly r uthe-

Keio University have shown . This

Organic molecules consist mainly

nium in a reaction thatfinding promises to make it cheaperof carbon and hydrogen atoms plus

can be used to generate

to produce complex organic mol-a few other ‘heteroatoms’, such as

diverse libraries of complex organic

ecules such as organic electronic

nitrogen, oxygen or chlorine. Chem-

Keio University researchers
have found a way to replace
the expensive precious metalruthenium (pictured) with asimple iron catalyst for the
carbon-hydrogen alkylation ofaromatic ketones by alkenes.
© SCIENCE PHOTO LIBRARY| December 2018 | JITSUGAKU | 023

ists have traditionally exploited theten expensive precious metals suchchiometric reactions gave us hints

reactivity of these heteroatoms toas rhodium, palladium or ruthenium.

to develop ir on-catalyzed or tho-build complex products from simple

There is thus a strong push to re-selective carbon-hydrogen alkylation

star ting molecules. This approach,place these precious metal catalysts

of aromatic ketones with alkenes,”

however, can require long sequenceswith cheaper catalysts made from

Kakiuchi explains.

of reactions to install the correct set

inexpensive, abundant metals suchof heteroatoms for a particular con-as iron.

The next frontier of carbon-hydrogen functionalization reactions is toNow, Fumitoshi Kakiuchi and co-

develop ‘regioselective’ catalysts thatworkers Naoki Kimura and Takuya

selectively target a particular carbon-

A more ef ficient way to make or-

Kochi at Keio University have shownhydrogen bond without needing aganic molecules is to directly manip-that a simple iron compound cata-

directing group such as a ketone.

ulate a molecule’s carbon-hydrogenlyzes the carbon-hydrogen alkylation“Regioselective carbon-hydrogenbonds. Known as carbon-hydrogenof aromatic ketones with alkenes.

functionalization of aromatic com-bond functionalization, this reaction

The iron compound does this bypounds without using a directing

involves breaking the bond between

bonding to the ketone group of thegroup is still quite dif ficult,” Kaki-carbon and hydrogen and then swap-

aromatic ring, which directs the in-uchi notes. “We intend to develop

ping the hydr ogen with anothercoming alkene molecule to attach tothis type of regioselective carbon-

element such as carbon, oxygen or

the adjacent, ‘or tho’ position of thehydrogen functionalization using ad-

nitrogen. But because organic mol-aromatic ring. The trio showed that

ditives or ligands.”

ecules typically contain many sucha wide variety of alkenes can be usedbonds, it is dif ficult to selectively

for this reaction.

version, making synthesis expensive
and time consuming.

trigger a reaction at only the desired
carbon-hydrogen bond.

Previous research had suggested
that iron could drive this transforma-

One way to achieve this selectivity

tion, but the iron was consumed in

is to use a catalyst, but these are of-the process. “These precedent stoi-

Reference
1. Kimura, N., Kochi, T. & Kakiuchi, F. Iron-catalyzed regioselective anti-Markovnikov additionof C-H bonds in aromatic ketones to alkenes.
Journal of the American Chemical Society 139,
14849-14852 (2017).

Politics of populism
behind Putin’s 2016 victory
Keio analyst Atsushi Ogushi argues that rising populism contributed
to Putin’s definitive result in the 2016 Russian Duma electionT024

he strong showing of Vladi-

all-impor tant. He says that the rise

was simply the next wave in popu-

mir Putin’s United Russia

of one signals the fall of the other, inlism. He notes that changes to theparty in the 2016 Duma elec-

direct proportion.

electoral system should have seention can be ascribed to theIt was through this lens thata marshalling of the forces of therecent rise in the politics of popu-

Ogushi analyzed the 2016 Dumapar ty machine, but there was little

lism in Russia, according to Atsushi

election, which saw United Russia

evidence that this took place. This

Ogushi, an associate professor inwin 76 per cent of the seats.

implies that the changes, along with

the Department of Political Science

Putin’s fluctuating popularity had

the relative popularity of United

at Keio University and an analyst ofreceived a boost due to his handling

Russia, helped the par ty win many

Russian politics1.

of the crisis in neighboring Ukraine.

seats.

Ogushi argues that populism,

However, Ogushi argues that the

however broadly it is defined, is theshift fr om machine politics had

opposite of machine politics, wherebeen a prominent feature of Russian

Ogushi believes the Kremlin em-

the par ty and its foot soldiers arepolitics in the past and that the 2016ployed two strategies to bolster Pu-| JITSUGAKU | December 2018 |Two-pronged approachfrom machine politics and toward a
populist regime.
“There is little doubt that Putin
will win the next presidential election, but that must be his last term,”
he says. “So successor str uggles
may take place within a few years,
but the great power concentrated in
Putin’s leadership will complicate
the succession. It will be ver y interesting to see how a personalized
political system can overcome thesuccession problem.”Ogushi’s analysis is born of onthe-ground experience with the RusAtsushi Ogushi has been interested in Russian politics at the Kremlin since before the demise of the USSRin 1991. © Elena Liseykina/Getty images

sian nation.
“I think it is ver y impor tant for

tin’s personal appeal. The first wasto oversee the running of the 2016

political scientists to conduct field-

to distance Putin from the United

election, and sur veillance cameras

work,” he says. “Sometimes they

Russia party so that he could appear

were deployed to encourage trans-

instead concentrate on cr eating

as standing above par ty politics. In

parency at polling stations. Although

theoretical models. That might be

his analysis, Ogushi comments, “it isvoter turn-out remained low, Ogushi

okay in a purely academic world, butmuch safer for Putin to stand apar t

says “it is widely acknowledged thatpolitical studies can have politicalfrom all parties, and this may be his

the 2016 Duma election was more

and policy implications. I think the

populist method for gaining support

open than the previous one.”‘theor y first’ mentality that forms

from people in general.”
The second strategy was to culti-

Looking aheadvate a ‘clean’ image for Putin, with

Ogushi notes that if Putin can

him attacking of ficials who were

sustain this level of popularity inpopularly perceived as being cor-the long run, it could signal a funda-

rupt. A new director was appointed

mental shift in Russian politics away

policies without a knowledge of theregion can be dangerous.”
Reference
1. Ogushi, A. Weakened machine politics andthe consolidation of a populist regime? Contextualization of the 2016 Duma election. Russian
Politics 2, 287-306 (2017).

Frontiers of haptics science:
Uncovering the secrets of thehuman body’s perception of touch
Insights into human touch and body perception and their utilization
for positive psychological and cognitive effects in our daily lives

T

he sense of touch:Who is shaking
hands with whom?

perceptions of the sense of touch isby human somatosensory (touch andstill limited. For example, during abody) perception and its utilization forhandshake, who is shaking whose

positive psychological and cognitive

Scientific research has

hand? The answer to this question iseffects in our daily lives,” says Naka-

yielded deep understanding on thejust one of the multifaceted aspects oftani, who commenced his research on

human senses of sight, hearing, smell,

touch being studied by ‘haptics scien-

the Shonan Fujisawa Campus (SFC),

and taste. But knowledge about bodily

tist’ Masashi Nakatani. “I am intrigued

Keio University, in April 2017. “I start| December 2018 | JITSUGAKU | 025

environments less manually and actively,” explains Nakatani.

Environment at the Keio
SFC campus promotesinterdisciplinar y research
The Keio SFC campus is also conducive for interdisciplinary research,
an impor tant factor for Nakatani tobe able to pursue his studies on haptics and other research field. “I amworking with a music-neuroscientist,
Dr. Shinya Fujii, on the relationshipbetween auditory and haptic feedbackon subjective frisson, that is the ‘feelFigure 1: Children from 0 to 6 years old explore their environments to collect information necessary for
their survival. © cocoiku by ISETAN SHINJUKU Storeing of being chilled and touched’,”says Nakatani. “One of my goals is
to clarify how body perception helps

ed studying touch modality 16 years

included haptics. “This sounded likeus acquire cognitive skills that areago as an undergraduate. My doctor-

a very cool concept and I decided tounique to human beings, par ticu-

ate was about human tactile percep-

collaborate to develop a parenting ser-larly in the modern information age”

tion for developing tactile displays

vice for children,” explains Nakatani.

(Fig.1).

that can provide information through“I’m studying how infants explore andthe skin surface.” After his doctorate,‘feel their world’ using their vision and

Nakatani investigated touch receptors

touch before they have even acquired

Nakatani and colleagues invented

embedded in the skin in a dermatol-

language skills. They are collecting

the TECHTILE toolkit to promote

ogy laborator y 1 and also worked in

information needed to sur vive.” Un-people to appreciate the sense ofindustry on developing tactile sensors

derscoring concerns about the effects

touch 3. “I think that modern haptic

of modern technology on children’s

devices must provide greater value

behavior, Nakatani is analyzing how

for us to enjoy our daily lives,” says

current technologies such as smart-

Nakatani. One of Nakatani’s students,

phones and tablet PCs af fect their

Kazuki Sakurada, has developed a2for evaluating cosmetics .

Focus on developmental
psychology in infants

TECHTILE toolkit

Now, Nakatani is concentrating on

visual and haptic explorator y behav-

smartphone-based haptic chat systemdevelopmental psychology in infants,

ior. “My working hypothesis is thatwith audio-vibrotactile feedback to

a topic that was triggered by a chancesome kids have less opportunities toprovide a sense of presence of others

meeting with an educator developing

explore with touch modality because

during text conversations. “This study

parenting classes for children fromof exposure to massive amounts of

may yield clues about the importance

0 to 6 years old, who wanted to use

information and communications via

of somatic feedback in emotional at-state-of-the-art media technology thatvisual modality, so that they explore

tachment with other people (Fig. 2),”says Nakatani. “In the long term, I
would like to enhance human abilities
to extract valuable knowledge fromoverwhelming, excessive informationin the environment.”

References
1. Maksimovic, S. et al. Epidermal Merkel cells

Figure 2 : Smartphone-based haptic text-based chat system with audio-vibrotactile feedback for sense ofpresence. © Kazuki Sakurada, SFC TOUCH LAB

026| JITSUGAKU | December 2018 |are mechanosensory cells that tune mammalian
touch receptors, Nature 509, 617-621 (2014).
2. Nakatani, M, et al. Softness sensor system forsimultaneously measuring the mechanical properties of superficial skin layer and whole skin. Skin
Res Technol. 19 (1), e332-8, 2013.
3. M. Nakatani, et al. TECHTILE Workshop for Creating Haptic Content. Pervasive Haptics: Science,
Design, and Application. 185-200.

Smart paper gives low-cost
diagnostics in living color
Inkjet printing technology transforms ordinary filter paper into devices
that can spot kidney disease or contaminated waterPaper-based analytical de-wax ink printers,” explains Citterio.

from cellulose in the paper substrate.

vices have come a long way“These barriers are three dimensional,

Most devices direct water along thefrom old-fashioned litmus

extending throughout the thickness of

paper’s surface, but the team obtained

strips used to measure pH.

the paper, and so they guide the liquid

better results when droplets were

Advanced printing techniques now

where we want it to go.”driven vertically. “Since optode mem-

enable quick, accurate testing for

Citterio and his co-workers special-branes are highly hydrophobic, liquids

multiple chemical or biological agentsize in paper analyzers that indicate

will try to avoid these zones in lateralon substrates that cost just pennies

the presence of specific compounds

channels,” says Citterio. “However,to produce. Researchers at Keio Uni-

through vivid color changes. One re-top-down flow forces the liquid to con-versity are showing how the efficient

cent project involved creating opticaltact the hydrophobic area, generating

display of color-based information may

electrodes, or ‘optodes’, that identify

stronger color signals.”

take such paper-based devices out of

aqueous ions such as sodium, making

the lab and into the real world for ap-

them useful for various applications,plications including medical and envi-

including water monitoring.

ronmental diagnostics1,2.

Guiding flow using
water-repelling inks

Simpler testing of urine
Another diagnostic device devel-

Optodes are also extremely sensi-

oped by the Keio researchers aims

tive to pH because they rely on theto improve a basic diagnostic tool —exchange of protons against the target

the urine dipstick. Their device alters

cation to initiate a color change. But

color in response to different protein

When water droplets come into con-this sensitivity normally requires us-

levels. “People normally don’t havetact with conventional filter paper, theyers to simultaneously measure pH andurine dipsticks at home because thespread uncontrollably in all directions

apply a correction to the sample. “Onecolor change is quite faint,” says Cit-as they absorb. To direct the flow of

big advantage of paper is that you canterio. “But if used correctly, they cansamples such as tiny blood drops,

put almost anything on it, including a

indicate signals of kidney disease.

Daniel Citterio from Keio University

pH buffer,” notes Citterio. By incor-

Doctors tell us that they can do more

and his team employ microfluidic pat-porating the buf fer layer into theirfor patients with earlier warnings.”

terning techniques based on water-re-device, the researchers ensured it au-

To avoid such uncer tainties, thepelling inks. “We create hydrophobic

tomatically adjusts for varying chemi-team developed a text-displaying

barriers using common inkjet or solid

cal conditions, including those arising

dipstick. Using inkjet printers and a
special ink that changes color at different biomolecular concentrations, they
printed symbols signifying different
levels of protein: from ‘trace’ to ‘+4’.
The paper device is then inserted into
the lower portion of three-dimensional
printed housing, and a screening
film is placed on top to hide the text.
Briefly immersing these devices intourine samples demonstrated that thisapproach can give the same accuracy
as commercial dipsticks but with readouts that are far simpler to interpret.

Reading the results of home urine tests can be challenging. Daniel Citterio and his team have developed a system that makes it much easier to interpret results. © 2018 Daniel Citterio“This could benefit people with color
vision anomalies,” notes Citterio. “And| December 2018 | JITSUGAKU | 027

this same concept could be applied
to any type of colorimetric indicator.
As long as you can read, you can’t gowrong.”

References
1. Shibata, H., Henares, T. G., Yamada, K., Suzuki,
K. & Citterio, D. Implementation of a plasticized
PVC-based cation-selective optode system intoa paper-based analytical device for colorimetricFaulty transporter
protein could underpin
delayed labor
A protein in the placental lining helps synthesize a fetal hormone that signals to pregnant mothers to begin contractions

Rsodium detection. Analyst 143, 678-686 (2018).
2. Yamada, K., Suzuki, K. & Citterio, D. Textdisplaying colorimetric paper-based analyticaldevice. ACS Sensors 2, 1247-1254 (2017).

from the placenta that invade the wallof the uterus and enable nutrients tocirculate between the fetus and themother.
In particular, the researchers lookedat the part of the syncytiotrophoblast
cell membrane that faces the fetal
side. They created tiny capsules fromthis membrane and found huge numbers of OAT4 proteins, which proved
to be essential for the passage of theestriol precursor.

ates of childbirth by cesar-

and kidney. It helps the developing

ean section are on the rise

fetus both to get rid of toxins and to

According to Tomi, most studies on

worldwide, and while there

synthesize various sex hormones, in-estrogen synthesis processes haveare some social reasonscluding estradiol, estrone, and estriol

focused on the action of enzymes. “Infor this increase, an all-Keio team of(collectively known as estrogens).

contrast, our study has highlighted

researchers has identified a potential

The impact of OAT4 on estradiol andthe impor tance of membrane trans-

biological one1. Specifically, Masatoshi

estrone signaling is better known thanporters,” he says. “Our finding will be

Tomi at Keio University’s Faculty of

its effect on estriol signaling, despite

a trigger to put more emphasis on the

Pharmacy and his colleagues foundestriol being the only estrogen thattransporter in estrogen synthesis bythat a transporter protein called OAT4

arises solely from a fetal-derived pre-the fetoplacental unit.”

is needed for the fetus to signal to its

cursor.

Recent studies from Tomi and his

mother to begin contractions. WhenTo test the role of OAT4 in convey-

colleagues have found that OAT4

this protein is faulty, labor gets de-ing the estriol precursor from the fe-

proteins in the same syncytiotropho-

layed, which may partially account for

tus across the placenta, Tomi and his

blast cells help the fetus transport an

the high incidence of cesarean sec-team studied a population of placental

antihistamine drug called levocetiri-

tions in Japan and elsewhere.

cells called syncytiotrophoblasts,zine and a blood pressure drug called

which cover finger-like projections

olmesartan. Notably, OAT4 is found

OAT4 is expressed in the placenta

only in primate cells; it does not occur
in rodents. That could help to explaina uniquely human side effect of antihyper tensive drugs such as olmesartan. In mouse models, agents fromthis drug class caused no problems todeveloping pups, but there is a highrisk of life-threatening kidney damage
in the fetuses of human mothers whotake the medicines. “It is plausiblethat this fetal toxicity is facilitated by
the presence of OAT4-mediated transport,” says Tomi.
Reference
1. Tomi, M., Eguchi, H., Ozaki, M., Tawara, T.,
A possible biological explanation for the increase in births by cesarean sections has been found by Keio
researchers. © SPUTNIK/SCIENCE PHOTO LIBRARY

028| JITSUGAKU | December 2018 |Nishimura, S. et al. Role of OAT4 in uptake of estriol precursor 16α-hydroxydehydroepiandrosterone
sulfate into human placental syncytiotrophoblasts
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THE KEIO MEDICAL SCIENCE PRIZE

The 2017 Keio Medical
Science Prize Laureates

OBJECTIVE
The Keio Medical Science Prize gives recognition to the outstanding and creative achievements of researchers in the fieldsof medicine and life sciences, in particular those contributing toscientific developments in medicine. It aims to promote worldwide advances in medicine and life sciences, to encourage theexpansion of researcher networks throughout the world, and tocontribute to the well-being of humankind.

PRIZE
Laureates receive a certificate of merit, a medal, and a monetary

John E. Dick
It is with gratitude that I accept the Keio Medical
Science Prize. Science is not done in isolation andI have had the good fortune to be surrounded bywonderful colleagues in Toronto who set the highest standards for scientific thought that continuously challenged me to tackle biological challenges with rigour and clear thinking. All of our workon the biology of normal and leukemic humanstem cells was the cumulative effort of many
students and post-docs who contributed so muchto the thinking and execution of the experimental
findings. I dedicate this award to them.

award.The award ceremony and commemorative lectures areheld at Keio University.

NOMINATION AND SELECTION
Nominees must be researchers in medicine or life sciences
closely related to medicine, and preferably currently active intheir field of research. The Keio Medical Science Prize is aninternational award.

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

YEARLY SCHEDULE (Subject to change)
Seiji Ogawa
It is a great honor to receive the prestigious Keio
Medical Science Prize and to join the ranks of therenowned previous laureates. The MRI phenomenon I encountered during my fundamental
research a quarter of century ago has seen applications in brain science far beyond my expectations at the time. The successful development of
the neuro-imaging field is the product of efforts bygreat many talented scientists around the world.

• Call for nominations: late January• Deadline for nominations: early March• Prize announcement: mid-September• Award ceremony: November or December at Keio University

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

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