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2 1 TABLE Guided by its motto “Always aim higher,” CHIBA UNIVERSITY strives to nurture globally minded students who have broad outlooks. The university values academic diversity OF and actively conducts leading-edge fundamental and applied research. CONTENTS Top Research Program Chiba University was founded as a national university in Japan in 1949, when Chiba Normal School, established in 1874, merged with Chiba Medical College and several other educational institutions.

Currently composed of 10 faculties and 13 graduate schools, Chiba University is one of Japan’s largest 06 08 10 national universities, having about 11,000 undergraduate students, 3,500 graduate students and 3,500 MUCOSAL IMMUNOLOGY AND INTERNATIONAL CENTER FOR CHIRAL faculty members on 4 campuses located near Tokyo. The main campus at Nishi-Chiba occupies an area of THERAPEUTICS HADRON ASTROPHYSICS MATERIALS SCIENCE almost 400,000 square meters (100 acres) and is conveniently located between Tokyo Station (about Fighting Pathogens at Their Revealing Hidden Messages from Using Light to Establish a New Point of Entry the Cosmos Field of Chiral Materials 40 minutes by train) and Narita International Airport. The 850-bed University Hospital, a core hospital for the region, is adjacent to the School of Medicine on the lnohana campus.

25 TRANSLATIONAL RESEARCH PROGRAM OF Research Incubator Program PSYCHIATRY AND PSYCHOLOGY Medical and Pharmaceutical Sciences Cognitive Behavioural Theraphy Comes of Age in Japan 14 PHYTOCHEMICAL PLANT MOLECULAR SCIENCES Unlocking the Potential of Phytochemicals Science and Engineering 15 CANCER EPIGENOME CENTER A Different Approach to Fighting Cancer 28 NEXT-GENERATION THREE-DIMENSIONAL DISPLAY AND MEASUREMENT Future Images More than Meets the Eye 16 MEDICAL MYCOLOGY RESEARCH CENTER — Manipulating Microbes for Human Health 29 MULTIMODAL MEDICAL ENGINEERING Toward Image-Based Disease Diagnostics 17 MEDICINE FOR RARE DISEASES Innovative Approach Offers Hope 30 CENTER FOR INNOVATIVE MICROWAVE for Intractable Problems REMOTE SENSING The Next Wave in Remote Sensing 18 GLYCOMEDICINE RESEARCH CENTER Sugar Science’s Immunotheraphy Play 31 IMAGING SCIENCE AND TECHNOLOGY FOR MATERIAL APPEARANCE 19 LABORATORY OF DDS DESIGN AND DRUG DISPOSITION Realness in Digital Images Big Hopes for Nanotechnology Based Drug Delivery Systems 32 INSECTS-INSPIRED BIG INNOVATION Looking to Nature to Revolutionize Flight

Humanities and Social Sciences 33 SOFT MOLECULAR ACTIVATION FOR INTELLIGENT MATERIALS 22 CHIBA STUDIES ON GLOBAL FAIR SOCIETY Catalyzing the Future of Smart Materials Forging a Fairer World 34 ADVANCED BONE-CONDUCTION 23 SMALL AREA ESTIMATION COMMUNICATION AND ITS APPLICATION Bone-conductionTechnology beyond Hearing Aid Improving Datasets Using Small Area Estimation 35 LYMPHEDEMA MONITOR 24 MULTI-PERSPECTIVE UNDERSTANDING Making Invisible Lymphedema Visible COGNITIVE BEHAVIOUR GROUP Predicting Human Behaviour

2 3 Top Research Program

MUCOSAL IMMUNOLOGY AND THERAPEUTICS Fighting Pathogens at Their Point of Entry

INTERNATIONAL CENTER FOR HADRON ASTROPHYSICS Revealing Hidden Messages From the Cosmos

CHIRAL MATERIALS SCIENCE Using Light to Establish a New Field of Chiral Materials

© iStock.com/gremlin 4 5 MUCOSAL IMMUNOLOGY AND THERAPEUTICS FIGHTING PATHOGENS -Vaccines that induce immune responses at mucosal AT THEIR POINT OF ENTRY membranes of the intestines, lungs and other organs could help prevent deadly infections. Research Keywords: Immunology, Mucosal Immunity, Allergy

MUCOUS MEMBRANE The mucous membranes that line many FROM BASIC RESEARCH TO IN THE AIRWAY of the tracts and structures in the body are CLINICAL APPLICATIONS the first lines of defense against foreign Before new treatments can be developed, invaders. Equipped with a powerful and however, much more needs to be learned highly specialized immune system, these about the molecular architecture of the Mucous coat layered mucosal sentinels protect the surfaces and, mucosal immune system. That is why the with tiny hairlike cila. by extension, the body interior, against the International Center of Excellence is fo- threat of gastrointestinal, respiratory and cusing on basic research while simultane- sexually transmitted infections, as well as ously advancing clinical applications. It is cancer, allergies and more. also strengthening ties between research- Immune cells in the If these immune cells let their guard ers and industry in the hope of translating mucous membrane down, pathogens such as bacteria and its discoveries into therapies for patients. protect the body viruses can invade. On the other hand, To this end, Nakayama is building a robust against invasion by if they are overly vigilant, hyper-reactive pipeline of talented scientists who can pathogens such as bacteria and viruses. conditions like asthma or autoimmune move research findings seamlessly from However, if they are inflammatory bowel disease can take hold. the lab bench to the hospital bedside. too vigilant, they can Getting the balance right is the goal of “The research system we are creating is cause disease. the International Center of Excellence unprecedented,” says Nakayama, who is in Mucosal Immunology and Innovative also vice president of Chiba University Allergy Therapeutics. and dean of the Graduate School of Med- Vaccines that directly Launched as a joint initiative between icine and the Faculty of Medicine. target the mucosal surface Chiba University and the University of Projects at the International Center of could provide more protection California, San Diego, in 2016, the center Excellence fall into three categories: than a typical injection. aims to harness the power of the muco- Hiroshi Kiyono is studying the basic sal immune system to develop the next mechanisms of mucosal immunology in generation of preventive vaccines against response to microbial infections and as- infectious, allergic and inflammatory sorted diseases; Nakayama and colleagues, diseases. including Atsushi Onodera, Motoko Most vaccines in use today are adminis- Kimura and Osamu Ohara, are focusing tered by injection. But since most infec- on allergic reactions and novel treatments tious agents enter the body at mucosal that target the mucosa; and Hiroshi surfaces, vaccinating through the nose, Nakajima, Yoshitaka Okamoto and Naoki mouth, or some other mucosal route Shimojo belong to the clinical research could provide more protection. Since team that is developing new vaccines and transmission often occurs at these sites, adjuvants for pathogens endemic to Japan Members boosting the body’s ability to block that and around the world. transmission could stop an infection or Chiba has initially committed US$2 Toshinori NAKAYAMA autoimmune reaction at its source. million over five years to this alliance. Professor, Graduate School of Medicine “While existing injectable vaccines are Together with a matching contribution able to prevent serious conditions from from UC San Diego, the project will facil- Yoshitaka OKAMOTO Naoki SHIMOJO developing, they are not effective enough itate joint research and exchanges between Hiroshi NAKAJIMA Hiroshi KIYONO to defend against infection,” notes pro- investigators and students on both sides Osamu OHARA Motoko KIMURA gram director, Toshinori Nakayama. of the Pacific. Atsushi ONODERA Akira SUTO Yosuke KURASHIMA © Science Photo Library / Alamy Stock Photo

6 7 INTERNATIONAL CENTER FOR HADRON ASTROPHYSICS REVEALING Two towers receive information from 5,160 light-detecting HIDDEN MESSAGES sensors buried 2,500 meters beneath the South Pole.

FROM THE COSMOS The IceCube Neutrino Observatory, at the South Pole's Amundsen-Scott station. The International Center for Hadron Astrophysics is part of the Research Keywords: global collaboration constructing IceCube. Neutrino Astronomy, Cosmic Rays, South Pole, Elementary Particle Experiment

-From a remarkable observatory buried deep in the south polar ice, Chiba University astrophysicists are helping to explore the origins of the Universe.

Humans have been observing the stars of cosmic plasma, have great potential to or hydrogen nucleus. Of the trillion, trillion for tens of thousands of years, first with finally resolve this mystery.” neutrinos that pass through IceCube every our eyes, then with optical telescopes, day, the facility records just a few hundred THE ICECUBE COLLABORATION and more recently using devices that can collisions from high-energy neutrinos detect light at the extremes of the electro- Neutrinos are the most abundant particles — a minute fraction of the neutrino flux magnetic spectrum far beyond the visible in the Universe after photons (light parti- but more than enough to stimulate some range. Yet despite phenomenal progress cles). They originate in some of the most very exciting research. “We are proud of in astronomy over the past half century, violent and least understood cosmological having been key players in the discovery much of the Universe remains complete- phenomena like supernovas, galactic cores of high-energy cosmic neutrinos, which ly hidden from view, obscured by other and black holes. After their birth, they astrophysicists have been dreaming matter, other radiation sources, and light’s travel in straight lines from their source about for more than 30 years,” says interaction with the interstellar medium. with almost no deflection or absorption, Yoshida talking about his team mem- Now, scientists are on the verge of being making them ideal messengers from the bers in ICEHAP. able to peer into some of the most myste- heart of these mysterious astronomical Another important contribution of ICE- rious corners of the cosmos using not light objects. But these same properties also HAP to understanding the high-energy but neutrinos — near-massless subatomic make them exceedingly difficult to detect. Universe is its supercomputer-based mas- particles that travel close to the speed of The IceCube collaboration, involving 300 sive numerical simulation program for deep light across the Universe without being physicists from 48 institutions in 12 coun- investigation of the physical mechanisms deflected by magnetic fields or absorbed tries, has gone to extreme lengths to detect behind high neutrino production. “Through by matter. these ghost-like, high-energy particles. our simulations we are helping to uncover The International Center for Hadron The IceCube observatory is a cubic the hidden messages carried by these neu- Astrophysics (ICEHAP) led by Shigeru kilometer of crystal-clear ice, deep below trinos and to reveal the physical mechanism Yoshida is part of the global collaboration South Pole Station — the only place on by which high-energy cosmic rays are Neutrinos are subatomic Members responsible for managing the IceCube Earth where such large volumes of clear, accelerated at their source,” says Yoshida. In particles that typically Neutrino Observatory deep in the ice at pure and stable ice can be found along 2018, the IceCube collaboration has finally pass freely through matter. Shigeru YOSHIDA Other particles cannot Professor, Graduate School of Science the South Pole’s Amundsen–Scott station. with the infrastructure needed to support discovered that a special type of galaxy, penetrate the Earth, so “One of the longest standing puzzles in scientific research. By suspending thou- TXS 0506+056, is a birthplace of cosmic below the 'Dark Sector' astrophysics is the origin of high-energy sands of delicate photodetectors on strings neutrinos. This achievement was selected near the South Pole, Aya ISHIHARA Keiicih MASE cosmic rays and neutrinos,” says Yoshi- in a network of vertical holes drilled as one of the top breakthroughs by Science. free from every other Ryo NAGAI Lu LU interference, it is quiet Simon ARCHAMBAULT Yuya MAKINO da. “The new windows to our Universe through the ice, physicists can capture In 2022, the team’s new detectors called enough for the neutrinos Kenichi KIN Colton HILL opened by neutrino observations, com- the rare explosion of energy that occurs “D-Egg” will be used at the South Pole. It to be detected. bined with powerful computer simulations when a neutrino collides with an oxygen clearly shows the steps being taken forward. Maximilian MEIER Ryoji MATSUMOTO Yosuke MATSUMOTO Tomoyuki HANAWA Tomoaki ISHIYAMA Hideyuki HOTTA

8 9 CHIRAL MATERIALS SCIENCE USING LIGHT TO ESTABLISH A NEW FIELD OF CHIRAL MATERIALS

Research Keywords: Applied Optics, Optical Vortex, Chirality

-Understanding the Of the many mysteries still to be unrav- inscribed on the material’s surface. The eled in the natural sciences, one of the modified surface can then react differently universal property of chirality most compelling is the origin and power to left- and right-handed chiral molecules could lead to new materials of chirality — the property of a molecule or helical light, giving rise to a range of or object that has two mirror-image forms interesting possibilities for chemical sens- and technologies for photonics — like our left and right hands. ing, synthesis and imaging. and other applications. Chirality is universal in biology, chemistry “We can use helical light to create nano- and physics. It critically affects the bio- structures such as twisted needles, twisted chemical processes underpinning life, is a reliefs and twisted fibers,” says Omatsu. vital aspect of drug discovery, and crops up “We have also found that the same process in particle physics. Light can have chiral can polymerize fullerene — a well-known properties that affect how it interacts with functional organic molecule that is nor- matter. But how can the power of chirality mally not conductive. This causes fullerene be harnessed and controlled? And what to form a novel conductive metallic phase, new discoveries and technologies might which could be used as the basis for fab- this give rise to? These are some of the ricating electronic devices without metals questions Takashige Omatsu and his team and semiconductors.” are asking. Omatsu believes ‘nanovortices’ will one Light beams can be chiral when they are day be used for nanoscale precision imparted with so-called helical wave- control of light polarization, electron fronts, that is, polarity that rotates either orbital motion and the aggregation of left or right. “We can use ‘optical vortices’ chiral molecules. “Our research will lead to twist the physical properties of metals, to materials for next-generation photonics semiconductors and organic materials on and electronics, and new applications in the nanoscale to create chiral nanostruc- chemical synthesis, pharmacy, biology and Members tures with unique features,” says Omatsu. medicine,” he says. “It might also allow us Takashige OMATSU “Our goal is to establish chiral photonic one day to answer the scientific mystery: Professor, Graduate School of Engineering materials as an original research field and ‘Why does handedness exist in nature?’” to pioneer new technologies such as chiral Omatsu has collaborated with many Hisao ISHII Masami SAKAMOTO plasmonics and metasurfaces for nanoscale Japanese and international researchers, Takeshi MURATA Peter KRÜGER chiral chemical reactors, chiral-selective and is always looking for students and Kazuyuki SAKAMOTO Hiroyuki YOSHIDA imagers and chiral sensors,” he explains. early career researchers. “Our research Kenichi OTO Toyokazu YAMADA center brings together physicists, chemists, LIGHT CORKSCREWS Nobuyuki AOKI Kazuki NAKAMURA biologists and even medical doctors, and Takayoshi ARAI Atsushi NISHIDA Omatsu’s team focuses on the interaction we frequently have brainstorming meet- Akira YANAGISAWA Midori ARAI between helical light and materials, and ings to think up ideas for new projects,” Shiki YAGAI Kazuhiro YOSHIDA the physical properties and potential uses he says. “Several international researchers Tetsuhiro NEMOTO Motohiro AKAZOME of such modified materials. The electro- work here. There is a wonderful diversity Akira MATSUURA Yoshihiro NISHIDA magnetic field of helical light rotates as of backgrounds and expertise.” Kohji ITO Hiroki TAKAHASHI the light moves through space. When this Daisuke UMENO Naohiko ANZAI field interacts with conductive materials Keisuke IIDA Satoshi OGASAWARA like metals, nanoscale corkscrew-like variations in physical properties can be © iStock.com/loops7

10 11 Medical and Pharmaceutical Sciences

PHYTOCHEMICAL PLANT MOLECULAR SCIENCES Unlocking the Potential of Phytochemicals

CANCER EPIGENOME CENTER A Different Approach to Fighting Cancer

MEDICAL MYCOLOGY RESEARCH CENTER Manipulating Microbes for Human Health

MEDICINE FOR RARE DISEASES Innovative Approach Offers Hope for Intractable Problems

GLYCOMEDICINE RESEARCH CENTER Sugar Science’s Immunotheraphy Play

LABORATORY OF DDS DESIGN AND DRUG DISPOSITION Big Hopes for Nanotechnology Based Drug Delivery Systems

© iStock.com/BlackJack3D PHYTOCHEMICAL PLANT MOLECULAR SCIENCES CANCER EPIGENOME CENTER UNLOCKING THE POTENTIAL A DIFFERENT APPROACH OF PHYTOCHEMICALS TO FIGHTING CANCER Members Atsushi KANEDA Professor, Graduate School of Medicine Research Keywords: Plant Molecular Science, Phytochemical, Gene Research Keywords: Cancer, Epigenome, Inhibitor Ichiro MANABE Tomoaki TANAKA Tetsuhiro NEMOTO Kiyoe URA Hisahiro MATSUBARA Ichiro YOSHINO -Advanced genetic and genomic techniques -A new center aims to combat cancer by rewriting Hideki HANAOKA Tomohiko ICHIKAWA are transforming our understanding of how the epigenetic modifications harbored by tumor cells. Hiroyuki MATSUE Emiko SAKAIDA Toyoyuki HANAZAWA Yoko SHINAGAWA phytochemicals can improve human health.

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ENLISTING PHYTOCHEMICALS UNRAVELING MOLECULAR Members Cancer is thought of as a genetic disease, TO FIGHT DISEASE with mutations to a cell’s DNA causing MECHANISMS Kazuki SAITO a normal cell to give birth to a malignant Professor, Graduate School of Pharmaceutical Sciences Kazuki Saito, who leads the Phytochemical group conducts animal trials to assess the tumor. Yet epigenetic alterations, which Kaneda points to ongoing investigations of The Cancer Epigenome Center includes re- Plant Molecular Sciences program, says that pharmaceutical potential of molecules. In leave the DNA sequence intact, can be just gastric cancer as an example of this strategy searchers from a wide range of backgrounds Mami YAMAZAKI Naoko YOSHIMOTO because phytochemicals display considerable particular, they have extensively investigated as important in a cell’s transformation to in action. Patients with this cancer exhibit and specialties. This multidisciplinary team Amit RAI Hiroki TAKAHASHI natural diversity, they have huge potential Lycopodium alkaloids (LAs), molecules cancer. Even though epigenetic regulation different levels of DNA methylation in their approach, says Kaneda, is essential for turn- Daisuke UMENO Takashi TSUCHIMATSU to fight disease. “Although phytochemicals found in the vascular plant Lycopodiaceae, through mechanisms such as methyl tags tumor cells, depending on the pathogen re- ing the center’s discoveries into clinically Hajime SATO Hiromitsu TAKAYAMA have been used in pharmaceuticals and which may help to treat Alzheimer’s disease and histone modifications does not alter the sponsible for the disease. The cancer-causing meaningful treatments and diagnostic tools. Masami ISHIBASHI Mariko KITAJIMA ancient remedies for many years, it is only and schizophrenia. DNA sequence, it can chemically modify bacterium Helicobacter pylori is one source “We will help determine the mechanisms Midori ARAI Noriyuki KOGURE now, with the advent of next-generation The third group is investigating how the genome to signal which genes should be of irregular methylation, infection with Ep- of cancers and develop new cancer drugs Tomoko IGAWA Mitsumasa HANAOKA DNA sequencing, that we can really begin plants respond to different environmental turned on and off. When tumor-suppressor stein Barr virus is another. Both seem to have through collaborating with experts in medi- Eiji GOTO Natsuko KAGAWA to understand how they work and unlock stresses by growing plants in different arti- genes are silenced or oncogenes are activated profound epigenetic impacts on stomach cine, physics and pharmacy,” he says. Takashi SHIMADA Hidenori SASSA their full potential,” says Saito. ficial environments and monitoring their in this way, many different forms of cancer cells, leading to the silencing of many tumor Yasumasa HARA Shinji KIKUCHI The program consists of three collabora- responses to change. can result. suppressors. tive research groups, each working on a “Our aim is to optimize plants so that they Fortunately for medicine, epigenetic Kaneda and his colleagues are using clinical specific theme. produce high-quality phytochemicals that we alterations are not permanent. They can be samples and cell experiments to unravel the Since ancient times, people have used the One group is focusing on the genomics of can harvest for use in medicines and func- undone to prevent or reverse cancer, leaving molecular mechanisms that induce hyperac- natural compounds in plants, known as medicinal plants and food crops with the tional foods,” explains Saito. “Our insights a cell with its entire complement of normal tive methylation patterns following infection phytochemicals, for medicinal and nutrition- key aim of revealing the genomic principles will enable us to grow rare plants more DNA intact. with these pathogenic agents. They ultimately al use. Now, scientists at Chiba University of phytochemical production. Employing successfully and will also inform agricultural This is exactly what researchers at the hope to stop the process in its tracks. Similar are using advanced genetic and genomic state-of-the-art technologies, the researchers practices for commercial crops in the future.” Cancer Epigenome Center are striving to projects are ongoing to combat colorectal techniques to verify how phytochemicals are identify and clarify the roles of unknown While the group is focusing on phytochem- do. Led by Atsushi Kaneda, the center is cancers — which Chiba researchers have generated in plants, how they can be ma- genes, as well as investigate plant metabolism. icals, it also conducts wide-ranging inter- seeking to understand the various epigenetic shown can be categorized into three types, nipulated to optimize certain plant groups, In 2016, Saito’s team assembled a draft disciplinary studies and hence welcomes drivers that contribute to different types depending on methylation levels — as well as and how they may help tackle lifestyle- and genome for licorice (Glycyrrhiza uralensis), researchers and students with backgrounds of cancer and then develop new drugs that blood cancers and other types of tumor. aging-related diseases. which is used worldwide as a natural sweet- in chemistry, horticulture, genetics and overturn these effects. With an eye to developing novel therapeu- Plants naturally generate chemicals for ener and a medicinal component. pharmacy who are interested in this exciting “We will explain key epigenomic aberrations tics, chemists at the Cancer Epigenome various purposes, including for attracting They identified several components known and rapidly developing area of research. and their molecular causes,” says Kaneda. Center are working on new methods to pollinators and defending themselves. These to play a positive role in human health “And then, taking advantage of small mole- efficiently synthesize molecules that can act specialized metabolites allow plants to colo- within the plant, while pinpointing key cules that bind to DNA in a sequence-spe- on epigenetic aberrations. One such group nize specific niches in the food chain, adapt genes, the manipulation of which could lead cific manner, we will develop drugs that of molecules is the pyrroleimidazole poly- to new environments and evolve to survive to crop improvements. can rewrite the accumulated epigenomic amides. These molecules can bind to DNA potential stressors. Crucially, phytochem- The second team is identifying novel phy- aberrations or prevent them accumulating in at specific sites in the genome, and when icals also exhibit properties that can help tochemicals and active products in a wide targeted genomic regions.” coupled to an epigenetic inhibitor they can treat human diseases. Examples in modern variety of plants, searching for drug com- prevent methylation-based gene silencing. medicine include morphine, the antimalarial ponents to tackle diseases such as cancer, Kaneda hopes to deploy the molecules to drug artemisinin and chemotherapy agents dementia and diabetes. As well as isolating edit the epigenome at targeted regions to © iStock.com/vitanovski derived from taxanes. and analyzing promising molecules, the regulate tumor formation.

14 15 MEDICAL MYCOLOGY RESEARCH CENTER MEDICINE FOR RARE DISEASES INNOVATIVE APPROACH MANIPULATING MICROBES OFFERS HOPE FOR FOR HUMAN HEALTH Members Research Keywords: Infection and Immunity, Microbiota, Superorganism INTRACTABLE PROBLEMS Mitsutoshi YONEYAMA Professor, Medical Mycology Research Center Research Keywords: Rare Disease, Intractable Cancer, iPS Cell

Shinobu SAIJO Koichi HIROSE -Detailed investigations of host–microbe interactions Tomohiro TAMACHI Akiko TAKAYA could yield new therapies against infectious agentsand Yoshiyuki GOTO Yuumi NAKAMURA-MATSUOKA -The ReDenim network is developing therapies to autoimmune diseases. Hiroshi ASHIDA Kinnosuke YAHIRO treat rare and intractable diseases. Arifumi IWATA Koji ONOMOTO

studying molecular interactions in different TWO-PRONGED APPROACH Members host-microbial systems. One, led by Shinobu Saijo and Yuumi Nakamura- Shinichiro MOTOHASHI Motohashi belongs to the tumor immunity Motohashi. And the two teams will also Matsuoka, is focused on fungal and Professor, Graduate School of Medicine team, which intends to capitalize on Chiba have access to support units at the universi- bacterial infections in the skin of mice and University’s expertise in developing cell- ty’s Core Clinical Research Hospital, a des- humans; another, led by Koichi Hirose, Hideki HANAOKA Koji ETO based immunotherapies. Their approach ignation granted to Chiba University under Tomohiro Tamachi, and Arifumi Iwata is Itsuko ISHII Masayuki KURODA uses tumor-destroying natural killer T-cells Japan’s Medical Care Act. Hideki Hanaoka investigating the microbes — both good Kiyoshi HIRAHARA Kotaro SUZUKI to search for combination therapies that and Itsuko Ishii develop the support units and bad — that reside in the respirato- Sonoko MISAWA Katsunori FUJII can further modulate the tumor immune to apply basic science toward therapeutic ry tract. A third group, which includes microenvironment in a favorable way. They applications. Yoshiyuki Goto, Hiroshi Ashida, and also intend to identify biomarkers that can This support includes consultation services Kinnosuke Yahiro, is concentrating on the Scientists at Chiba University have a predict how individual patients will respond on issues such as intellectual property, gut microbiome and how opportunistic long track record of excellence in clinical to these treatments. project management, clinical trial design intestinal infections gain a foothold; while research, particularly for investigations in Led by Sonoko Misawa, the rare-disease and other steps needed to fulfill the promise The human body is made up of a staggering how hosts and commensal microbes commu- the fourth, led by Akiko Takaya, is patients with immune-related diseases. team, including Masayuki Kuroda and of translational medicine. “Our ultimate goal 30 trillion cells or so. But just as numerous, if nicate as a superorganism.” working on more basic mechanisms of And Chiba University researchers have Katsunori Fujii, is using immune-modu- is to form a therapeutic cluster that can be not more so, are the several hundred trillions Creating a superorganism is an apt meta- immunological memory in response to made a number of important breakthroughs lating drugs and gene therapies to address applied to a wide variety of rare and intrac- of microbial co-inhabitants that teem in and phor for what Yoneyama is trying to achieve microbial invaders. in basic immunology and disease biology. immune-related peripheral nerve disease table diseases,” Motohashi says. He can even on us. These microbiotas are essential to our because, through the melding of minds from “Results obtained from our projects will However, connecting these two areas, a and hereditary disease. Kotaro Suzuki and foresee a day when the infrastructure created well-being, and a distortion in its balance can across Chiba and around the world, the help efforts to create innovative new field known as translational research, has Kiyoshi Hirahara are aiming to develop new through ReDenim could be used to develop trigger a wide range of disorders. center can make a far greater impact than any therapeutics against infectious diseases and often been less successful. treatments based on the analysis of patho- new therapies for common diseases, such as Only recently, however, have scientists come individual scientist working independently. will eventually lead to improvements in That is a problem that Shinichiro Moto- logical conditions using animal models of diabetes or lung cancer. to appreciate just how critical this collection At Chiba University, the investigators come human health,” says Yoneyama, whose own hashi wants to fix. Motohashi leads Chiba’s autoimmune diseases and tissue fibrosis. Koji Judging by the progress they have made so of microbiota is for determining human from the Medical Mycology Research Center, research focuses on the mechanisms of Research and Development Network of Eto and his collaborators of orthopedics and far, Motohashi and his coworkers are well on health and disease. They are also becoming the Graduate School of Medicine, and the innate antiviral immunity with Koji Innovative Medicine for Rare and Intrac- plastic surgery, Seiji Ohtori, Sumihisa Orita, their way to fulfilling their dream, and their excited about the prospect of how manipulat- Graduate School of Pharmaceutical Sciences, Onomoto. table Diseases — ReDenim. The network is Yasuhiro Shiga, and Nobuyuki Mitsukawa, potential is widely recognized. ReDenim has ing this microbial ecosystem could form the while external collaborators are based in the To assist all these research projects, aiming to provide the clinical support and are developing a new method of wound already forged collaborations with some of basis for the next generation of life-saving United States, Germany, and elsewhere in Ja- investigators from each group have access resources needed to take discoveries from healing using platelet-rich plasma derived the world’s leading experts in cancer immu- therapeutics. Led by Mitsutoshi Yoneyama, pan. These scholars, together with others from to the Japanese government’s network the lab to the clinic. from iPS cells. Kuroda is also working notherapy and rare diseases, and is working researchers at the Medical Mycology Re- around the world, convene each November of core facilities — a resource known as In particular, ReDenim has singled out two with the tumor immunity team to develop with Japanese drug companies to partner on search Center have launched a comprehen- at the Medical Mycology Research Center the Joint Usage/Research Center, which disease areas for which there are currently transgenic adipocyte technology that can additional research projects. sive research effort to dissect the intricacies for the annual Global Network Forum on is staffed by specialized researchers and no good treatment options — deadly forms be applied to cancer treatments, in addition of host-microbe interactions in the skin, lung, Infection and Immunity. technicians who can run state-of-the- of cancer, such as head and neck tumors; to his research target, hereditary metabolic intestines, and bone marrow. art experiments, including with fungi and and rare diseases that each afflict fewer than diseases. “Dysregulation of host-microbe interactions EXPLORING HOST–MICROBE other microbes. A bioinformatics unit at 50,000 people in Japan, but collectively Importantly, both teams will share research can give rise to a wide variety of human INTERACTIONS Chiba led by Hiroki Takahashi helps with affect about 10 percent of the population. experiences, technology platforms and man- disorders, including opportunistic infections, computational analyses. ufacturing facilities. “Sharing the know-how allergies, and autoimmune disease,” explains The team that Yoneyama has put together to treat each disease within the network will Yoneyama. “It is hence crucial to understand is roughly divided into four groups, each accelerate drug development,” says

16 17 GLYCOMEDICINE RESEARCH CENTER LABORATORY OF DDS DESIGN AND DRUG DISPOSITION

SUGAR SCIENCE'S BIG HOPES FOR Members Members Hidetaka AKITA IMMUNOTHERAPHY PLAY Professor, Graduate School of Pharmaceutical Sciences Hiroto KAWASHIMA NANOTECHNOLOGY BASED Research Keywords: Immunology, Biochemistry, Glycobiology Professor, Graduate School of Pharmaceutical Sciences Akihiro HISAKA Naohiko ANZAI DRUG DELIVERY SYSYEMS Kousei ITO Takeshi MURATA Motoyuki ITOH Yuzuru IKEHARA Kunikazu MORIBE Satoshi OGASAWARA Hirofumi DOHI Noritaka NISHIDA Research Keywords: Drug Delivery, Nanobio, Vaccine Hiroki TANAKA Kenjirou HIGASHI -By bridging the gap between glycoscience and medicine, Keisuke UEDA Shigeki AOKI major advances in immunology and drug development Hiroto HATAKEYAMA Hiromi SATO are imminent. -Drug delivery systems that nanocarriers could enhance the Yu SAKURAI

effectiveness of therapies ranging from genetics-based cancer treatments Alzheimer's medicines. Lymphocytes are the body’s warrior cells. glycans produced by two enzymes — glycans,” Kawashima says. “Some specialize They circulate through the bloodstream N-acetylglucosamine-6-O-sulfotransferase in biological functions, while others focus on and arrive at sites in the body such as the 1 (GlcNAc6ST-1) and GlcNAc6ST-2 — synthesis or analyze glycan structures. The also showed that ssPalmE-LNP enhanced spleen and lymph nodes, where they combat are essential for the binding of lymphocytes, idea is to bring all of these researchers togeth- the therapeutic effect of an antibody used harmful bacteria, viruses and even cancer and consequently play a vital role in con- er, build new collaborations and understand to combat immune system supressing cells. Sugars, or glycans, are integral to this trolling lymphocyte homing in mice. the function of glycans across many programmed cell death protein 1 (PD-1), migratory process called lymphocyte After working on this study at California’s biological phenomena.” raising hopes for combination therapies to homing, which is of intense interest to Burnham Institute, Kawashima returned The new centre has plans to collaborate combat cancer. researchers. These scientists hope to target to Japan in 2005, bringing with him the with teams both nationally, for example, at Brain disorder treatments also stand to glycans to find new immunotherapies and ‘knockout’ mice (deficient in the two key the Glycomedicine Technology Research benefit from nanocarriers. Recent studies drugs for autoimmune diseases. enzymes) he had developed. At Chiba he Center and the National Institute of Ad- suggest that using ssPalm as an alternative “We now know that glycans — chains of has used these to continue hunting for new vanced Industrial Science and Technology to viruses that deliver genetic material sugar molecules that have diverse func- antibodies that target glycans. (AIST), and internationally. could improve treatments. tions in our bodies — play an essential Already, Kawashima has developed antibod- In experiments with Hokkaido University GLYCOMEDICINE TAKES OFF in 2018, Akita’s team used ssPalm in the role in lymphocyte homing,” says Hiroto ies that will specifically bind to the building © iStock.com/Dr_Microbe Kawashima, a professor at Chiba Univer- blocks of glycans and disable them in studies delivery of messenger RNA (mRNA) to sity’s Graduate School of Pharmaceutical Today, the expanding fields of glycoscience published in The Journal of Biological neurons and astrocytes — star-shaped cells Sciences, Laboratory of Microbiology and (the study of glycans) and glycomedicine Chemistry in 2010 and 2015. This could halt Drug delivery systems that nanocarriers could ed amines enable membrane destabilisation. found in the brain and spinal cord increas- Immunology. (combining glycoscience and medicine) are the dysfunctions involved in autoimmune enhance the effectiveness of therapies ranging The other, a disulfide bond (SS) that can be ingly implicated in neurodevelopment and “These glycans are found on the surface leading to breakthroughs in drug devel- disease, in which the immune system is from genetics-based cancer treatments to cleaved in a reducing environment such as in disease. of endothelial cells in lymph nodes,” he opment and diagnostics for autoimmune overreacting. Alzheimer’s medicines. the cytoplasmic material inside cells, triggers By surpassing the limitations of other forms explains. “Thanks to glycans, lymphocytes diseases. “Usually, it’s very difficult to generate mono- Personalised medicine — tailoring medical the release of NABDs in specific cells. of delivery (such as DNA-based artificial recognize and bind to the surface of those Chiba University’s Glycomedicine Research clonal antibodies against carbohydrates,” treatments to individual needs — may no In proof-of-concept studies in mice in 2016, gene carriers), mRNA therapeutics could cells.” Lymph nodes activate lymphocytes Center, which opened in August 2017, marks says Kawashima. This difficulty in producing longer be far-off. the researchers showed that lipid-based be used to treat many conditions, includ- to fight disease. a shift towards accelerating such break- clones of these antibodies is because carbohy- Developments in nanocarriers have progressed nanoparticles, formed using ssPalm, enabled ing Alzheimer’s, Parkinson’s, Huntington’s In a study published in Nature Immunology throughs in Japan. drate antigens are not generally very antigen- rapidly, promising targeted delivery and efficient delivery to the liver of a genetic disease and other neurological disorders. in 2005, Kawashima and his colleagues in “Many researchers here at Chiba Univer- ic. “To get around this problem, we immu- release of nucleic acid-based drugs (NABDs), treatment that uses small interfering RNA. “Our strengths at the Faculty of Pharma- Japan and the United States showed that sity have been working independently on nized knockout mice with cells expressing the an emerging class of therapeutics designed to They have since gone on to develop sec- ceutical Science include our expertise in missing sugar chains, which are highly prone target diseases at the genetic level. ond-generation ssPalm, which uses Vitamin characterizing physicochemical properties, to stimulating the production of antibodies.” E as a waterproofing scaffold (ssPalmE). and evaluation of pharmacokinetics and The next step will be to further investigate and A BREAKTHROUGH MOLECULE One of the biggest challenges for cancer pharmacodynamics, as well as safety,” Akita identify new ideas for drug development and therapeutics researchers, Akita explains, explains. These skills could potentially to collaborate with pharmaceutical companies In 2013, Akita’s group reported on SS-cleav- will be “to develop DNA- and RNA-based contribute to a wide range of fields he says, to bring them to market. able Proton-Activated Lipid-like Material vaccines that could target unique genetic including immunology and cancer research. “Right now, there are lots of antibody drugs,” (ssPalm), a molecule designed and tested changes in individual cancers.” “We need to keep our eyes open to societal says Kawashima. These immunotherapies over five years that showed promise for The hope is that the versatility of ssPalm needs,” Akita adds. “Until now, we have target issues such as rheumatoid arthritis and drug delivery. could help maximise drug efficacy while been concentrating on materials science. cancer, but, he says, new advances are limited The molecule itself consists of two main reducing side effects. For example, in mouse We have only just begun to enter the arena by a shortage of molecules to target. “Glycans components: One, tertiary amines, are acti- studies performed in 2018, Akita’s group of nucleic acid-based therapeutics. I believe have unexplored potential, so this is an excit- vated in response to an acidic environment, demonstrated that a plasmid DNA- innovations arise when you can look beyond © Akiko Sato ing time to be looking into developing new such as the endosome compartment inside encapsulating lipid nanoparticle (ssPalmE your own particular filed, and apply original candidate drugs based on glycoscience.” the cells of plants and animals. These activat- -LNP) induced anti-tumour effects. They technologies in unexpected ways.”

18 19 Humanities and Social Sciences

CHIBA STUDIES ON GLOBAL FAIR SOCIETY Forging a Fairer World

SMALL AREA ESTIMATION AND ITS APPLICATION Improving Datasets Using Small Area Estimation

MULTI-PERSPECTIVE UNDERSTANDING COGNITIVE BEHAVIOUR GROUP Predicting Human Behaviour

TRANSLATIONAL RESEARCH PROGRAM OF PSYCHIATRY AND PSYCHOLOGY Cognitive Behavioural Theraphy Comes of Age in Japan

© piick/Shutterstock.com 20 21 CHIBA STUDIES ON GLOBAL FAIR SOCIETY SMALL AREA ESTIMATION AND ITS APPLICATION FORGING A IMPROVING DATASETS FAIRER WORLD USING SMALL AREA Members Research Keywords: Global Welfare Society, Multidisciplinary Social Science, Fairness ESTIMATION Genya KOBAYASHI Associate Professor, Graduate School of Social Science Research Keywords: Economic Statistics, Baysian Statistics, Small Area Estimation

Yuki KAWAKUBO Eisaku SATO -A multidisciplinary team of researchers looks at Shimpei SANO Hiromi SAITO how to create a fair society — on a global scale. -Statistical techniques can improve the accuracy and Tsubasa ITO Yuta YAMAUCHI Ryota YUASA Syonosuke SUGASAWA scope of limited information, saving time and money. Yukiko OMATA

With globalization comes the need to HOW DO WE ACHIEVE Collecting comprehensive data on popula- Survey of Family Income and Expenditure dataset of taps. The group found that access ensure that people from all cultures, A FAIR SOCIETY? tions is not always possible, or even the best (NSFIE). The sample sizes in the NSFIE to clean water accounted for 41.3 percent of countries and backgrounds are treated use of resources. Surveys can be expensive are much larger than in the FIES and thus the improvement in Tokyo’s crude death rate fairly and equally. The drive to create a just The project consists of four interrelated symposiums. “Many of our members are and time-consuming, so improving the more reliable, but because the survey is time between 1921 and 1937. This paper adds global society requires solid foundations in research groups and a further six teams involved in local and national policymaking accuracy of data with “small area problems” consuming and costly, it’s only carried out to discussions on the relative importance all countries, backed by informed govern- working to publicize the findings to a wide committees, and they are key to informing can stretch data resources further. every five years. of nutrition and clean water on mortality. ment policies and strong support networks audience. Their focus is on challenging and policy makers of our work,” says Mizushima. “Small area problems happen when an The FIES and the NSFIE collect area-level Kobayashi hopes that everyone from policy at local, regional and national levels. overcoming unfair practices on all scales, in- The project has published books and papers estimator, such as sample mean for a small aggregated data, so Kobayashi’s group used makers to businesses will soon come to Much previous research into justice and vestigating issues such as gender inequality, both in Japanese and English based on their area, becomes very unstable because of small the Fay-Herriot, a mixed regression model the group to add a finer resolution to their social change has been dominated by widening income gaps, migration, and the research outcomes, and welcomes those in- sample sizes,” explains Associate Professor routinely used in SAE. datasets. studies of Western societies, but the rapid collapse of regional and marginal communi- terested in all aspects of social science, from Genya Kobayashi, who is part of a new Chi- However, when data is in other formats changes experienced by Asian countries in ties, both in Japan and around the world. law and politics to sociology and economics. ba project called Small Area Estimation and more appropriate SAE models must be de- recent decades have spawned a growing In particular, the researchers believe that Its Application to the Analyses of Poverty, veloped. Recently, for example, Kobayashi’s field of research focused on building fair proposals and practices aimed at closing the Public Health and Disaster. group has been working to improve an societies in Asia. gap between large cities and local cities and His group is focused on overcoming such income map of Japan based on the Statistic Researchers in law, politics, economics and resolving gender gaps are essential to over- issues by developing small area estimation Bureau’s Housing and Land Survey (HLS). social sciences have recently established coming the divides. (SAE) techniques that borrow statistical Using a new statistical model that accounts the Chiba Studies on Global Fair Society The key aims of the project are to investigate strength from supplementary data. for the grouped data format of the HLS and project, with the aim of creating an inter- the development, transformation and lim- additional data from the Population Census, disciplinary research base to inform future itations of existing welfare state models and OVERCOMING INEQUITY AND they measurably reduced the uncertainty of local, national and international policies. to provide empirical evidence for how a fair PUBLIC HEALTH INSIGHTS the HLS’s income estimates. Lead researcher on the project, Jiro society can be achieved in the 21st century. SAE’s scope isn’t limited to stabilizing data, Mizushima, says the key concept is fairness. Mizushima has spent considerable time While the applications of SAE are broad, adds Kobayashi. SAE techniques can add “We define fairness as the basic element of researching aspects of the welfare state in the “small area problems arise particularly within information. For example, the HLS mod- justice,” he explains. “In fact, we argue that Netherlands, including how it has responded official statistics on which governments make el could also infer income in areas where it exceeds justice in most cases. At the same to social challenges such as global economic important political decisions. Hence, small data is missing. Using a mixture modeling time, we embrace values such as equality fluctuations and an aging population. Members area estimation techniques could lead to more approach, the team recently estimated the and liberty.” “Fairness has been the core of legal and effective policy making,” notes Kobayashi. distribution of land prices around train Jiro MIZUSHIMA Mizushima, whose research interests lie political philosophy since ancient times, and An example crops up in the monthly Family stations in and around Tokyo by making Professor, Graduate School of Social Science in welfare state reform in Europe, says the so one of our teams is examining equality Income and Expenditure Survey (FIES) inferences across areas. project aims to go beyond the traditional and fairness from a historical perspective, conducted by Japan’s Statistics Bureau. Contributing to public health discussions, in Masaya KOBAYASHI Akiko OISHI discussion of equality — it seeks to con- comparing political, economic and legal Although FIES provides the latest informa- 2018 Kobayashi collaborated on a paper that Hikari ISHIDO Masahiro OGIYAMA struct new principles that value diversity standpoints over time,” he says. “Another tion on household income and expenditure, used a spatial Poisson regression model to Hiroyuki MINAGAWA Seiichi IGARASHI among people in a global society. group will analyze the meaning of fairness at a small area level, such as a city level, the look the links between access to clean water in the 21st century, providing us with funda- Iwao FUJISAWA Kentaro SATO sample size of FIES becomes so small that and dropping mortality rates in the early mental guidelines to underpin our program.” Takayuki KAWASE Chiyo YONEMURA direct estimators are unstable and can’t grasp 1900s. Kobayashi and collaborators at the The team plans to form networks of academ- Reiko OGAWA Li XIANG detailed trends. Tokyo Institute of Technology and Duke ics across the globe. To this end, they have But FIES, says Kobayashi, can borrow University in the United States looked hosted five highly successful international statistical strength from data in the National at death rates in Tokyo in 1930 against a

22 23 MULTI-PERSPECTIVE UNDERSTANDING COGNITIVE BEHAVIOUR GROUP TRANSLATIONAL RESEARCH PROGRAM OF PSYCHIATRY AND PSYCHOLOGY

PREDICTING Members Makoto ICHIKAWA COGNITIVE Professor, Graduate School of Humanities and Studies on Public Affiars HUMAN BEHAVIOUR BEHAVIOURAL THERAPHY Members Tomokazu USHITANI Eiji KIMURA COMES OF AGE IN JAPAN Eiji SHIMIZU Rumi TOKUNAGA Midori TANAKA Director and Professor, Research Center for Research Keywords: Experimental Psychology, Cognitive Science, Data Mining Yasuharu DEN Toshihiko MATSUKA Research Keywords: Psychiatry, Psychology, Cognitive Behavioral Therapy Child Mental Development Kazuhiko KAWAMOTO Yoko MIZOKAMI Noriko YATA Akinori ABE Eiji KIMURA Makoto ICHIKAWA Sachiyo ARAI Hiroo SEKIYA Chikae ISOBE Miho IWATA -Understanding the mind’s influence on what we Yoshitsugu MANABE Takahiko HORIUCHI -Better access to mental health care in schools, at work Fumiko SUNAGAMI Keito NAKAMICHI perceive may help researchers model human behaviour Keita HIRAI Nobuyoshi KOMURO and online could help people of all age groups suffering Tomihisa NIITSU Aika TOMOTO to create better smart devices. Shoko IMAIZUMI Satoru SHIMIZU from anxiety, depression and other related conditions. Yoshiyuki HIRANO Toshiyuki OTANI NGUYEN KIEN Kenichiro SHIMAI Kensuke YOSHIMURA

THOUGHTS As computers become more powerful, related to changes in room temperature and effect on perception. For example, while hat we think affects contributed to the first study that visu- nuanced modelling of human decisions is humidity. Virtual reality, says Ichikawa, can sitting in a stationary car, some may have how we feel and act alised changes in brain activity during becoming possible. At the same time, new reveal the effects of situational elements felt like they have moved backwards if a psychotherapy in 2015. Using functional technologies are also bringing fresh tools such as illumination, luminance, noise and neighbouring vehicle creeps forward. This magnetic resonance imaging (fMRI), the and disciplines to researchers at Chiba space on physiological reactions, ranging sense of ‘induced motion’ is an optical illu- results indicated that the left posterior University studying the hidden relationships from metabolism to circadian rhythm. sion created in the mind. parietal cortex plays a vital role in cog- between behaviour and phenomena, ranging These developments, he says, are not only In a recent paper published in the journal CBT nitive restructuring — a process used in from the physiological to the physical. exciting to psychologists, but will also pro- Perception, Ichikawa and his colleagues EMOTIONS BEHAVIOURS CHANGING PERCEPTIONS CBT that enables people to challenge “With the help of environmental engineers vide the basis for creating more believable examined why one part of a visual illusion hat we feel affects hat we do affects existing beliefs. and using deep learning and virtual reality digital worlds. (concentric circles) appeared to be moving how we think and act how we think and feel In 2016, Shimizu and his colleagues showed techniques we can expect big developments Ichikawa’s work is being complemented by with or against another part of the illusion. that CBT can help reduce social anxiety for pa- in the cognitive sciences,” says Professor mathematicians, such as findings published They found that whether the parts of the © www.betterhelp.com tients ineffectively treated with antidepressants. Makoto Ichikawa, part a diverse group in 2016 by Chiba University computer sci- image appeared to moved together or in In recognition of the growing need for known as the Multiperspective Under- entists. In their paper, they proposed a new opposition is linked to a person’s thoughts professional CBT care, at the end of 2018 standing of Cognitive Behaviour (MUCB) method for predicting pedestrian dynamics. on the connection between the parts. Major efforts are underway to help treat and Shimizu of Chiba University’s Research the Japanese government began to certify Group. Using a technique from geostatistics called In some configurations, the two parts ap- prevent anxiety-related disorders in Japan Center for Child Mental Development licensed psychologists. The national health Ichikawa and his colleagues have been ex- ‘kriging’ the researchers were able to predict peared to be moving in opposite directions. —where as many as one in four people and Chiba University Hospital’s Cognitive insurance system has been updated to cover amining the reactions of individuals during trajectories up to 10 steps ahead more than As in the car example, if one object appears experience mental health problems during Behavioral Therapy Center. “However, CBT doctor-administered CBT for patients with a digitally created fire event in a virtual 80 per cent of the time. This, they say, could to be accelerating away from another, the their lifetime. resources in Japan are still relatively scarce.” depressive disorders, anxiety disorders and reality environment. While psychologists lead to exciting developments in navigation, stationary or slower parts may seem to be Social Anxiety Disorder (social phobia), one Chiba University and its affiliated hospital bulimia nervosa. often use methods such as questionnaires group-behaviour analysis and abnormal-be- moving in the opposite direction. of the most prevalent, is characterised by are spearheading efforts to address this. There are also moves to introduce CBT- to understand reactions and decisions, haviour detection. However, a recognition of a common fate, an intense fear of social situations. In some The Chiba Improving Access to Psycho- based anxiety prevention programs in Ichikawa’s colleagues are also able to use which is an appreciation for the linked cases, social phobia can lead to addiction, logical Therapies (Chiba-IAPT) program, Japanese elementary schools. virtual reality scenarios to study biological THE COMMON FATE INFLUENCE nature of the parts, may encourage partic- depression or suicidal behaviour. adapted from a UK model, became the first A 2018 study, designed by Yuko Urao and parameters – such as blood pressure, heart ipants to see the elements move together. Many doctors, legislators and patients now post-qualification training course of its supervised by Shimizu, examined the effec- rate and pupil dilation – in real-time. At the To accurately model human behaviour, it’s The researchers suggest this stems from a recognise cognitive behavioural therapy kind in 2010. tiveness of an anxiety prevention program same time, they can also record reactions also important to also understand the mind’s principle from the German Gestalt school (CBT) as an effective treatment for social “It’s important to tailor treatments to named Journey of the Brave, targeted at of psychology that seeks to explain how phobia. By changing negative patterns reflect not only cultural differences, but also children aged 10–12 years. Consisting of our brains create order in the world. of thinking and behavior, CBT can help personal differences,” Shimizu adds. His ten 45-minute sessions held during school The common fate principle suggests that children overcome anxiety and the fear of team are developing new tailored interven- hours, the program involved deepening un- because logical patterns tend to take prece- uncertainty, adolescents better manage de- tions, such as internet-based CBT (iCBT), derstandings of anxiety, monitoring feelings, dence over individual elements in how we pression and irritability, and adults deal with which are low-cost, easy to use, and provide and developing assertiveness skills to reduce see the world, a flock of birds, for example, a host of stressful life experiences. optional anonymity. social stress. may seem to be moving as one. In 2017, his group released a study protocol While further follow-up studies are planned, All of these findings, Ichikawa says, will A LEADING CENTRE FOR CBT for iCBT on patients with persistent insom- preliminary results indicate that the program RESEARCH AND EDUCATION have important ramifications for how we nia. They have also produced a simplified, can help children manage their anxiety levels. display motion, and group and individual five-minute program that can be used to “Our hope is that in ten years’ time, all dynamics, on digital devices, in cinematog- We are now actively trying to increase the help reduce depressive symptoms. children in Japan will have access to this number of CBT experts in Japan,” says Eiji © iStock.com/spfdigital raphy and in virtual reality. As part of his wider research, Shimizu program,” Shimizu says.

24 25 Science and Engineering

NEXT-GENERATION THREE-DIMENSIONAL DISPLAY AND MEASUREMENT

Future Images —More than Meets the Eye

MULTIMODAL MEDICAL ENGINEERING Toward Image-Based Disease Diagnostics

CENTER FOR INNOVATIVE MICROWAVE REMOTE SENSING The Next Wave in Remote Sensing

IMAGING SCIENCE AND TECHNOLOGY FOR MATERIAL APPEARANCE Realness in Digital Images

INSECTS-INSPIRED BIG INNOVATION Looking to Nature to Revolutionize Flight

SOFT MOLECULAR ACTIVATION FOR INTELLIGENT MATERIALS Catalyzing the Future of Smart Materials

ADVANCED BONE-CONDUCTION COMMUNICATION Bone-conductionTechnology beyond Hearing Aid

LYMPHEDEMA MONITOR Making Invisible Lymphedema Visible

© iStock.com/Nongkran_ch 26 27 NEXT-GENERATION THREE-DIMENSIONAL DISPLAY AND MEASUREMENT MULTIMODAL MEDICAL ENGINEERING FUTURE IMAGES Members TOWARD IMAGE-BASED Hideaki HANEISHI Professor, Center for Frontier Medical Engineer MORE THAN MEETS THE EYE DISEASE DIAGNOSTICS Tadashi YAMAGUCHI Hideki HAYASHI Kenji YOSHIDA Kazuyuki SAITO Research Keywords: Computer Holography, Volumetric Display, High Performance Computing Research Keywords: Medical Engineering, Physical Measurement, Multimodality Kazuya KAWAMURA Takashi UNO Toshiya NAKAGUCHI Mikio SUGA Takashi ONISHI Yuzuru IKEHARA Yasuo IWADATE Koichi HAYANO -Advances in three-dimensional image display and -Novel, high-precision imaging techniques are being Hao LIU Ken-ichi TSUBOTA measurement techniques have applications in multiple fields, used to provide non-invasive disease diagnosis and guide WenWei YU Hiroki SUYARI from medicine to communication and entertainment. future treatments.

Members holographic imaging techniques.” somewhere else will see completely different Non-invasive, precise diagnosis of diseases registration method that transforms two data standing of different diseases,” says Haneishi. Among the team’s recent successes is a small, information. using advanced medical imaging tech- sets into one coordinated system using MRI The Multimodal Medical Engineering Tomoyoshi SHIMOBABA inexpensive, zoomable holographic projec- “Our volumetric display simultaneously nologies could one day replace traditional and pathological images of brain tumors. program has access to highly specialized Professor, Graduate School of Engineering tion system, suitable for use in classrooms, provides several observers with different techniques based on biopsy and dissection. “If we can establish the technology for equipment and technologies that can help medical applications and entertainment information,” explains Shimobaba. “This With this prospect in mind, researchers at registering two kinds of images, then MRI realize researchers’ ideas. Takashi KAKUE Takashi OKAMOTO products. Shimobaba’s team refined math- very exciting feature is quite new, and we the Multimodal Medical Engineering pro- features that are strongly related to the patho- “We welcome engineers and medical Atsushi SHIRAKI Tomoyoshi ITO ematical image manipulation techniques to are considering new applications for using gram are combining medical and engineer- logical features of tumors can be highlighted. researchers who wish to work at the cut- Seiichi KOAKUTSU Michiko TAKAGAKI ensure a high-resolution, non-grainy holo- it, such as developing multi-language ing expertise to create novel, noninvasive This may eventually allow us to diagnose us- ting-edge of research and development with graphic image even when zooming in and signage for the Tokyo Olympics in 2020,” imaging-based methods for diagnosing and ing only MRI,” says Haneishi. “Determining direct clinical applications,” says Haneishi. out. The researchers are further developing he says. Such 3D displays may benefit from treating disease. the relationships between different data sets Technologies based on three-dimensional algorithms that can reduce ‘speckle noise’ in advanced aerial projection techniques, also The program uses various scanning tech- helps us build up detailed pictures of what is (3D) image displays and holography may reconstructed images to avoid degradation under development by Shimobaba’s team. niques, or ‘modalities’, including comput- going on inside the body, not only for diag- conjure up visions of science fiction, but the in image quality. “Networking is the key to our success,” erized tomography, magnetic resonance nosis but also to improve our understanding Next-generation Three-dimensional Display says Shimobaba. “Many students who have imaging (MRI) and ultrasound, to analyze of disease development,” he adds. and Measurement program aims to make ONE IMAGE, MULTIPLE VIEWS graduated from our laboratory move on to cellular and organ variations caused by these advanced tools part of everyday life. conduct research in academia or in private different diseases. NOVEL OPTICAL PROBES Holograms create true three-dimensional Another aim is to reconstruct large 3D companies, and we continue to work with The program’s goal is to develop highly images, which allow the viewer to see an images with a large viewing angle — them. In this way, we expand our project and precise, non-invasive imaging methods, Alongside conventional imaging techniques, object from all angles. They are created using something that is difficult to realize using build fruitful working relationships across while boosting existing imaging techniques the researchers are also exploring novel opti- coherent light sources such as lasers, which current technologies. academia and industry.” to improve resolution and enable more-de- cal probes. One example involves a method can store the complex light interference pat- “We are also developing accurate holographic tailed tissue analysis, says program leader for monitoring microcirculation — the flow terns required to accurately recreate an entire measurement systems, which will be invalu- Hideaki Haneishi. of red blood cells — in the body. The probe 3D object in full color. However, the main able in medical science because they allow “Many current disease diagnostics, partic- comprises multicolored light-emitting di- drawback of holography is the immense com- researchers to image and measure samples in ularly for cancer, involve highly invasive, odes (LEDs). As the LED light is scattered putational burden of producing high-quality 3D alongside visualizing moving phenomena unpleasant procedures to clarify the type and through the tissue, it is partly absorbed by holograms, not to mention creating moving in real time,” explains Shimobaba. stage of the disease,” explains Haneishi. “We molecules in the red blood cells, generating 3D video images in real time. In another exciting field of research, the are investigating, for example, the develop- a clear, detailed picture of the cells and their Leader of the 3D program, Tomoyoshi Shi- team is exploring a form of 3D image ment of a system to diagnose breast cancer microcirculatory network. mobaba says his team is developing ultrafast creation called volumetric displays — the using very-high-frequency ultrasound.” Building on previous work, the team hopes algorithms and dedicated computers for ho- difference being that, while holograms can Rather than physically sampling and dissect- to use this probe to estimate features such as lography to create the world’s first real-time only be seen clearly by a few people at a ing lymph nodes from potentially cancerous the oxygen saturation of each blood vessel holographic 3D display system. time, volumetric displays can be viewed by tissue, his team has shown that it is possible in areas around suspected tumors in real “These dedicated computers will have a com- multiple people from different viewpoints. to analyse cell characteristics of lymph nodes time. This could aid diagnosis and further our putational speed three or four orders of mag- And, in an even more challenging concept, using ultrasound. Their technique highlights understanding of vascular behavior in and nitude higher than the household computers they are trying to create multi-viewpoint metastasis positive and negative cells in lymph around tumors. “Ultimately, we would like to of today,” adds Tomoyoshi Ito, advisor on the images with plural information appearing nodes, enabling rapid, painless diagnosis. build on these imaging techniques and use project. “Based on this dedicated technology, in specific directions. In other words, one Haneishi and his team are also devising ways machine learning and artificial intelligence we will investigate holographic projection, person standing at one place will see one to combine data from two or more modalities. technologies to relate measured signals and digital holographic microscopy and ultrarapid piece of information, while another standing For example, in 2016 they developed an image diagnoses, to develop a comprehensive under-

28 29 CENTER FOR INNOVATIVE MICROWAVE REMOTE SENSING IMAGING SCIENCE AND TECHNOLOGY FOR MATERIAL APPEARANCE THE NEXT WAVE REALNESS IN REMOTE SENSING IN DIGITAL IMAGES

Research Keywords: Microwave Remote Sensing, Synthetic Aperture Radar, Research Keywords: Engineering for Material Appearance, Image Sensing, Visual Psychology Environment and Disaster Monitoring Members

Jasaphat Tetuko SRI SUMANTYO -Microsatellites and remote imaging technology are Professor, Center for Environmental Remote Sensing -Understanding how the human brain interprets images revolutionizing the way we predict earthquakes and Kazuteru NAMBA Wen LIU could underpin the future of internet shopping, cosmetics, monitor disaster zones. Katsumi HATTORI Hiroyuki NAKATA digital fabrication and even non-invasive medicine. Chiharu HONGO Akira KATO

© iStock.com/wacomka When internet purchases arrive and seem FILTERED THROUGH THE BRAIN nothing like their picture, it can be a disap- have been deployed on both large and small pointing experience for shoppers. So, while Among the work done by the diverse group remarkable success in one crucial, but quite aircraft, as well as on the JX-1. The CP- big e-commerce players are increasingly is a study examining texture. Viewers, unique area — medical diagnostics. SAR sensor is the first of its kind, utilizing investing in technologies to help personalize suggest the researchers, often see the broad These researchers have carefully studied interference between left- and right-handed products or shop via phone or virtual reality design of patinas printed on fabric, but some the optical properties of haemoglobin in circularly polarized light to obtain precise headset, a significant stumbling block is ren- textures contribute to a blurring out of finer skin using images taken on a simple DSLR information about the Earth’s surface in a dering realistic, digitally produced images. details. In contrast, high-resolution digital camera. Incredibly, they found they could compact, lightweight and inexpensive sensor. “To achieve a realistic rendering of some- images with very accurate representations of measure both the heart rate and its vari- We have developed several techniques based thing, we also need to deeply consider the same material seem unnaturally sharp. ability with 99 percent accuracy. This opens on SAR imaging to monitor infrastructure human perception,” explains Keita Hirai, To explore this, the researchers developed the door to everything from non-invasive and areas affected by disasters such as forest a member of the Imaging Science and different ‘blurriness’ filters linked to material medical diagnosis to a better understand- fires, landslides, subsidence and volcanic Technology for Material Appearance group qualities and fine-tuned them by asking ing of physical exertion using a simple © iStock.com/Sirintra_Pumsopa eruptions,” says Sri Sumantyo. at Chiba University’s Graduate School of participants in their experiment to rate the smartphone app. Engineers in this team are developing Engineering. How we perceive a material, naturalness of the images. The Microwave Remote Sensing Labora- an earthquake or a landslide, researchers can two novel microsatellites. One is equipped he says, can also be linked to cognition, not Another group found that our perception of tory is far more than a laboratory. It is an determine how much the land has moved. with radio occultation and electron density just physical phenomena. colour is affected by our understanding of experimental aerospace workshop where The research team has a well-developed temperature probe sensors for measuring the To examine the complex effect of the mind’s its dimensionality. The same viewer looking world experts in remote sensing collaborate research-and-development program with atmospheric signatures thought to precede eye, Chiba University have drawn from at the same image saw colours differently with mechanical and aerospace engineers 15 researchers, 25 students and facilities for earthquakes, while the other is a CP-SAR a diverse range of researchers, including depending on whether they interpreted the to construct state-of-the-art microsatellites designing, manufacturing, calibrating and satellite with lightweight gold-coated mesh engineers, psychologists, and medical and image as two dimensional or three dimen- and airborne sensors. The research team operating SAR for both aircraft and micro- antenna. These satellites are poised to take the cognitive scientists. sional. Viewing images with one eye or specializes in microwave-radar technology satellite applications. lab’s research beyond the stratosphere. Recently, Hirai’s team developed a new both, and whether the image or the viewer’s for detecting ground movements and earth- “Our microsatellite program is very exciting system for texture evaluation, and through head was moving, also affected how natural quake predictors as part of a new generation ADVANCED AEROSPACE FACILITIES for future SAR sensor applications and plan- participant feedback have devised a set of the image seemed. This work, says Hirai, is of remote sensing technologies. etary exploration,” says Sri Sumantyo. “We algorithms that can produce more realistic important for better smart device produc- “Microwave radiation is particularly useful for “Our facilities include an anechoic chamber eventually aim to have five microsatellites in digital representations of patinas and colours tion. “A more informed colour management remote sensing because it penetrates cloud, for calibrating sensors, a satellite–ground orbit, which will provide real-time monitoring overlaid onto textured fabrics in digital system, for example, may help realize more haze and fog, allowing us to observe the Earth’s communication system, and microsatellite for global disaster mitigation and research.” images. The aim, he says, is to one day digital- accurate colour reproduction between differ- surface from space,” explains Josaphat Tetuko calibration and measurement systems. We The team has strong collaborations with ly simulate photo-real fabric appearance via ent devices: displays, cameras and printers,” Sri Sumantyo who leads this research project. also have a simulator for designing micro- Japanese and overseas research institu- a smart device. Hirai points out that this will he explains. Members The core area in this research project is the wave circuits and antennas, along with a tions and industry — it has more than 50 not only be helpful to internet shoppers, but Hirai says the group’s work will influence Norimichi TSUMURA development of synthetic aperture radars suite of manufacturing equipment,” says Sri agreements with research and industry that these algorithms could also find applica- the most cutting-edge imaging technology, Associate Professor, Graduate School of Engineering (SARs) for microwave remote sensing to Sumantyo. “We even have our own 6-meter partners throughout the world. The group tions in rapidly advancing digital fabrication such as the omni-directional 3D camera monitor land deformation. SAR emits a experimental unmanned aerial vehicle, the also encourages short- and long-stay pro- techniques, such as printing digital patinas systems and virtual reality headsets com- Takahiko HORIUCHI Keita HIRAI microwave signal in the direction of the JX-1, which we developed in this laboratory.” grams under various government programs, onto fabrics or objects, and manufacturing ing from technology giants such as Sony, Yoko MIZOKAMI Shoko IMAIZUMI target and then detects microwaves scattered They have already developed SAR sensors through which more than 500 students and representative digitally-designed 3D products. Panasonic, Canon and Nikon. While he Michinari KOHRI Noriko YATA from the target. By comparing SAR images for circularly polarized (CP) microwave researchers from many different countries In fact, the group aims to contribute to indus- also mentions cosmetics and automotive Toshihiko MATSUKA obtained before and after a change such as radiation in the L, C and X bands, which have worked at the lab. tries as diverse as cosmetics and medicine. painting, one team have already had some

30 31 INSECTS-INSPIRED BIG INNOVATION SOFT MOLECULAR ACTIVATION FOR INTELLIGENT MATERIALS Members

Takayoshi ARAI LOOKING TO NATURE TO CATALYZING THE FUTURE OF Professor, Graduate School of Science

Members Hirofumi KANOH Shoji MATSUMOTO Katsuhiko MORIYAMA Yasushi YOSHIDA REVOLUTIONIZE FLIGHT Hao LIU SMART MATERIALS Nobuyuki ICHIKUNI Tomonori OHBA Professor, Graduate School of Engineering Research Keywords: Bioinspired Engineering, Biological flight, Drone Yasuhiro YAMADA Shoichi KATSUTA Research Keywords: Synthetic Chemistry, Catalytic Reaction, Iodine Bond Takeshi MORITA Hyuma MASU Akio NAMIKI Kazuya OKAWA Fumio SAKANE Takeshi MURATA Toshiyuki NAKATA Michinari KOHRI Midori ARAI Takuya HASHIMOTO Toshihiko MATSUKA Tomokazu USHITANI Shigeru ARAI Kazuhiro YOSHIDA -The beating wings of insects hold the secrets Arii WATANABE Yuma TAKAHASHI -Catalysts developed from soft iodine, graphene Takashi MINO Hideaki SHIROTA Hiroyuki ISHIKAWA Akira KATO to controlled low-speed flight and Micro Aerial Vehicles. and metal complexes could transform smart material Masaya NAKAJIMA Shinji HARADA technologies. Shingo HARADA Tomoya UEHARA Mamoru TAKADA Keisuke IIDA Yasuhiro YAMADA

Inspired by the fascinating flying ability of ultra-low-speed wind tunnel capable of air- more reliable and agile than anything based The very idea of materials that change their catalysts, predominantly using iodine, can and ring-shaped molecules. “We are lucky insects and humming birds, Chiba Universi- flow as slow as half a metre a second. They on today’s rotor-based technology. We hope shape or function as required sparks the be used to develop highly targeted medi- that Chiba prefecture in Japan is one of the ty’s Biomechanical Engineering Laboratory use it to observe and analyse the flight of that this will also lead to a new mechanism imagination. Smart materials are impres- cations,” he explains. “A second type is ‘soft world’s leading producers of iodine,” says has been conducting pioneering research on live birds and insects such as moths, beetles of flight with potentially much broader ap- sive artificial molecules, often inspired by Π-electron’ using carbon nanotubes and Arai. “In fact, the Chiba Iodine Resource beating-wing flight for more than 20 years. and dragonflies, as well as micro air vehicles plications. In the meantime, we continue to naturally occurring chemicals, which have the graphene, which would provide a unique Innovation Center (CIRIC) has opened at Headed by Professor Hao Liu, the lab is on (MAVs), very small drones with potential collaborate on the development of advanced, potential to revolutionize design. They under- reaction sphere for catalysis. The third type, Chiba University in July, 2018. A key goal of the verge of revolutionizing the very concept uses in disaster relief and covert operations. flapping MAVs, as well as help improve the go changes that are reversible and repeatable, ‘soft metal’ catalysts allow us to introduce our program is to perfect iodine-based soft of flight itself. “Using high-speed imaging and particle reliability of rotor-based drones by introduc- meaning they can function as molecular soft elements such as gold and copper into molecular activation.” “Insects have this amazing ability to hover image velocimetry data, we were able to ing flexible wing technology.” switches, valves and sensors. Other smart target molecules.” Recent success for Arai’s team includes and execute highly controlled flight in both create a computer model of an insect and materials include shape-memory alloys that the development of an aminoiminophe- still air and turbulent wind gusts,” says Liu. its flight mechanism, and from there we return to their original shape after bending, NEW CATALYST DESIGN noxy-copper carboxylate catalyst that can “Scientists once knew very little about how made an experimental robot insect that metal-bearing polymers that can switch from trigger high yields of O-cyclized molecules. insects generate aerodynamic force in tur- actually flew. That was another pioneering insulator to conductor and drug-delivery Arai says one of the main goals of the pro- These can, in turn, be used to generate a bulent environments, and even less about breakthrough,” says Liu. systems that slowly release pharmaceuticals gram is to create new asymmetric catalysts, particular chiral compound that is invaluable how they are able to maintain such agile “Our research brings together biology, engi- where and when they are needed. which are used to generate large numbers for use in antimicrobial and antiosteoporotic control in flight.” neering, computational physics, biorobotics Researchers at the Soft Molecular Activa- of very specific molecules. Most biological compounds. and neuroscience, and we collaborate with tion for Intelligent Materials program are molecules are chiral, meaning they exist in “A crucial part of our research is designing BIOLOGY INSPIRES MICRO the likes of Cambridge and the Universi- leading investigations into catalysts made one of two mirror-image forms called enan- catalysts that can be reused multiple times, AIR VEHICLES ty of London on some really interesting from soft molecules that could one day tiomers. Many drugs and smart materials use thereby creating cost-effective, sustainable international, cooperative projects. Chiba transform smart material design. just one specific enantiomer, and so catalysts methods for generating useful compounds,” Conventional flight is based on the unin- is definitely a world leader in this area with Lead researcher Takayoshi Arai says the are needed to direct the chemical reactions says Arai. His team recently designed a terrupted flow of air over the curved upper a strong interdisciplinary team and world- program is focused on developing powerful toward forming the correct enantiomer. recyclable catalyst made from a zinc-poly- and lower surfaces of a wing, which causes a class facilities.” catalysts to create novel smart materials us- For example, iodine has been used to help meric ligand complex. The polymeric ligand ‘suction’ effect that lifts the wing upward. The lab’s research now focuses on develop- ing three catalyst types. “Firstly, soft halogen synthesize specific enantiomers of cyclic allows the catalyst to be separated from the “Fixed wings need smooth airflow to gener- ing insect-inspired flight systems, which he final product by a simple filtration process, ate lift,” explains Liu. “Turbulence over the expects to lead to big developments in the meaning it can be reused — indeed, poly-Zn wing can lead to disaster. Our first major design of insect- and bird-size MAVs. remained a stable and active catalyst for breakthrough in unravelling the mystery “For example, we think it’s wing flexibility creating iodine-based ring-shaped molecules of insect flight was that most flying insects that gives insects much of their resilience more than five times. in fact generate most of their lift force by to wind gusts, but we are also seeing that “By introducing soft elements to target mol- creating a vortex on the leading edge of the insects use their body much more than we ecules, our research will facilitate the devel- flapping wing. It’s a completely different thought to control direction and movement, opment of smart materials with smooth and principle of flight to conventional flight.” both actively and passively. This is com- rapid responses,” says Arai. “We welcome It all started in 1996 with Liu’s development pletely different to the conventional wing- anyone interested in research at the forefront of the first computational fluid dynamics based control used by planes today and has of iodine-related soft molecular activation simulation for insect flight, which led to the potential to revolutionize flight control chemistry to come and work in this diverse the discovery of the universal leading-edge strategies in general,” says Liu. and challenging field at Chiba.” vortex mechanism in insect and bird flight. “Ultimately we want to develop an in- © Akiko Sato To delve deeper, the laboratory installed an sect-inspired autonomous drone that is far

32 33 ADVANCED BONE-CONDUCTION COMMUNICATION LYMPHEDEMA MONITOR

BONE-CONDUCTION Members MAKING INVISIBLE Members Seiji NAKAGAWA Masahiro TAKEI TECHNOLOGY BEYOND Professor, Center for Frontier Medical Engineering LYMPHEDEMA VISIBLE Professor, Graduate School of Engineering

Shingo KUROIWA Yoshihiro SHIMOMURA Shinsuke AKITA Ryoji YAGI HEARING AID Yasuo HORIUCHI Keita ISHIBASHI Keisuke KONO Yoshihiro SHIMOMURA Sho OTSUKA Satoki ZENBUTSU Michiko SUGAWARA Nobuyuki MITSUKAWA Research Keywords: Bone Conduction, Hearing Aid, Biomedical Engineering Research Keywords: Electrical Impedance Tomography (EIT), lymphedema, Cloud Computing Masashi SEKINE Akira MITSUHASHI Takafumi SANGAI Takuro HORIKOSHI Tadashi YAMAGUCHI Ichiro MANABE Mikio SUGA -Elucidating the perceptual mechanisms of ultrasonic bone conduction -A low-cost and easy-to-use tomography device can ensure early Kenji YOSHIDA and cartilage conduction with a view to new device development detection and proper understanding of lymphedema.

Against the background of the aging society cartilage conduction, and try to apply them to standards and hearing-related safety stan- “Lymphedema,” or stagnant lymph flow and construction of a new electric tomography using machine learning and big data analysis and diversifying lifestyles, there is a grow- hearing aids and smartphones. dards. Fundamental understanding of the abnormal swelling of the arms and legs that began at the University of Manchester, UK. of the lymphedema images. With this de- ing need for a broader range of options in perceptual mechanisms is essential to solving may occur following the removal of lymph Takei had also participated in this project vice, patients can check their edema stage by hearing aids and audio devices. Among the PERCEPTUAL MECHANISMS AND these challenges. nodes by surgery or radiotherapy, occurs in called “European Action.” Several challenges themselves at home. various technologies used for hearing aids, DEVICE DEVELOPMENT “Research on ultrasonic bone conduction about 30% of patients who had surgery for occurred during this project, and the mem- To elucidate the mechanism of development bone conduction has mainly been used for and cartilage conduction have just begun, gynecological cancers such as breast cancer ber researchers tried to solve these problems and progression of lymphedema, not only compensating conductive hearing loss caused Bone-conducted ultrasonic waves can and most of their perceptual mechanisms and uterine cancer. “It has been considered one by one. They developed the sensors, the engineering and medical knowledge but also by middle or outer ear disorders. In recent be perceived as a sound even by severely are still unknown. For example, the mecha- as an abandoned sequela for a long time and electrical circuits to reduce noise and speed- pharmaceutical and scientific considerations years, the incidental benefits of bone conduc- hearing-impaired people who cannot hear nisms of how the bone-conducted ultrasonic has only recently garnered the attention of ing up, the image reconstruction software are crucial. By implementing the knowledge tion technology, such as benefits in speech even with the use of a conventional hearing waves are propagated and easily perceived are researchers,” says Masahiro Takei. “The risk with mathematical inverse problem-solving gained from such integrated research to the perception under noisy conditions, less sound aid. Prototype testing of an ultrasonic bone unclear when the vibrator is attached to the of lymphedema onset lasts for a lifetime, capability, and proceeded with developing prototype, Takei’s team aim to improve the leakage, and usability in water, have come to conduction hearing device showed that, with neck, chest, or even the upper arm. Most of and the condition cannot be fully cured if the appropriate procedures for industrial accuracy and convenience of the machine. attract attention. However, the perceptual the use of this device, about half of severe- the technical challenges of bone conduction detected late, so the patients are forced to and biological use. However, the prototype “Ultimately, we want to visualize the medi- mechanism of bone conduction is complicat- ly hearing-impaired persons were able to cannot be solved without understanding the have a significant psychological burden. For equipment had cost millions of yen, and the cal condition in real-time on a mobile device ed and has yet to be fully understood. perceive verbal sounds, and around 30% were perceptual characteristics and propagation a good prognosis, early detection of stages accuracy was not sufficient for practical use. and to reduce the pain of patients.” “The sound we usually hear through our able to identify the words being spoken. The process of bone conduction.” 0 and 1 of lymphedema is critical, but there “At that time, I thought it would be inno- earholes is called air conduction. While there cartilage conduction is technology in which Nakagawa believes that if he advances bone is still no effective detection device for this vative if we could easily see our inside of is only one pathway for air conduction, the vibrator is attached to the pinna cartilage, conduction technology based on a deep purpose.” the body with a machine that costs around there are at least four pathways available for and now it is applied to hearing aids for understanding of such mechanisms, it opens Takei is now forming a research team of tens of thousands of yen,” says Takei. Thus bone conduction,” says Seiji Nakagawa. “The patients with atresia of the ear canal and also up possibilities for new applications. engineering, medical, pharmaceutical, and emerged the breakthrough technology—a perceptions of bone-conducted sound largely to speakerless smartphones. “For example, we are now going to develop scientific experts from Chiba University, small electric tomography with diagnostic changes according to frequency and location, The cartilage conduction and the ultrasonic bone conduction headphones and micro- aiming to improve the accuracy of detection function. The new system works as follows: and at times differ largely from the sound bone conduction are both ground-breaking phones that can be used even under severely by developing IoT lymphedema tomograph- several electrodes are placed on the body, and perceptions by air conduction.” Nakagawa approaches. There are still some challenges noisy conditions, and an earphone for infants ic monitor with artificial intelligence (AI) a weak electric current is passed through the and his team are working to elucidate audi- before applying them to practical products who often resist the use of conventional system that can be used at home. body. The system produces images showing tory perceptual mechanisms with a focus on for widespread use: improvement of sound earphones or headphones. Furthermore, bone the distribution of conductivity and dielec- ground-breaking bone conduction phenome- transmission performance, wearability and conduction is also suitable as an interface for A SMALL ELECTRIC TOMOGRAPHY tric constant in the body at each frequency na, including ultrasonic bone conduction and comfort of use, and development of industry smart glasses, which people think to be the using a wearable sensor to measure the next-generation information terminal.” As a mechanical engineer, Takei’s belief is potential, small hardware, and mathematical “Chiba University has many faculty members “to make invisible things visible by using a algorithms. with expertise and knowledge in human machine.” So far, he has been working on Currently, Takei’s research team is working interface technology and acoustic signal developing hardware and software related on developing an easy-to-use IoT lymph- processing. We can develop new devices by to electrical tomography. Tomography refers edema tomographic monitor. First, with bringing those strengths together for projects to cross-section visualization measurement, the monitor, impedance data measured by a centered on bone conduction technology. as in computed tomography (CT). Medical small unit from the multi-electrode winded We also have collaborative partnerships with CT is a large machine that costs hundreds sensors are sent to the cloud computing businesses in Japan and abroad and hope to of millions of yen, and it is impossible for unit. Next, 4D images of limb cross-sections achieve innovation by pursuing fundamental patients themselves to use it easily at home. are reconstructed at high speed on the cloud research for mechanism elucidation as well This challenge has been recognized around using specialized software. Finally, edema as the development of practical applications,” the world. In the 1990s, the theoretical (including early-stage edema) is diagnosed says Nakagawa.

34 35 RELATED RESEARCH CENTERS INSTITUTE FOR GLOBAL PROMINENT RESEARCH

· Center for Environmental Remote Sensing · Medical Mycology Research Center · Soft Molecular Activation Research Center, To accelerate innovative research beyond the borders of academic disciplines, the Chiba Iodine Resource Innovation Center IGPR was founded as a core institution at Chiba University in 2016. Aiming at fos- · Molecular Chirality Research Center tering seeds and delivering the fruits to the world, IGPR has been actively support- · Center for Frontier Medical Engineering ing research projects with potential impact as a global hub for top-class research. · Center for Environment, Health and Field Science · Research Center for Child Mental Development The institute is also focused on developing young human resources who will lead · Plant Molecular Science Center new research fields in the next generation. Currently, IGPR is supporting more than · International Center for Hadron Astrophysics 20 research projects in diverse areas. · Center for Aerial Intelligent Vehicles · International Center of Excellence in the Mucosal Immunology and Innovative Allergy Therapeutics · Center for Artificial Intelligence Research in Therapeutics TEL : +81-43-290-2986 Mail : [email protected] · Shanghai Jiao Tong University and Chiba University URL : igpr.chiba-u.jp/global International Cooperative Research Center © iStock.com/farakos

36 37 MESSAGE FROM ABOUT THE DIRECTOR OF IGPR THIS MAGAZINE

Copyright © 2020 Chiba University. All rights reserved.

The information in this publication was correct at the time of going IGPR and the findings produced by achieved last year. to press in January 2020. The views each of the research projects it supports In October, Professor Toshinori Na- expressed by contributors in this are being increasingly recognized. kayama and his research team studying publication are not necessarily In June, the findings of our bioin- mucosal immunology identified the cell spired engineering research team led populations that induce fibrosis in lung those of Chiba University. by Professor Hao Liu were covered in tissue caused by exposure to fungal the science column of Asahi Shimbun antigens and elucidated the mechanism (Newspaper), and a month-long exhi- that leads to tissue fibrosis which was bition “Observing, Understanding and previously unknown. Pulmonary fibrosis Takeshi Tokuhisa Imitating Living Creatures” was held caused by fungal infections leads to the Director, IGPR and on campus starting from October 18. development of refractory conditions President of Chiba University While Professor Liu’s laboratory has such as shortness of breath, breathing been studying the mechanisms of flap- difficulties and chronic coughing,and ping flight for more than two decades, it is anticipated that an effective treat- It is my great pleasure to have the bioinspired engineering is attracting ment may be developed by targeting fourth issue of CHIBA RESEARCH more public attention than ever now. the highly pathogenic cell populations. available here for you. All of the re- The exhibition enjoyed a great number IGPR supported projects were covered search projects introduced in this issue of visitors including those who visited in a total of approximately 100 articles have been carried out with the support the campus during the Chiba University published by Japanese and overseas from the Institute for Global Promi- Festival. media. Furthermore, IGPR held a sym- nent Research (IGPR), a university-wide In August it was officially announced posium in December as part of IGPR’s organization of Chiba University. The that D-Egg, a new optical sensor de- initiative to foster next-generation IGPR was established in 2016, with the veloped by the International Center for researchers. Approximately 90 young goal to enhance prominent internation- Hadron Astrophysics led by Professor researchers from diverse fields were al research projects of Chiba University Shigeru Yoshida, would be installed given a chance to brush up their skills and foster young scientists who will for the upgrade of IceCube Neutrino to concisely communicate their research become leaders of next-generation Observatory in Antarctica. At present, findings to people outside of their spe- research. This is an original attempt in 5,160 optical sensors are buried under cialization. that research resources are brought thick ice at the South Pole, and 700 Through the IGPR to promote the 1-33 Yayoi-cho, Inage-ku, together from all sources throughout more are planned to be added in the world prominent research projects, Chiba-shi, Chiba, the university, and a variety of research near future. D-Egg will account for 300 Chiba University continues our efforts 263-8522 Japan of the 700 sensors to be newly installed. to further contribute to society. I strong- fields are comprehensively support- www.chiba-u.jp/e ed. This approach is possible because The upgrading works will start in De- ly hope that this issue of CHIBA RE- Chiba University is a multidisciplinary cember 2022 and it is expected that the SEARCH can help you to have deeper university and cannot be found in any of upgrade may lead to further exciting appreciation of Chiba University’s front the colleges or universities in Japan. discoveries following the world’s first edge research activities. The year 2019 was the fourth year for identification of a neutrino source

38 WHERE IS PUBLIC TRANSPORT CHIBA UNIVERSITY? TO CHIBA

Ōmiya

Fuchuhonmachi CHIBA Prefecture is located at the east edge of the South Kanto Kashiwanoha Campus region. It has a population of approximately 6 million, the 6th largest HOKKAIDO among the 47 prefectures in Japan. Chiba is the center of Keiyo Indus- KASHIWA-NO-HA Minami-Nagareyama trial Area and has the well-developed industry. The three sides of Tsukuba CAMPUS the prefecture are surrounded by the sea, which helps Chiba's Kita-Senju Matsudo Abiko Suido growth in the seafood industry as well. Nippori MATSUDO Chiba University has 4 campuses in Chiba Prefecture. CAMPUS

Nishichiba Campus (Main Campus) is located between Narita Interna- tional Airport and Tokyo Station. It takes about 30 to 40 minutes by Ueno Mitaka Ichikawa train to Tokyo Station and also Narita International Airport. Shinjuku Akihabara Shin Kamagawa Nishi-Funabashi Tokyo Narita Airport Hamamatsu Cho Funabashi TOHOKU Minami-Funabashi Narita Haneda Airport Shinagawa Tsudanuma

Keisei Tsudanuma Sakura Kurihama Inage Chōshi Midoridai NISHI-CHIBA

Nishi-chiba CAMPUS

Keisei Chiba Chiba KANTO INOHANA CAMPUS CHUBU Chiba 1. KASHIWA-NO-HA CAMPUS Chiharadai 5-min walk from the Tsukuba Express Kashiwanoha-campus Station. KANSAI Take the Tobu buses bound for National Cancer Center or Kashiwanoha Park from Kimitsu Kazusa-Ichinomiya CHUGOKU bus stop No2 at JR Kashiwa Station or near the east exit of Tobu Kashiwa Station.

2. MATSUDO CAMPUS SHIKOKU 10-min walk from Matsudo Station (JR Joban line, Tokyo Metro Chiyoda Line, Shin-Keisei Line)

KYUSHU Tsukuba Express Line 3. NISHI-CHIBA CAMPUS Yamanote Line 2-min walk from JR Nishi-Chiba Station to the South Gate of Nishi-Chiba Campus Sōbu Line [Local Train] Narita Airport 7-min walk from Keisei Midoridai Station to the Center Gate of Nishi-Chiba- Campus Sōbu Line [Rapid Service] 10-min walk from Chiba Monorail Tendai Station to the North Gate Keisei Line Tokyo Yamanote Line 4. INOHANA CAMPUS Joban Line [Rapid Service] Narita Line Musashino Line Chiba After arriving Chiba Station (JR) a bus stop can be found in front of east exit 7 (this bus Keiyo Line University can also be taken if you get off at Keisei Chiba Station). Take buses bound for Chiba Tokyo Monorail University Hospital or Minami-Yahagi and get off at the School of Medicine Entrance Keikyu Airport Line bus stop, or, to get to the university hospital, get off the bus at the Chiba University Uchibo/Sotobo Line Hospital stop. Tobu Urban Park Line