A variety of wideband services is demanded in the present mobile communication systems. However, a severe signal distortion encountered in a mobile wireless channel prevents high-quality digital signal transmissions. He has been conducting the research on wideband transmission technology using code division multiple access (CDMA) and developed an advanced equalization technique based on known pilot signals periodically transmitted for estimation of the signal distortion. Furthermore, he developed CDMA spreading codes, known worldwide as the orthogonal variable spreading factor (OVSF) codes, for allowing multiplexing users of various data rates. These achievements became an important technical basis of Wideband CDMA, which is one of the technical standards used in third generation mobile communication systems. They can also be applied for advanced wireless communication systems, which will appear in the near future.

Asymmetric conjugate addition of aryl and alkenyl groups to electron deficient olefins was found to proceed with high enantioselectivity in the presence of a rhodium catalyst coordinated with chiral phosphine ligand. The scope of this asymmetric addition is very broad, a,b-unsaturated ketones, esters, amides, 1-alkenylphosphonates, and 1-nitroalkenes being efficiently converted into the corresponding optically active 1, 4-addition products with over 95% enantioselectivity. The catalytic cycle is proposed to involve the enantioselective addition of aryl- or alkenyl-rhodium intermediate to carbon-carbon double bond of the electron deficient olefins as a key step.

Immunoglobulin heavy chain gene locus is altered by two mechanisms to combat pathogens after encountering the antigen. One is class switch recombination that gives rise to IgG, IgE, and IgA from IgM-encoding gene to increase diversity of effector function of antibody. The other is somatic hypermutation that is driving force of affinity maturation of antibody. These two phenomena have been known for a few decades; however, the enzyme that is responsible for these two has not been identified. What we found for the last five years is 1), identification of activation-induced cytidine deaminase AID, 2), to prove that AID is essential and required for class switch recombination and somatic hypermutation, and 3), mutation of AID results in hyper-IgM syndrome type II with collaboration with Drs. A. Fisher and A. Durandy. After discovery of AID, many scientists joined in this field, so that the field expanded and now it encloses other fields such as oncogenesis, HIV infection, and DNA repair.

"For Ultrafine-grained metallic materials produced using severe plastic deformation"

We have shown that the process of equal-channel angular pressing (ECAP) can produce ultrafine-grained microstructures in metallic materials through intense shear. The grain size is refined to the submicrometer or nanometer range and this grain refinement is achieved expeditiously through the introduction of the shear in multi-directions. The materials processed by the ECAP exhibit higher strength with enhanced ductility. Furthermore, the grain refinement using ECAP leads to superplastic ductility when tested at high strain rates and/or lower temperatures. The ECAP process can scale up so that the grain refinement is feasible in large bulk materials. Such improvements of mechanical properties are attained without relying on alloying elements so that the ECAP process has a great potential for high recycling performance.

In 1999, we discovered and determined the structure of a novel ligand from rat stomach as an endogenous ligand for GHS receptor. We named the growth hormone-releasing peptide "ghrelin" ("ghre" is the Proto-Indo-European root of the word "grow"). Ghrelin is a 28-amino acid peptide with a marvelous structure modified by fatty acid (n-octanoic acid). In addition to the stimulation of growth hormone release, ghrelin is also involved in the stimulation of feeding, and the regulation of cardiovascular systems and energy metabolism. Thus, ghrelin has multifaceted roles in maintaining homeostasis of human body. The studies for therapeutic application of ghrelin on various diseases including heart failure and anorexia are now going on.

Superconductivity is a phenomenon in which electrical resistance disappears at low temperatures. Maeno’s group discovered superconductivity in a ruthenium oxide in 1994. This superconductor is now established as a long-sought spin-triplet superconductor. Electrons can take two states, called spin up or down. In all conventional superconductors, electrons with opposite spins form pairs (spin-singlet superconductivity). However, in a spin-triplet superconductor electrons with the same spin are paired. Studies of the ruthenium-oxide superconductivity have established the realization of the spin-triplet superconductivity in detail. Since not only the "charge," but also the "spins" exhibit superfluid properties, the spin-triplet superconductor is expected to be applicable, for example, for a novel device for quantum information.

Cytokinins are a class of hormones important for the regulation of cell division and differentiation in higher plants. Since this particular plant hormone was discovered 50 years ago, many plant researchers have long been looking for the cellular receptors for this hormone and its underlying molecular mechanism of intracellular signal transduction. But the progress was very slow. During the last few years, however, we and other researchers eventually and independently identified the histidine protein kinases that serve primarily as cytokinine receptors in the model plant Arabidopsis thaliana. We also provided a number of evidence supporting the novel view that the immediate responses of plants to the hormone can be formulated as the histidine kinase-mediated phosphorelay signal transduction circuitry. These findings will provide a landmark for the plant hormone researches.

We have been working on the etiology and pathogenesis of sporadic Parkinson’s disease for many years. Furthermore, we focused on the pathogenesis of familial Parkinson’s disease to find a common pathway between sporadic and familial forms. Subsequently, we identified a novel causative gene, parkin, for autosomal recessive Parkinson’s disease. Then we found that parkin was an ubiquitin-protein ligase of the ubiquitin-proteasome pathway. In many other neurodegenerative disorders, ubiquitinated proteins are accumulated in the diseased regions. Thus protein handling in the ubiquitin-proteasome system appears to be affected in these neurodegenerative disorders. Thus, the discovery of parkin opened a gateway for elucidating the pathogenesis of not only Parkinson’s disease but also other neurodegenerative disorders.

G protein-coupled receptors (GPCR) constitute the largest membrane protein family in the human genome. About half of the current commercially available drugs are thought to act on these receptors. Because they share a common septahelical transmembrane motif and some highly conserved amino acids, it was highly desirable to obtain the experimental three-dimensional structure of any member in the GPCR family. We have succeeded in the first determination of the x-ray crystal structure of GPCR, a visual photoreceptor rhodopsin. This achievement has remarkably facilitated the recent research efforts for the homology modeling and the structure-function studies on the other drug-target GPCRs whose structures are still unknown.

Biopolymers based nanocomposites have a great deal of future promise for potential applications as high-performance and -function biodegradable materials. These are entirely new types of materials based on plant and natural materials.

p53 was discovered in 1979 and named like this because it was a protein of molecular weight 53 Kd. It is inactivated by mutation in about 50% of human cancers, and is recognized as the most important protein for elucidation of the mechanism of carcinogenesis as well as development of new cancer therapy methods. When DNA of cells is damaged, p53 induces arrest of cellular proliferation or apoptosis, cellular suicide. The mechanism was, however, not known. I have generated antibodies to distinguish all of 13 phosphorylation sites of p53, and using these antibodies, I have shown that phosphorylation of specific sites on p53 are induced by DNA damage through activation of specific kinases, leading to the regulation of a variety of physiological functions of p53.

We have found that the Indian Ocean can give birth to an interannual ocean-atmosphere coupled mode now called the Indian Ocean Dipole.  We have also clarified, using coupled general circulation models, its evolutionary mechanism.  The phenomenon in the Indian Ocean induces abnormal weather conditions not only in surrounding countries such as India, Australia, and Kenya, but also in Europe and East Asia.   Its impact is found to be global, just like El Niño in the Pacific.  To predict the phenomenon, it is important to obtain ocean-atmosphere data for model initialization.   Several international bodies are now supporting the plan to implement an ocean-observing system in the Indian Ocean.

We have been studying molecular mechanisms how the animal body responds to the toxic effects of food (electrophiles) and oxygen (reactive oxygen species; ROS). Animal cells have acquired the intricate defense mechanism against these toxicities during evolution. A battery of genes encoding detoxifying and anti-oxidative stress enzymes are coordinately induced upon exposure to electrophiles and ROS. We discovered that this coordinated response is regulated through a heterodimer of Nrf2 and small Maf protein. We also identified Keap1, which serves as a sensor for electrophiles and ROS and directly regulates the Nrf2 activity. Shedding light on the molecular mechanisms governing the function of the Nrf2-Keap1 pathway will make great strides in both basic and applied medicine in the near future.