For innovative designs of coastal structures, Numerical Wave Flumes (NWFs), which are solvers of Navier-Stokes equation for free-surface flows, are key tools. In this article, various methods and techniques for NWFs are overviewed. In the former half, key techniques of NWFs, namely the interface capturing (MAC, VOF, C-CUP) and significance of NWFs in comparison with the conventional wave models are described. In the latter part of this article, recent improvements of the particle method are shown as one of cores of NWFs. Methods for attenuating unphysical pressure fluctuation and improving accuracy, such as CMPS method for momentum conservation, Higher-order Source of Poisson Pressure Equation (PPE), Higher-order Laplacian, Error-Compensating Source in PPE, and Gradient Correction for ensuring Taylor-series consistency, are reviewed briefly. Finally, the latest new frontier of the accurate particle method, including Dynamic Stabilization for providing minimum-required artificial repulsive force to improve stability of computation, and Space Potential Particle for describing the exact free-surface boundary condition, is described.

Crown gall of grapevine, which is caused by tumorigenic Rhizobium vitis, is the most important bacterial disease of grapevine throughout the world. Screening tests of biological control agents resulted in the discovery of a nonpathogenic R. vitis strain ARK-1. By soaking grapevine roots with a cell suspension of strain ARK-1 prior to planting in the field, ARK-1 treatment significantly reduced the number of plants with crown gall symptoms. Several field trials result indicated that ARK-1 was very useful in the field, not only for grapevine but also for various other plant species. In experiments where a mixture of ARK-1 and a tumorigenic strain at a 1 : 1 cell ratio was examined in vitro and in planta, expression levels of the virulence genes virD2 and virE2 of the tumorigenic strain were significantly lower. The suppression of virulence genes, which can result in a reduction of gall formation and the pathogen population, seems to be a unique mechanism of ARK-1. These results indicated that ARK-1 is a promising new agent to control grapevine crown gall.

We have been working on functional genomics using C. elegans as a model organism. We first used cell-type specific markers and preexisting mutants to investigate how genotype-phenotype causal relationships are regulated. With the aid of transgenic methods, we analyzed various biological processes in C. elegans. We have developed efficient methods to isolate gene knockout strains. Thousands of strains isolated this way are used by many researchers and have revealed many biological mechanisms. We have also developed methods to examine the functions of genes in a comprehensive manner by integrating transgenes into chromosomes, designing conditional knockouts, and creating balancers for lethal mutations. A combination of these biological resources and techniques will be useful to understand the functions of genes in C. elegans, which has many genes that are orthologous to those of higher organisms including humans.

Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular sensor that detects small peptides derived from the cell wall component of intestinal microflora. NOD1 is expressed in both non-hematopoietic cells such as epithelial cells and hematopoietic cells such as antigen-presenting cells. Detection of its ligand by NOD1 leads to innate immune responses through activation of nuclear factor kappa B and type I interferon as well as induction of autophagy. Innate immune responses through NOD1 activation play an indispensable role both in host defense against microbial infection and in the development of gastrointestinal disorders. Of particular importance, NOD1-mediated innate immune responses are associated with mucosal host defenses against Helicobacter pylori (H. pylori) infection of the stomach and with the development of pancreatitis. In this review, we discuss the molecular mechanisms by which NOD1 activation leads to the development of H. pylori-related gastric diseases and pancreatitis.

Molecules involved in the disease process facilitated our understanding of pathogenesis of the disease with unknown etiology such as immune-mediated and inflammatory diseases. Moreover, the targeted therapies against the proposed molecular targets by biological agents provide enormous benefits to the patients and societies. Here, I will review recent progress of the biological treatment in the immune-inflammatory diseases by focusing on the rheumatoid arthritis, the disease characterized by persistent polyarthritis leading to joint destruction and disability with autoimmune features, as a role model.

Recent advances in basic and clinical medicine have resulted in major improvements in human health. Currently sleep has been considered an essential factor in maintaining and promoting a healthy life expectancy. Sleep disorders include more than 60 diseases. Sleep disordered breathings (SDB) have 17 disorders, including sleep apnea. SDB usually induces hypoxemia and hypercapnia, which would have significant effects on cells, organs, and the whole body. We have investigated SDB for nearly 35 years. We found that SDB has significant associations with humoral factors, including coagulation systems, the body’s protective factors against diseases, and metabolic and organ diseases. Currently we have been giving attention to the associations among SDB, short sleep duration, and obesity. In addition, SDB is important not only in the home but under critical care such as in the perioperative stage. In this review, I would like to describe several aspects of SDB in relation to systemic diseases and overall health based mainly on our published reports.

F-type ATPase is a ubiquitous molecular motor. Investigations on thermophilic F₁-ATPase and its subunits, β and ε, by NMR were reviewed. Using specific isotope labeling, pK_a of the putative catalytic carboxylate in β was estimated. Segmental isotope-labeling enabled us to monitor most residues of β, revealing that the conformational conversion from open to closed form of β on nucleotide binding found in ATPase was an intrinsic property of β and could work as a driving force of the rotational catalysis. A stepwise conformational change was driven by switching of the hydrogen bond networks involving Walker A and B motifs. Segmentally labeled ATPase provided a well resolved NMR spectra, revealing while the open form of β was identical for β monomer and ATPase, its closed form could be different. ATP-binding was also a critical factor in the conformational conversion of ε, an ATP hydrolysis inhibitor. Its structural elucidation was described.

A mixture of (E,Z)-isomers of methyl 12-trishomofarnesoate (methyl 3,7,11-trimethyl-2,6,10-pentadecatrienoate), a juvenile hormone mimic, was synthesized in nine steps (32.6% overall yield) by starting from only four commercially available materials: 2-hexanone, vinylmagnesium bromide, methyl acetoacetate and trimethyl phosphonoacetate. The mimic is useful in increasing the yield of silk by elongating the larval period of the silkworm, Bombyx mori (L.).