The tsunami science and engineering began in Japan, the country the most frequently hit by local and distant tsunamis. The gate to the tsunami science was opened in 1896 by a giant local tsunami of the highest run-up height of 38 m that claimed 22,000 lives. The crucial key was a tide record to conclude that this tsunami was generated by a “tsunami earthquake”. In 1933, the same area was hit again by another giant tsunami. A total system of tsunami disaster mitigation including 10 “hard” and “soft” countermeasures was proposed. Relocation of dwelling houses to high ground was the major countermeasures. The tsunami forecasting began in 1941. In 1960, the Chilean Tsunami damaged the whole Japanese Pacific coast. The height of this tsunami was 5–6 m at most. The countermeasures were the construction of structures including the tsunami breakwater which was the first one in the world. Since the late 1970s, tsunami numerical simulation was developed in Japan and refined to become the UNESCO standard scheme that was transformed to 22 different countries. In 1983, photos and videos of a tsunami in the Japan Sea revealed many faces of tsunami such as soliton fission and edge bores. The 1993 tsunami devastated a town protected by seawalls 4.5 m high. This experience introduced again the idea of comprehensive countermeasures, consisted of defense structure, tsunami-resistant town development and evacuation based on warning.
Fluorine (from “le fluor”, meaning “to flow”) is a second row element of Group 17 in the periodic table. When bound to carbon it forms the strongest bond in organic chemistry to give organofluorine compounds. The scientific field treating them, organofluorine chemistry, started before elemental fluorine itself was isolated. Applying the fruits in academia, industrial organofluorine chemistry has developed over 80 years via dramatic changes during World War II. Nowadays, it provides various materials essential for our society. Recently, it utilizes elemental fluorine itself as a reagent for the introduction of fluorine atoms to organic molecules in leading-edge industries. This paper overviews the historical development of organofluorine chemistry especially from the viewpoint of material industry.
This review focuses on the development of dynamic ammonium salt catalysis for selective organic transformations conducted in our laboratory since 2002. Several important concepts in designing of catalysts are described with some examples. In particular, the practial synthesis of chiral 1,1’-binaphthyl-2,2’-disulfonic acid (BINSA) and its application in chiral ammonium salt catalysis for the enantioselective direct Mannich-type reaction are described.
Transforming growth factor-β (TGF-β) is a multifunctional cytokine that induces growth arrest, tissue fibrosis, and epithelial-mesenchymal transition (EMT) through activation of Smad and non-Smad signaling pathways. EMT is the differentiation switch by which polarized epithelial cells differentiate into contractile and motile mesenchymal cells. Cell motility and invasive capacity are activated upon EMT. Multiple transcription factors, including δEF1/ZEB1, SIP1/ZEB2, and Snail/SNAI1, are induced by TGF-β–Smad signaling and play critical roles in TGF-β-induced EMT. In addition, both non-Smad signaling activated by TGF-β and cross-talk with other signaling pathways play important roles in induction of EMT. Of these, Ras signaling synergizes with TGF-β-Smad signaling, and plays an important role in the induction of EMT. TGF-β inhibitors prevent invasion and metastasis of advanced cancer through multiple mechanisms, including inhibition of EMT. The discovery of molecules that inhibit TGF-β-induced EMT but not TGF-β-induced growth arrest may be an ideal strategy for treatment of invasion and metastasis of cancer.
Cilia are microtubule-based cellular organelles that are widely distributed in vertebrate tissues. They were first observed hundreds of years ago. Recent studies indicate that this small organelle plays important roles in numerous physiological phenomena, including tissue morphogenesis, signal transduction, determination of left-right asymmetry during development, and adult neurogenesis. Ciliopathies, syndromes resulting from a genetic disorder of cilial components, frequently have complex effects involving many organ systems, owing to the broad distribution of cilia in the body.
After two generations of backcrossing six different Y-consomic strains onto a C57BL/6J inbred mouse strain with a dominant hemimelia (Dh) mutation, a small percentage of Dh/+ males containing a Y chromosome from the AKR/J or RF/J strain showed hermaphrodism; they lacked the right testis and had an ovary and a uterus instead. Approximately 15% of Dh/+ females considered to be phenotypically normal had the Sry gene from the AKR/J or RF/J strain; they were actually sex-reversed XY females. Backcrossing of Y chromosomes from BALB/cA, C3H/HeJ, C57BL/6J, DH/Sgn, and DDD/Sgn onto the C57BL/6J strain with Dh did not result in hermaphrodism or sex reversal in adult mice. Subsequent linkage mapping analysis revealed that at least one C57BL/6J-derived homozygous allele at a locus on chromosome 13 was required for hermaphrodism and sex reversal. This condition was genetically distinct from known inherited sex-reversal conditions. It therefore offers a novel opportunity to investigate the genetic basis of sex determination in mammals.
Induced pluripotent stem cells (iPSC) have been generated from somatic cells by introducing reprogramming factors. Integration of foreign genes into the host genome is a technical hurdle for the clinical application. Here, we show that Sendai virus (SeV), an RNA virus and carries no risk of altering host genome, is an efficient solution for generating safe iPSC. Sendai-viral human iPSC expressed pluripotency genes, showed demethylation characteristic of reprogrammed cells. SeV-derived transgenes were decreased during cell division. Moreover, viruses were able to be easily removed by antibody-mediated negative selection utilizing cell surface marker HN that is expressed on SeV-infected cells. Viral-free iPSC differentiated to mature cells of the three embryonic germ layers in vivo and in vitro including beating cardiomyocytes, neurons, bone and pancreatic cells. Our data demonstrated that highly-efficient, non-integrating SeV-based vector system provides a critical solution for reprogramming somatic cells and will accelerate the clinical application.