Neyagawa, Japan
Neyagawa, Japan

Setsunan University is a private university in Neyagawa, Osaka, Japan. The predecessor of the school was founded in 1922, and it was chartered as a university in 1975. Wikipedia.

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Sugiyama Y.,University of Tokyo | Yamashita S.,Setsunan University
Advanced Drug Delivery Reviews | Year: 2011

The microdose (MD) clinical study enables to select a "better" compound for new drug candidate that shows desirable PK profiles in human. This new methodology is highly expected to streamline the drug development and to increase the success probability in the clinical trial. Since only a small amount of the test compound (less than 100 μg) is administered, the risk of harmful events to a human subject is regarded as minimal in the MD clinical study. However, the low dose also incurs the arguments about the usefulness of this method, since it may result in different PK profiles of drugs from that at the therapeutic dose. In addition, information on the efficacy/safety of the test compound cannot be obtained from the MD clinical study. On the other hand, PBPK model analysis based on the data of both the MD clinical study and in vitro study on metabolism, transport and binding enables the accurate prediction of PK profiles in humans at the therapeutic dose. PET molecular imaging technology further enhances the usability and applicability of the MD clinical study by offering the information on efficacy/safety. These methodologies, if coordinated effectively, are expected to innovate the new drug discovery and development. © 2010 Elsevier B.V.

Takeuchi K.,Setsunan University | Ito F.,Setsunan University
Biological and Pharmaceutical Bulletin | Year: 2011

The majority of growth factor receptors are composed of extracellular, transmembrane, and cytoplasmic tyrosine kinase (TK) domains. Receptor tyrosine kinase (RTK) activation regulates many key processes including cell growth and survival. However, dysregulation of RTK has been found in a wide range of cancers, and it has been shown to correlate with the development and progression of numerous cancers. Therefore, RTK has become an attractive therapeutic target. One way to effectively block signaling from RTK is inhibition of its catalytic activity with small-molecule inhibitors. Low-molecular-weight TK inhibitors (TKIs), such as imatinib, targeting tumors with mutant c-Kit, and gefitinib, targeting non-small cell lung cancer with mutant epidermal growth factor receptor (EGFR), have received marketing approval in Japan. MET, fibroblast growth factor receptor (FGFR), and insulin-like growth factor-I receptor (IGF-IR) are frequently genetically altered in advanced cancers. TKIs of these receptors have not yet appeared on the market, but many anticancer drug candidates are currently undergoing clinical trials. Most of these TKIs were designed to compete with ATP at the ATP-binding site within the TK domain. This review will focus on small-molecule TKIs targeting MET, FGFR, and IGF-IR and discuss the merits and demerits of two types of agents, i.e., those with only one or a few targets and those directed at multiple targets. Targeting agents specifically inhibiting the target kinase were previously searched for based on the hypothesis that a narrow target window might reduce unexpected side effects, but agents with multiple targets have been recently developed to overcome tumors resistant against a single-targeting agent. © 2011 Pharmaceutical Society of Japan.

Ogasa M.,Dainippon Sumitomo | Ogasa M.,Kanazawa University | Kimura T.,Dainippon Sumitomo | Nakamura M.,Setsunan University | Guarino J.,Sunovion Pharmaceuticals
Psychopharmacology | Year: 2013

Rationale: There is an unmet need in the treatment of schizophrenia for effective medications with fewer adverse effects. Objective: This study aims to evaluate the efficacy and safety of lurasidone, an atypical antipsychotic, for the treatment of schizophrenia. Methods: Patients with an acute exacerbation of schizophrenia were randomized to 6 weeks of double-blind treatment with once-daily, fixed-dose lurasidone 40 mg (N = 50), lurasidone 120 mg (N = 49), or placebo (N = 50). The primary efficacy measure was mean change from baseline to day 42 (last observation carried forward) in the Brief Psychiatric Rating Scale derived (BPRSd) from the Positive and Negative Syndrome Scale (PANSS). Results: Mean change in BPRSd was significantly greater in patients receiving lurasidone 40 and 120 mg/day versus placebo (-9.4 and -11.0 versus -3.8; p = 0.018 and 0.004, respectively). Treatment with lurasidone 120 mg/day was superior to placebo across all secondary measures, including PANSS total (p = 0.009), PANSS positive (p = 0.005), PANSS negative (p = 0.011), and PANSS general psychopathology (p = 0.023) subscales and Clinical Global Impression of Severity (CGI-S; p = 0.001). Treatment with lurasidone 40 mg/day was superior to placebo on the PANSS positive subscale (p = 0.018) and CGI-S (p = 0.002). The most common adverse events for patients receiving lurasidone were nausea (16.2 versus 4.0 % for placebo) and sedation (16.2 versus 10.0 % for placebo). Minimal changes in weight, cholesterol, triglyceride, and glucose levels were observed. Conclusions: In this study, which was limited by a relatively high discontinuation rate, lurasidone provided effective treatment for patients with acute exacerbation of chronic schizophrenia and had minimal effects on weight and metabolic parameters. © 2012 The Author(s).

Azuma T.,Setsunan University | Morita T.,University of Kentucky | Takeuchi S.,Shanghai JiaoTong University
Physical Review Letters | Year: 2014

It is expected that the Gregory-Laflamme (GL) instability in the black string in gravity is related to the Rayleigh-Plateau instability in fluid mechanics. Especially, the orders of the phase transitions associated with these instabilities depend on the number of the transverse space dimensions, and they are of first and second order below and above the critical dimension. Through the gauge-gravity correspondence, the GL instability is conjectured to be thermodynamically related to the Hagedorn instability in large-N gauge theories, and it leads to a prediction that the order of the confinement-deconfinement transition associated with the Hagedorn instability may depend on the transverse dimension. We test this conjecture in the D-dimensional bosonic D0-brane model using numerical simulation and the 1/D expansion, and confirm the expected D dependence. © 2014 American Physical Society.

In a study published in Current Biology, Andrew Singson, a professor in the Department of Genetics in the School of Arts and Sciences, and colleagues from the National Institutes of Health and the College of William and Mary in Virginia, identified a protein, SPE-45, on the sperm of C. elegan worms that help bind sperm to eggs during fertilization. It is the same as the Izumo protein considered essential for humans and other mammals to reproduce that was discovered a decade ago by Japanese scientists who named it after a marriage shrine in Japan. "Humans and worms are connected by a common ancestor that lived more than 700 million years ago and this discovery will give us insight into their shared genetics and fertility pathways," said Singson, a principal investigator at the Waksman Institute of Microbiology. The research suggests that a common ancestor to both worms and humans had a SPE-45/Izumo-like gene that was required for sperm to function properly at fertilization, said Singson, who has been researching the biological process of fertility for the past two decades. "Twenty years ago when we started this research, we predicted that we would find the genes that are required for fertility from worms to humans," said Singson. "Now we know that this kind of molecule functions the same way beyond the mammalian branch of the tree of life." In the United States, one in eight couples has fertility problems. While about 70 percent of the cases can be attributed equally to the man or woman, 30 percent of the time no explanation can be found. In the new Rutgers study, scientists found that worms produced normal-looking sperm but could not create offspring because the sperm cell lacked the SPE-45 protein on its surface similar to sperm in humans and other mammals that lacked the Izumo protein. Blocking the protein prevents sperm from binding and fusing with the egg. "The protein works like molecular Velcro and helps the sperm and egg bind and fuse," said Singson. "This type of finding can play an indispensable role in understanding the biological process." The discovery was corroborated by a team of scientists working at Emory University in Georgia and Setsunan University in Japan. Taking a different approach and using computer analysis to look at DNA sequences, this international team came up with the same conclusion which was also published in Current Biology. Comparing the worm and mammalian DNA sequences they created a hybrid SPE-45/Izumo molecule that can cure infertility in worms. "This makes the results much more solid because two research groups have basically validated the results of the other," Signson said. Since studying human infertility directly is very challenging due to many ethical and experimental limitations, making a genetic connection between worms and humans will help in future treatments because scientists can do experiments in worms to learn more about the function of Izumo-like molecules that they cannot do in mammals, Singson said. "Finding new fertility genes in the worm can help us further understand the molecular basis of human fertility," he said. "The end result of this knowledge could be more informed and effective treatments for human infertility and reliable contraceptives for both sexes."

Hashimoto T.,Osaka University | Amemiya T.,Setsunan University
IEEE Transactions on Automatic Control | Year: 2011

In this paper, the controllability and observability of linear time-invariant uncertain systems are investigated. The systems under consideration contain time-invariant uncertain parameters that may take arbitrarily large values. In such a situation, the locations of uncertain parameters in system matrices play an important role. We examine the permissible locations of uncertain parameters in system matrices for a linear uncertain system to be controllable and observable independently of the bounds of the uncertain parameters. The objective of this paper is to show that a linear uncertain system is controllable and observable, irrespective of the bounds of uncertain parameters, if and only if the system has a particular configuration called a complete generalized antisymmetric stepwise configuration (CGASC). Furthermore, the dual configuration of a CGASC is introduced and studied here. © 2010 IEEE.

The relationships between the properties of urban canopy components and the radiant environment in an urban street canyon are examined considering the introduction of appropriate urban heat island mitigation technologies. Radiant heat transfers between walls and roads are calculated according to Gebhart's radiant absorption coefficients and using the Monte Carlo method. Roads are classified as either north-south or east-west; intersections are also considered. The key property of an urban street canyon is expressed by its aspect ratio W/. H. A simple street canyon model and two actual urban street canyon areas are used as the objects of examination. Distributions of surface temperatures and solar radiation gains on street canyon roofs, roads, and walls are analyzed. The top priority for the implementation of urban heat island mitigation measures concerns the buildings with large roof areas. The other high-priority areas for implementing mitigation measures focus on smaller roofs and roads for which the street canyon aspect ratio W/. H is greater than 1.5; the lowest-priority area is the walls. © 2012 Elsevier Ltd.

Nabe T.,Setsunan University
Journal of Pharmacological Sciences | Year: 2014

Interleukin (IL)-33, a member of the IL-1 family of cytokines, is produced when epithelial and endothelial cells are exposed to stimuli. Hematopoietic cells such as macrophages also produce IL-33. IL-33 is considered to function as an 'alarmin', activating various immune cells through its receptor ST2, which leads to the production of various molecules. The IL-33-induced production of pro-inflammatory cytokines is a critical event that aggravates atopic diseases such as asthma, atopic dermatitis, and pollenosis and suggests that IL-33-blocking agents could represent new therapeutic drugs. The anti-IL-33 antibody was effective in allergic models, whereas the anti-ST2 antibody has yielded controversial results because soluble ST2 functions as a decoy receptor for IL-33. IL-33-mediated pulmonary inflammation may be glucocorticoidresistant especially when other cytokines act synergistically. Anti-tumor necrosis factor (TNF)-α therapy may also be effective against IL-33-mediated diseases. ERK1/2 inhibitors have also been shown to suppress the production of IL-33. On the other hand, activation of β2-receptors enhanced the expression of IL-33 mRNA in dendritic cells by activating protein kinase A (PKA), suggesting that PKA inhibitors may be candidates for IL-33-blocking agents. The effects of IL-33-blocking agents on atopic diseases need to be pharmacologically assessed in experimental and clinical studies. © The Japanese Pharmacological Society.

Aizawa H.,Setsunan University
Journal of Applied Crystallography | Year: 2010

The structures of micelles of the surfactant polysorbate 80 (Tween 80) in 0-50% aqueous dimethyl sulfoxide (DMSO) solutions (pH 7.2, ionic strength 2.44 mM) were investigated by means of small-angle X-ray scattering. At DMSO concentrations of 0-20%, core-shell cylinder micelles formed, and at 30-50% DMSO, core-shell discus micelles formed, that is, changing the hydrophobicity of the DMSO solvent mixture changed the micelles from core-shell cylinder micelles to core-shell discus micelles. © 2010 International Union of Crystallography Printed in Singapore - all rights reserved.

Miyao T.,Setsunan University
Reviews in Mathematical Physics | Year: 2011

The self-dual cone - the central object of this review - is introduced. Several operator inequalities associated with the self-dual cone are defined and mathematical properties of those are investigated. In general there are infinitely many choices of self-dual cones in a Hilbert space. Each of these lead to a distinct family of operator inequalities in the Hilbert space which enables us to analyze quantum physical models with respect to several aspects. We refer to these applications as self-dual cone analysis. The focus of this review lies on the self-dual cone analysis of models in condensed matter physics. In particular, by taking a physically proper self-dual cone, the interaction term of the Hamiltonian of the system becomes attractive from a viewpoint of our new operator inequalities. This attractive term enables us to analyze the system and various aspects of physical interest in detail. For instance, if the attractive term is ergodic, it is shown that the ground state is unique. By the uniqueness and the conservation laws, the physically symmetric state is realized as the ground state. This could be regarded as a physical order. As applications, the BCS model and the one-dimensional Fröhlich model are studied. We explain, from a viewpoint of the self-dual cone analysis, the appearance of macroscopic phase angles in the superconductors, Josephson effect and the Peierls instability. © 2011 World Scientific Publishing Company.

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