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      • Time Scales in Epigenetic Dynamics and Phenotypic Heterogeneity of Embryonic Stem Cells

        Sasai, Masaki,Kawabata, Yudai,Makishi, Koh,Itoh, Kazuhito,Terada, Tomoki P.,Marti-Renom, Marc A. Public Library of Science 2013 PLoS computational biology Vol.9 No.12

        <▼1><P>A remarkable feature of the self-renewing population of embryonic stem cells (ESCs) is their phenotypic heterogeneity: Nanog and other marker proteins of ESCs show large cell-to-cell variation in their expression level, which should significantly influence the differentiation process of individual cells. The molecular mechanism and biological implication of this heterogeneity, however, still remain elusive. We address this problem by constructing a model of the core gene-network of mouse ESCs. The model takes account of processes of binding/unbinding of transcription factors, formation/dissolution of transcription apparatus, and modification of histone code at each locus of genes in the network. These processes are hierarchically interrelated to each other forming the dynamical feedback loops. By simulating stochastic dynamics of this model, we show that the phenotypic heterogeneity of ESCs can be explained when the chromatin at the <I>Nanog</I> locus undergoes the large scale reorganization in formation/dissolution of transcription apparatus, which should have the timescale similar to the cell cycle period. With this slow transcriptional switching of <I>Nanog</I>, the simulated ESCs fluctuate among multiple transient states, which can trigger the differentiation into the lineage-specific cell states. From the simulated transitions among cell states, the epigenetic landscape underlying transitions is calculated. The slow <I>Nanog</I> switching gives rise to the wide basin of ESC states in the landscape. The bimodal Nanog distribution arising from the kinetic flow running through this ESC basin prevents transdifferentiation and promotes the definite decision of the cell fate. These results show that the distribution of timescales of the regulatory processes is decisively important to characterize the fluctuation of cells and their differentiation process. The analyses through the epigenetic landscape and the kinetic flow on the landscape should provide a guideline to engineer cell differentiation.</P></▼1><▼2><P><B>Author Summary</B></P><P>Embryonic stem cells (ESCs) can proliferate indefinitely by keeping pluripotency, i.e., the ability to differentiate into any cell-lineage. ESCs, therefore, have been the focus of intense biological and medical interests. A remarkable feature of ESCs is their phenotypic heterogeneity: ESCs show large cell-to-cell fluctuation in the expression level of Nanog, which is a key factor to maintain pluripotency. Since Nanog regulates many genes in ESCs, this fluctuation should seriously affect individual cells when they start differentiation. In this paper we analyze this phenotypic fluctuation by simulating the stochastic dynamics of gene network in ESCs. The model takes account of the mutually interrelated processes of gene regulation such as binding/unbinding of transcription factors, formation/dissolution of transcription apparatus, and histone-code modification. We show the distribution of timescales of these processes is decisively important to characterize the dynamical behavior of the gene network, and that the slow formation/dissolution of transcription apparatus at the <I>Nanog</I> locus explains the observed large fluctuation of ESCs. The epigenetic landscapes are calculated based on the stochastic simulation, and the role of the phenotypic fluctuation in the differentiation process is analyzed through the landscape picture.</P></▼2>

      • KCI등재

        Calculating the Eigenvalue Spectrum and the Eigenvectors of a Large Matrix: an Efficient Scheme with Application to Electron Transport

        Shigetoshi Sota,Masaki Itoh 한국물리학회 2009 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.54 No.1

        The kernel polynomial method (KPM), developed by Voter et al, has been recognized as an effective order-N method for calculating the eigenvalue spectrum of a large Hamiltonian. The efficiency of its algorithm is due to the three-term recurrence formula of the polynomial. The central issue is, however, how the Gibbs oscillation can be suppressed and the technique of the Gibbs damping factor has been used with the aid of a particular property of the Chebysheff polynoimial. In this study, we propose a new method that substitutes for the original KPM by using Legendre polynomial. Instead of using the damping factor, we introduce a new basis set by regulating the polynomial in such a way that the series is bound to converge to the exact Green's function without having Gibbs oscillations. The scheme is general enough to deal with the entire family of physical quantities that can be related to the Green's function. This includes the two-particle properties such as electron transport. It further enables the eigenvectors to be calculated in the same algorithm. In all these calculations, the numerical precision is unlimited and is controlled solely by the order of the truncation. The accuracy is confirmed up to six digits in our numerical tests for the dynamics of a simple cubic lattice of 19^3 atoms. We also show a preliminary calculation of the dc transport for the 2D-Anderson model. The kernel polynomial method (KPM), developed by Voter et al, has been recognized as an effective order-N method for calculating the eigenvalue spectrum of a large Hamiltonian. The efficiency of its algorithm is due to the three-term recurrence formula of the polynomial. The central issue is, however, how the Gibbs oscillation can be suppressed and the technique of the Gibbs damping factor has been used with the aid of a particular property of the Chebysheff polynoimial. In this study, we propose a new method that substitutes for the original KPM by using Legendre polynomial. Instead of using the damping factor, we introduce a new basis set by regulating the polynomial in such a way that the series is bound to converge to the exact Green's function without having Gibbs oscillations. The scheme is general enough to deal with the entire family of physical quantities that can be related to the Green's function. This includes the two-particle properties such as electron transport. It further enables the eigenvectors to be calculated in the same algorithm. In all these calculations, the numerical precision is unlimited and is controlled solely by the order of the truncation. The accuracy is confirmed up to six digits in our numerical tests for the dynamics of a simple cubic lattice of 19^3 atoms. We also show a preliminary calculation of the dc transport for the 2D-Anderson model.

      • KCI등재

        Growth of Ferroelectric Micro Region in SrTiO3 and SrTi(18O0.23 16O0.77)3 Studied by Raman Scattering

        Hiroki Taniguchi,Masaki Takesada,Mitsuru Itoh,Toshirou Yagi 한국물리학회 2005 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.46 No.1

        The oxygen-isotope exchange eect on the ferroelectric micro-regions (FMR) in SrTiO3 is investigated by Raman scattering in the low-temperature region near 1 K by using a 3He cryostat. With decreasing temperature, the intensity of the FMR spectra decreases and a sharp peak newly appears with increasing intensity. The sharp peak is assigned to be the polar Eu mode activated by local symmetry breaking induced by the growth of FMR.

      • KCI등재

        Numerical Study of Roton-Like Collective Excitations in Glassy Materials

        Shigetoshi Sota,Masaki Itoh 한국물리학회 2009 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.54 No.1

        Roton-like collective excitations of non-quantum origin have been recognized for quite a long time in many structurally disordered materials. A classical study is attempted of a computer-quenched Lennard-Jones glass in the present article. We show that the collective excitations involve vortex motions, as argued by Feynman for quantum liquids. Adopting the harmonic approximation, we constructed the dynamical structure factor and calculated its eigenvectors at several frequencies in order to visualize the respective atomic motions. Some of them are just like those predicted by Feynman, although we obtained them irrelevant of the Bose statistics. We also calculated the dynamical structure factor and confirmed the characteristic roton minimum in the dispersion relation, which is quantitatively close to that observed for liquid Ar.

      • Development of membrane filtration technology and its application to water supply

        Kunikane, Shoichi,Itoh, Masaki,Magara, Yasumoto 嶺南大學校 環境問題硏究所 1998 環境硏究 Vol.18 No.1

        Abstract 'MAC 21' and 'New 21' Projects were implemented for the development of membrane technology in Japan. 'MAC 21' Project included a series of pilot-scale experiment on micro- and ultrafiltration (MF and UF, respectively). As the result, it has been shown that MF and UF are excellent in the removal of turbidity and bacteria. 'New MAC 21' Project included various pilot-scale experiments on 1) nanofiltration (NF) after MF/UF, and 2) MF/UF combined with advanced treatment processes such as activated carbon treatment, ozonation and biological treatment. As the result, it has been shown that both of these two treatment systems can remove organic contaminants such as precursors of disinfection by-products well, and, especially, NF is excellent in their removal.

      • Advanced membrane technology for application to water treatment

        Magara, Yasumoto,Kunikane, Shoichi,Itoh, Masaki 嶺南大學校 環境問題硏究所 1997 環境硏究 Vol.16 No.2

        AbstractFollowing the successful implementation of the MAC21 Project, the New MAC21 Project is being implemented for further development of membrane technology in Japan. The project includes various pilot-scale and laboratory experiments on 1) nanofiltration system, and 2) MF/UF system combined with advanced treatment processes such as activated carbon treatment, ozonation and biological treatment. As the result, it has been shown that both systems are applicable to drinking water treatment. Although a NF system was very effective for the removal of organic contaminants such as precursors of disinfection by-products, it is considered that the development of a proper treatment method for the concentrate will by very important in the future.

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