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Search Results: 1 - 10 of 785 matches for " Toshiyuki Bohgaki "
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DNA double-strand break signaling and human disorders
Toshiyuki Bohgaki, Miyuki Bohgaki, Razqallah Hakem
Genome Integrity , 2010, DOI: 10.1186/2041-9414-1-15
Abstract: Mammalian cells and organisms have evolved elegant ways to maintain their genomic integrity and respond to the various DNA lesions that they continuously face. DNA damage can result from exogenous stresses, such as ionizing radiation (IR), ultraviolet (UV) light and chemical compounds, or from endogenous insults such as reactive oxygen species (ROS) and DNA replication errors [1].DNA double-strand breaks (DSBs) are among the most serious and lethal types of DNA damage, as a single DSB is sufficient to kill a cell or disturb its genomic integrity [1]. DSBs are generated in response to exogenous and endogenous DNA insults. For instance, DSBs are induced in response to oncogenic activation [2]. In human precancerous lesions, oncogene activation has been shown to lead to continuous formation of DNA DSBs [3,4]. These DSBs activate the tumor suppressor p53 that mediate apoptosis and/or senescence to restrain the growth of the precancerous cells. In the presence of additional mutations that inactivate p53, precancerous cells become cancerous as they escape p53 mediated apoptosis and/or senescence [5,6]. In addition to the induced DSBs, there are also programmed DSBs that are critical for physiological processes such as meiosis and T and B-cell receptor rearrangements [7,8].DNA damage response (DDR) to various types of DNA insults is a well orchestrated process and is required to maintain genomic integrity (Figure 1) [9-12]. In response to DSBs, a signaling process activates cell cycle checkpoints and pauses cell cycle progression, thus granting time for damaged cells to repair their DNA (Figure 2 and section 2s) [13]. Two major repair pathways for DSBs exist in mammalian cells; the homologous recombination (HR) and the non-homologous end-joining (NHEJ) pathways [14]. The HR pathway is error free but requires an intact homologous template such as a sister chromatid. The NHEJ recombination pathway is the prominent pathway for DSB repair in mammalian cells; however this pathw
Genomic Instability, Defective Spermatogenesis, Immunodeficiency, and Cancer in a Mouse Model of the RIDDLE Syndrome
Toshiyuki Bohgaki equal contributor,Miyuki Bohgaki equal contributor,Renato Cardoso,Stephanie Panier,Dimphy Zeegers,Li Li,Grant S. Stewart,Otto Sanchez,M. Prakash Hande,Daniel Durocher,Anne Hakem ,Razqallah Hakem
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1001381
Abstract: Eukaryotic cells have evolved to use complex pathways for DNA damage signaling and repair to maintain genomic integrity. RNF168 is a novel E3 ligase that functions downstream of ATM,γ-H2A.X, MDC1, and RNF8. It has been shown to ubiquitylate histone H2A and to facilitate the recruitment of other DNA damage response proteins, including 53BP1, to sites of DNA break. In addition, RNF168 mutations have been causally linked to the human RIDDLE syndrome. In this study, we report that Rnf168?/? mice are immunodeficient and exhibit increased radiosensitivity. Rnf168?/? males suffer from impaired spermatogenesis in an age-dependent manner. Interestingly, in contrast to H2a.x?/?, Mdc1?/?, and Rnf8?/? cells, transient recruitment of 53bp1 to DNA double-strand breaks was abolished in Rnf168?/? cells. Remarkably, similar to 53bp1 inactivation, but different from H2a.x deficiency, inactivation of Rnf168 impairs long-range V(D)J recombination in thymocytes and results in long insertions at the class-switch junctions of B-cells. Loss of Rnf168 increases genomic instability and synergizes with p53 inactivation in promoting tumorigenesis. Our data reveal the important physiological functions of Rnf168 and support its role in both γ-H2a.x-Mdc1-Rnf8-dependent and -independent signaling pathways of DNA double-strand breaks. These results highlight a central role for RNF168 in the hierarchical network of DNA break signaling that maintains genomic integrity and suppresses cancer development in mammals.
Pain-Relief Effects of Aroma Touch Therapy with Citrus junos Oil Evaluated by Quantitative EEG Occipital Alpha-2 Rhythm Powers  [PDF]
Tomomi Bohgaki, Yoshitada Katagiri, Makoto Usami
Journal of Behavioral and Brain Science (JBBS) , 2014, DOI: 10.4236/jbbs.2014.41002
Abstract:


Aroma touch therapy is widely used in clinical fields for alleviating pain-related symptoms; however, few studies have reported the pain-relief mechanisms. The present study aimed to elucidate the analgesic effects of aroma touch therapy with Citrus junos oil based on the quantitative evaluation of deep brain network (DBN) activity using electroencephalogram (EEG) occipital alpha-2 rhythm (10-13 Hz) powers. Experimental investigations were performed with 13 healthy volunteers using the cold pressor task for simulating chronic pain in three different sessions: a baseline session with no therapies, a control session with a touch therapy, and an aroma touch therapy. We have found for the first time that the interviewed pain ratings represented by Numeric Rating Scale (NRS) scores were strongly correlated with a DBN activity index, which was derived from the slow fluctuation components of occipital EEG alpha-2 rhythm powers. The correlation was characterized by a V-shaped curve in the DBN activity index versus the pain rating, i.e., the NRS score, which provided the complete analgesic states (NRS = 0) for some subjects under aroma touch therapy at an appropriate DBN activity index. Such analgesic states were not so strongly correlated with emotional valence. In conclusion, aroma touch therapy may directly modulate DBN activity so that pain-induced outcomes are minimized.


Characteristics of Unsteady Boundary Layer Induced by the Compression Wave Propagating in a Tunnel  [PDF]
Toshiyuki Tanaka, Toshiyuki Aoki
Open Journal of Fluid Dynamics (OJFD) , 2012, DOI: 10.4236/ojfd.2012.24A030
Abstract:

A compression wave is generated ahead of a high-speed train, while entering a tunnel. This compression wave propa- gates to the tunnel exit and spouts out as a micro pressure wave, causing an exploding sound. In order to estimate the magnitude correctly, the mechanism of the attenuation and distortion of a compression wave propagating along a tunnel must be understood and experimental information on these phenomena is required. An experimental and numerical in- vestigation is carried out to clarify the mechanism of the propagating compression wave in a tube. The final objective of our study is to understand the mechanism of the attenuation and distortion of propagating compression waves in a tun- nel. In the present paper, experimental investigations are carried out on the transition of the unsteady boundary layer induced by a propagating compression wave in a model tunnel by means of a developed laser differential interferometry technique.

The Menu-Induced Core of an Economy with an Excludable Public Good  [PDF]
Toshiyuki Hirai
Theoretical Economics Letters (TEL) , 2014, DOI: 10.4236/tel.2014.44039
Abstract:

This paper introduces a core concept in an economy with an excludable public good. In the economy, we assume that each coalition is allowed to achieve an allocation via a menu, a kind of a nonlinear price. Our core concept is called the menu-induced core that is defined as the set of allocations achievable by menus that are robust against all coalitional improvements achieved via menus. We show that the menu-induced core is nonempty. We also investigate certain properties of the menu-induced core that show the difference between the menu-induced core and the core defined in a standard way.

A Review of Measurement-Integrated Simulation of Complex Real Flows  [PDF]
Toshiyuki Hayase
Journal of Flow Control, Measurement & Visualization (JFCMV) , 2015, DOI: 10.4236/jfcmv.2015.32006
Abstract: In spite of the inherent difficulty, reproducing the exact structure of real flows is a critically important issue in many fields, such as weather forecasting or feedback flow control. In order to obtain information on real flows, extensive studies have been carried out on methodology to integrate measurement and simulation, for example, the four-dimensional variational data assimilation method (4D-Var) or the state estimator such as the Kalman filter or the state observer. Measurement-integrated (MI) simulation is a state observer in which a computational fluid dynamics (CFD) scheme is used as a mathematical model of the physical system instead of a small dimensional linear dynamical system usually used in state observers. A large dimensional nonlinear CFD model makes it possible to accurately reproduce real flows for properly designed feedback signals. This review article surveys the theoretical formulations and applications of MI simulation. Formulations of MI simulation are presented, including governing equations of a flow field observer, those of a linearized error dynamics describing the convergence of the observer, and stabilization of the numerical scheme, which is important in implementation of MI simulation. Applications of MI simulation are presented ranging from fundamental turbulent flows in pipes and Karman vortices in a wind tunnel to clinical application in diagnosis of blood flows in a human body.
Preconditioned Iterative Method for Regular Splitting  [PDF]
Toshiyuki Kohno
Advances in Pure Mathematics (APM) , 2017, DOI: 10.4236/apm.2017.72009
Abstract: Several preconditioners are proposed for improving the convergence rate of the iterative method derived from splitting. In this paper, the comparison theorem of preconditioned iterative method for regular splitting is proved. And the convergence and comparison theorem for any preconditioner are indicated. This comparison theorem indicates the possibility of finding new preconditioner and splitting. The purpose of this paper is to show that the preconditioned iterative method yields a new splitting satisfying the regular or weak regular splitting. And new combination preconditioners are proposed. In order to denote the validity of the comparison theorem, some numerical examples are shown.
Flows of a Rarefied Gas between Coaxial Circular Cylinders with Nonuniform Surface Properties  [PDF]
Toshiyuki Doi
Open Journal of Fluid Dynamics (OJFD) , 2019, DOI: 10.4236/ojfd.2019.91002
Abstract: Flows of a rarefied gas between coaxial circular cylinders with nonuniform surface properties are studied on the basis of kinetic theory. It is assumed that the outer cylinder is a diffuse reflection boundary and the inner cylinder is a Maxwell-type boundary whose accommodation coefficient varies in the circumferential direction. Three fundamental flows are studied: 1) a flow caused by the rotation of the outer cylinder (Couette flow), 2) a flow induced between the cylinders at rest kept at different temperatures (heat transfer problem), and 3) a flow induced by the circumferential temperature distribution along the cylindrical surfaces (thermal creep flow). The linearized ES-BGK model of the Boltzmann equation is numerically analyzed using a finite difference method. The time-independent behavior of the gas is studied over a wide range of the gas rarefaction degree, the radii ratio, and a parameter characterizing the distribution of the accommodation coefficient. Due to an effect of nonuniform surface properties, a local heat transfer occurs between the gas and the cylindrical surfaces in Couette flow; a local tangential stress arises in the heat transfer problem. However, the total heat transfer between the two cylinders in Couette flow and the total torque acting on the inner cylinder in the heat transfer problem vanish irrespective of the flow parameters. Two nondegenerate reciprocity relations arise due to the effect of nonuniform surface properties. The reciprocity relations among the above-mentioned three flows are numerically confirmed over a wide range of the flow parameters. The force on the inner cylinder, which also arises due to the effect of nonuniform surface properties in Couette flow and the heat transfer problems, is studied.
Autonomous Adaptive Agent with Intrinsic Motivation for Sustainable HAI*  [PDF]
Takayuki Nozawa, Toshiyuki Kondo
Journal of Intelligent Learning Systems and Applications (JILSA) , 2010, DOI: 10.4236/jilsa.2010.24020
Abstract: For most applications of human-agent interaction (HAI) research, maintaining the user’s interest and continuation of interaction are the issues of primary importance. To achieve sustainable HAI, we proposed a new model of intrinsically motivated adaptive agent, which learns about the human partner and behaves to satisfy its intrinsic motivation. Simulation of interaction with several types of other agents demonstrated how the model seeks new relationships with the partner and avoids situations which are not learnable. To investigate effectiveness of the model, we conducted a comparative HAI experiment with a simple interaction setting. The results showed that the model was effective in inducing subjective impressions of higher enjoyability, charm, and sustainability. Information theoretic analysis of the interaction suggested that a balanced information transfer between the agent and human partner would be important. The participants’ brain activity measured by functional near-infrared spectroscopy (fNIRS) indicated higher variability of activity at the dorsolateral prefrontal cortex during the interaction with the proposed agent. These results suggest that the intrinsically motivated adaptive agent successfully maintained the participants’ interest, by affecting their attention level.
Pitfalls and Remedies in DEA Applications: How to Handle an Occurrence of Zero in Multipliers by Strong Complementary Slackness Conditions  [PDF]
Toshiyuki Sueyoshi, Mika Goto
Engineering (ENG) , 2013, DOI: 10.4236/eng.2013.55A005
Abstract: This study discusses a guideline on a proper use of Data Envelopment Analysis (DEA) that has been widely used for performance analysis in public and private sectors. The use of DEA is equipped with Strong Complementary Slackness Conditions (SCSCs) in this study, but an application of DEA/SCSCs depends upon its careful use, as summarized in the guideline. The guideline consists of the five suggestions. First, a data set used in the DEA applications should not have a ratio variable (e.g., financial ratios) in an input(s) and/or an output(s). Second, radial DEA models under variable and constant Returns to Scale (RTS) need a special treatment on zero in a data set. Third, the DEA evaluation needs to drop an outlier. Fourth, an imprecise number (e.g., 1/3) may suffer from a round-off error because DEA needs to specify it in a precise expression to operate a computer code. Finally, when a large input or output variable may dominate other variables in DEA computation, it is necessary to normalize the data set or simply to divide each observation by its average. Such a simple treatment produces more reliable DEA results than the one without any data adjustment. This study also discusses how to handle an occurrence of zero in DEA multipliers by applying SCSCs. The DEA/SCSCs can serve for a multiplier restriction approach without any prior information. Thus, the propesed DEA/SCSCs can provide more reliable results than a straight use of DEA.
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