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Keio University , abbreviated as Keio or Keidai , is a Japanese university located in Minato, Tokyo. It is known as the oldest institute of higher education in Japan. Founder Fukuzawa Yukichi originally established it as a school for Western studies in 1858 in Edo . It has eleven campuses in Tokyo and Kanagawa. It has ten faculties: Letters, Economics, Law, Business and Commerce, Medicine, Science and Technology, Policy Management, Environment and Information Studies, Nursing and Medical Care, and Pharmacy.The alumni include Japanese prime ministers and prominent political, administrative, legal, medical and corporate leaders. In particular, alumni of the Faculty of Economics has had significant influence on Japanese business world. Keio ranks third in the world for the number of alumni holding CEO positions in Fortune Global 500 companies. It also ranks 9th in the world in the Times Higher Education's Alma Mater Index. The university is one of the Japanese Ministry of Education, Culture, Sports, Science and Technology's thirteen "Global 30" Project universities. Wikipedia.

Shizawa K.,Keio University
Nihon Kikai Gakkai Ronbunshu, A Hen/Transactions of the Japan Society of Mechanical Engineers, Part A | Year: 2013

The fracture of ductile polymers occurs on a boundary between the molecular chain-oriented region and the non-oriented region after the neck propagation. This behavior is caused by the concentration of craze that is a microscopic damage typically observed in polymers. In this paper, the craze evolution behavior is decomposed into the nucleation and the growth of craze. A craze evolution equation is newly developed on the basis of chemical kinetics introducing strain rate and stain dependencies into an activation energy. Furthermore, in order to reflect the damage effect to the constitutive equation of molecular chain plasticity model, damaged and pseudo-undamaged configurations are defined. Then, using a multiscale material model homogenizing mixed structure of the glassy phase expressed by the molecular chain plasticity model and the crystalline phase represented by the usual crystal plasticity model in an unit cell, a FE simulation coupling with the craze evolution equation is carried out for a crystalline polymer subjected to the uniaxial load. It is attempted to computationally reproduce characteristic behaviors of craze evolution, i.e., the propagation of craze concentration region with the neck propagation in macroscopic specimen, the cessation of increase of craze in the molecular chain-oriented region and the craze nucleation before the macroscopic yielding. © 2013 The Japan Society of Mechanical Engineers.

Maruyama T.,Keio University
Frontiers in bioscience (Elite edition) | Year: 2012

Proposed hypothetical causes of endometriosis include retrograde menstruation, lymphatic and vascular metastasis, iatrogenic direct implantation, coelomic metaplasia, embryonic rest, and mesenchymal cell differentiation (induction). Each theory, individually, fails to account for all types of endometriotic lesions, thereby implicating combined and/or type-specific mechanisms. Recent evidence supports the presence of endometrial stem/progenitor cells and their possible involvement in eutopic endometrial regeneration and differentiation. Thus an additional novel mechanism for the origin of endometriotic lesions is that they arise from ectopic endometrial stem/progenitor cells.

Machne R.,University of Vienna | Murray D.B.,Keio University
PLoS ONE | Year: 2012

When grown in continuous culture, budding yeast cells tend to synchronize their respiratory activity to form a stable oscillation that percolates throughout cellular physiology and involves the majority of the protein-coding transcriptome. Oscillations in batch culture and at single cell level support the idea that these dynamics constitute a general growth principle. The precise molecular mechanisms and biological functions of the oscillation remain elusive. Fourier analysis of transcriptome time series datasets from two different oscillation periods (0.7 h and 5 h) reveals seven distinct co-expression clusters common to both systems (34% of all yeast ORF), which consolidate into two superclusters when correlated with a compilation of 1,327 unrelated transcriptome datasets. These superclusters encode for cell growth and anabolism during the phase of high, and mitochondrial growth, catabolism and stress response during the phase of low oxygen uptake. The promoters of each cluster are characterized by different nucleotide contents, promoter nucleosome configurations, and dependence on ATP-dependent nucleosome remodeling complexes. We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling. We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries. Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions. © 2012 Machné, Murray.

Wakui M.,Keio University
Rinsho byori. The Japanese journal of clinical pathology | Year: 2013

Single nucleotide polymorphisms (SNPs) are DNA sequence variations occurring when a single nucleotide in the genome differs in paired chromosomes. Some SNPs in the coding region change the amino acid sequence of a protein, and others in the coding region do not affect the protein sequence. SNPs outside the coding region may also affect transcription factor binding, gene splicing, or mRNA degradation. With or without such impacts on the biological function of gene products, SNPs are strongly useful as markers to examine linkage disequilibrium and to explore genetic polymorphisms in the research of population genetics and medical science. Knowledge about SNPs is expected to help in identifying susceptibility genes for complex diseases, drug susceptibility genes, and histocompatibility genes for transfusion or transplantation. Recent breakthroughs in DNA technology, such as high-throughput universal SNP microarrays and next-generation sequencers, have made it possible to carry out comprehensive analyses of DNA at the whole genome level, resulting in the implementation of a genome-wide association study(GWAS). In GWAS, SNPs are used as high-solution markers in gene mapping related to diseases versus normal traits. The outcomes of GWAS provide a number of supportive findings for the promotion of personalized medicine based on genome informatics. This article presents a review of SNP analysis with respect to its scientific significance and current progress.

Watanabe S.,Keio University
Brain Research | Year: 2015

Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. © 2015 Elsevier B.V. All rights reserved.

Hanada M.,University of Washington | Matsuura S.,Keio University | Sugino F.,Okayama Institute for Quantum Physics
Nuclear Physics B | Year: 2012

In this paper, we consider two-dimensional N=(4,4) supersymmetric Yang-Mills (SYM) theory and deform it by a mass parameter M with keeping all supercharges. We further add another mass parameter m in a manner to respect two of the eight supercharges and put the deformed theory on a two-dimensional square lattice, on which the two supercharges are exactly preserved. The flat directions of scalar fields are stabilized due to the mass deformations, which gives discrete minima representing fuzzy spheres. We show in the perturbation theory that the lattice continuum limit can be taken without any fine tuning. Around the trivial minimum, this lattice theory serves as a non-perturbative definition of two-dimensional N=(4,4) SYM theory. We also discuss that the same lattice theory realizes four-dimensional N=2 U(k) SYM on R2×(Fuzzy R2) around the minimum of k-coincident fuzzy spheres. © 2011 Elsevier B.V.

Zhang Y.,Keio University
Journal of Micromechanics and Microengineering | Year: 2010

A microscale biomimetic tactile sensor with epidermal ridges is proposed to enhance the sensitivity of force detection. Guided by the principles of the human tactile perception mechanism, specifically the epidermal ridges, artificial epidermal ridges made of polydimethylsiloxane (PDMS) were designed and placed on micro-fabricated metal strain gauge arrays. A polyimide layer was fabricated to facilitate attachment between the metal and PDMS, so that patterned copper could be deposited on the polyimide to function as the strain gauges. The aspect ratio of the artificial epidermal ridges was optimized using material stability calculations and finite element method (FEM) simulations, and the optimal structure obtained was 400 μm in width and 110 μm in height. Experiments verified the effectiveness of enhancing the sensitivity of such a tactile sensor with the artificial epidermal ridges, in that the outputs of the strain gauges were 1.8 times more sensitive than those of a tactile sensor without ridges. The proposed artificial epidermal ridges are readily applicable to any developed tactile sensors for performance enhancement. © 2010 IOP Publishing Ltd.

Abe J.,Kanagawa University | Kamimura Y.,Keio University
Journal of Evolutionary Biology | Year: 2012

Sex allocation theories provide excellent opportunities to investigate not only the extent to which individuals' behaviour is adaptive, but also how they use relevant information for their decision-making. Here, we investigated whether female parasitoid wasps recognize the sex ratios of other females and adjust their laying sex ratios accordingly. Specifically, we tested the prediction of reciprocal cooperation over sex allocation. Theory predicts more female-biased (cooperative) sex ratios than in the interest of individual benefit, when a restricted number of ovipositing females interact for a long period and their offspring mate within the natal patch. This is because the female-biased sex ratio reduces competition for mates among the male offspring of the females and increases the overall reproductive productivity of the patch. In this case, females would be expected to respond to more even (noncooperative) sex ratios by others and to retaliate by also producing a less female-biased sex ratio to avoid exploitation by defectors. However, contrary to this prediction, our experiment using a sterile male technique showed that female Melittobia australica did not change their offspring sex ratios in response to the sex ratios produced by other females. This suggests that their extremely female-biased sex ratios cannot be explained by reciprocity. A meta-analysis of studies examining sex recognition ability in parasitoid wasps also did not support the predicted pattern of relevant sex ratio adjustment, suggesting that parasitoid females do not possess this ability. Here, we discuss the conditions necessary for the evolution of reciprocity linked to recognition ability. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Shimazaki T.,Keio University
Keio Journal of Medicine | Year: 2016

Natural recovery from disease and damage in the adult mammalian central nervous system (CNS) is limited compared with that in lower vertebrate species, including fish and salamanders. Species-specific differences in the plasticity of the CNS reflect these differences in regenerative capacity. Despite numerous extensive studies in the field of CNS regeneration, our understanding of the molecular mechanisms determining the regenerative capacity of the CNS is still relatively poor. The discovery of adult neural stem cells (aNSCs) in mammals, including humans, in the early 1990s has opened up new possibilities for the treatment of CNS disorders via self-regeneration through the mobilization of these cells. However, we now know that aNSCs in mammals are not plastic enough to induce significant regeneration. In contrast, aNSCs in some regenerative species have been found to be as highly plastic as early embryonic neural stem cells (NSCs). We must expand our knowledge of NSCs and of regenerative processes in lower vertebrates in an effort to develop effective regenerative treatments for damaged CNS in humans. © 2016 by The Keio Journal of Medicine.

The purpose of the present study was to determine whether teriparatide and monthly minodronic acid would have an additive effect on cancellous bone mass in ovariectomized rats. Seven-week-old female Sprague-Dawley rats were randomized into five groups of 10 animals each, including a sham-operation. +. vehicle group, an ovariectomy (OVX). +. vehicle group, an OVX. +. minodronic acid (6. μg/kg. s.c., every 4. weeks) group, an OVX. +. teriparatide (20. μg/kg. s.c., daily) group, and an OVX. +. minodronic acid. +. teriparatide group. After the 12-week experimental period, static and dynamic histomorphometric analyses were performed on the cancellous bone of the tibial proximal metaphysis. OVX decreased the bone volume per total volume (BV/TV) and the trabecular number (Tb.N) and increased the trabecular separation (Tb.Sp) as a result of increased bone remodeling. Minodronic acid prevented the OVX-induced decreases in BV/TV, while teriparatide increased the BV/TV and trabecular width (Tb.Wi) beyond the values of the sham controls. Minodronic acid prevented, but teriparatide only mitigated, the OVX-induced decrease in Tb.N, although both drugs similarly prevented the OVX-induced increase in Tb.Sp. A combination of teriparatide and minodronic acid further increased the BV/TV and Tb.N and decreased the Tb.Sp as a result of the suppression of bone remodeling, compared with teriparatide alone. These results suggest the differential effect of teriparatide and monthly minodronic acid on cancellous bone structure and the additive effect of the two drugs on cancellous bone mass in OVX rats. © 2014 Elsevier Inc.

Mitsantisuk C.,Nagaoka University of Technology | Ohishi K.,Nagaoka University of Technology | Katsura S.,Keio University
IEEE Transactions on Industrial Electronics | Year: 2012

As haptic technology has advanced in the past decade, many sensor devices have been built and commercialized for providing the sense of action/reaction forces or moment feedback to the human operator. In the ideal bilateral control of the haptic system, the force and position control should achieve with the same actions of force and motion movements. An external force should be sensed quickly after contact with an unknown environment. This paper presents formulation and application of a Kalman filtering technique for control of master-slave robots contacting environment in a bilateral control. The different types of motion sensors are mounted on each robot to provide the position and acceleration data in the horizontal dimension. A Kalman-filter-based state observer and a Kalman-filter-based disturbance observer have been designed to estimate action/reaction forces. This paper also deals with the construction of bilateral control with the use of data provided by the different types of motion sensors. Compared to the other conventional disturbance observer or state observer, the bilateral control system based on the proposed method offers the advantages of wider bandwidth, faster response, and free from sensor noise. Thus, it is possible to provide high transparency and good perception of the environmental stiffness. The experimental results are provided to illustrate the performance of the proposed algorithms. © 2011 IEEE.

Endo J.,Keio University | Arita M.,RIKEN | Arita M.,Yokohama City University
Journal of Cardiology | Year: 2016

Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid and docosahexaenoic acid, are widely regarded as cardioprotective. Several large-scale, randomized clinical trials have shown that dietary intake of omega-3 PUFAs improves the prognosis of patients with symptomatic heart failure or recent myocardial infarction. Therefore, dietary consumption of omega-3 PUFA is recommended in international guidelines for the general population to prevent the occurrence of cardiovascular diseases (CVDs). However, the precise mechanisms underlying the cardioprotective effects of omega-3 PUFAs are not fully understood. Omega-3 PUFAs can be incorporated into the phospholipid bilayer of cell membranes and can affect membrane fluidity, lipid microdomain formation, and signaling across membranes. Omega-3 PUFAs also modulate the function of membrane ion channels, such as Na and L-type Ca channels, to prevent lethal arrhythmias. Moreover, omega-3 PUFAs also prevent the conversion of arachidonic acid into pro-inflammatory eicosanoids by serving as an alternative substrate for cyclooxygenase or lipoxygenase, resulting in the production of less potent products. In addition, a number of enzymatically oxygenated metabolites derived from omega-3 PUFAs were recently identified as anti-inflammatory mediators. These omega-3 metabolites may contribute to the beneficial effects against CVDs that are attributed to omega-3 PUFAs. © 2015 Japanese College of Cardiology.

Kimura T.,Keio University
Nippon Seramikkusu Kyokai Gakujutsu Ronbunshi/Journal of the Ceramic Society of Japan | Year: 2016

Templated and reactivelated grain growth is a convenient preparation method for textured ceramics. In this method, green compacts composed of aligned template grains and randomly oriented matrix grains are sintered. The matrix grains must be eliminated to obtain highly textured materials and an understanding of the growth behavior for both template and matrix grains is essential to the design of the conditions for effective elimination of matrix grains. This review paper addresses the microstructure development in BaBi4Ti4O15 and Bi4Ti3O12 prepared by the templated grain growth method and in Bi0.5(Na11-xKx)0.5- TiO3 and K0.5Na0.5NbO3 textured by the reactivelated grain growth method. The grains of these materials are faceted, and critical driving force is required for the growth of faceted grains. It is illustrated that the relative magnitude of the driving force of the template grains and the critical driving force determines the mode of grain growth behavior and the microstructure of the final products. A discussion on the grain growth behavior is presented to give the criteria for designing the preparation conditions. © 2016 The Ceramic Society of Japan. All rights reserved.

Mitsantisuk C.,Nagaoka University of Technology | Ohishi K.,Nagaoka University of Technology | Katsura S.,Keio University
IEEE Transactions on Industrial Electronics | Year: 2012

In this paper, a novel wire-based robot system with consideration of the different levels of wire rope tension is introduced, and its performance while executing a task in an unknown environment is analyzed. An adaptable wire rope tension control, called a twin direct-drive motor system, provides a unique structure for a robot interaction system. Compared with conventional industrial robots, it significantly becomes the preferred approach for improving the level of reliability and providing safe user interaction because the wire rope mechanism is a low friction and lightweight device. In addition, from the identification results, the bandwidth of the robot system can be regulated by changing the wire rope tension. In the controller design, dual disturbance observers with respect to two operation modes, namely, the common mode and the differential mode, are designed and applied for controlling the wire rope tension and interaction force. A variable wire rope tension algorithm is proposed to change the mechanical bandwidth based on the movements of a human. The advantages of a high mechanical bandwidth and low stiffness transmission are combined. With regard to the rejection of the vibration effects and the generation of a smooth interaction force, the variable wire rope tension control is found to give the best results in an experimental setup. © 2011 IEEE.

Shibata T.,Otsumanakano Junior and Senior High School | Murakami T.,Keio University
IEEE Transactions on Industrial Electronics | Year: 2012

This paper proposes a new power-assist control in pushing task as an intelligent function of wheelchair by repulsive compliance control. In this strategy, the reaction force of human input into object is estimated without torque/force sensor and is utilized to generate the power-assist torque for wheel driving. The proposed approach brings a sophisticated function that makes it easy to carry out pushing task by wheelchair rider. First, human acceleration estimation observer (HAOB) and workspace disturbance observer (WDOB) are employed. HAOB can abstract human input as equivalent acceleration without torque/force sensor. WDOB guarantees robustness of the whole control system against disturbances. Second, HAOB-based compliance control is constructed to generate the motion command of pushing task for power-assist control. The generated motion command is determined so that the wheelchair accelerates according to human input. From this point of view, the proposed control is called repulsive compliance control. The compliance control itself is passive control, and stable and flexible responses are expected. Simulations and experiments are conducted to confirm the validity of the proposed approach. © 2011 IEEE.

Tsunashima N.,Sony Corporation | Katsura S.,Keio University
IEEE Transactions on Industrial Electronics | Year: 2012

Currently, the development of a leading-edge technology for saving and reproducing human motions in terms of haptic information is required for various fields. To address these requirements, a motion-copying system has already been proposed. This system is a key technology that enables the realization of the acquisition, preservation, and reproduction of real-world haptic information. In order to apply this system to various fields, the use of the concept involving two types of coupling is important: that involving spatial and temporal couplings. In this paper, the use of the concept mentioned earlier is proposed, and the related system is named spatiotemporal coupler. The proposed coupler is divided into two couplers. One is a spatial coupler, and the other is a temporal coupler. The spatial coupler connects human motions that are saved by haptic devices with different configurations according to the information for a human model. On the other hand, the temporal coupler integrates the saved motions temporally, and the integrated motion is reproduced as a single motion. The proposed concept is applied to finger motion in the experiments. The experimental results validate the proposed technology. © 2011 IEEE.

Kishimoto N.,Nagoya City University | Kishimoto N.,Keio University | Sawamoto K.,Nagoya City University
Differentiation | Year: 2012

Ependymal cells, epithelial cells that line the cerebral ventricles of the adult brain in various animals, extend multiple motile cilia from their apical surface into the ventricles. These cilia move rapidly, beating in a direction determined by the ependymal planar cell polarity (PCP). Ciliary dysfunction interferes with cerebrospinal fluid circulation and alters neuronal migration. In this review, we summarize recent studies on the cellular and molecular mechanisms underlying two distinct types of ependymal PCP. Ciliary beating in the direction of fluid flow is established by a combination of hydrodynamic forces and intracellular planar polarity signaling. The ciliary basal bodies' anterior position on the apical surface of the cell is determined in the embryonic radial glial cells, inherited by ependymal cells, and established by non-muscle myosin II in early postnatal development. © 2011 International Society of Differentiation.

Koo B.-K.,Hubrecht Institute for Developmental Biology and Stem Cell Research | Stange D.E.,Hubrecht Institute for Developmental Biology and Stem Cell Research | Sato T.,Hubrecht Institute for Developmental Biology and Stem Cell Research | Sato T.,Keio University | And 5 more authors.
Nature Methods | Year: 2012

The study of gene function in endodermal epithelia such as of stomach, small intestine and colon relies heavily on transgenic approaches. Establishing such animal models is laborious, expensive and time-consuming. We present here a method based on Cre recombinaseinducible retrovirus vectors that allows the conditional manipulation of gene expression in primary mouse organoid culture systems. © 2012 Nature America, Inc. All rights reserved.

Eto M.,Yamagata University | Nitta M.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

Topologically stable non-Abelian sine-Gordon solitons have been found recently in the U(N) chiral Lagrangian and a U(N) gauge theory with two N by N complex scalar fields coupled to each other. We construct the effective theory on a non-Abelian sine-Gordon soliton that is a nonlinear sigma model with the target space R×CPN-1. We then show that CPN-1 lumps on it represent SU(N) Skyrmions in the bulk point of view, providing a physical realization of the rational map ansatz for Skyrmions of the translational (Donaldson) type. We find therefore that Skyrmions can exist stably without the Skyrme term. © 2015 American Physical Society.

Gudnason S.B.,CAS Lanzhou Institute of Modern Physics | Gudnason S.B.,KTH Royal Institute of Technology | Nitta M.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We study a Skyrme-type model with a quadratic potential for a field with S2 vacua. We consider two flavors of the model, the first is the Skyrme model and the second has a sixth-order derivative term instead of the Skyrme term; both with the added quadratic potential. The model contains molecules of half Skyrmions, each of them is a global (anti)monopole with baryon number 1/2. We numerically construct solutions with baryon numbers one through six, and find stable solutions which look like beads on rings. We also construct a molecule with fractional Skyrmions having the baryon numbers 1/3+2/3, by adding a linear potential term. © 2015 American Physical Society.

Mycobacterial spindle cell pseudotumor (MSP) is a rare mass-forming lesion caused by mycobacterial infection, mostly in immunocompromised patients. Since it is composed of a proliferation of spindle-shaped fibrohistiocytic cells without forming epithelioid cell granulomas, histological distinction from other spindle cell lesions is often difficult and its pathophysiology is poorly understood. MSP arising in the nasal cavity is extremely rare, and only two cases have been reported previously. Here we report a case of MSP of the nasal cavity in an 83-year-old man with no evidence of immunodeficient state. The resected tumor consisted of spindle cells, which contained numerous acid-fast bacilli in the cytoplasm. By polymerase chain reaction and sequencing using DNA extracted from the paraffin sections, the bacilli were identified as Mycobacterium intracellulare. Immunohistochemistry revealed that the spindle cells were positive for CD68, CD11c and S100 protein, confirming the histiocytic nature of these cells. They were also positive for CD163 and CD204, suggesting that they showed a phenotype similar to alternatively activated (M2) macrophages and the phenotype might contribute to the maintenance of mycobacterial infection despite apparent immunocompetence of the host. © 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Yamamoto D.,Waseda University | Marmorini G.,RIKEN | Marmorini G.,Keio University | Danshita I.,Kyoto University | Danshita I.,RIKEN
Physical Review Letters | Year: 2015

Magnetization processes of spin-1/2 layered triangular-lattice antiferromagnets (TLAFs) under a magnetic field H are studied by means of a numerical cluster mean-field method with a scaling scheme. We find that small antiferromagnetic couplings between the layers give rise to several types of extra quantum phase transitions among different high-field coplanar phases. Especially, a field-induced first-order transition is found to occur at H≈0.7Hs, where Hs is the saturation field, as another common quantum effect of ideal TLAFs in addition to the well-established one-third plateau. Our microscopic model calculation with appropriate parameters shows excellent agreement with experiments on Ba3CoSb2O9 [T. Susuki et al., Phys. Rev. Lett. 110, 267201 (2013)]. Given this fact, we suggest that the Co2+-based compounds may allow for quantum simulations of intriguing properties of this simple frustrated model, such as quantum criticality and supersolid states. © 2015 American Physical Society.

Increasing evidence demonstrates that members of the sirtuin family, most of which work as NAD(+)-dependent protein deacetylases, mediate the preferable effects of caloric restriction. Since mitochondria play a central role in cardiac reactive oxygen species production, targeted modification of mitochondrial proteins and subsequent improvement in mitochondrial function have the potential for controlling cardiovascular senescence and managing cardiovascular diseases such as ischemia/reperfusion. We showed that caloric restriction primes cardiac mitochondria for ischemic stress by deacetylating specific mitochondrial proteins of the electron transport chain. We speculate that deacetylation of specific mitochondrial proteins by sirtuin preserves mitochondrial function and attenuates myocardial oxidative damage during ischemia/reperfusion. Copyright © 2013 Elsevier Inc. All rights reserved.

Kanazawa T.,RIKEN | Yamamoto N.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We show, without using semiclassical approximations, that, in high-temperature QCD with chiral symmetry restoration and U(1)A symmetry breaking, the partition function for sufficiently light quarks can be expressed as an ensemble of noninteracting objects with topological charge that obey the Poisson statistics. We argue that the topological objects are "quasi-instantons" (rather than bare instantons) taking into account quantum effects. Our result is valid even close to the (pseudo)critical temperature of the chiral phase transition. © 2015 American Physical Society.

Yamamoto N.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

Bloch theorem states the impossibility of persistent electric currents in the ground state of nonrelativistic fermion systems. We extend this theorem to generic systems based on the gauged particle number symmetry and study its consequences on the example of chiral transport phenomena. We show that the chiral magnetic effect can be understood as a generalization of the Bloch theorem to a nonequilibrium steady state, similarly to the integer quantum Hall effect. On the other hand, persistent axial currents are not prohibited by the Bloch theorem and they can be regarded as Pauli paramagnetism of relativistic matter. An application of the generalized Bloch theorem to quantum time crystals is also discussed. © 2015 American Physical Society.

Yamamoto N.,Keio University
Physical Review Letters | Year: 2015

We study the hydrodynamic regime of chiral plasmas at high temperature. We find a new type of gapless collective excitation induced by chiral effects in an external magnetic field. This is a transverse wave, and it is present even in incompressible fluids, unlike the chiral magnetic and chiral vortical waves. The velocity is proportional to the coefficient of the gravitational anomaly. We briefly discuss the possible relevance of this "chiral Alfvén wave" in physical systems. © 2015 American Physical Society.

Nitta M.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

The non-Abelian Josephson junction is a junction of non-Abelian color superconductors sandwiching an insulator, or a non-Abelian domain wall if flexible, whose low-energy dynamics is described by a U(N) principal chiral model with the conventional pion mass. A non-Abelian Josephson vortex is a non-Abelian vortex (color magnetic flux tube) residing inside the junction, that is described as a non-Abelian sine-Gordon soliton. In this paper, we propose Josephson instantons and Josephson monopoles, that is, Yang-Mills instantons and monopoles inside a non-Abelian Josephson junction, respectively, and show that they are described as SU(N) Skyrmions and U(1)N-1 vortices in the U(N) principal chiral model without and with a twisted-mass term, respectively. Instantons with a twisted boundary condition are reduced (or T-dual) to monopoles, implying that CPN-1 lumps are T-dual to CPN-1 kinks inside a vortex. Here we find SU(N) Skyrmions are T-dual to U(1)N-1 vortices inside a wall. Our configurations suggest a yet another duality between CPN-1 lumps and SU(N) Skyrmions as well as that between CPN-1 kinks and U(1)N-1 vortices, viewed from different host solitons. They also suggest a duality between fractional instantons and bions in the CPN-1 model and those in the SU(N) principal chiral model. © 2015 American Physical Society.

Suzuki S.,Keio University
Brain and Nerve | Year: 2010

Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular disorder in which autoantibodies inhibit the presynaptic release of acetylcholine. Autoantibodies against P/Q-type voltage-gated calcium channels (VGCC) are detected in 85% of patients with LEMS. In addition, autoantibodies to synaptotagmin, an M1-type muscarinic acetylcholine receptor and SOX1 are also found in the sera of patients with LEMS. LEMS is closely associated with small cell lung cancer (SCLC) in 50-60% of patients. Patients with SCLC who have anti-VGCC antibodies have been reported to have a favorable prognosis. In contrast to paraneoplatic LEMS, other forms of LEMS may have an autoimmune aspect because of the established association between human leukocyte antigen and a family history of other autoimmune disorders in this condition. The clinical features of LEMS include proximal weakness, areflexia, ptosis, cerebellar ataxia and autonomic dysfunction. The findings of electrophysiological examination show that LEMS is characterized by compound muscle action potential potentials with a low amplitude and increment upon repetitive nerve stimulation at a high rate. Tumor removal is the primary treatment of LEMS. The efficacy of 3,4-diaminopyridine for the treatment of LEMS has also been established. Patients with LEMS require the immunotherapies such as plasma exchange and the administration of high doses of immunoglobulin and prednisolone.

Yuzaki M.,Keio University
Neural Networks | Year: 2013

Synaptic plasticity, such as long-term potentiation and long-term depression (LTD), is believed to underlie learning and memory processes in vivo. The cerebellum is an ideal brain region to obtain definitive proof for this hypothesis. The current belief is that the acquisition of motor learning is stored by LTD at the parallel fiber (PF)-Purkinje cell synapse in the cerebellar cortex. Recently, however, several lines of mutant mice that display normal motor learning in the absence of cerebellar LTD have been reported. A similar dichotomy between synaptic plasticity at the circuitry level and learning at the behavioral level has also been reported in the hippocampus. One possible explanation for this dichotomy is that compensatory pathways at the molecular and circuitry levels play an important role in mice that have been genetically modified for their entire lives. Mice that are genetically modified to be deficient in or to express mutant versions of the δ2 glutamate receptor (GluD2) serve as an interesting model due to the predominant expression of GluD2 at PF-Purkinje cell synapses. Furthermore, two major functions of GluD2-PF synapse formation and LTD induction-can be mechanistically dissociated so that the role of LTD in motor learning can be investigated in the absence of morphological abnormalities caused by altered synapse formation. Therefore, genetic manipulations of GluD2 will help to clarify the relationship between LTD and motor learning in the cerebellum. © 2012 Elsevier Ltd.

Increasing evidence demonstrates that members of the sirtuin family, most of which work as NAD+-dependent protein deacetylases, mediate the preferable effects of caloric restriction. Since mitochondria play a central role in cardiac reactive oxygen species production, targeted modification of mitochondrial proteins and subsequent improvement in mitochondrial function have the potential for controlling cardiovascular senescence and managing cardiovascular diseases such as ischemia/reperfusion. We showed that caloric restriction primes cardiac mitochondria for ischemic stress by deacetylating specific mitochondrial proteins of the electron transport chain. We speculate that deacetylation of specific mitochondrial proteins by sirtuin preserves mitochondrial function and attenuates myocardial oxidative damage during ischemia/reperfusion. © 2013 Elsevier Inc.

Tajima K.,Keio University
Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand | Year: 2012

On treating distal radius fracture with intramedullary nailing (MICRONAIL, Wright Medical), completed anatomical reduction is indispensable before inserting the nail. However, complete reduction in percutaneous pinning or in Kapandji intrafocal pinning is troublesome. Thus, majority of the operation time is usually spent on reducing the fracture appropriately. We have commenced the "intrafocal elastic-spring pinning" as a reduction technique and have simplified the reduction prior to nailing. First, curve the 1.5 mm Kirschner wire properly. Next, pins are introduced percutaneously and intrafocally into the marrow cavity. The nail is then inserted in a standard manner. With this technique, an average of 16 consecutive intraoperative surgical times was 32.1 minutes (range, 16-55); apparently shorter than other previous reports. The bending-induced tension in the pins counteracts the postero-lateral displacing forces, and is especially efficient in comminuted or osteoporotic fractures. The nail will just brush aside the elastic pins when the pins interfere with the nail insertion.

Kato M.,Keio University | Hachisu I.,University of Tokyo
Bulletin of the Astronomical Society of India | Year: 2012

Recurrent novae are binaries harboring a very massive white dwarf (WD), as massive as the Chandrasekhar mass, because of their short recurrence periods of nova outbursts of 10-100 years. Thus, recurrent novae are considered as candidates of progenitors of Type Ia supernovae (SNe Ia). In fact, the SN Ia PTF 11kx showed evidence that its progenitor is a symbiotic recurrent nova. The binary parameters of recurrent novae have been well determined, especially for the ones with frequent outbursts, U Sco and RS Oph, which provide useful information on the elementary processes in binary evolution toward SNe Ia. Therefore we use them as testbeds for binary evolution models. For example, the original double degenerate (DD) scenario cannot reproduce RS Oph type recurrent novae, whereas the new single degenerate (SD) scenario proposed by Hachisu et al. (1999) naturally can. We review main differences between the SD and DD scenarios, especially for their basic processes of binary evolution. We also discuss observational support for each physical process. The original DD scenario is based on the physics in 1980s, whereas the SD scenario on more recent physics including the new opacity, mass-growth efficiency of WDs, and optically thick winds developed in nova outbursts.

Jones N.C.,Stanford University | Van Meter R.,Keio University | Fowler A.G.,University of Melbourne | McMahon P.L.,Stanford University | And 5 more authors.
Physical Review X | Year: 2012

We develop a layered quantum-computer architecture, which is a systematic framework for tackling the individual challenges of developing a quantum computer while constructing a cohesive device design. We discuss many of the prominent techniques for implementing circuit-model quantum computing and introduce several new methods, with an emphasis on employing surface-code quantum error correction. In doing so, we propose a new quantum-computer architecture based on optical control of quantum dots. The time scales of physical-hardware operations and logical, error-corrected quantum gates differ by several orders of magnitude. By dividing functionality into layers, we can design and analyze subsystems independently, demonstrating the value of our layered architectural approach. Using this concrete hardware platform, we provide resource analysis for executing fault-tolerant quantum algorithms for integer factoring and quantum simulation, finding that the quantum-dot architecture we study could solve such problems on the time scale of days.

Itoyama H.,Osaka City University | Maru N.,Keio University
International Journal of Modern Physics A | Year: 2012

Under a few mild assumptions, ${\mathcal N} = 1$ supersymmetry (SUSY) in four dimensions is shown to be spontaneously broken in a metastable vacuum in a self-consistent HartreeFock approximation of BardeenCooperSchrieffer/NambuJona-Lasinio (BCS/NJL) type to the leading order, in the gauge theory specified by the gauge kinetic function and the superpotential of adjoint chiral superfields, in particular, that possess ${\mathcal N} = 2$ extended SUSY spontaneously broken to ${\mathcal N} = 1$ at tree level. We derive an explicit form of the gap equation, showing the existence of a nontrivial solution. The ${\mathcal N} = 2$ gauginos in the observable sector receive mixed MajoranaDirac masses and are split due to both the nonvanishing 〈D 0〉 and 〈F 0〉 induced with 〈D 0〉. It is argued that proper physical applications and assessment of the range of the validity of our framework are made possible by rendering the approximation into $\frac{1}{N 2}$ expansion. © 2012 World Scientific Publishing Company.

Watanabe S.,Keio University | Mayer U.,Bielefeld University | Bischof H.-J.,Bielefeld University
Behavioural Brain Research | Year: 2011

Quite a lot of studies have tried to elucidate the differences in function of the two telencephalic targets of the avian visual system. We have tried to find out how the two systems are involved in orientation towards a food tray which is either marked by a special pattern or has to be identified by its relation to spatial cues. In this report, we compared in the zebra finch the effects of Wulst lesions on pattern discrimination with Wulst lesion effects on spatial discrimination, and we examined the effect of entopallium lesions on spatial discrimination. Birds with Wulst lesions showed deficits in spatial discrimination, but not in pattern discrimination. Entopallial lesions caused no deficits in spatial discrimination tasks. Combining the present results with a previous study revealing an impairment of pattern discrimination by such entopallial lesions [19], we are able to demonstrate a double dissociation: namely, an impairment of pattern discrimination by entopallial lesions and impairment of spatial discrimination by Wulst lesions, but no effects of the opposite pairing of task and lesion site. The entopallium is thus involved if the food source is identified by a pattern, and the Wulst if it has to be found by spatial cues. © 2011 Elsevier B.V.

Yokota R.,Boston University | Barba L.A.,Boston University | Narumi T.,University of Electro - Communications | Yasuoka K.,Keio University
Computer Physics Communications | Year: 2013

This paper reports large-scale direct numerical simulations of homogeneous-isotropic fluid turbulence, achieving sustained performance of 1.08 petaflop/s on gpu hardware using single precision. The simulations use a vortex particle method to solve the Navier-Stokes equations, with a highly parallel fast multipole method (fmm) as numerical engine, and match the current record in mesh size for this application, a cube of 40963 computational points solved with a spectral method. The standard numerical approach used in this field is the pseudo-spectral method, relying on the fft algorithm as the numerical engine. The particle-based simulations presented in this paper quantitatively match the kinetic energy spectrum obtained with a pseudo-spectral method, using a trusted code. In terms of parallel performance, weak scaling results show the fmm-based vortex method achieving 74% parallel efficiency on 4096 processes (one gpu per mpi process, 3 gpus per node of the tsubame-2.0 system). The fft-based spectral method is able to achieve just 14% parallel efficiency on the same number of mpi processes (using only cpu cores), due to the all-to-All communication pattern of the fft algorithm. The calculation time for one time step was 108 s for the vortex method and 154 s for the spectral method, under these conditions. Computing with 69 billion particles, this work exceeds by an order of magnitude the largest vortex-method calculations to date. © 2012 Elsevier B.V. All rights reserved.

Kato M.,Keio University | Hachisu I.,University of Tokyo
Astrophysical Journal | Year: 2011

Two types of nova evolutions can occur in low-mass white dwarfs of 0.5-0.7 M, i.e., an evolution with optically thick winds like in usual classical novae, or an another type of evolution without them like in the symbiotic nova PU Vul. The latter type is characterized by spectra with no indication of strong winds as well as a long-lasting flat optical peak in its light curve. We propose a transition from evolution with no optically thick wind to usual evolution with optically thick winds as a new outburst model for slow novae that show a relatively long-lasting multipeak phase followed by a wind phase like in the slow novae V723 Cas, HR Del, and V5558 Sgr. We calculated nova envelopes with one-dimensional approximation of the companion's effects and found that when the companion star is deeply embedded in the extended nova envelope, the structure of the static envelope approaches that of the optically thick wind solution. Thus, the transition from static to wind solution is triggered by the effect of the companion. The transition occurs in a close binary nova like V723 Cas, but is not triggered in a long-period binary like PU Vul. We reconfirm our previous results that the frictional energy deposition is negligibly small in almost all hydrogen/helium novae because of the low envelope density at the orbit. © 2011. The American Astronomical Society. All rights reserved.

Fukushima K.,Keio University | Su N.,Bielefeld University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We evaluate the thermodynamic quantities of Yang-Mills theory using the Gribov quantization, which deals with nonperturbative resummation. The magnetic scale is automatically incorporated into the framework and we find it efficient to stabilize the perturbative expansion of the free energy. In the temperature range T=Tc∼2Tc the major uncertainty in our results comes from the nonperturbative running coupling that is adopted from the lattice simulation, while the convergence above 2Tc is impressively robust. We also present the corresponding interaction measure (i.e., trace anomaly) up to close to Tc. © 2013 American Physical Society.

PURPOSE:: To report that spontaneous postkeratoplasty wound dehiscence or gaps caused by suture removal may occur years after penetrating and deep lamellar keratoplasty.METHODS:: We retrospectively reviewed the medical records of 667 keratoplasty patients (890 eyes). This study included 8 eyes of 8 patients (3 men and 5 women) aged 64 to 86 years who suffered from spontaneous wound dehiscence or gaps caused by suture removal. We examined their clinical backgrounds such as surgical procedure, reason for suture removal, and time interval between keratoplasty and suture removal.RESULTS:: The surgical procedures included 6 penetrating keratoplasties and 2 deep anterior lamellar keratoplasties. The most common reason for suture removal was high corneal astigmatism. Time interval between keratoplasty and suture removal was 15.9 ± 7.7 months (7–26 months). Three patients underwent suture removal from 6 months to 1 year after keratoplasty, 3 patients from 1 to 2 years, and 2 patients after more than 2 years.CONCLUSIONS:: Whenever postoperative keratoplasty suture is removed, it is important to consider that wound dehiscence or gaps may occur without incidence of trauma. © 2014 by Lippincott Williams & Wilkins.

Okubo T.,Keio University
Journal of Regional Science | Year: 2012

This paper studies antiagglomeration subsidies in a core-periphery setting when firms are heterogeneous in labor productivity, focusing on the effects of a relocation subsidy on firm location in various tax-financing schemes (local vs. global). I discuss how a subsidy can enhance welfare and average productivity in the periphery. As a result, I find that a subsidy proportional to profits can induce the relocation of high-productivity firms and thus increase welfare and average productivity in the periphery. Concerning tax-financing schemes, a local tax-financing scheme has an optimal level of subsidy. © 2011, Wiley Periodicals, Inc.

Yoshida K.,Keio University
Robotics and Autonomous Systems | Year: 2010

Artifact systems created by humans interact with the surrounding natural world and have a large-scale influence on our human lives. The most creditable concept to this critical issue of scientific and technological development seems to be "System Life" that is an innovative competence to be embodied into any artifact system for creating harmony in the world of natural entities and artifact systems interacting with each other. System life is defined as a seamless system of sensing, processing, activating and expressing mechanisms governed by system life information. This paper introduces a design approach of robots possessing system life. First, this paper presents the concept of system life comparing it with the conventional design methodology of intelligent systems. Second, the paper introduces an intelligent control methodology using the cubic neural network that the author developed in order to cope with unpredicted failures. Finally, the paper presents various intelligent robots, a skiing robot, autonomous soccer robots, a game playing robot, as new concrete artifact systems designed using the system life concept. © 2010 Published by Elsevier B.V.

Glucocorticoid-induced osteoporosis is mediated primarily by activity of glucocorticoid receptors expressed in osteoblasts, osteocytes and osteoclasts. Bone matrix harbors numerous osteocyte lacunae containing osteocytes. Each osteocyte extends numerous dendrites into canaliculi where dendrite tips make contact with dendrites of nearby neighboring osteocytes and form gap junctions between osteocytes. Osteocytes near the bone surface also contact osteoblasts and osteoclasts through dendrites, thereby establishing communication within an entire bone. Curiously, osteocytes themselves have been shown to dissolve bone matrix under several conditions in a process known as osteocytic osteolysis. The estimated surface area of osteocyte lacunae and canaliculi is huge, and the lacuno-canalicular network is well connected to the blood circulation, suggesting that osteocytic osteolysis may function in pathogenesis and treatment of osteoporosis. Glucocorticoids decrease bone formation by osteoblasts and induce apoptosis in osteocytes. Moreover, glucocorticoids reportedly increase the size of osteocyte lacunae, and enhance perilacunar remodeling. In this review, we discuss whether and how osteocytic osteolysis contributes to glucocorticoid-induced osteoporosis using mouse models.

Nakanishi Y.,Keio University
Proceedings of the Designing Interactive Systems Conference, DIS '12 | Year: 2012

In the development of augmented spaces, it is often difficult to perform frequent prototyping and testing. A range of related problems arise, especially when the cost of operation is high or when it is difficult to implement simulation in advance within the installation space. To address these problems, the authors created an integrated environment for iteration-based development of augmented spaces that allows interactive system developers to create systems using iterative virtual simulation and trial-and-error. With this system, hybrid prototyping using both virtual and miniature simulation can be performed. This paper introduces virtual simulation based on visualization. The authors studied four prototyping and deployment processes for two interactive public displays using both methods in order to clarify their characteristics, and the respective merits and demerits were discussed. Based on the results, a prototyping strategy for interactive public displays was proposed. Basic software operations and ideal positioning of input and output devices were investigated within virtual space, problems arising from differences between virtual and real space were clarified within miniature model space, and the addition of features to the code and related adjustment were iterated within both spaces. © 2012 ACM.

Arai N.,University of Electro - Communications | Yausoka K.,Keio University | Zeng X.C.,University of Nebraska - Lincoln
Journal of Chemical Theory and Computation | Year: 2013

We have performed molecular simulations to investigate morphologies and the phase diagram of the self-assembled triblock Janus nanoparticle confined to nanotubes. The triblock Janus nanoparticle is decorated with two hydrophobic caps at the north and south poles with a tunable area, separated by an electrically charged middle band. On the basis of the observed pressure- and tube-radius-dependent morphologies, we derive semiquantitative phase diagrams of the axial pressure versus the ratio of the radius of the nanoparticle to the radius of the nanotube. Three distinct walls of the nanotube, namely, hydrophobic, hydrophilic, and hydroneutral, are considered. We find that the three phase diagrams corresponding to three chemically different walls of the nanotube show some universal features. These features can be illustrated through a schematic assembly map and a roadmap on the variation of coordination number of the nanoparticles. In particular, we find that highly ordered morphologies tend to form when the coordination number of Janus particles is a multiple of 2. The orientation ordering and self-assembly behavior of the Janus nanoparticles can be qualitatively predicted when the chemical nature of the nanotube wall is known. © 2012 American Chemical Society.

Hori S.,Keio University
Nihon rinsho. Japanese journal of clinical medicine | Year: 2013

Sudden death during bathing accounts for 10 to 15% of all out-of hospital cardiac arrests in Japan. Surveys in Tokyo revealed 1,085 victims of accidents during bathing transported by ambulance from October 1999 to March 2000. 53% of them were cardiac arrest and 25% were those who needed rescue from bath tub because of consciousness disturbance (rescued group). Clinical observation of the rescued group patients indicated they suffered from transient loss of consciousness probably because of elevated body temperature. The current hypothesis of the accidents during bathing is a unique type of heat illness exposed by high water temperature(41-43 degrees C). Geriatric population is vulnerable to the bathing induced heat illness.

Borgh M.O.,University of Southampton | Nitta M.,Keio University | Ruostekoski J.,University of Southampton
Physical Review Letters | Year: 2016

We show how a singly quantized vortex can exhibit energetically stable defect cores with different symmetries in an atomic spin-1 polar Bose-Einstein condensate, and how a stable topologically nontrivial Skyrmion texture of lower dimensionality can be confined inside the core. The core isotropy and the stability of the confined texture are sensitive to Zeeman level shifts. The observed structures have analogies, respectively, in pressure-dependent symmetries of superfluid liquid He3 vortices and in the models of superconducting cosmic strings. © 2016 American Physical Society.

Kuwahara T.,University of Tokyo | Kuwahara T.,Tohoku University | Mori T.,University of Tokyo | Saito K.,Keio University
Annals of Physics | Year: 2016

This work explores a fundamental dynamical structure for a wide range of many-body quantum systems under periodic driving. Generically, in the thermodynamic limit, such systems are known to heat up to infinite temperature states in the long-time limit irrespective of dynamical details, which kills all the specific properties of the system. In the present study, instead of considering infinitely long-time scale, we aim to provide a general framework to understand the long but finite time behavior, namely the transient dynamics. In our analysis, we focus on the Floquet-Magnus (FM) expansion that gives a formal expression of the effective Hamiltonian on the system. Although in general the full series expansion is not convergent in the thermodynamics limit, we give a clear relationship between the FM expansion and the transient dynamics. More precisely, we rigorously show that a truncated version of the FM expansion accurately describes the exact dynamics for a certain time-scale. Our theory reveals an experimental time-scale for which non-trivial dynamical phenomena can be reliably observed. We discuss several dynamical phenomena, such as the effect of small integrability breaking, efficient numerical simulation of periodically driven systems, dynamical localization and thermalization. Especially on thermalization, we discuss a generic scenario on the prethermalization phenomenon in periodically driven systems. © 2016 Elsevier Inc.

Azegami T.,Tokyo International University | Azegami T.,Keio University | Yuki Y.,Tokyo International University | Kiyono H.,Tokyo International University
International Immunology | Year: 2014

The mucosal surface is the largest route through which pathogens enter the human body. To control the outbreak of mucosal infectious diseases, we must use our knowledge of the mucosal immune system to create vaccines that elicit protective mucosal and systemic immunity. Mucosal vaccines have advantages over traditional injectable vaccines in that they not only induce effective mucosal immune responses, but they also do not cause physical or psychological discomfort. Mucosal vaccines currently licensed for human use include oral vaccines against Vibrio cholerae, Salmonella typhi, poliovirus and rotavirus, and nasal vaccines against influenza virus. To further improve the existing vaccines, it will be necessary to develop novel vaccine production, storage and delivery systems through innovative strategies derived from interdisciplinary scientific research. Our accumulated knowledge of the innate and acquired arms of the mucosal immune system and the recent scientific and technical advancements in the fields of molecular biology, plant biology, bio-engineering and chemical engineering, genome biology and systems biology have created a unique research and development platform for the development of the next generation of mucosal vaccines. This review summarizes the current perspectives and future directions of mucosal vaccine development with emphasis on oral and nasal vaccines for the control of infectious diseases. © The Japanese Society for Immunology. 2014. All rights reserved.

Mitani F.,Keio University | Mitani F.,Waseda University
Proceedings of the Japan Academy Series B: Physical and Biological Sciences | Year: 2014

The adrenal cortex of mammals consists of three concentric zones, i.e., the zona glomerulosa (zG), the zona fasciculata (zF), and the zona reticularis (zR), which secrete mineralocorticoids, glucocorticoids, and adrenal androgens, respectively. In 1994, we identified immunohistochemically a new zone between zG and zF of the rat adrenal gland. The zone appeared to be devoid of any significant endocrine functions specific to adrenocortical zones, therefore, we designated the zone as "undifferentiated cell zone (zU)′. Further, BrdU (5-bromo-2B-deoxyuridine)-incorporating cells (cells in S-phase) were concentrated at the outer region and the inner region of zU, and these cells proliferated and migrated bidirectionally: toward zG centrifugally and toward zF centripetally. We proposed that cells in and around zU are stem/progenitor cells of the rat adrenal cortex, maintaining functional zonation of the adrenal cortex. The view is consistent with observations reported recently that Sonic hedgehog (Shh), an important factor in embryonic development and adult stem cell maintenance, exists in zU of the rat adrenal gland and the Shhcontaining cells seem to migrate bidirectionally. © 2014 The Japan Academy.

Marzan L.W.,Kyushu Institute of Technology | Shimizu K.,Kyushu Institute of Technology | Shimizu K.,Keio University
Microbial Cell Factories | Year: 2011

Background: The phosphorus compounds serve as major building blocks of many biomolecules, and have important roles in signal transduction. The phosphate is involved in many biochemical reactions by the transfer of phosphoryl groups. All living cells sophisticatedly regulate the phosphate uptake, and survive even under phosphate-limiting condition, and thus phosphate metabolism is closely related to the diverse metabolism including energy and central carbon metabolism. In particular, phosphorylation may play important roles in the metabolic regulation at acidic condition and nitrogen limiting condition, which typically appears at the late growth phase in the batch culture. Moreover, phosphate starvation is a relatively inexpensive means of gene induction in practice, and the phoA promoter has been used for overexpression of heterologous genes. A better understanding of phosphate regulation would allow for optimization of such processes.Results: The effect of phosphate (P) concentration on the metabolism in Escherichia coli was investigated in terms of fermentation characteristics and gene transcript levels for the aerobic continuous culture at the dilution rate of 0.2 h -1. The result indicates that the specific glucose consumption rate and the specific acetate production rate significantly increased, while the cell concentration decreased at low P concentration (10% of the M9 medium). The increase in the specific glucose uptake rate may be due to ATP demand caused by limited ATP production under P-limitation. The lower cell concentration was also caused by less ATP production. The less ATP production by H +-ATPase may have caused less cytochrome reaction affecting in quinone pool, and caused up-regulation of ArcA/B, which repressed TCA cycle genes and caused more acetate production. In the case of phoB mutant (and also phoR mutant), the fermentation characteristics were less affected by P-limitation as compared to the wild type where the PhoB regulated genes were down-regulated, while phoR and phoU changed little. The phoR gene knockout caused phoB gene to be down-regulated as well as PhoB regulated genes, while phoU and phoM changed little. The effect of pH together with lower P concentration on the metabolic regulation was also investigated. In accordance with up-regulation of arcA gene expression, the expressions of the TCA cycle genes such as sdhC and mdh were down-regulated at acidic condition. The gene expression of rpoS was up-regulated, and the expression of gadA was up-regulated at pH 6.0. In accordance with this, PhoB regulated genes were up-regulated in the wild type under P-rich and P-limited conditions at pH 6.0 as compared to those at pH 7.0. Moreover, the effect of nitrogen limitation on the metabolic regulation was investigated, where the result indicates that phoB gene was up-regulated, and PhoB regulated genes were also up-regulated under N-limitation, as well as nitrogen-regulated genes.Conclusion: The present result shows the complicated nature of the metabolic regulation for the fermentation characteristics upon phosphate limitation, acidic condition, and nitrogen limitation based on the transcript levels of selected genes. The result implies that the regulations under phosphate limitation, acidic condition, and nitrogen limitation, which occur typically at the late growth phase of the batch culture, are interconnected through RpoS and RpoD together with Pho genes. © 2011 Marzan and Shimizu; licensee BioMed Central Ltd.

Shimazaki J.,Tokyo Dental College | Shimazaki J.,Keio University | Iseda A.,Tokyo Dental College | Satake Y.,Tokyo Dental College | Shimazaki-Den S.,Tokyo Dental College
Ophthalmology | Year: 2012

Purpose: Endothelial rejection remains a major cause of graft failure after penetrating keratoplasty (PKP). Topical corticosteroids are the gold standard for preventing rejection; however, protocols for corticosteroid treatment have been diverse. The aim of the present study was to examine the efficacy and safety of long-term use of corticosteroid eye drops after PKP in a randomized, clinical trial. Design: Randomized, nonblinded, clinical trial. Participants: We enrolled 42 patients (21 males and 21 females) with a mean age of 65.3 years who underwent PKP and maintained graft clarity for >1 year with topical steroid eye drops. Intervention: Patients were randomly assigned to 1 of 2 groups: Administration of 0.1% fluorometholone 3 times a day (steroid group) or discontinuation of steroid eye drops (no steroid group). All patients were followed for 12 months. Main Outcome Measures: Proportion of eyes without endothelial rejection and the proportion of eyes with clear grafts and the incidence of local or systemic side effects. Results: Of the initial 42 patients, 4 in the steroid group and 6 in the no steroid group did not complete the trial. Of the patients who completed the trial, 1 patient in the steroid group and 6 in the no steroid group developed endothelial rejection at an average of 5.2±4.5 (mean ± standard deviation) months after study enrollment. The difference in the incidence of rejection between groups was found to be significant by both chi-square (P = 0.027) and KaplanMeier analyses (log-rank test, P = 0.032). No difference was observed between the 2 groups in visual acuity, intraocular pressure, epithelial damage, tear-film break-up time, cataract progression, infection, or incidence of systemic side effects. Conclusions: Prolonged use of 0.1% fluorometholone was beneficial for the prevention of rejection after PKP. Because no adverse consequences were noted, we recommend continuing use of the low-dose corticosteroids, even in nonhigh-risk cases. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. © 2012 American Academy of Ophthalmology.

Gudnason S.B.,CAS Lanzhou Institute of Modern Physics | Nitta M.,Keio University | Sasaki S.,Kitasato University
Journal of High Energy Physics | Year: 2016

Abstract: Construction of a supersymmetric extension of the Skyrme term was a long-standing problem because of the auxiliary field problem; that is, the auxiliary field may propagate and cannot be eliminated, and the problem of having fourth-order time derivative terms. In this paper, we construct for the first time a supersymmetric extension of the Skyrme term in four spacetime dimensions, in the manifestly supersymmetric superfield formalism that does not suffer from the auxiliary field problem. Chiral symmetry breaking in supersymmetric theories results not only in Nambu-Goldstone (NG) bosons (pions) but also in the same number of quasi-NG bosons so that the low-energy theory is described by an SL(N, (Formula presented.))-valued matrix field instead of SU(N) for NG bosons. The solution of auxiliary fields is trivial on the canonical branch of the auxiliary field equation, in which case our model results in a fourth-order derivative term that is not the Skyrme term. For the case of SL(2, (Formula presented.)), we find explicitly a nontrivial solution to the algebraic auxiliary field equations that we call a non-canonical branch, which when substituted back into the Lagrangian gives a Skyrme-like model. If we restrict to a submanifold, where quasi-NG bosons are turned off, which is tantamount to restricting the Skyrme field to SU(2), then the fourth-order derivative term reduces exactly to the standard Skyrme term. Our model is the first example of a nontrivial auxiliary field solution in a multi-component model. © 2016, The Author(s).

Kimura T.,Keio University | Kimura T.,Tokyo Institute of Technology
Journal of High Energy Physics | Year: 2016

We study two-dimensional (Formula presented.) gauge theory and its dualized system in terms of complex (linear) superfields and their alternatives. Although this technique itself is not new, we can obtain a new model, the so-called “semi-doubled” GLSM. Similar to doubled sigma model, this involves both the original and dual degrees of freedom simultaneously, whilst the latter only contribute to the system via topological interactions. Applying this to the (Formula presented.) GLSM for H-monopoles, i.e., smeared NS5-branes, we obtain its T-dualized systems in quite an easy way. As a bonus, we also obtain the semi-doubled GLSM for an exotic 52 3-brane whose background is locally nongeometric. In the low energy limit, we construct the semi-doubled NLSM which also generates the conventional string world-sheet sigma models. In the case of the NLSM for 52 3-brane, however, we find that the Dirac monopole equation does not make sense any more because the physical information is absorbed into the divergent part via the smearing procedure. This is nothing but the signal which indicates that the nongeometric feature emerges in the considering model. © 2016, The Author(s).

Takamura E.,Tokyo Womens Medical University | Tsubota K.,Keio University | Watanabe H.,Kansai Rosai Hospital | Ohashi Y.,Ehime University
British Journal of Ophthalmology | Year: 2012

Aims: To compare the efficacy and safety of 3% diquafosol ophthalmic solution with those of 0.1% sodium hyaluronate ophthalmic solution in dry eye patients, using mean changes in fluorescein and rose bengal staining scores as endpoints. Trial design and methods: In this multicenter, randomised, double-masked, parallel study of 286 dry eye patients with fluorescein and rose bengal staining scores of ≥3 were randomised to the treatment groups in a 1:1 ratio. Efficacy and safety were evaluated after drop-wise instillation of the study drug, six times daily for 4 weeks. Results: After 4 weeks, the intergroup difference in the mean change from baseline in fluorescein staining score was -0.03; this verified the non-inferiority of diquafosol. The mean change from baseline in rose bengal staining score was significantly lower in the diquafosol group (p=0.010), thus verifying its superiority. The incidence of adverse events was 26.4% and 18.9% in the diquafosol and sodium hyaluronate groups, respectively, with no significant difference. Conclusions: Diquafosol (3%) and sodium hyaluronate (0.1%) exhibit similar efficacy in improving fluorescein staining scores of dry eye patients, whereas, diquafosol exhibits superior efficacy in improving rose bengal staining scores. Diquafosol has high clinical efficacy and is well tolerated with a good safety profile.

The investigation of the surface area of atmospheric aerosols is important as it provides a metric for their adverse health effects; however, few previous studies have considered this parameter. This study investigated the BET specific surface areas of aerosols, as well as the particle size distributions and chemical compositions of the three commercially available atmospheric aerosol reference materials; namely SRM1649a, CRM#28 and CRM#8. SRM1649a and CRM#28 consist mainly of coarse particles, while CRM#8 consists mainly of fine (or ultrafine) particles. The specific surface areas of the reference materials were; SRM1649a: 2.0±0.2m2g-1, CRM#28: 2.0±0.2m2g-1 and CRM#8: 35.7±5.3m2g-1. CRM#8 had a higher value for the specific surface area. The specific surface area for CRM#8 was likely to be associated with the characteristics of diesel particulate matters. When the estimation of specific surface area of aerosol particles is based on the assumption that all particles are spherical and not aggregates/agglomerates, using particle number and mass distribution, the estimated value is likely to be significantly lower than the actual value, in particular, for fine or ultrafine particles. The actual specific surface area of atmospheric aerosols should be measured to avoid the underestimation of their adverse health effects. © 2013 Elsevier Ltd.

Toda I.,Minamiaoyama Eye Clinic | Ide T.,Minamiaoyama Eye Clinic | Fukumoto T.,Minamiaoyama Eye Clinic | Ichihashi Y.,Minamiaoyama Eye Clinic | Tsubota K.,Keio University
American Journal of Ophthalmology | Year: 2014

Purpose To evaluate the possible advantages of combination therapy with diquafosol tetrasodium and sodium hyaluronate for dry eye after laser in situ keratomileusis (LASIK). Design Prospective randomized comparative trial. Methods A total of 206 eyes of 105 patients who underwent LASIK were enrolled in this study. Patients were randomly assigned to 1 of 4 treatment groups according to the postoperative treatment: artificial tears, sodium hyaluronate, diquafosol tetrasodium, and a combination of hyaluronate and diquafosol. Questionnaire responses reflecting subjective dry eye symptoms, uncorrected and corrected visual acuity, functional visual acuity, manifest refraction, tear break-up time, fluorescein corneal staining, Schirmer test, and corneal sensitivity were examined before and 1 week and 1 month after LASIK. Results Distance uncorrected visual acuity was significantly better in the combination group than in the hyaluronate group 1 week and 1 month after LASIK. Near uncorrected visual acuity was significantly better in the combination group than in the artificial tear and diquafosol groups 1 week and 1 month after LASIK. Distance functional visual acuity improved significantly only in the combination group 1 month after LASIK. The Schirmer value in the combination group was significantly higher than that in the hyaluronate group at 1 month after LASIK. Subjective dry eye symptoms in the combination group improved significantly compared with those in the other groups 1 week after surgery. Conclusions Our results suggest that hyaluronate and diquafosol combination therapy is beneficial for early stabilization of visual performance and improvement of subjective dry eye symptoms in patients after LASIK.

Ohyama M.,Keio University
Dermatologica Sinica | Year: 2010

The treatment of hair loss diseases is sometimes difficult because of insufficient efficacy and limited options. However, recent advances in understanding of the pathophysiology and development of new remedies have improved the treatment of refractory hair loss conditions. In this article, an update on the management of hair loss diseases is provided, especially focusing on recently reported therapeutic approaches for alopecia areata (AA). An accurate diagnosis is indispensable to optimize treatment. Dry dermoscopy represents new diagnostic techniques, which could enable the differentiation of barely indistinguishable alopecias, e.g. AA and trichotillomania. An organized scalp biopsy adopting both vertical and transverse sectioning approaches also provides a deep insight into the pathophysiology of ongoing alopecias. Among various treatments for AA, intraregional corticosteroid and contact immunotherapy have been recognized as first-line therapies. However, some AA cases are refractory to both treatments. Recent studies have demonstrated the efficacy of pulse corticosteroid therapy or the combination of oral psoralen ultraviolet A therapy and systemic corticosteroids for severe AA. Previous clinical observations have suggested the potential role of antihistamines as supportive medications for AA. Experimental evaluation using AA model mice further supports their effectiveness in AA treatment. Finasteride opens up new possibilities for the treatment of androgenetic alopecia. For androgenetic alopecia patients refractory to finasteride, the combination of finasteride with topical minoxidil or the administration of dutasteride, another 5 alpha-reductase inhibitor, may provide better outcomes. Scarring alopecia is the most difficult form of hair loss disorder to treat. The bulge stem cell area is destroyed by unnecessary immune reactions with resultant permanent loss of hair follicle structures in scarring alopecia. Currently, treatment options for this hair loss disorder are extremely limited. The development of effective therapies for this form of intractable alopecia represents an important issue to be resolved. Copyright © 2010, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC. All rights reserved.

Down syndrome (DS), also known as Trisomy 21, is the most common chromosome aneuploidy in live-born children and displays a complicated symptom. To date, several kinds of mouse models have been generated to understand the molecular pathology of DS, yet the gene dosage effects and gene(s)-phenotype(s) correlation are not well understood. In this study, we established a novel method to generate a partial trisomy mice using the mouse ES cells that harbor a single copy of human artificial chromosome (HAC), into which a small human DNA segment containing human chromosome 21 genes cloned in a bacterial artificial chromosome (BAC) was recombined. The produced mice were found to maintain the HAC carrying human genes as a mini-chromosome, hence termed as a Trans-Mini-Chromosomal (TMC) mouse, and HAC was transmitted for more than twenty generations independent from endogenous mouse chromosomes. The three human transgenes including cystathionine β-synthase, U2 auxiliary factor and crystalline alpha A were expressed in several mouse tissues with various expression levels relative to mouse endogenous genes. The novel system is applicable to any of human and/or mouse BAC clones. Thus, the TMC mouse carrying a HAC with a limited number of genes would provide a novel tool for studying gene dosage effects involved in the DS molecular pathogenesis and the gene(s)-phenotype(s) correlation.

Saisho Y.,Keio University
International Journal of Molecular Sciences | Year: 2014

Diabetes is associated with a two to three-fold increase in risk of cardiovascular disease. However, intensive glucose-lowering therapy aiming at reducing HbA1c to a near-normal level failed to suppress cardiovascular events in recent randomized controlled trials. HbA1c reflects average glucose level rather than glycemic variability. In in vivo and in vitro studies, glycemic variability has been shown to be associated with greater reactive oxygen species production and vascular damage, compared to chronic hyperglycemia. These findings suggest that management of glycemic variability may reduce cardiovascular disease in patients with diabetes; however, clinical studies have shown conflicting results. This review summarizes the current knowledge on glycemic variability and oxidative stress, and discusses the clinical implications. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

Hasobe T.,Keio University
Journal of Physical Chemistry Letters | Year: 2013

Photofunctional molecular architectures with well-defined shapes and sizes are of great interest because of various applications such as photovoltaics, photocatalysis, and electronics. Porphyrins are promising building blocks for organized nanoscale superstructures, which perform many of the essential light-harvesting and photoinduced electron/energy transfer reaction. In this Perspective, we present the recent advances in supramolecular architectures of porphyrins for solar energy conversion. First, we state preparation and light energy conversion properties of porphyrin (donor: D) and fullerene (acceptor: A)-based composite spherical nanoassemblies. The interfacial control of D/A molecules based on our supramolecular strategy successfully demonstrates the drastic enhancement of light energy conversion properties as compared to the corresponding nonorganized systems. Then, bar-shaped structures composed of two different D and A molecules with separated inside and outside layers are discussed. This unusual rod formation shows a possibility for a novel zeolite-like photoreaction cavity with efficient visible light absorption. Finally, photophysical and phoelectrochemical properties of supramolecular composites between porphyrins and carbon naotubes/graphenes are briefly described. © 2013 American Chemical Society.

Creutzig T.,TU Darmstadt | Hikida Y.,Keio University | Ronne P.B.,University of Cologne
Journal of High Energy Physics | Year: 2013

In a previous work we have proposed that the Prokushkin-Vasiliev higher spin N = 2 supergravity on AdS3 is dual to a large N limit of the N = (2,2) ℂPN Kazama- Suzuki model. There is now strong evidence supporting this proposal based on symmetry and spectrum comparison. In this paper we will give further evidence for the duality by studying correlation functions. We compute boundary three point functions with two fermionic operators and one higher spin bosonic current in terms of the bulk supergravity theory. Then we compare with the results in the dual CFT, where the supersymmetry of the theory turns out to be very helpful. In particular we use it to confirm results conjectured in the bosonic case. Moreover, correlators with a fermionic current can be obtained via supersymmetry. © 2013 SISSA, Trieste, Italy.

Creutzig T.,TU Darmstadt | Hikida Y.,Keio University | Ronne P.B.,University of Cologne
Journal of High Energy Physics | Year: 2013

We propose a duality between a higher spin N=1 supergravity on AdS 3 and a large N limit of a family of N=(1,1) superconformal field theories. The gravity theory is an N=1 truncation of the N=2 supergravity found by Prokushkin and Vasiliev, and the dual conformal field theory is defined by a supersymmetric coset model. We check this conjecture by comparing one loop partition functions and find agreement. Moreover, we study the symmetry of the dual coset model and in particular compute fields of the coset algebra of dimension 3/2, 2, 2 and 5/2 explicitly. © 2013 SISSA, Trieste, Italy.

Iwasa T.,JST ERATO | Nakajima A.,Keio University
Chemical Physics Letters | Year: 2013

We present the physicochemical properties for the lowest-energy isomer of a boron-doped aluminum cluster of B2Al21-. The isomer was obtained by basin-hopping minimization based on the density functional theory, starting from a face-sharing bi-icosahedral structure in which two boron atoms were endohedrally doped to each icosahedron. The lowest-energy isomer is a triangular form in which an aluminum cage encapsulates two boron atoms endohedrally. The electronic structure was analyzed by projecting Kohn-Sham orbitals onto the spherical harmonics; occupied and unoccupied frontier orbitals are dominantly G- and H-symmetries, respectively. Optical absorption is mainly assigned to G to H transitions. © 2013 Elsevier B.V. All rights reserved.

Yukawa M.,Keio University
IEEE Transactions on Signal Processing | Year: 2015

We propose a novel adaptive learning algorithm based on iterative orthogonal projections in the Cartesian product of multiple reproducing kernel Hilbert spaces (RKHSs). The objective is to estimate or track nonlinear functions that are supposed to contain multiple components such as i) linear and nonlinear components and ii) high-and low-frequency components. In this case, the use of multiple RKHSs permits a compact representation of multicomponent functions. The proposed algorithm is where two different methods of the author meet: multikernel adaptive filtering and the algorithm of hyperplane projection along affine subspace (HYPASS). In a particular case, the 'sum' space of the RKHSs is isomorphic, under a straightforward correspondence, to the product space, and hence the proposed algorithm can also be regarded as an iterative projection method in the sum space. The efficacy of the proposed algorithm is shown by numerical examples. © 2015 IEEE.

Koda Y.,Keio University
[Rinshō ketsueki] The Japanese journal of clinical hematology | Year: 2012

We herein report two patients (70- and 45-year-old men) with refractory multiple myeloma who developed paralytic ileus shortly after starting bortezomib therapy. Bortezomib (1.3 mg/m(2)) was given on days 1, 4, 8, and 11 with daily oral solution itraconazole or voriconazole. Twelve and 15 days after beginning the therapy, each patient developed paralytic ileus. Interestingly, no other signs of peripheral neuropathy such as fingertip numbness were observed at the onset of ileus. Sporadic cases of paralytic ileus after bortezomib therapy have been reported, most of which developed ileus after several courses of bortezomib therapy. Our cases developed paralytic ileus shortly after initiating bortezomib, strongly suggesting that autonomic neuropathy due to bortezomib was induced by the concomitant use of itraconazole or voriconazole.

Horsman C.,University of Oxford | Horsman C.,Keio University
New Journal of Physics | Year: 2011

Topological quantum computing (QC) is a way of allowing recise quantum computations to run on noisy and imperfect hardware. One mplementation uses surface codes created by forming defects in a highlyentangled uster state. Such a method of computing is a leading candidate for rge-scale QC. However, there has been a lack of sufficiently powerful highlevel anguages to describe computing in this form without resorting to singlequbit perations, which quickly become prohibitively complex as the system size ncreases. In this paper, we apply the category-theoretic work of Abramsky and oecke to the topological cluster-state model of QC to give a high-level graphical anguage that enables direct translation between quantum processes and physical tterns of measurement in a computer-a 'compiler language'. We give the quivalence between the graphical and topological information flows, and show he applicable rewrite algebra for this computing model. We show that this gives s a native graphical language for the design and analysis of topological quantum lgorithms, and finish by discussing the possibilities for automating this process a large scale. © lishing Ltd and Deutsche Physikalische Gesellschaft.

Fujii C.,Keio University
Vascular Health and Risk Management | Year: 2013

Background: Complications resulting from venipuncture include vein and nerve damage, hematoma, and neuropathic pain. Although the basic procedures are understood, few analyses of actual data exist. It is important to improve the safety standards of this technique during venipuncture. This study aimed to obtain data on actual needle movement during vacuum venipuncture in order to develop appropriate educational procedures. Methods: Six experienced nurses were recruited to collect blood samples from 64 subjects. These procedures were recorded using a digital camera. Software was then used to track and analyze motion without the use of a marker in order to maintain the sterility of the needle. Movement along the X-and Y-axes during blood sampling was examined. Results: Approximately 2.5 cm of the needle was inserted into the body, of which 6 mm resulted from advancing or moving the needle following puncture. The mean calculated puncture angle was 15.2°. Given the hazards posed by attaching and removing the blood collection tube, as well as by manipulating the needle to fix its position, the needle became unstable whether it was fixed or not fixed. Conclusion: This study examined venipuncture procedures and showed that the method was influenced by increased needle movement. Focusing on skills for puncturing the skin, inserting the needle into the vein, and changing hands while being conscious of needle-tip stability may be essential for improving the safety of venipuncture. © 2013 Fujii, publisher and licensee Dove Medical Press Ltd.

Naganuma M.,Keio University
Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society | Year: 2014

Conventional ileocolonoscopy and barium small bowel follow-through are useful techniques for assessing the extension and severity of disease in patients with inflammatory bowel disease (IBD). More recently, novel techniques to enable IBD diagnosis have been developed, such as capsule endoscopy (CE), balloon enteroscopy (BE), computed tomography enterography (CTE) and magnetic resonance enterography (MRE). The advantages of CE and BE are that they enable mucosal assessment directly whereas the usefulness of CTE/MRE is in its ability to enable detection of transmural inflammation, stenosis, and extraintestinal lesions including abscesses and fistulas. In ulcerative colitis (UC), colitis-associated dysplasia/cancer is one of the critical complications in patients with chronic disease. Detection of colitis-associated cancer is difficult in cases with inflammation. Magnification colonoscopy has been used to detect dysplasia in patients with chronic UC. Furthermore, colon CE and endocytoscopy have also developed and these might be used for selected patients in the near future. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

Yan X.,Keio University
Journal of the American Heart Association | Year: 2012

Left ventricular (LV) remodeling leads to chronic heart failure and is a main determinant of morbidity and mortality after myocardial infarction (MI). At the present time, therapeutic options to prevent LV remodeling are limited. We created a large MI by permanent ligation of the coronary artery and identified a potential link between the interleukin (IL)-23/IL-17A axis and γδT cells that affects late-stage LV remodeling after MI. Despite the finsinf that infarct size 24 hours after surgery was similar to that in wild-type mice, a deficiency in IL-23, IL-17A, or γδT cells improved survival after 7 days, limiting infarct expansion and fibrosis in noninfarcted myocardium and alleviating LV dilatation and systolic dysfunction on day 28 post-MI. M(1) macrophages and neutrophils were the major cellular source of IL-23, whereas >90% of IL-17A-producing T cells in infarcted heart were CD4(-) TCRγδ(+) (γδT) cells. Toll-like receptor signaling and IL-1β worked in concert with IL-23 to drive expansion and IL-17A production in cardiac γδT cells, whereas the sphingosine-1-phosphate receptor and CCL20/CCR6 signaling pathways mediated γδT cell recruitment into infarcted heart. IL-17A was not involved in the acute inflammatory response, but it functioned specifically in the late remodeling stages by promoting sustained infiltration of neutrophils and macrophages, stimulating macrophages to produce proinflammatory cytokines, aggravating cardiomyocyte death, and enhancing fibroblast proliferation and profibrotic gene expression. The IL-23/IL-17A immune axis and γδT cells are potentially promising therapeutic targets after MI to prevent progression to end-stage dilated cardiomyopathy.

Fukushima K.,Keio University
Acta Physica Polonica B | Year: 2011

We present a pedagogical introduction to the theoretical framework of the Color Glass Condensate (CGC) and the McLerran-Venugopalan (MV) model. We discuss the application of the MV model to describe the early-time dynamics of the relativistic heavy-ion collision. Without longitudinal fluctuations the classical time evolution maintains boost invariance, while an instability develops once fluctuations that break boost invariance are included. We show that this "Glasma instability" enhances rapidity-dependent variations as long as self-interactions among unstable modes stay weak and the system resides in the linear regime. Eventually the amplitude of unstable modes becomes so large that the growth of instability gets saturated. In this non-linear regime the numerical simulations of the Glasma lead to turbulent energy flow from low-frequency modes to higher-frequency modes, which results in a characteristic power-law spectrum. The power found in numerical simulation of the expanding Glasma system turns out to be consistent with Kolmogorov's -5/3 scaling.

Saisho Y.,Keio University
Vascular Health and Risk Management | Year: 2015

Dipeptidyl peptidase-4 (DPP-4) inhibitors, a new class of oral hypoglycemic agents, augment glucose-dependent insulin secretion and suppress glucagon levels through enhancement of the action of endogenous incretin by inhibiting DPP-4, an incretin-degrading enzyme. DPP-4 inhibitors are generally well tolerated because of their low risk of hypoglycemia and other adverse events. Moreover, with their potential to improve beta cell function, a core defect of type 2 diabetes, DPP-4 inhibitors are becoming a major component of treatment of type 2 diabetes. Alogliptin benzoate is a newly developed, highly selective DPP-4 inhibitor which has been approved in many countries throughout the world. Once-daily administration of alogliptin as either monotherapy or combination therapy with other oral antidiabetic drugs or insulin has a potent glucose-lowering effect which is similar to that of other DPP-4 inhibitors, with a low risk of hypoglycemia and weight gain. The cardiovascular safety of this drug has been confirmed in a recent randomized controlled trial. This review summarizes the efficacy and safety of alogliptin, and discusses the role of DPP-4 inhibitors in the treatment of type 2 diabetes. © 2015 Saisho.

Aoki D.,Keio University
Journal of Obstetrics and Gynaecology Research | Year: 2014

We present the Patient Annual Report in 2011 and the Treatment Annual Report in 2005 that were collected and analyzed by the Japan Society of Obstetrics and Gynecology. Data on 15 698 patients with cervical cancer, 7713 with endometrial cancer and 4672 with ovarian cancer in whom treatment was started in 2011 and data on the prognosis of 2985 patients with cervical cancer, 2812 with endometrial cancer, and 1839 with ovarian cancer who were started on treatment in 2005 were analyzed and summarized. Patient Annual Report in 2011: Stage 0 accounted for 58%, stage I for 24%, stage II for 9%, stage III for 5%, and stage IV for 4% of all the patients with cervical cancer. Stage 0 accounted for 6%, stage I for 61%, stage II for 8%, stage III for 18%, and stage IV for 7% of patients with endometrial cancer. Stage I accounted for 43%, stage II for 9%, stage III for 29%, and stage IV for 8% of patients with ovarian cancer. Treatment Annual Report in 2005: The 5-year overall survival rates of patients with cervical cancer were 91% in stage I, 78% in stage II, 57% in stage III, and 30% in stage IV. The 5-year overall survival rates of patients with endometrial cancer were 95% in stage I, 89% in stage II, 77% in stage III, and 23% in stage IV. The 5-year overall survival rates of patients with ovarian surface epithelialstromal tumors were 92% in stage I, 75% in stage II, 50% in stage III and 39% in stage IV. © 2014 Japan Society of Obstetrics and Gynecology.

Mori T.,University of Tokyo | Kuwahara T.,University of Tokyo | Kuwahara T.,Tohoku University | Saito K.,Keio University
Physical Review Letters | Year: 2016

We discuss the universal nature of relaxation in isolated many-body quantum systems subjected to global and strong periodic driving. Our rigorous Floquet analysis shows that the energy of the system remains almost constant up to an exponentially long time in frequency for arbitrary initial states and that an effective Hamiltonian obtained by a truncation of the Floquet-Magnus expansion is a quasiconserved quantity in a long time scale. These two general properties lead to an intriguing classification on the initial stage of relaxation, one of which is similar to the prethermalization phenomenon in nearly integrable systems. © 2016 American Physical Society.

The position of a colloidal particle trapped in an external field thermally fluctuates at equilibrium. As is well known, the ambient fluid is not a simple heat bath and the particle mass appears to increase, which influences the mean square velocity of the particle. In this study, we suppose that the particle is surrounded by a binary fluid mixture in the homogeneous phase near, but not too close to, the critical point. Usually, one component is preferably attracted by the particle surface, and the resultant adsorption layer becomes significant because of the near-criticality. When the particle fluctuates in this situation, its mean square displacement should also be influenced by the ambient fluid because the adsorption layer does not follow the particle motion totally. We calculate the influence in a simple case, where a rigid spherical particle fluctuates with a small amplitude and its surface attracts one component weakly. We utilize the hydrodynamics in the limit of no dissipation to examine the contribution from the ambient mixture to the equal-time correlation. According to our result, the mean square displacement is reduced by an additional stress, including osmotic pressure. © 2016 The Physical Society of Japan.

Mitsantisuk C.,Nagaoka University of Technology | Katsura S.,Keio University | Ohishi K.,Nagaoka University of Technology
IEEE Transactions on Industrial Electronics | Year: 2010

Future robot systems are required to focus on developing more flexible systems for use with human operator. These robots must operate more slowly and be more compliant to safe user interaction. This paper proposes an improved design methodology for the humanrobot interaction system. The main contribution of the work described in this paper is the design of dual disturbance observers combined with modal space design for the twin direct-drive motor system. Two of the same direct-drive motors are required and connected by wire rope mechanism. Since both direct-drive motors have almost the same value of the friction effect and other nonlinearities, it is easy for the proposed system to compensate these deterioration effects. The proposed force control system is independently controlled in acceleration dimension by realizing the system based on common mode and differential mode. In the common mode, it is utilized for control of vibration suppression and wire rope tension. Moreover, the bandwidth and the stiffness of mechanism can be regulated by changing the wire rope tension control. In the differential mode, the purity of human external force with compensation of friction force is obtained. This mode is useful for control of the interaction force of human. The effectiveness of the proposed method is verified by experimental results. © 2010 IEEE.

Maruyama T.,Keio University
Reproductive Medicine and Biology | Year: 2010

The human uterus is unique in that it possesses the tremendous regenerative capacity required for cyclical regeneration and remodeling throughout a woman's reproductive life. Not only must the uterus rapidly enlarge to accommodate the developing fetus, the endometrium must also regenerate with each menstrual cycle. This plasticity of the reproductive system has recently been highlighted. My research group and collaborators showed that functional endometrial tissue could be regenerated from only a small number of singly dispersed human endometrial cells, transplanted beneath the kidney capsule of severely immunodeficient mice. This artificially generated endometrium resembles the natural endometrium, and contains human blood vessels that invade the mouse kidney parenchyma. Additionally, it mimics normal hormone-dependent changes including proliferation, differentiation, and tissue breakdown (menstruation). The regenerative capacity of endometrial cells makes them ideal candidates for tissue reconstitution, angiogenesis, and human-mouse chimeric vessel formation. The smooth muscle cells of the uterus (myometrium) share the plasticity of the endometrium. This is evidenced by their capacity for dramatic, repeatable, pregnancy-induced enlargement. Regeneration and remodeling in the female reproductive tract allude to the existence of endometrial and myometrial stem cell systems. We have recently isolated candidate populations of adult stem cells from both the human endometrium and myometrium. Characterization of these endometrial and myometrial cells, along with the study of the mechanisms controlling their regeneration, will improve the understanding of the physiology and pathophysiology of the female reproductive tract. Furthermore, myometrial and endometrial stem-like cells might also represent a novel source of biological material that could be used for the reconstruction of not only the human uterus but other organs as well. © 2009 Japan Society for Reproductive Medicine.

Shimoda M.,Keio University | Shimoda M.,Paterson Institute for Cancer Research | Mellody K.T.,Paterson Institute for Cancer Research | Orimo A.,Paterson Institute for Cancer Research
Seminars in Cell and Developmental Biology | Year: 2010

Tumours are highly complex tissues composed of carcinoma cells and surrounding stroma, which is constructed by various different types of mesenchymal cells and an extracellular matrix (ECM). Carcinoma-associated fibroblasts (CAFs), which consist of both fibroblasts and myofibroblasts, are frequently observed in the stroma of human carcinomas, and their presence in large numbers is often associated with the development of high-grade malignancies and poor prognoses. Moreover, in human tumour xenograft models, CAFs extracted from the tumour are more capable of promoting tumour growth through their interactions with carcinoma cells when compared to those isolated from non-cancerous stroma. Taken together, these observations strongly suggest that CAFs actively contribute to tumour progression. In this review we highlight the emerging roles of these cells in promoting tumourigenesis, and we discuss the molecular mechanisms underlying their tumour-promoting capabilities and their cellular origin. © 2009 Elsevier Ltd. All rights reserved.

Matsubara Y.,Keio University
Blood | Year: 2013

In this issue of Blood, Kudo et al demonstrate a critical role for mucin-type O-glycans in terminal differentiation of megakaryocytes and platelet release, using conditional knockout mouse for the catalytic enzyme for O-glycosylation. This article provides a model for understanding what role such near ubiquitous modifiers may have in terminal hematopoietic differentiation.

Ogihara N.,Keio University | Makishima H.,Kyoto University | Nakatsukasa M.,Kyoto University
Journal of Human Evolution | Year: 2010

Studying the bipedal locomotion of non-human primates is important for clarifying the evolution of habitual bipedalism in the human lineage. However, quantitative descriptions of three-dimensional kinematics of bipedal locomotion in non-human primates are very scarce, due to difficulties associated with measurements. In this study, we performed a kinematic analysis of bipedal locomotion on two highly trained (performing) Japanese macaques walking on a treadmill at different speeds and estimated three-dimensional angular motions of hindlimb and trunk segments, based on a model-based registration method. Our results demonstrated a considerable degree of axial rotation occurring at the trunk and hip joints during bipedal locomotion, suggesting that bipedal locomotion in Japanese macaques is essentially three-dimensional. In addition, ranges of angular motions at the hip and ankle joints were larger and the knee joint was more flexed in the mid-stance phase with increasing speed, indicating that gait kinematics are modulated depending on speed. Furthermore, macaques were confirmed to have actually acquired, at least to some extent, the energy conservation mechanism of walking due to pendular exchange of potential and kinetic energy, but effective utilization of this mutual exchange of energy was found to occur only at comparatively low velocity. Spring-like running mechanics were probably more exploited at higher speed because the duty factor was above 0.5. Fundamental differences in bipedal strategy seem to exist between human and non-human primate bipedal locomotion. © 2009 Elsevier Ltd. All rights reserved.

Amagai M.,Keio University | Stanley J.R.,University of Pennsylvania
Journal of Investigative Dermatology | Year: 2012

Much of the original research on desmosomes and their biochemical components was through analysis of skin and mucous membranes. The identification of desmogleins 1 and 3, desmosomal adhesion glycoproteins, as targets in pemphigus, a fatal autoimmune blistering disease of the skin and mucous membranes, provided the first link between desmosomes, desmogleins, and human diseases. The clinical and histological similarities of staphylococcal scalded skin syndrome or bullous impetigo and pemphigus foliaceus led us to identify desmoglein 1 as the proteolytic target of staphylococcal exfoliative toxins. Genetic analysis of striate palmoplantar keratoderma and hypotrichosis identified their responsible genes as desmogleins 1 and 4, respectively. More recently, these fundamental findings in cutaneous biology were extended beyond the skin. Desmoglein 2, which is expressed earliest among the four isoforms of desmoglein in development and found in all desmosome-bearing epithelial cells, was found to be mutated in arrythmogenic right ventricular cardiomyopathy and has also been identified as a receptor for a subset of adenoviruses that cause respiratory and urinary tract infections. The story of desmoglein research illuminates how dermatological research, originally focused on one skin disease, pemphigus, has contributed to understanding the biology and pathophysiology of many seemingly unrelated tissues and diseases. © 2012 The Society for Investigative Dermatology.

Sawamura T.,Shinshu University | Wakabayashi I.,Hyogo College of Medicine | Okamura T.,Keio University
Clinica Chimica Acta | Year: 2015

Oxidized low-density lipoprotein (LDL) exhibits various biological activities and accumulates in atheromas. LOX-1 (lectin-like oxidized LDL receptor) is the receptor that mediates oxidized LDL activity in vascular endothelial cells. Activation of LOX-1 results in oxidized LDL-induced endothelial dysfunction and hyperlipidemia-induced vascular lipid deposition. We hypothesized that LOX-1 is a candidate risk factor beyond LDL cholesterol (LDLC) and developed a novel assay to quantify LOX-1 ligand containing apoB (LAB). In men from the United States, serum LAB showed a significant positive association with carotid intima-media thickness, independent of LDLC. LAB and the LOX index (obtained by multiplying LAB by sLOX-1) were significantly associated with the incidence of coronary artery disease and ischemic stroke after adjusting for confounding factors, including non-HDL cholesterol. sLOX-1 is thought to be a better biomarker for early diagnosis of acute coronary syndrome than traditional biomarkers, including troponin T. LAB was associated with various atherosclerotic risk factors such as smoking, obesity, diabetes, diastolic hypertension, hypertriglyceridemia, and metabolic syndrome. Measurement of the soluble form of LOX-1 (sLOX-1) and LAB seems to be useful for evaluating the state and risk of atherosclerosis and atherosclerosis-related diseases. Further prospective studies using large populations and randomized clinical trials on sLOX-1, LAB, and the LOX index are needed. © 2014 Elsevier B.V.

Campbell J.C.,University of Michigan | Ikegami N.,Keio University
Health Affairs | Year: 2010

The U.S. Congress is considering the Community Living Assistance Services and Supports (CLASS) Act, a voluntary insurance program that would help pay for long-term services and supports to disabled Americans. In Germany and Japan, social insurance programs are universal, support family caregivers, and allow individuals considerable flexibility in securing the services they require. We explored differences between Germany and Japan in program goals, eligibility process, scope, size, and sustainability for possible applications in the United States. Moreover, when we compared public spending on longterm care, we found that spending in the United States is actually higher than in Germany even now, prior to enactment of the CLASS Act, and is only slightly lower than in Japan. © 2010 Project HOPE-The People-to-People Health Foundation, Inc.

Honda K.,Keio University | Honda K.,RIKEN | Honda K.,Chiyoda Corporation
Cell Host and Microbe | Year: 2015

In this issue of Cell Host & Microbe, Kubinak et al. (2015) demonstrate that gut microbiota-mediated signaling through MyD88 in CD4+ T cells induces their differentiation into T follicular helper (TFH) cells that promote affinity-matured microbiota antigen-specific immunoglobulin A (IgA) responses. These TFH-driven IgA responses are essential for maintaining gut bacterial diversity and a healthy microbiota. © 2015 Elsevier Inc.

Iwamoto J.,Keio University | Sato Y.,Mitate Hospital
Expert Opinion on Pharmacotherapy | Year: 2013

Introduction: The effect of the anti-osteoporosis medicine, menatetrenone (vitamin K2; menaquinone-4) on the skeleton remains a matter of controversy. The objective of the present review study was to evaluate the effect of menatetrenone on the skeleton of postmenopausal women, men and glucocorticoid-treated patients. Methods: PubMed was used to search the literature for randomized controlled trials (RCTs), meta-analyses and systematic reviews. Thirteen RCTs, one meta-analysis and one systematic review were available for analysis. Results: Except for one large Japanese RCT (Phase IV trial: Osteoporotic Fracture (OF) study, n = 4378), RCTs with small sample size showed non-significant or modest effect on bone mineral density (BMD) in postmenopausal women and patients treated with glucocorticoid, positive effect on hip geometry in postmenopausal women and efficacy against fractures (mainly vertebral fractures) in postmenopausal women with osteoporosis. A post hoc analysis of the OF study showed that the incidence of vertebral fractures decreased in postmenopausal women with at least five vertebral fractures. A meta-analysis study, but not a systematic review study, showed efficacy against vertebral and non-vertebral fractures mainly in postmenopausal women with osteoporosis. There was no available evidence for men with osteoporosis. Conclusion: The present review of the literature revealed some evidence of a positive effect of menatetrenone on the skeleton of postmenopausal women and in patients treated with glucocorticoid. Expert opinion: Menatetrenone is considered to be a second-line medicine for postmenopausal osteoporotic women with an increased risk for vertebral fractures. © 2013 Informa UK, Ltd.

Sugimoto S.,Keio University | Mizukami T.,Endoscopy Center
World Journal of Gastroenterology | Year: 2015

Colonoscopy techniques combining or replacing air insufflation with water infusion are becoming increasingly popular. They were originally designed to reduce colonic spasms, facilitate cecal intubation, and lower patient discomfort and the need for sedation. These maneuvers straighten the rectosigmoid colon and enable the colonoscope to be inserted deeply without causing looping of the colon. Water-immersion colonoscopy minimizes colonic distension and improves visibility by introducing a small amount of water. In addition, since pain during colonoscopy indicates risk of bowel perforation and sedation masks this important warning, this method has the potential to be the favored insertion technique because it promotes patient safety without sedation. Recently, this water-immersion method has not only been used for colonoscope insertion, but has also been applied to therapy for sigmoid volvulus, removal of lesions, lower gastrointestinal bleeding, and therapeutic diagnosis of abnormal bowel morphology and irritable bowel syndrome. Although a larger sample size and prospective head-to-head-designed studies will be needed, this review focuses on the usefulness of water-immersion colonoscopy for diagnostic and therapeutic applications. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.

Iwamoto J.,Keio University
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists | Year: 2010

The purpose of this study was to clarify the efficacy of conservative or surgical treatment in athletes with lumbar disc herniation by reviewing the literature. A search of the literature was performed through PubMed, seeking studies published from 1990 to 2009 with regard to the outcomes of conservative or surgical treatment of lumbar disc herniation in athletes. The percentage of athletes who returned to their original levels of sports activities and the period until their return after the start of treatment were assessed. One prospective and six retrospective studies were identified. One study was for conservative treatment, three for microdiscectomy, and the remaining three for percutaneous discectomy. The respective percentages of athletes who returned to original levels of sports activities (the period until their return) were 78.9% (4.7 mos), 85.1% (5.2-5.8 mos), and 69.9% (7.0 wks to 12 mos). The efficacy of conservative treatment and microdiscectomy, but not percutaneous discectomy, was comparable. No studies were found available for conventional open discectomy, percutaneous laser discectomy, or microendoscopic discectomy. It was revealed that the outcomes of conservative treatment or microdiscectomy in athletes with lumbar disc herniation seemed to be satisfactory in terms of their ability to return the injured athletes to their original levels of sports activities.

Ichihara A.,Tokyo Womens Medical University | Kinouchi K.,Keio University
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System | Year: 2011

The (pro)renin receptor (P)RR is a receptor for renin and prorenin, not only allowing local production of angiotensin I from angiotensinogen, but also inducing intracellular signaling. Intriguingly, (P)RR is also called ATP6AP2 because a (P)RR fragment was demonstrated to be associated with vacuolar-type H+-ATPase (V-ATPase), which is of importance for the maintenance of intracellular pH. Recent studies implicate that deletion of (P)RR results in the dysfunction of V-ATPase, suggesting that the (P)RR is essential for its role as a proton pump. Furthermore, the novel function of (P)RR as an adaptor protein between the Wnt receptor complex and the V-ATPase was discovered. Thus, (P)RR is a multi-functional molecule with functions beyond renin and prorenin. This review focuses on the current knowledge and issues of (P)RR and V-ATPase. © SAGE Publications 2011.

Objectives: This study identifies the most significant readability factors and examines ways of improving and evaluating Japanese health information text in terms of ease of reading and understanding. Methods: Six different Japanese texts were prepared based on an original short text written by a medical doctor for a hospital web site intended for laypersons regarding chronic suppurative otitis media. Four were revised for single readability factor (syntax, vocabulary, or text structure) and two were modified in all three factors. Using a web-based survey, 270 high school students read one of the seven texts, including the original, completed two kinds of comprehension tests, and answered questions on their impressions of the text's readability. Results: Significantly higher comprehension test scores were shown in the true or false test for a mixed text that presented important information first for better text structure. They were also found in the cloze test for a text using common vocabulary and a cohesive mixed text. Conclusions: Vocabulary could be a critical single readability factor when presumably combined with better text structure. Using multiple evaluation methods can help assess comprehensive readability. The findings on improvement and evaluation methods of readability can be applied to support effective health communication. © 2013 Health Libraries Group Health Information and Libraries Journal.

Sato Y.,Mitate Hospital | Iwamoto J.,Keio University | Honda Y.,Mitate Hospital
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2011

Background: Incidence of a fracture, particularly in the hip joint, is high in Parkinson's disease (PD), owing to the immobilisation-induced bone resorption and vitamin D deficiency with reduced bone mineral density (BMD). The authors previously demonstrated the lowered incidence of hip fractures in PD by daily administration of risedronate and vitamin D. Methods: This randomised, double-blind, placebo-controlled study was conducted to determine the efficacy of 17.5 mg once-weekly risedronate in the prevention of hip fracture in women with PD. Patients were randomly assigned to 17.5 mg risedronate once a week (n=136) or a placebo (n=136) combined with daily 1000 IU of ergocalciferol. Incidence of hip fractures was compared between the two groups during the 2-year follow-up. Results: Hip fractures occurred in 15 patients in the placebo group and 3 patients in the risedronate group. The RR for hip fractures in the risedronate group as compared with the placebo group was 0.20 (95% CI 0.06 to 0.66). In the risedronate group, serum calcium levels decreased during the follow-up, while the levels in the placebo group increased. BMD increased by 3.4% in the risedronate group and decreased by 3.2% in the placebo group (p<0.01). Conclusions: Treatment with once-weekly risedronate and ergocalciferol prevents hip fractures in older women with PD.

Aramaki K.,Keio University
Zairyo to Kankyo/ Corrosion Engineering | Year: 2014

Permeation of anions into a passive film of iron was investigated by X-ray photoelectron spectroscopy of a passivated Fe surface previously immersed in an anion solution for the time before breakdown occurred. Hard base anions like CH3CO2 -and F-were impermeable into the passive film, leading to dif ficulty in passive film breakdown. However, I-belonging to soft base anions and SCN-to soft and hard base anions penetrated into the film. It was believed that I-inhibits and SCN-stimulates the anodic process of iron corrosion in an acid solution within a tiny metastable pit forming before breakdown, resulting in suppression and acceleration of passive film breakdown, respectively.

Einaga Y.,Keio University | Foord J.S.,University of Oxford | Swain G.M.,Michigan State University
MRS Bulletin | Year: 2014

Boron-doped diamond electrodes have attracted increasing interest from researchers due to their outstanding properties for electroanalysis and other electrochemical applications. Material quality and availability have come a long way since the initial reports on the basic electrochemical properties back in the late 1980s and early 1990s. In this review, we highlight how diamond electrochemistry has diversified and matured in recent years in terms of the understanding of structure-property relationships and the development of new applications of materials in electroanalytical chemistry. © Materials Research Society 2014.

Kameyama M.,Keio University
Journal of Cerebral Blood Flow and Metabolism | Year: 2014

Brain perfusion tracers like [ 99m Tc] d,l-hexamethyl-propyeneamine oxime (99m Tc-HMPAO) and [ 99m Tc] ethyl-cysteinate dimer (99m Tc-ECD) underestimate regional cerebral blood flow (rCBF) at high flow values. To improve linearity between tracer accumulation and rCBF, two different models have been proposed. One is Lassen's correction algorithm for back-diffusion of tracer, and the other is based on the permeability-surface (PS) model for correction of low first-pass extraction. Although both these models have the same goal, they have completely different forms of equation. It was demonstrated that mathematical approximation of the PS model equation leads to Lassen's equation. In this process, the relationship between PS, CBF values and Lassen's parameter was acquired, and how to correct both the back-diffusion and low first-pass extraction was also demonstrated. A computer simulation confirmed that the two models provided similar consequences when the parameter value is chosen according to the relationship found. Lassen's equation can be used to correct not only back-diffusion but also low first-pass extraction. To perform overall correction, the parameter value we have been using for decades may be too weak. I estimated that the parameter value for overall correction of HMPAO would be around 0.5, and that of ECD would be around 0.65. © 2014 ISCBFM.

It has long been believed that a damaged central nervous system (CNS) is difficult to regenerate; however, as a result of the rapid progress in biomedical science, including stem cell biology, there has been a renewed and an increasing interest in developing regenerative therapies for the CNS. Driving this interest has been the discovery of neural stem cells in the adult mammalian CNS, including the human CNS, and the finding that neurogenesis occurs in the adult brain. To achieve regeneration of a damaged CNS, our main strategies encompass: (1) axonal regeneration, (2) replenishment of lost neural cells, and (3) functional recovery. In this review, achievements using these approaches will be outlined. © 2011 by Lippincott Williams & Wilkins.

Tasaka S.,Keio University | Tokuda H.,Social Insurance Central General Hospital
Journal of Infection and Chemotherapy | Year: 2012

In human immunodeficiency virus (HIV)-infected patients, Pneumocystis jirovecii pneumonia (PCP) is a well-known opportunistic infection, and its management has been established. However, PCP is an emerging threat to immunocompromised patients without HIV infection, such as those receiving novel immunosuppressive therapeutics for malignancy, organ transplantation, or connective tissue diseases. Clinical manifestations of PCP are quite different between patients with and without HIV infections. In patients without HIV infection, PCP rapidly progresses, is difficult to diagnose correctly, and causes severe respiratory failure with a poor prognosis. High-resolution computed tomography findings are different between PCP patients with HIV infection and those without. These differences in clinical and radiologic features are the result of severe or dysregulated inflammatory responses that are evoked by a relatively small number of Pneumocystis organisms in patients without HIV infection. In recent years, the usefulness of PCR and serum β-d-glucan assay for rapid and noninvasive diagnosis of PCP has been revealed. Although corticosteroid adjunctive to anti-Pneumocystis agents has been shown to be beneficial in some populations, the optimal dose and duration remain to be determined. Recent investigations revealed that Pneumocystis colonization is prevalent, and that asymptomatic carriers are at risk for developing PCP and can serve as the reservoir for the spread of Pneumocystis by person-to-person transmission. These findings suggest the need for chemoprophylaxis in immunocompromised patients without HIV infection, although its indication and duration are still controversial. Because a variety of novel immunosuppressive therapeutics have been emerging in medical practice, further innovations in the diagnosis and treatment of PCP are needed. © 2012 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.

We describe a standardized method of fixation, antigen retrieval, and image contrasting for post-embedding immunoelectron microscopy. Tissues are fixed with formaldehyde solutions containing Ca 2+ and Mg 2+ ions at pH 7.4 and then at pH 8.5. After dehydration with dimethylformamide, the specimens are embedded in LR-White resin. For antigen retrieval, ultrathin sections are heated in 20 mM Tris-HCl buffer (pH 9.0) for 1 h at 95°C. After immunogold labeling, the sections are treated with a mixture of tannic acid and glutaraldehyde, with OsO 4 solution, and then double-stained with uranyl acetate and lead citrate. The standardized method yields strong and reproducible immunoreactions for many antigens showing excellent image contrast without destruction of fine structures. © Springer Science+Business Media, LLC 2010.

Tsay R.S.,University of Chicago | Ando T.,Keio University
Computational Statistics and Data Analysis | Year: 2012

The effects of recent subprime financial crisis on the US stock market are analyzed. To investigate this problem, a Bayesian panel data analysis to identify common factors that explain the movement of stock returns when the dimension is high is developed. For high-dimensional panel data, it is known that previously proposed approaches cannot estimate accurately the variance-covariance matrix. An advantage of the proposed method is that it considers parameter uncertainty in variance-covariance estimation and factor selection. Two new criteria for determining the number of factors in the data are developed and the consistency of the selection criteria as both the number of observations and the cross-section dimension tend to infinity is established. An empirical analysis indicates that the US stock market was subject to 8 common factors before the outbreak of the subprime crisis, but the number of factors reduced substantially after the outbreak. In particular, a small number of common factors govern the fluctuations of the stock market after the collapse of Lehman Brothers. In other words, empirical evidence that the structure of US stock market has changed drastically after the subprime crisis is obtained. It is also shown that the factor models selected by the proposed criteria work well in out-of-sample forecasting of asset returns. © 2010 Elsevier B.V. All rights reserved.

Kourist R.,Ruhr University Bochum | Guterl J.-K.,TU Munich | Miyamoto K.,Keio University | Sieber V.,TU Munich
ChemCatChem | Year: 2014

Decarboxylases are very useful tools for the defunctionalization of organic molecules under very mild reaction conditions. They have been applied for the synthesis of alcohols, carboxylic acids, diamines, terminal olefins, and other important chemicals. Moreover, several decarboxylases catalyze the fixation of carbon dioxide, which makes them promising catalysts for the utilization of this resource. Interestingly, several decarboxylases show promiscuous activities such as enzymatic racemization and stereoselective hydration. Despite this very high synthetic potential, large-scale processes are still rare and are mostly limited to fermentative approaches or to small-volume products. This Minireview gives an overview of the several recent, very promising applications both for the synthesis of high-value fine chemicals and biogenic bulk products and summarizes chances and limitations of this emerging class of biocatalysts. Defunct(ionalizing) organics: Enzymatic decarboxylation is an emerging tool for the defunctionalization of organic molecules. Recent applications span from the synthesis of high-value fine chemicals to the preparation of bio-based commodities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hori S.,Keio University
Keio Journal of Medicine | Year: 2010

There have been few reports published in English on emergency medicine (EM) in Japan; the main reason for this is that the concept of EM was different in Japan from that in western countries. In the 1960s, legislation was passed in Japan that implemented emergency medical services, and emergency hospitals were designated by the government. There were no emergency medicine specialists, and so surgeons/physicians without specialist training in emergency medicine provided care to emergency patients (the multispecialist-type model). The Japanese Association for Acute Medicine (JAAM), an academic society for emergency physicians, was founded in 1973. In its pioneering days, this association focused mostly on trauma/burn care and also influenced policymaking. In 1977, the government built emergency medical service centers (the ICU-type model) and reorganized all emergency medical facilities into three levels. With the aging of society, the number of non-trauma patients presenting at hospitals, especially in the elderly population, has increased and has resulted in some cases of refusal by hospitals to accept emergency patients. A new postgraduate medical education curriculum was legislated in 2004 that mandated EM training for all postgraduates and encouraged reinforcement of emergency departments in teaching hospitals. The JAAM established a committee to promote the ER-type model of EM in 2003. By 2007, more than 150 JAAM-affiliated hospitals had implemented this type of EM. In conclusion, emergency medicine in Japan is currently based on a mixture of three models: the multispecialist-type, the ICU-type and the ER-type models.

Marumoto T.,Medical Institute of Bioregulation | Saya H.,Keio University
Advances in Experimental Medicine and Biology | Year: 2012

Glioblastoma (GBM) is the most aggressive form of glioma. Despite ceaseless efforts by researchers and physicians to find new therapeutic strategies, there have been no significant advances in the treatment of GBMs for several decades and most patients with GBM die within one and half years of diagnosis. Undoubtedly, one reason for this is the insufficient understanding of the initiation and progression of GBMs at the molecular level. However, recent information regarding the genetic and epigenetic alterations and the microRNAs that are aberrantly activated or inactivated in GBMs has helped elucidate the formation of GBM in more detail. Here, we describe recent advances in the understanding of the biology of GBMs. © 2012 Landes Bioscience and Springer Science+Business Media.

Yoshimura A.,Keio University
Current topics in microbiology and immunology | Year: 2011

Transforming growth factor-β (TGF-β) has been shown to play an essential role in establishing immunological tolerance, yet recent studies have revealed the pro-inflammatory roles of TGF-β in inflammatory responses. TGF-β induces Foxp3-positive regulatory T cells (iTregs), while in the presence of IL-6, it induces pathogenic IL-17 producing Th17 cells. TGF-β inhibits the proliferation of T cells as well as cytokine production via Foxp3-dependent and independent mechanisms. On the one hand, little is known about molecular mechanisms involved in immune suppression via TGF-β; however, recent studies suggest that Smad2 as well as Smad3 play essential roles in Foxp3 induction and cytokine suppression, whereas Th17 differentiation is promoted via the Smad-independent pathway. Mutual suppression of signaling between TGF-β and inflammatory cytokines has been shown to be necessary for the balance of immunity and tolerance.

Creutzig T.,University of North Carolina at Chapel Hill | Hikida Y.,Keio University
Nuclear Physics B | Year: 2011

The boundary OSP(1|2) WZNW model possesses two types of branes, which are localized on supersymmetric Euclidean AdS 2 and on two-dimensional superspheres. We compute the coupling of closed strings to these branes with two different methods. The first one uses factorization constraints and the other one a correspondence to boundary N=1 super-Liouville field theory, which we proof with path integral techniques. We check that the results obey the Cardy condition and reproduce the semi-classical computations. For the check we also compute the spectral density of open strings that are attached to the non-compact branes. © 2010 Elsevier B.V.

Ohyama M.,Keio University
Journal of Dermatology | Year: 2012

Primary cicatricial alopecias (PCA) are a rare group of disorders, in which the hair follicle is the main target of destructive inflammation resulting in irreversible hair loss with scarring of affected lesions. The most typical clinical manifestation of PCA is the loss of visible follicular ostia. The histopathological hallmark of a fully developed lesion is the replacement of the hair follicle structure by fibrous tissue. PCA could share similar clinical manifestations and eventually lead to "burn-out" alopecia. Some subsets are hardly distinguishable histopathologically and the mechanisms that elicit such a destructive reaction have not been fully elucidated. Thus, the management of PCA represents one of the most challenging clinical problems for dermatologists. The aim of this review is to provide a concise and comprehensive summary of recent advances in PCA management, especially focusing on novel methodologies to aid diagnosis, and updates on our understanding of the etiopathogenesis. Dermoscopy, a new pathological preparation technique and direct immunofluorescence analysis enable more accurate clinicopathological diagnosis of PCA. Microarray analysis may be beneficial to distinguish PCA subtypes. Currently suggested mechanisms underlying PCA include loss of immune protection of stem cells, impaired stem cell self-maintenance, enhanced autoimmunity by pro-inflammatory cytokines and environmental/genetic predispositions. Interestingly, recent data indicates the association between lipid metabolism dysregulation and PCA development, implying an important role of the sebaceous gland dysfunction in the etiopathogenesis. Based on that hypothesis and observations, novel therapeutic approaches have been proposed, including the use of peroxisome proliferator-activated receptor-γ agonist for lichen planopilaris. © 2011 Japanese Dermatological Association.

Licatalosi D.D.,Rockefeller University | Licatalosi D.D.,Case Western Reserve University | Yano M.,Rockefeller University | Yano M.,Keio University | And 6 more authors.
Genes and Development | Year: 2012

Two polypyrimidine tract RNA-binding proteins (PTBs), one near-ubiquitously expressed (Ptbp1) and another highly tissue-restricted (Ptbp2), regulate RNA in interrelated but incompletely understood ways. Ptbp1, a splicing regulator, is replaced in the brain and differentiated neuronal cell lines by Ptbp2. To define the roles of Ptbp2 in the nervous system, we generated two independent Ptbp2-null strains, unexpectedly revealing that Ptbp2 is expressed in neuronal progenitors and is essential for postnatal survival. A HITS-CLIP (high-throughput sequencing crosslinking immunoprecipitation)-generated map of reproducible Ptbp2-RNA interactions in the developing mouse neocortex, combined with results from splicing-sensitive microarrays, demonstrated that the major action of Ptbp2 is to inhibit adult-specific alternative exons by binding pyrimidine-rich sequences upstream of and/or within them. These regulated exons are present in mRNAs encoding proteins associated with control of cell fate, proliferation, and the actin cytoskeleton, suggesting a role for Ptbp2 in neurogenesis. Indeed, neuronal progenitors in the Ptbp2-null brain exhibited an aberrant polarity and were associated with regions of premature neurogenesis and reduced progenitor pools. Thus, Ptbp2 inhibition of a discrete set of adult neuronal exons underlies early brain development prior to neuronal differentiation and is essential for postnatal survival. © 2012 by Cold Spring Harbor Laboratory Press.

Takahashi K.Z.,Keio University
Journal of Computational Chemistry | Year: 2014

In our previous study (Takahashi et al., J. Chem. Theory Comput. 2012, 8, 4503), we developed the linear-combination-based isotropic periodic sum (LIPS) method. The LIPS method is based on the extended isotropic periodic sum theory that produces a ubiquitous interaction potential function to estimate homogeneous and heterogeneous systems. The LIPS theory also provides the procedure to design a periodic reaction field. To demonstrate this, in the present work, a novel reaction field of the LIPS method was developed. The novel reaction field was labeled LIPS-SW, because it provides an interaction potential function with a shape that resembles that of the switch function method. To evaluate the ability of the LIPS-SW method to describe in homogeneous and heterogeneous systems, we carried out molecular dynamics (MD) simulations of bulk water and water-vapor interfacial systems using the LIPS-SW method. The results of these simulations show that the LIPS-SW method gives higher accuracy than the conventional interaction potential function of the LIPS method. The accuracy of simulating water-vapor interfacial systems was greatly improved, while that of bulk water systems was maintained using the LIPS-SW method. We conclude that the LIPS-SW method shows great potential for high-accuracy, high-performance computing to allow large scale MD simulations. © 2014 Wiley Periodicals, Inc. A linear-combination-based isotropic periodic sum (LIPS) method provides a procedure for the design of a periodic reaction field. To demonstrate this, a novel reaction field of the LIPS method, LIPS-SW, is developed. The LIPS-SW successfully estimates water-vapor interfacial systems by using much shorter cutoff radii than that of the conventional IPS techniques, while maintaining accuracy for bulk water systems. This novel reaction field method is expected to be a useful technique for high-accuracy and high-performance computing for large-scale molecular dynamics simulations. © 2014 Wiley Periodicals, Inc.

Fujitani Y.,Keio University
Journal of the Physical Society of Japan | Year: 2013

We consider a circular liquid domain in a flat fluid membrane surrounded by three-dimensional fluids, and assume that the membrane outside the domain is a two-dimensional near-critical binary fluid mixture. The membrane viscosity outside the domain is assumed to be uniform, irrespective of the local composition, and to be the same as that of the domain. Using the Gaussian free-energy functional, we show that the drag coefficient of the domain can be decreased by the preferential attraction between the domain and a component of the mixture, unlike that of a rigid sphere in a three-dimensional near-critical binary fluid mixture studied recently. © 2013 The Physical Society of Japan.

Yamamoto D.,RIKEN | Marmorini G.,RIKEN | Marmorini G.,Keio University | Danshita I.,RIKEN | Danshita I.,Kyoto University
Physical Review Letters | Year: 2014

The triangular lattice of S=1/2 spins with XXZ anisotropy is a ubiquitous model for various frustrated systems in different contexts. We determine the quantum phase diagram of the model in the plane of the anisotropy parameter and the magnetic field by means of a large-size cluster mean-field method with a scaling scheme. We find that quantum fluctuations break up the nontrivial continuous degeneracy into two first-order phase transitions. In between the two transition boundaries, the degeneracy-lifting results in the emergence of a new coplanar phase not predicted in the classical counterpart of the model. We suggest that the quantum phase transition to the nonclassical coplanar state can be observed in triangular-lattice antiferromagnets with large easy-plane anisotropy or in the corresponding optical-lattice systems. © 2014 American Physical Society.

Fukushima K.,Keio University | Kamikado K.,Kyoto University | Klein B.,TU Munich
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

We investigate phase transitions in scalar field theories using the functional renormalization group (RG) equation. We analyze a system with U(2)×U(2) symmetry, in which there is a parameter λ2 that controls the strength of the first-order phase transition driven by fluctuations. In the limit of λ2→0, the U(2)×U(2) theory is reduced to an O(8) scalar theory that exhibits a second-order phase transition in three dimensions. We develop a new insight for the understanding of the fluctuation-induced first-order phase transition as a smooth continuation from the standard RG flow in the O(8) system. In our view from the RG flow diagram on coupling parameter space, the region that favors the first-order transition emerges from the unphysical region to the physical one as λ2 increases from zero. We give this interpretation based on the Taylor expansion of the functional RG equations up to the fourth order in terms of the field, which encompasses the ε-expansion results. We compare results from the expansion and from the full numerical calculation and find that the fourth-order expansion is only of qualitative use and that the sixth-order expansion improves the quantitative agreement. © 2011 American Physical Society.

Saito K.,Keio University | Kato T.,University of Tokyo
Physical Review Letters | Year: 2013

We study the Kondo effect in heat transport via a local two-state system. This system is described by the spin-boson Hamiltonian with Ohmic dissipation, which can be mapped onto the Kondo model with anisotropic exchange coupling. We calculate thermal conductance by the Monte Carlo method based on the exact formula. Thermal conductance has a scaling form κ=(kB2T K/â.,?)f(α,T/TK), where TK and α indicate the Kondo temperature and dimensionless coupling strength, respectively. Temperature dependence of conductance is classified by the Kondo temperature as κâ̂?(T/TK)3 for T≠TK and κâ̂?(kBT/â.,? ωc)2α-1 for Tâ‰TK. Similarities to the Kondo signature in electric transport are discussed. © 2013 American Physical Society.

Fujitani Y.,Keio University
Journal of the Physical Society of Japan | Year: 2013

It is thought that, in a biomembrane, some minor lipid constituents are concentrated in a domain called the lipid raft. Some raftlike domains in a lipid-bilayer membrane can be regarded as two-dimensional droplets. The membrane viscosities inside and outside the domain are generally different. The present author previously studied the drag coefficient of a circular liquid domain in a flat fluid membrane surrounded by three-dimensional fluids, which occupy the semi-infinite spaces on both sides of the membrane. Here we generalize this problem by assuming that the surrounding fluids are confined by container walls parallel to the membrane. Errors in the present author's previous studies are also corrected in this paper. © 2013 The Physical Society of Japan.

Akimoto T.,Keio University | Miyaguchi T.,Osaka City University
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2010

Statistical properties of the transport coefficient for deterministic subdiffusion are investigated from the viewpoint of infinite ergodic theory. We find that the averaged diffusion coefficient is characterized by the infinite invariant measure of the reduced map. We also show that when the time difference is much smaller than the total observation time, the time-averaged mean square displacement depends linearly on the time difference. Furthermore, the diffusion coefficient becomes a random variable and its limit distribution is characterized by the universal law called the Mittag-Leffler distribution. © 2010 The American Physical Society.

Cipriani M.,University of Pisa | Cipriani M.,National Institute of Nuclear Physics, Italy | Nitta M.,Keio University
Physical Review Letters | Year: 2013

We study the effects of the internal coherent (Rabi) coupling in vortex lattices in two-component BECs under rotation. We find how the vortex lattices without the Rabi coupling known before are connected to the Abrikosov lattice of integer vortices with increasing the Rabi coupling. We find that (1) for small Rabi couplings, fractional vortices in a triangular or square lattice for small or large intercomponent coupling constitute hexamers or tetramers, namely multidimer bound states made of six or four vortices, respectively, (2) these bound states are broken into a set of dimers at intermediate Rabi couplings, and (3) vortices change their partners in various ways depending on the intercomponent coupling, to organize themselves for constituting the Abrikosov lattice of integer vortices at strong Rabi couplings. © 2013 American Physical Society.

Yamamoto N.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2016

We argue that the effective theory for electromagnetic fields in spatially varying meson condensations in dense nuclear and quark matter is given by the axion electrodynamics. We show that one of the helicity states of photons there has the nonrelativistic gapless dispersion relation ω∼k2 at small momentum, while the other is gapped. This "nonrelativistic photon" may also be realized at the interface between topological and trivial insulators in condensed matter systems. © 2016 American Physical Society.

Yamamoto N.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2016

We study the turbulent regime of chiral (magneto)hydrodynamics for charged and neutral matter with chirality imbalance. We find that the chiral magnetohydrodynamics for charged plasmas possesses a unique scaling symmetry, only without fluid helicity under the local charge neutrality. We also find a different type of unique scaling symmetry in the chiral hydrodynamics for neutral matter with fluid helicity in the inertial range. We show that these symmetries dictate the self-similar inverse cascade of the magnetic and kinetic energies. Our results imply the possible inverse energy cascade in core-collapse supernovae due to the chiral transport of neutrinos. © 2016 American Physical Society.

Haryu E.,University of Tokyo | Imai M.,Keio University | Okada H.,Tamagawa University
Child Development | Year: 2011

Young children often fail to generalize a novel verb based on sameness of action since they have difficulty focusing on the relational similarity across events while at the same time ignoring the objects that are involved. Study 1, with Japanese-speaking 3- and 4-year-olds (N=28 in each group), found that similarity of objects involved in action events plays a scaffolding role in children's extraction of relational similarity across events when they extend a verb. Study 2, with 4-year-olds (N=47), further showed that repeated experience of action-based verb extension supported by object similarity leads children to be better able to extend a novel verb based on sameness of action, even without support from object similarity. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc..

Inoue H.,Keio University
Yakugaku Zasshi | Year: 2014

In respect to policy and involvement in social cognition of Advanced Science and Technology, people desire to recognize the scientific understanding and social understanding hierarchically and simultaneously. However, the understandings of some sciences and technologies are dependent on the amount of information given and how easy it is to understand it. Nuclear power and radiation are a typical example of such sciences and technologies because their advantages and disadvantages are clear. On the other hand, the Fukushima Nuclear Plant Accident that occurred in March 2011 caused the myth about the safety and security of nuclear power to collapse. Concerns about nuclear power and radiation increased abruptly after the accident. Also the scientific understanding of 'nuclear power' and radiation increased. The content and level of radiation education was highly significant than before the accident. However, it is essential to propose a more detailed explanation for people that are concerned about radioactive contamination of food and also for people living in areas that still have relatively high dose of radioactive material. Although some technical problems such as the influences on the human body by low-dose exposure remain unresolved, not only specialists on nuclear power and radiation, but also the persons that have studied the radiation are desired to explain radiation for familiar people. As a result, in Japan, the learning of individuals spread to society because the Japanese are highly interested in nuclear power and radiation and the understanding of historical background. © 2014 The Pharmaceutical Society of Japan.

Sakai T.,Tokyo Metroplitan University | Somiya S.,Keio University
Mechanics of Time-Dependent Materials | Year: 2011

Plastics and fiber-reinforced plastics (FRP) are used in the aerospace industry because of their mechanical properties. However, despite their excellent high-temperature mechanical properties, plastics and FRP eventually deform visco-elastically at high temperatures. Most of the research has focused on the creep behavior of FRPs, but few studies have investigated the linear visco-elastic behavior. Linear visco-elastic behavior and nonlinear visco-elastic behavior occur with physical aging in these plastics. In this study, the non-linear visco-elastic behavior of plastics and FRP was investigated based on the bending creep deformation of polycarbonate (PC) and polyoxymethylene (POM). Moreover, the effects of the fiber volume fraction on the creep characteristics were investigated using glass fiber-reinforced polycarbonate (GFRPC). The creep deformation was calculated using the linear visco-elastic theory based on these effects, and comparison between experimental and estimated data showed that the creep analysis sufficiently predicted the creep behavior. © 2011 Springer Science+Business Media, B. V.

Yamamoto N.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2016

Chirality of neutrinos modifies the conventional kinetic theory and hydrodynamics, leading to unusual chiral transport related to quantum anomalies in field theory. We argue that these corrections have new phenomenological consequences for hot and dense neutrino gases, especially in core-collapse supernovae. We find that the neutrino density can be converted to the fluid helicity through the chiral vortical effect. This fluid helicity effectively acts as a chiral chemical potential for electrons via the momentum exchange with neutrinos and induces a "helical plasma instability" that generates a strong helical magnetic field. This provides a new mechanism for converting the gravitational energy released by the core collapse to the electromagnetic energy and potentially explains the origin of magnetars. The other possible applications of the neutrino chiral transport theory are also discussed. © 2016 American Physical Society.

Itaya M.,Mitsubishi Group | Itaya M.,Keio University | Kaneko S.,Mitsubishi Group | Kaneko S.,Tokyo Institute of Technology
Nucleic Acids Research | Year: 2010

The stable cloning of giant DNA is a necessary process in the production of recombinant/synthetic genomes. Handling DNA molecules in test tubes becomes increasingly difficult as their size increases, particularly above 100 kb. The need to prepare such large DNA molecules in a regular manner has limited giant DNA cloning to certain laboratories. Recently, we found stable plasmid DNA of up to 100 kb in Escherichia coli culture medium during the infection and propagation of lambda phage. The extracellular plasmid DNA (excpDNA) released from lysed E. coli was demonstrably stable enough to be taken up by competent Bacillus subtilis also present in the medium. ExcpDNA transfer, induced by simply mixing E. coli lysate with recipient B. subtilis, required no biochemical purification of the DNA. Here, this simple protocol was used to integrate excpDNA into a B. subtilis genome, designated the 'BGM vector'. A slightly modified protocol for DNA cloning in BGM is presented for DNA fragments >100 kb. This technique should facilitate giant DNA cloning in the BGM vector and allow its application to other hosts that can undergo natural transformation. © The Author(s) 2010. Published by Oxford University Press.

Kobayashi M.,University of Tokyo | Nitta M.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We construct a stable domain wall ring with lump beads on it in a baby Skyrme model with a potential consisting of two terms linear and quadratic in fields. © 2013 American Physical Society.

Nitta M.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

It is known that monopoles can be confined by vortex strings in d=3+1 while vortices can be confined by domain lines in d=2+1. Here, as a higher dimensional generalization of these, we show that Yang-Mills instantons can be confined by monopole strings in d=4+1. We achieve this by putting the system into the Higgs phase in which the configuration can be constructed inside a non-Abelian vortex sheet. © 2013 American Physical Society.

Fukushima K.,Keio University | Hidaka Y.,RIKEN
Physical Review Letters | Year: 2013

We discuss the fate of chiral symmetry in an extremely strong magnetic field B. We investigate not only quark fluctuations but also neutral meson effects. The former enhances the chiral-symmetry breaking at finite B according to the magnetic catalysis, while the latter suppresses the chiral condensate once B exceeds the scale of the hadron structure. Using a chiral model, we demonstrate how neutral mesons are subject to the dimensional reduction and the low dimensionality favors the chiral-symmetric phase. We point out that this effect, the magnetic inhibition, can be a feasible explanation for recent lattice-QCD data indicating the decreasing behavior of the chiral-restoration temperature with increasing B. © 2013 American Physical Society.

Fujitani Y.,Keio University
Journal of the Physical Society of Japan | Year: 2013

To the Gaussian model of a two-component fluid membrane with a spherical shape, we apply the mode coupling theory to study the hydrodynamic effect on the relaxation coefficient of concentration fluctuation in the homogeneous phase close to the critical point. In particular, when the viscosities of the three-dimensional fluids are the same inside and outside the vesicle, we obtain a concise analytical expression representing the hydrodynamic effect on the smallest wave-number mode. We derive its approximate expressions in various parameter regions to discuss the size effect of the vesicle. Much larger wave-number modes are studied numerically by means of our theoretical result. It is suggested that the hydrodynamic effect be diffusion-like, irrespective of the vesicle size, as long as the wavelength is much longer than the correlation length. © 2013 The Physical Society of Japan.

Park J.,KAIST | Lee G.,KAIST | Sung Y.,KAIST | Yukawa M.,Keio University
IEEE Transactions on Signal Processing | Year: 2013

In this paper, coordinated beamforming based on relaxed zero forcing (RZF) for K transmitter-receiver pair multiple-input single-output (MISO) and multiple-input multiple-output (MIMO) interference channels is considered. In the RZF coordinated beamforming, conventional zero-forcing interference leakage constraints are relaxed so that some predetermined interference leakage to undesired receivers is allowed in order to increase the beam design space for larger rates than those of the zero-forcing (ZF) scheme or to make beam design feasible when ZF is impossible. In the MISO case, it is shown that the rate-maximizing beam vector under the RZF framework for a given set of interference leakage levels can be obtained by sequential orthogonal projection combining (SOPC). Based on this, exact and approximate closed-form solutions are provided in two-user and three-user cases, respectively, and an efficient beam design algorithm for RZF coordinated beamforming is provided in general cases. Furthermore, the rate control problem under the RZF framework is considered. A centralized approach and a distributed heuristic approach are proposed to control the position of the designed rate-tuple in the achievable rate region. Finally, the RZF framework is extended to MIMO interference channels by deriving a new lower bound on the rate of each user. © 1991-2012 IEEE.

To meet the increasing demand for liver tissue engineering, various three-dimensional (3D) liver cell culture techniques have been developed. Nevertheless, conventional liver cell culture techniques involving the suspending cells in extracellular matrix (ECM) components and the seeding of cells into 3D biodegradable scaffolds have an intrinsic shortcoming, low cell-scaffold ratios. We have developed a microporous membrane-based liver cell culture technique. Cell behaviors and tissue organization can be controlled by membrane geometry, and cell-dense thick tissues can be reconstructed by layering cells cultured on biodegradable microporous membranes. Applications extend from liver parenchymal cell monoculture to multi-cell type cultures for the reconstruction of 3D functional liver tissue. This review focuses on the expanding role for microporous membranes in liver tissue engineering, primarily from our research.

Maruyama T.,Keio University
Journal of Obstetrics and Gynaecology Research | Year: 2014

Human endometrium regenerates and regresses with each menstrual cycle under hormonal control throughout a woman's reproductive life. The cyclical regeneration and remodeling potentials allude to the existence of stem/progenitor cells in the endometrium. There is increasing evidence that human endometrium contains small numbers of stem-like cells capable of self-renewal, multiple differentiation and tissue reconstitution. Although the precise identity of endometrial stem/progenitor cells remains elusive, these cells are thought to play pivotal role(s) in the physiological remodeling and regeneration of the human endometrium and also in the pathogenesis of endometrium-associated diseases, such as endometriosis. © 2014 The Author.

Suzuki H.,Keio University | Moayyedi P.,McMaster University
Nature Reviews Gastroenterology and Hepatology | Year: 2013

Functional dyspepsia is the most common reason for patients to experience chronic epigastric pain or discomfort. The causes of functional dyspepsia are multifactorial but Helicobacter pylori infection is one likely candidate. Infection with this bacterial pathogen clearly results in chronic mucosal inflammation in the stomach and duodenum, which, in turn, might lead to abnormalities in gastroduodenal motility and sensitivity. Chronic gastritis might also affect a variety of endocrine functions of the stomach including the production of the gastrointestinal hormones and neurotransmitters somatostatin, gastrin and ghrelin. Although these abnormalities might generate symptoms in some patients with functional dyspepsia, the clinical evidence needs to be critically evaluated before this hypothesis can be confirmed. A Cochrane review reported that eradication of H. pylori in these patients had a small but statistically significant long-term effect on symptom relief when compared with placebo, lasting at least 12 months after 1 week of eradication therapy. The efficacy of eradication therapy was seen in all symptom subtypes of functional dyspepsia, but was more marked in Asian than Western patients. This evidence has led to alterations in most of the major guidelines throughout the world, which now recommend H. pylori eradication in patients with functional dyspepsia if they test positive for this bacterium. © 2013 Macmillan Publishers Limited. All rights reserved.

Miura T.,Keio University | Miura T.,Niigata University
Journal of Physical Chemistry B | Year: 2013

Spin selectivity in long-lived charge separation at the micellar interface is studied using the magnetic field effect (MFE). An amphiphilic viologen is complexed with a nonionic surfactant to form a supramolecular acceptor cage, of which the size is controlled by the acceptor concentration, as confirmed by dynamic light scattering measurement. Photoinduced electron transfer (ET) from a guest polyaromatic molecule to the viologen moiety is observed spin-dependently with time-resolved fluorescence (trFL) and transient absorption (TA). A negative MFE on the radical yield is successfully observed, which indicates generation of singlet-born long-lived radical pair that is realized by supramolecular control of the donor-acceptor (D-A) distances. The dominance of the singlet-precursor MFE is sensitive to the acceptor concentration, which presumably affects the D-A distance as well as the cage size. However, theoretical analysis of the MFE gives large recombination rates of ca. 10 8 s-1, which indicate the contribution of spin-allowed recombination of the pseudocontact radical pair generated by still active in-cage diffusion. Dependence of the viologen concentration and alkyl chain length on the recombination and escape dynamics is discussed in terms of precursor spin states and the microenvironments in the cage. © 2013 American Chemical Society.

Misumi T.,Keio University | Kanazawa T.,RIKEN
Journal of High Energy Physics | Year: 2014

We investigate QCD with adjoint Dirac fermions on ℝ3 × S1 with generic boundary conditions for fermions along S 1. By means of perturbation theory, semiclassical methods and a chiral effective model, we elucidate a rich phase structure in the space spanned by the S1 compactification scale L, twisted fermionic boundary condition φ and the fermion mass m. We found various phases with or without chiral and center symmetry breaking, separated by first- and second-order phase transitions, which in specific limits (φ = 0, φ = π, L → 0 and m → ∞) reproduce known results in the literature. In the center- symmetric phase at small L, we show that Ünsal's bion-induced confinement mechanism is at work but is substantially weakened at φ ≠ 0 by a linear potential between monopoles. Through an analytic and numerical study of the PNJL model, we show that the order parameters for center and chiral symmetries (i.e., Polyakov loop and chiral condensate) are strongly intertwined at φ ≠ 0. Due to this correlation, a deconfined phase can intervene between a weak-coupling center-symmetric phase at small L and a strong-coupling one at large L. Whether this happens or not depends on the ratio of the dynamical fermion mass to the energy scale of the Yang-Mills theory. Implication of this possibility for resurgence in gauge theories is briefly discussed. In an appendix, we study the index of the adjoint Dirac operator on ℝ3 × S1 with twisted boundary conditions, which is important for semiclassical analysis of monopoles. © 2014 The Author(s).

Aramaki K.,Keio University
Zairyo to Kankyo/ Corrosion Engineering | Year: 2013

In order to estimate the effects of anions on passive film breakdown, the values of the time required for breakdown, tbd were determined for a passivated iron electrode in aqueous solutions of 0.1 M various anions. Relationships between log tbd and the hardness of anion base, H were discussed on the basis of the hard and soft acids and bases principle. According to the principle, anions were classified into four groups, hard base, oxidative hard base, soft and hard base, and soft base. For the former three groups, log tbd increased with H but in reverse, decreased with an increase in H for the latter. The former relationships could be interpreted by suppression of anion incorporation into the film due to stable hard acid-hard base interaction. However, the relationship could not be explained by this interaction for the group of soft base anions.

Ando K.,Tohoku University | Ando K.,Keio University | Watanabe S.,University of Cambridge | Mooser S.,University of Cambridge | And 4 more authors.
Nature Materials | Year: 2013

Conjugated polymers and small organic molecules are enabling new, flexible, large-area, low-cost optoelectronic devices, such as organic light-emitting diodes, transistors and solar cells. Owing to their exceptionally long spin lifetimes, these carbon-based materials could also have an important impact on spintronics, where carrier spins play a key role in transmitting, processing and storing information. However, to exploit this potential, a method for direct conversion of spin information into an electric signal is indispensable. Here we show that a pure spin current can be produced in a solution-processed conducting polymer by pumping spins through a ferromagnetic resonance in an adjacent magnetic insulator, and that this generates an electric voltage across the polymer film. We demonstrate that the experimental characteristics of the generated voltage are consistent with it being generated through an inverse spin Hall effect in the conducting polymer. In contrast with inorganic materials, the conducting polymer exhibits coexistence of high spin-current to charge-current conversion efficiency and long spin lifetimes. Our discovery opens a route for a new generation of molecular-structure-engineered spintronic devices, which could lead to important advances in plastic spintronics. © 2013 Macmillan Publishers Limited. All rights reserved.

Lim O.T.,University of Ulsan | Iida N.,Keio University
Experimental Thermal and Fluid Science | Year: 2012

The HCCI combustion mode poses its own set of narrow engine operating by knocking. In order to solve this, inhomogeneity method of mixture and temperature is suggested. The purpose of this research is to get fundamental knowledge about the effect of thermal stratification on HCCI combustion of DME/. n-Butane-air mixture. The temperature stratification is made by buoyancy effect in combustion chamber of RCM. The analysis items are pressure, temperature of in-cylinder gas and combustion duration. In addition, the structure of flames using the two dimensional chemiluminescence's images by a framing camera are analyzed. Under stratification, the LTR starting time and the HTR starting time are advanced than that of homogeneous. Further, the LTR period of homogeneous conditions became shorter than that of the stratified conditions. With the case of homogeneous condition, the luminosity duration becomes shorter than the case of stratified condition. Additionally, under stratified condition, the brightest luminosity intensity is delayed longer than at homogeneous condition. © 2012.

Kishimoto N.,Nagoya City University | Kishimoto N.,Keio University | Shimizu K.,Nagoya City University | Sawamoto K.,Nagoya City University
DMM Disease Models and Mechanisms | Year: 2012

Neural stem cells in the subventricular zone (SVZ) of the adult mammalian forebrain are a potential source of neurons for neural tissue repair after brain insults such as ischemic stroke and traumatic brain injury (TBI). Recent studies show that neurogenesis in the ventricular zone (VZ) of the adult zebrafish telencephalon has features in common with neurogenesis in the adult mammalian SVZ. Here, we established a zebrafish model to study injury-induced neurogenesis in the adult brain. We show that the adult zebrafish brain possesses a remarkable capacity for neuronal regeneration. Telencephalon injury prompted the proliferation of neuronal precursor cells (NPCs) in the VZ of the injured hemisphere, compared with in the contralateral hemisphere. The distribution of NPCs, viewed by BrdU labeling and ngn1-promoter-driven GFP, suggested that they migrated laterally and reached the injury site via the subpallium and pallium. The number of NPCs reaching the injury site significantly decreased when the fish were treated with an inhibitor of &γαμμα;-secretase, a component of the Notch signaling pathway, suggesting that injury-induced neurogenesis mechanisms are at least partly conserved between fish and mammals. The injury-induced NPCs differentiated into mature neurons in the regions surrounding the injury site within a week after the injury. Most of these cells expressed T-box brain protein (Tbr1), suggesting they had adopted the normal neuronal fate in this region. These results suggest that the telencephalic VZ contributes to neural tissue recovery following telencephalic injury in the adult zebrafish, and that the adult zebrafish is a useful model for regenerative medicine. © 2012. Published by The Company of Biologists Ltd.

Prediction of biochemical (metabolic) pathways has a wide range of applications, including the optimization of drug candidates, and the elucidation of toxicity mechanisms. Recently, several methods have been developed for pathway prediction to derive a goal compound from a start compound. However, these methods require high computational costs, and cannot perform comprehensive prediction of novel metabolic pathways. Our aim of this study is to develop a de novo prediction method for reconstructions of metabolic pathways and predictions of unknown biosynthetic pathways in the sense that it does not require any initial network such as KEGG metabolic network to be explored. We formulated pathway prediction between a start compound and a goal compound as the shortest path search problem in terms of the number of enzyme reactions applied. We propose an efficient search method based on A* algorithm and heuristic techniques utilizing Linear Programming (LP) solution for estimation of the distance to the goal. First, a chemical compound is represented by a feature vector which counts frequencies of substructure occurrences in the structural formula. Second, an enzyme reaction is represented as an operator vector by detecting the structural changes to compounds before and after the reaction. By defining compound vectors as nodes and operator vectors as edges, prediction of the reaction pathway is reduced to the shortest path search problem in the vector space. In experiments on the DDT degradation pathway, we verify that the shortest paths predicted by our method are biologically correct pathways registered in the KEGG database. The results also demonstrate that the LP heuristics can achieve significant reduction in computation time. Furthermore, we apply our method to a secondary metabolite pathway of plant origin, and successfully find a novel biochemical pathway which cannot be predicted by the existing method. For the reconstruction of a known biochemical pathway, our method is over 40 times as fast as the existing method. Our method enables fast and accurate de novo pathway predictions and novel pathway detection.

Mitsutake A.,Keio University
Methods in molecular biology (Clifton, N.J.) | Year: 2013

In biomolecular systems (especially all-atom models) with many degrees of freedom such as proteins and nucleic acids, there exist an astronomically large number of local-minimum-energy states. Conventional simulations in the canonical ensemble are of little use, because they tend to get trapped in states of these energy local minima. Enhanced conformational sampling techniques are thus in great demand. A simulation in generalized ensemble performs a random walk in potential energy space and can overcome this difficulty. From only one simulation run, one can obtain canonical-ensemble averages of physical quantities as functions of temperature by the single-histogram and/or multiple-histogram reweighting techniques. In this article we review uses of the generalized-ensemble algorithms in biomolecular systems. Three well-known methods, namely, multicanonical algorithm, simulated tempering, and replica-exchange method, are described first. Both Monte Carlo and molecular dynamics versions of the algorithms are given. We then present various extensions of these three generalized-ensemble algorithms. The effectiveness of the methods is tested with short peptide and protein systems.

Hachisu I.,University of Tokyo | Kato M.,Keio University
Astrophysical Journal | Year: 2015

We analyzed light curves of seven relatively slower novae, PW Vul, V705 Cas, GQ Mus, RR Pic, V5558 Sgr, HR Del, and V723 Cas, based on an optically thick wind theory of nova outbursts. For fast novae, free-free emission dominates the spectrum in optical bands rather than photospheric emission, and nova optical light curves follow the universal decline law. Faster novae blow stronger winds with larger mass-loss rates. Because the brightness of free-free emission depends directly on the wind mass-loss rate, faster novae show brighter optical maxima. In slower novae, however, we must take into account photospheric emission because of their lower wind mass-loss rates. We calculated three model light curves of free-free emission, photospheric emission, and their sum for various white dwarf (WD) masses with various chemical compositions of their envelopes and fitted reasonably with observational data of optical, near-IR (NIR), and UV bands. From light curve fittings of the seven novae, we estimated their absolute magnitudes, distances, and WD masses. In PW Vul and V705 Cas, free-free emission still dominates the spectrum in the optical and NIR bands. In the very slow novae, RR Pic, V5558 Sgr, HR Del, and V723 Cas, photospheric emission dominates the spectrum rather than free-free emission, which makes a deviation from the universal decline law. We have confirmed that the absolute brightnesses of our model light curves are consistent with the distance moduli of four classical novae with known distances (GK Per, V603 Aql, RR Pic, and DQ Her). We also discussed the reason why the very slow novae are about ∼1 mag brighter than the proposed maximum magnitude versus rate of decline relation. © 2015. The American Astronomical Society. All rights reserved..

Yukawa M.,Keio University | Sung Y.,KAIST | Lee G.,KAIST
IEEE Transactions on Signal Processing | Year: 2013

In this paper, a novel adaptive beamforming algorithm is proposed under a linearly and quadratically constrained minimum variance (LQCMV) beamforming framework, based on a dual-domain projection approach that can efficiently implement a quadratic-inequality constraint with a possibly rank-deficient positive semi-definite matrix, and the properties of the proposed algorithm are analyzed. As an application, relaxed zero-forcing (RZF) beamforming is presented which adopts a specific quadratic constraint that bounds the power of residual interference in the beamformer output with the aid of interference-channel side-information available typically in wireless multiple-access systems. The dual-domain projection in this case plays a role in guiding the adaptive algorithm towards a better direction to minimize the interference and noise, leading to considerably faster convergence. The robustness issue against channel mismatch and ill-posedness is also addressed. Numerical examples show that the efficient use of interference side-information brings considerable gains. © 1991-2012 IEEE.

Kanda T.,Keio University
Nihon rinsho. Japanese journal of clinical medicine | Year: 2012

The renin-angiotensin-aldosterone system(RAAS) plays a crucial role in the regulation of physiological homeostasis and diseases such as hypertension, coronary artery disease and chronic renal failure. In this cascade, the ACE/Ang II/AT1 receptor axis induces pathological effects, such as vasoconstriction, cell proliferation and fibrosis. Recently the ACE2/Ang(1-7)/Mas receptor axis has been recognized as a negative regulator of the RAAS. ACE2 metabolizes Ang II into Ang(1-7), which has opposite properties of Ang II through Mas receptor activation. Both animal and human studies provide strong evidence that the ACE2/Ang(1-7)/Mas receptor axis is protective for end-organ damage. Therefore, the ACE2/Ang(1-7)/Mas receptor axis could be a therapeutic target for coronary artery disease and chronic renal failure.

Abe J.,Kanagawa University | Kamimura Y.,Keio University
American Naturalist | Year: 2015

Why females of many species mate multiply is a major question in evolutionary biology. Furthermore, if females accept matings more than once, ejaculates from different males compete for fertilization (sperm competition), which confronts males with the decision of how to allocate their reproductive resources to each mating event. Although most existing models have examined either female mating frequency or male ejaculate allocation while assuming fixed levels of the opposite sex’s strategies, these strategies are likely to coevolve. To investigate how the interaction of the two sexes’ strategies is influenced by the level of sperm limitation in the population, we developed models in which females adjust their number of allowable matings and males allocate their ejaculate in each mating. Our model predicts that females mate only once or less than once at an even sex ratio or in an extremely female-biased condition, because of female resistance and sperm limitation in the population, respectively. However, in a moderately female-biased condition, males favor partitioning their reproductive budgets across many females, whereas females favor multiple matings to obtain sufficient sperm, which contradicts the predictions of most existing models. We discuss our model’s predictions and relationships with the existing models and demonstrate applications for empirical findings. © 2015 by The University of Chicago.

Nitta M.,Keio University | Shifman M.,University of Minnesota | Vinci W.,University of Pisa | Vinci W.,University College London
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Kelvin waves, or Kelvons, have been known for a long time as gapless excitations propagating along superfluid vortices. These modes can be interpreted as the Nambu-Goldstone excitations arising from the spontaneous breaking of the translational symmetry. Recently a different type of gapless excitation localized on strings - the so-called non-Abelian mode - attracted much attention in high-energy physics. We discuss their relevance in condensed matter physics. Non-Abelian rotational quasigapless excitations could appear on the mass vortices in the B phase of the superfluid He3, due to the fact that the order parameter in He3-B is tensorial. While the U(1) rotational excitations are well established in vortices with asymmetric cores, the non-Abelian rotational excitations belonging to the same family were not considered. © 2013 American Physical Society.

Itoyama H.,Osaka City University | Maru N.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We present the mechanism of the dynamical supersymmetry breaking at the metastable vacuum recently uncovered in the N=1 U(N) supersymmetric gauge theory that contains adjoint superfields and that is specified by Kähler and noncanonical gauge kinetic functions and a superpotential whose tree vacua preserve N=1 supersymmetry. The overall U(1) serves as the hidden sector, and no messenger superfield is required. The dynamical supersymmetry breaking is triggered by the nonvanishing D term coupled to the observable sector and is realized by the self-consistent Hartree-Fock approximation of the Nambu-Jona-Lasinio type while it eventually brings us the nonvanishing F term as well. It is shown that theoretical analysis is resolved as a variational problem of the effective potential for three kinds of background fields, namely, the complex scalar, and the two order parameters D and F of supersymmetry, the last one being treated perturbatively. We determine the stationary point and numerically check the consistency of such treatment as well as the local stability of the scalar potential. The coupling to the N=1 supergravity is given, and the gravitino mass formula is derived. © 2013 American Physical Society.

Nitta M.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

A lump (2D Skyrmion) can be constructed as a sine-Gordon kink (1D Skyrmion) inside a domain wall in the massive O(3) sigma model. In this paper, we discuss relations between Skyrmions in 2+1 and 3+1 dimensions. We first construct a Bogomol'nyi-Prasad-Sommerfield 3D Skyrmion as a lump inside a non-Abelian domain wall in an O(4) sigma model with a potential term admitting two discrete vacua. Next, we construct a conventional 3D Skyrmion as a baby Skyrmion in a non-Abelian domain wall in the Skyrme model with a modified mass term admitting two discrete vacua. We also construct a spinning 3D Skyrmion as a Q lump in the non-Abelian domain wall. © 2013 American Physical Society.

Maru N.,Keio University | Okada N.,University of Alabama
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

In the context of the gauge-Higgs unification scenario in a 5-dimensional flat spacetime, we investigate Higgs boson production via gluon fusion and its diphoton decay mode at the LHC. We show that the signal strength of the Higgs diphoton decay mode observed at ATLAS and CMS, which is considerably larger than the Standard Model expectation, can be explained by a simple gauge-Higgs unification model with color-singlet bulk fermions to which a half-periodic boundary condition is assigned. The bulk fermions also play a crucial role in reproducing the observed Higgs boson mass around 125 GeV. © 2013 American Physical Society.

Ono M.,Keio University
Proceedings of the American Control Conference | Year: 2012

Resolvability or recursive feasibility is an essential property for robust model predictive controllers. However, when an unbounded stochastic uncertainty is present, it is generally impossible to guarantee resolvability. We propose a new concept called probabilistic resolvability. A model-predictive control (MPC) algorithm is probabilistically resolvable if it has feasible solutions at future time steps with a certain probability, given a feasible solution at the current time. We propose a novel joint chance-constrained MPC algorithm that guarantees probabilistic resolvability. The proposed algorithm also guarantees the satisfaction of a joint chance-constraint, which specifies a lower bound on the probability of satisfying a set of state constraints over a finite horizon. Furthermore, with moderate conditions, the finite-horizon optimal control problem solved at each time step in the proposed algorithm is a convex optimization problem. © 2012 AACC American Automatic Control Council).

Koishi T.,University of Fukui | Yasuoka K.,Keio University | Fujikawa S.,RIKEN | Fujikawa S.,Japan Science and Technology Agency | Zeng X.C.,University of Nebraska - Lincoln
ACS Nano | Year: 2011

We perform large-scale molecular dynamics simulations to measure the contact-angle hysteresis for a nanodroplet of water placed on a nanopillared surface. The water droplet can be in either the Cassie state (droplet being on top of the nanopillared surface) or the Wenzel state (droplet being in contact with the bottom of nanopillar grooves). To measure the contact-angle hysteresis in a quantitative fashion, the molecular dynamics simulation is designed such that the number of water molecules in the droplets can be systematically varied, but the number of base nanopillars that are in direct contact with the droplets is fixed. We find that the contact-angle hysteresis for the droplet in the Cassie state is weaker than that in the Wenzel state. This conclusion is consistent with the experimental observation. We also test a different definition of the contact-angle hysteresis, which can be extended to estimate hysteresis between the Cassie and Wenzel state. The idea is motivated from the appearance of the hysteresis loop typically seen in computer simulation of the first-order phase transition, which stems from the metastability of a system in different thermodynamic states. Since the initial shape of the droplet can be controlled arbitrarily in the computer simulation, the number of base nanopillars that are in contact with the droplet can be controlled as well. We show that the measured contact-angle hysteresis according to the second definition is indeed very sensitive to the initial shape of the droplet. Nevertheless, the contact-angle hystereses measured based on the conventional and new definition seem converging in the large droplet limit. © 2011 American Chemical Society.

Sato S.,Keio University
Nihon Kikai Gakkai Ronbunshu, C Hen/Transactions of the Japan Society of Mechanical Engineers, Part C | Year: 2013

Recent years, it has been required accurate and agile attitude control of satellites. For this purpose, the necessity of Control Moment Gyros (CMGs) has been increasing, which can generate much higher torque than Reaction Wheel which is used for a conventional spacecraft actuator. CMGs have singularity problem that they cannot output a desired torque. Several singularity avoidance methods have been proposed, but they can fail to output the desired torque through the mission because of their singularity avoidance action. In this paper, we focus on singularity and CMGs' angular momentum and propose a singularity avoidance method by planning path in angular momentum space. Because output torque from CMGs depends on path of angular momentum, we plan the angular momentum path that avoids singularity and its length is short as possible by application of A* algorithm. It is shown from the simulations that the proposed method can realize desired output torque and assured singularity avoidance. © 2013 The Japan Society of Mechanical Engineers.

Kuroda T.,Keio University
Pediatric Surgery International | Year: 2011

Neuroblastoma is known for its peculiar cellular kinetics, which has provoked some controversy regarding surgical treatment. Highly sensitive exploration systems using reverse transcription polymerase chain reaction (RT-PCR) methods have been developed to detect neuroblastoma cells. In our series of 49 patients with advanced neuroblastoma, circulating tumor cells (CTC) were detected by this system in 55.6% of the stage 4 patients who were examined, suggesting that the primary lesion may release tumor cells into the peripheral blood. The Kaplan-Meier survival rate was significantly lower among the patients with CTC or chemotherapy-insensitive bone marrow micrometastasis, compared with those without detectable micrometastasis (33.8 vs. 87.5%, P<0.05). In contrast, a stage 3 patient with MYCN amplification exhibited drastic local relapse without systemic dissemination of the disease. Two patients were positive for CTC without an identifiable primary site. These observations indicate that the local growth of the primary tumor and tumor cell dissemination may be regulated by different molecular mechanisms in neuroblastomas. MYCN amplification seemed to be more closely associated with localized tumor growth but was minimally correlated with CTC positivity. High-risk neuroblastoma may include two separate subgroups characterized by different cellular kinetics: a local risk cohort and a systemic risk cohort. Surgical strategies for neuroblastoma should be determined with taking this cellular kinetics into consideration. © 2011 Springer-Verlag.

Kobayashi K.,Keio University | Hoshi M.,Chiba University
Frontiers in Zoology | Year: 2011

Background: The mechanisms underlying the switching from an asexual to a sexual mode of reproduction, and vice versa, remain unknown in metazoans. In planarians, asexual worms acquire cryptic sexuality when fed with sexual worms, indicating that sexual worms contain a sex-inducing substance. Although such a chemical compound will provide clues about the mechanisms underlying the switching, information on the sex-inducing substance is poor. In order to identify this substance, we have established an assay system for sexual induction in asexual worms of Dugesia ryukyuensis by feeding them with sexual worms. Here, we carried out an isolation study on the sex-inducing substance using this assay system.Results: After centrifugation of sexual worms homogenised in saline solution, we found that not only did the precipitate have a sex-inducing effect on the asexual worms, which has been shown previously, but the cytosolic fraction did as well. We confirmed that the sex-inducing activity in the cytosolic fraction was recovered in a hydrophilic fraction separated on an octadecylsilane (ODS) column. We showed that the sex-inducing substance in the hydrophilic fraction is papain-resistant and a putative low-molecular-weight compound of less than 500. We also suggest the presence of an enhancer of sexual induction with a molecular weight (MW) of more than 5 K in the hydrophilic fraction.Conclusion: Our experiments showed the existence of a sex-inducing substance and an enhancer of sex-induction in a hydrophilic fraction, and a putative hydrophobic sex-inducing substance in the precipitate. Sexual induction in the asexual worms might be triggered by additive or synergistic effects of these chemical compounds. © 2011 Kobayashi and Hoshi; licensee BioMed Central Ltd.

Sano M.,Keio University
Circulation Journal | Year: 2010

Everyone encounters various stressors (causes of stress), such as psychological pressure, mental fluctuations, and physical burdens, in their everyday life. It is well accepted that the highest levels of perceived stress correlate with early onset of cardiovascular disease. Conversely, appropriate (mild to moderate) stressors, such as physical activity, have been shown to promote health. This bidirectional dose - response relationship of treatments that are beneficial at low levels but noxious at higher levels is referred to as "hormesis". In the fields of toxicology, pharmacology, radiation biology, and medicine, the significance of the biological effects of low-level exposure to various agents has attracted considerable attention. It is very important to understand how biological systems respond to low levels of stress and their implications within society. Aldehydes, the major endproducts of lipid peroxidation, have been implicated in the pathogenesis of oxidative stress-associated diseases. In addition to the pathogenic effect associated with oxidative stress, sublethal levels of aldehydes interact with signaling systems to upregulate the expression of genes to counteract the stressor challenge and to re-establish homeostasis. The present review article discusses current discoveries regarding the hormetic response to aldehyde and its clinical significance in cardioprotection.

Selvarajoo K.,Keio University
Cell Communication and Signaling | Year: 2011

Stimulating the receptors of a single cell generates stochastic intracellular signaling. The fluctuating response has been attributed to the low abundance of signaling molecules and the spatio-temporal effects of diffusion and crowding. At population level, however, cells are able to execute well-defined deterministic biological processes such as growth, division, differentiation and immune response. These data reflect biology as a system possessing microscopic and macroscopic dynamics. This commentary discusses the average population response of the Toll-like receptor (TLR) 3 and 4 signaling. Without requiring detailed experimental data, linear response equations together with the fundamental law of information conservation have been used to decipher novel network features such as unknown intermediates, processes and cross-talk mechanisms. For single cell response, however, such simplicity seems far from reality. Thus, as observed in any other complex systems, biology can be considered to possess order and disorder, inheriting a mixture of predictable population level and unpredictable single cell outcomes. © 2011 Selvarajoo; licensee BioMed Central Ltd.

Kuroda T.,Keio University
Digest of Technical Papers - Symposium on VLSI Technology | Year: 2012

This paper describes a wireless inter-chip link using inductive coupling, namely ThruChip Interface (TCI). TCI is a digital CMOS circuit solution in a standard CMOS technology. It is less expensive than TSV but bears comparison in performance. © 2012 IEEE.

Hachisu I.,University of Tokyo | Kato M.,Keio University
Astrophysical Journal | Year: 2014

We identified a general course of classical nova outbursts in the B-V versus U-B color-color diagram. It is reported that novae show spectra similar to those of A-F supergiants near optical light maximum. However, they do not follow the supergiant sequence in the color-color diagram, neither the blackbody nor the main-sequence sequence. Instead, we found that novae evolve along a new sequence in the pre-maximum and near-maximum phases, which we call "the nova-giant sequence." This sequence is parallel to but Δ(U-B) -0.2 mag bluer than the supergiant sequence. This is because the mass of a nova envelope is much (10-4 times) less than that of a normal supergiant. After optical maximum, its color quickly evolves back blueward along the same nova-giant sequence and reaches the point of free-free emission (B-V = -0.03, U-B = -0.97), which coincides with the intersection of the blackbody sequence and the nova-giant sequence, and remains there for a while. Then the color evolves leftward (blueward in B-V but almost constant in U-B), owing mainly to the development of strong emission lines. This is the general course of nova outbursts in the color-color diagram, which was deduced from eight well-observed novae in various speed classes. For a nova with unknown extinction, we can determine a reliable value of the color excess by matching the observed track of the target nova with this general course. This is a new and convenient method for obtaining the color excesses of classical novae. Using this method, we redetermined the color excesses of 20 well-observed novae. The obtained color excesses are in reasonable agreement with the previous results, which in turn support the idea of our general track of nova outbursts. Additionally, we estimated the absolute V magnitudes of about 30 novae using a method for time-stretching nova light curves to analyze the distance-reddening relations of the novae. © 2014. The American Astronomical Society. All rights reserved..

In this review, our work on CHARGE syndrome will be used to exemplify the role of rare cases in birth defects research. The analysis of 29 cases with mutations of CHD7, the causative gene for CHARGE syndrome, clarified the relative importance of the cardinal features, including facial nerve palsy and facial asymmetry. Concurrently, in situ hybridization using chick embryos studies were performed to delineate the expression pattern of Chd7. The Chd7-positive regions in the chick embryos and the anatomical defects commonly seen in patients with CHARGE syndrome were well correlated: expression in the optic placode corresponded with defects such as coloboma, neural tube with mental retardation, and otic placode with ear abnormalities. The correlation between expression in the branchial arches and nasal placode with the clinical symptoms of CHARGE syndrome, however, became apparent when we encountered two unique CHARGE syndrome patients: one with a DiGeorge syndrome phenotype and the other with a Kallman syndrome phenotype. A unifying hypothesis that could explain both the DiGeorge syndrome phenotype and the Kallman syndrome phenotype in patients with CHARGE syndrome may be that the mutation in CHD7 is likely to exert its effect in the common branch of the two pathways of neural crest cells. As exemplified in CHARGE syndrome research, rare cases play a critical role in deciphering the mechanisms of human development. Close collaboration among animal researchers, epidemiologists and clinicians hopefully will enhance and maximize the scientific value of rare cases. © 2011 The Author. Congenital Anomalies © 2011 Japanese Teratology Society.

Hamatani T.,Keio University
Reproductive BioMedicine Online | Year: 2011

Human spermatozoal RNAs were recently profiled using microarrays and explored as clinical markers of male infertility. An appropriate study design with a considerable number of biological replicates (sperm samples) is necessary to validate the accuracy and reproducibility of these microarray data. If the genes identified as sperm quality markers by microarray studies are successfully attributed to the pathogenesis of male infertility, then the microarray strategy may be used as a clinical diagnostic tool for male infertility. On the other hand, spermatozoal RNAs may contain not only remnant RNAs after spermatogenesis, but also RNAs that may contribute extragenomically to early embryonic development. Therefore, spermatozoal RNA profiling may enable a better understanding of what is contributed to the oocyte by sperm, in addition to their genome, to facilitate early embryonic development. © 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Kourist R.,TU Munich | Dominguez De Maria P.,RWTH Aachen | Miyamoto K.,Keio University
Green Chemistry | Year: 2011

The profen family belongs to the most important non-steroidal anti-inflammatory drugs (NSAIDs). A considerable number of biocatalytic processes for the synthesis of optically pure (S)-profens have been proposed. Despite of the excellent enantioselectivity and the large advantages that enzyme catalysis offers in terms of sustainability, biocatalytic processes have failed so far to meet the technical and economic challenges of commercialization. This critical review outlines recent trends and developments of novel applications that appear very promising in terms of enantioselectivity, efficiency, sustainability and yield. Special emphasis is placed on the contribution of protein engineering in overcoming the limitations of these enzymes for technical applications, and thus providing promising biocatalysts for the preparation of pharmaceutical products. The natural catalytic diversity, assisted by modern methods of protein engineering, provides novel concepts and leads for the environmentally friendly synthesis of pharmacologically important drugs. Considerable progress can be expected in the coming decades. Furthermore, aspects regarding ecological footprints and the impact of each biocatalytic route are critically addressed, considering aspects like the type of solvent, waste produced, availability of substrate, etc. When possible, suggestions for combining efficiency with more sustainable synthetic approaches are also given. © 2011 The Royal Society of Chemistry.

Mizushima T.,Kumamoto University | Mizushima T.,Keio University
Journal of Biochemistry | Year: 2011

As a new strategy for drug discovery and development, I focus on drug re-profiling as a way to identify new treatments for diseases. In this strategy, the actions of existing medicines, whose safety and pharmacokinetic effects in humans have already been confirmed clinically and approved for use, are examined comprehensively at the molecular level and the results used for the development of new medicines. This strategy is based on the fact that we still do not understand the underlying mechanisms of action of many existing medicines, and as such the cellular responses that give rise to their main effects and side effects are yet to be elucidated. To this extent, identification of the mechanisms underlying the side effects of medicines offers a means for us to develop safer drugs. The results can also be used for developing existing drugs for use as medicines for the treatment of other diseases. Promoting this research strategy could provide breakthroughs in drug discovery and development. The Authors 2011. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved2011 © The Authors 2011. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

A Langmuir monolayer of carbonic anhydrase (CA) unfolded at an air/water interface was transferred onto the hydrophobic surface of a silicon wafer by means of the Langmuir-Schaefer technique. The transferred CA film was biotinylated and was incubated in a streptavidin (SAv) solution to obtain a densely packed SAv layer by biotin-SAv linkage. Biotinylated proteins including ferritin, catalase, alcohol dehydrogenase, and carbonic anhydrase were incubated with the SAv layer and binding of these proteins was examined by atomic force microscopy. High-density binding of the biotinylated proteins was observed, whereas the amount of adsorbed non-biotinylated proteins was low or negligible. The SAv layer on the Langmuir-Schaefer film of unfolded protein could become a basic architecture for protein immobilization studies. © 2016 Elsevier B.V. All rights reserved.

Imai H.,Keio University
Nippon Seramikkusu Kyokai Gakujutsu Ronbunshi/Journal of the Ceramic Society of Japan | Year: 2014

Generally, mesocrystals are known to be biological and bio-inspired mesoscale structures consisting of oriented nanometric crystalline units. In this article, mesocrystals are broadly categorized in a new family of crystalline materials as intermediate states between single crystals and polycrystals regardless of their unit size and degree of crystalline order. Here, the formation routes and the specific properties of a variety of mesocrystals and their related structures are described. Moreover, the potential of the novel crystalline materials having a high crystallinity and a high specific surface area is presented on the basis of their functions. © 2014 The Ceramic Society of Japan. All rights reserved.

Complete Freund's Adjuvant (CFA) is known to arrest autoimmune diabetes development in non-obese diabetic (NOD) mice. However, CFA alone cannot induce effective remission in diabetic NOD mice. Previously, we reported that anti-CXC chemokine ligand 10 (CXCL10) antibody can promote beta-cell proliferation in NOD mice. In the present study, we aimed to examine whether anti-CXCL10 plus CFA treatment can effectively reverse autoimmune diabetes development. Systemic supply of anti-CXCL10 antibody by CXCL10 DNA vaccination in combination with CFA injection was performed in new-onset diabetic NOD mice. Remission rate of diabetes, histological characteristics of residual insulitis lesions, residual beta-cell mass, and regulatory T cell population in local pancreas were examined. A high frequency of diabetes reversal was observed after combination treatment with anti-CXCL10 plus CFA. In mice showing diabetes reversal, residual beta-cell mass was significantly increased, and some beta-cells were in a proliferative state. Although systemic cytokine profiles were unaffected, the frequency of "hybrid regulatory T cells", i.e. regulatory T cells expressing CXCR3, was significantly increased in local pancreatic lesions. This was possibly associated with the regulation of anti-islet autoimmunity. Anti-CXCL10 plus appropriate immune adjuvant therapy arrested, and reversed, type 1 diabetes development.

Kobayashi M.,Kyoto University | Nitta M.,Keio University
Physical Review Letters | Year: 2014

We show that a momentum operator of a translational symmetry may not commute with an internal symmetry operator in the presence of a topological soliton in nonrelativistic theories. As a striking consequence, there appears a coupled Nambu-Goldstone mode with a quadratic dispersion consisting of translational and internal zero modes in the vicinity of a domain wall in an O(3) σ model, a magnetic domain wall in ferromagnets with an easy axis. © 2014 American Physical Society.

Ogawa H.,Hokkaido University | Ogawa H.,Japan Science and Technology Agency | Oka K.,Keio University
Journal of Neuroscience | Year: 2015

Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of habituation to frequent stimuli and novelty detection. However, neither the cellular mechanism underlying SSA nor the link between SSA-like neuronal plasticity and behavioral modulation is well understood. The wind-detection system in crickets is one of the best models for investigating the neural basis of SSA. We found that crickets exhibit stimulus-direction-specific adaptation in wind-elicited avoidance behavior. Repetitive air currents inducing this behavioral adaptation reduced firings to the stimulus and the amplitude of excitatory synaptic potentials in wind-sensitive giant interneurons (GIs) related to the avoidance behavior. Injection of a Ca2+ chelator into GIs diminished both the attenuation of firings and the synaptic depression induced by the repetitive stimulation, suggesting that adaptation of GIs induced by this stimulation results in Ca2+-mediated modulation of postsynaptic responses, including postsynaptic short-term depression. Some types of GIs showed specific adaptation to the direction of repetitive stimuli, resulting in an alteration of their directional tuning curves. The types of GIs for which directional tuning was altered displayed heterogeneous direction selectivity in their Ca2+ dynamics that was restricted to a specific area of dendrites. In contrast, other types of GIs with constant directionality exhibited direction-independent global Ca2+ elevation throughout the dendritic arbor. These results suggest that depression induced by local Ca2+ accumulation at repetitively activated synapses of key neurons underlies direction-specific behavioral adaptation. This input-selective depression mediated by heterogeneous Ca2+ dynamics could confer the ability to detect novelty at the earliest stages of sensory processing in crickets. © 2015 the authors.

Urakami J.,Keio University
Computers in Human Behavior | Year: 2014

Goal was to study cultural differences between Japanese and Germans gesture use when interacting with a map and a video walkthrough application for a table top system. Japanese and Germans' choice of gestures was compared in a quasi-experimental design. Gestures had to be generated for two different scenarios, an electronic map and a video walkthrough. Data revealed that physical aspects of hand gestures such as hand shape, focus on motion pattern, and preference of simple, one-hand gestures are similar between Japanese and Germans. However, Japanese and Germans differed in the choice of symbolic and metaphorical gestures and in the frame of reference and perspective taken for performing gestures. Furthermore, differences between Germans and Japanese were larger for the map application than for the video walkthrough. Culture partly affects the choice of hand gestures for table top systems. Designers of gesture vocabularies for tabletop systems have to carefully consider which referents are carried out by hand gestures alone. Gesture input appears to be appropriate for the direct manipulation of objects or real world applications. However, abstract functions or artificial realities should not be handled by gestures alone. Also, designers should consider the development of culture-centered interfaces. © 2014 Elsevier Ltd. All rights reserved.

Aramaki K.,Keio University
Zairyo to Kankyo/ Corrosion Engineering | Year: 2013

It has been reported in the previous studies that anions like Cl -, Br-, and I- inhibit and those like SCN -, SH-, and S2O3 2- stimulate the anodic process of iron corrosion in 1 M HClO4. These effects of anions on the anodic process were interpreted on the basis of the hard and soft acids and bases principle. The former three anions classified into the soft bases suppress the anodic process by the formation of a stable adsorption bond on bare iron, a soft acid. The latter three anions of the soft and hard bases accelerate the process due to soft acid-soft base and hard acid-hard base interactions.

Okano H.,Keio University | Yamanaka S.,Kyoto University | Yamanaka S.,Gladstone
Molecular Brain | Year: 2014

In 2006, we demonstrated that mature somatic cells can be reprogrammed to a pluripotent state by gene transfer, generating induced pluripotent stem (iPS) cells. Since that time, there has been an enormous increase in interest regarding the application of iPS cell technologies to medical science, in particular for regenerative medicine and human disease modeling. In this review article, we outline the current status of applications of iPS technology to cell therapies (particularly for spinal cord injury), as well as neurological disease-specific iPS cell research (particularly for Parkinson's disease and Alzheimer's disease). Finally, future directions of iPS cell research are discussed including a) development of an accurate assay system for disease-associated phenotypes, b) demonstration of causative relationships between genotypes and phenotypes by genome editing, c) application to sporadic and common diseases, and d) application to preemptive medicine. © 2014 Okano and Yamanaka; licensee BioMed Central Ltd.

Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Fukushima K.,Keio University
Physical Review C - Nuclear Physics | Year: 2014

We propose a picture of turbulent pattern formation in the relativistic heavy-ion collision, which follows an efficient process to break color strings and dispose energy in the whole phase space. We perform numerical simulations using the SU(2) pure Yang-Mills theory in a nonexpanding box to observe a dynamical phenomenon in the transverse plane akin to the domain growth in time-dependent spin systems. © 2014 American Physical Society.

Fukuda S.,Keio University | Fukuda S.,RIKEN | Ohno H.,RIKEN
Seminars in Immunopathology | Year: 2014

The prevalence of obesity and obesity-related disorders is increasing worldwide. In the last decade, the gut microbiota has emerged as an important factor in the development of obesity and metabolic syndrome, through its interactions with dietary, environmental, and host genetic factors. Various studies have shown that alteration of the gut microbiota, shifting it toward increased energy harvest, is associated with an obese phenotype. However, the molecular mechanisms by which the gut microbiota affects host metabolism are still obscure. In this review, we discuss the complexity of the gut microbiota and its relationship to obesity and obesity-related diseases. Furthermore, we discuss the anti-obesity potential of probiotics and prebiotics. © 2013 Springer-Verlag.

Takeuchi T.,Keio University
Annals of the rheumatic diseases | Year: 2012

The prototype autoimmune disease, systemic lupus erythematosus (SLE), has been known to be associated with deficiency of ζ chain, a component of the T-cell receptor-CD3 complex. Comprehensive analysis has shown that expression of the CD3 ζ chain is attenuated or absent in over half of SLE patients. Furthermore, aberrant transcripts of the CD3 ζ chain, including spliced variants lacking exon 7 or having a short 3'-untranslated region, have been detected in SLE T cells. Although attenuated expression of the CD3 ζ chain is also observed in cancer patients, infections and other autoimmune diseases, sustained attenuation of the CD3 ζ expression accompanied with aberrant transcripts are only observed in SLE. In this study, the authors review the unique features of CD3 ζ defects observed in SLE and discuss the molecular basis of the defects by recent findings in animal models, single-nucleotide polymorphisms and genome-wide association studies.

Objective: To evaluate the impact of the policy to encourage nursing homes to provide end-of-life care by comparing facility and resident variables associated with dying within the nursing home and not in hospitals, and by comparing life sustaining treatment (LST) respectively provided. Method: Questionnaires mailed to an 11% random sample of 653 nursing homes in 2009. Facility characteristics from 371 nursing homes (57%) and resident characteristics of the 1158 who had been discharged due to death were obtained from 241 facilities (37%). Results: Facility characteristics related to dying in nursing homes were their policy of providing end-of-life care and physicians being based in home care supporting clinics. Resident characteristics related were not having pneumonia as the cause of death, the family's preference of the nursing home as the site of death and agreement within the family. Preferences on the use of LST were adhered more in residents who had died in nursing homes. Conclusion: Although the percentage of residents dying within the facility has increased, the nursing home as a site of death still composes only 3.2% of the total. To increase the latter, nursing homes should refocus their function to providing end-of-life care to those not preferring aggressive treatment. © 2012 Elsevier Ireland Ltd.

Accurate evaluation of liver fibrosis in patients with chronic liver damage is required to determine the appropriate treatment. Various approaches, including laboratory tests and transient elastography, have been used to evaluate liver fibrosis. Recently, transient elastography with acoustic radiation force impulse (ARFI) has been developed and applied with conventional ultrasonography. The aim of this study was to evaluate the clinical utility of transient elastography with ARFI and to compare the results with this method and those of the Fibroscan(®) procedure. One hundred and thirty-one patients with liver damage, who underwent liver biopsy at our department, were enrolled prospectively in this study. Elastography with ARFI (applied with ACUSON S2000(®)), and Fibroscan(®) was performed at the same time as liver biopsy. These measurements were compared with histological findings in liver biopsy specimens, and measurement accuracy was evaluated by receiver-operating characteristic analysis. Elastography values with both procedures were significantly correlated with the stages of liver fibrosis and there was little difference in the results obtained using the 2 procedures. The accuracy of differential diagnosis between no fibrosis at F0 and more than F1 stage was insufficient with ARFI, but this procedure was sufficient for diagnosing advanced fibrosis. The accuracy of ARFI was almost equivalent to that of the Fibroscan(®) method. Moreover, both ARFI and Fibroscan(®) values increased in proportion to the severity of hepatic inflammation when fibrosis stage is low, but not in proportion to the severity of steatosis. Transient elastography with ARFI is simple, non-invasive and useful for diagnosing the stage of fibrosis in chronic liver disease. The utility of ARFI was almost equivalent to that of the Fibroscan(®) method.

McLeod J.D.,Indiana University | Uemura R.,Keio University | Rohrman S.,Indiana University
Journal of Health and Social Behavior | Year: 2012

Prior research on the association of mental health and behavior problems with academic achievement is limited because it does not consider multiple problems simultaneously, take co-occurring problems into account, and control for academic aptitude. We addressed these limitations using data from the National Longitudinal Study of Adolescent Health (N = 6,315). We estimated the associations of depression, attention problems, delinquency, and substance use with two indicators of academic achievement (high school GPA and highest degree received) with controls for academic aptitude. Attention problems, delinquency, and substance use were significantly associated with diminished achievement, but depression was not. Combinations of problems involving substance use were especially consequential. Our results demonstrate that the social consequences of mental health problems are not the inevitable result of diminished functional ability but, rather, reflect negative social responses. These results also encourage a broader perspective on mental health by demonstrating that behavior problems heighten the negative consequences of more traditional forms of distress. © American Sociological Association 2012.

Tadano K.-I.,Keio University
Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry | Year: 2011

In this article, the author outlines five total syntheses of structurally unique and biologically intriguing natural products, which were matters of attractive concern in the author's group during these two decades. The following natural product syntheses are summarized in this article: (, 1) a mycotoxin, (+) -asteltoxin, (2) sex-attracting insect pheromones, (-) -anastrephin and (-) -epianastrephin, (3) a bisabolene-type sesquiterpenoid, (+) -paniculide B, (4; 17-memberd tetra-and pentacyclic antibiotics, (+) -macquarimicins, and (5) cytotoxic and immunosuppressive caryophyllene-type sesquiterpenoid, (+ ) -pestalotiopsin A and its (-) -enantiomer. In conjunction with these total syntheses, the multigram-scale access to two versatile and enantiomerically homogeneous building blocks from D-glucose is also described. The synthetic utility of the both building blocks was convincingly demonstrated through the total syntheses of the above three natural products.

Mayer U.,Bielefeld University | Watanabe S.,Keio University | Bischof H.-J.,Bielefeld University
Journal of Physiology Paris | Year: 2013

The aim of the present review is to show that spatial learning and memory is not a specialty of just a few avian species, and to describe the role of the avian hippocampus in spatial learning, memory and orientation. Based on our own research in zebra finches, we try to give an (not complete and probably biased) overview of this topic, and we also discuss the question of functional equivalence of hippocampus in birds and in mammals in that we question how far theories developed for mammalian hippocampus can also be applied to the avian hippocampal formation. © 2012 Elsevier Ltd.

Kanazawa H.,Keio University | Okano T.,Tokyo Womens Medical University
Journal of Chromatography A | Year: 2011

Temperature-responsive chromatography for the separation of biomolecules utilizing poly (N-isopropylacrylamide) (PNIPAAm) and its copolymer-modified stationary phase is performed with an aqueous mobile phase without using organic solvent. The surface properties and function of the stationary phase are controlled by external temperature changes without changing the mobile-phase composition. This analytical system is based on nonspecific adsorption by the reversible transition of a hydrophilic-hydrophobic PNIPAAm-grafted surface. The driving force for retention is hydrophobic interaction between the solute molecules and the hydrophobized polymer chains on the stationary phase surface. The separation of the biomolecules, such as nucleotides and proteins was achieved by a dual temperature- and pH-responsive chromatography system. The electrostatic and hydrophobic interactions could be modulated simultaneously with the temperature in an aqueous mobile phase, thus the separation system would have potential applications in the separation of biomolecules. Additionally, chromatographic matrices prepared by a surface-initiated atom transfer radical polymerization (ATRP) exhibit a strong interaction with analytes, because the polymerization procedure forms a densely packed polymer, called a polymer brush, on the surfaces. The copolymer brush grafted surfaces prepared by ATRP was an effective tool for separating basic biomolecules by modulating the electrostatic and hydrophobic interactions. Applications of thermally responsive columns for the separations of biomolecules are reviewed here. © 2011 Elsevier B.V.

Sanada Y.,Keio University
IEEE Vehicular Technology Conference | Year: 2012

This paper presents a signal de-multiplexing scheme in branch metric calculation of soft decision decoding for a spatially multiplexed MIMO system. In a conventional MIMO system, de-multiplexing is carried out over the symbols received by multiple antenna elements and is separated from decoding. Therefore, the de-multiplexing requires multiple uncorrelated antenna elements in order to realize a full rank channel matrix. This leads to the limitation of the system capacity by the number of the receive antenna elements. Instead of splitting de-multiplexing and decoding, in this paper, a de-multiplexing scheme at branch metric calculation in soft decision decoding is proposed. Based on ideal interleaving, independence among the coded symbols is assumed. Thus, the full rank channel matrix with the size of minimum free distance can be realized for signal de-multiplexing. As examples of the proposed system, the performance of repetition codes, block codes, and convolutional codes with MMSE de-multiplexing and soft decision Viterbi decoding on a Rayleigh fading channel is investigated. It is shown through numerical analysis that a lower BER can be achieved with a larger minimum free distance for the same normalized transmission rate that is given as the product of the coding rate and the number of multiplexed signal streams. © 2012 IEEE.

Kuwana M.,Keio University
World Journal of Gastroenterology | Year: 2014

Immune thrombocytopenia (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies. There is growing evidence that the eradication of Helicobacter pylori (H. pylori) effectively increases platelet count in a considerable proportion of ITP patients infected with this bacterium. In the majority of ITP patients responding to H. pylori eradication therapy, the anti-platelet autoantibody response is completely resolved with no relapse for more than 7 years, indicating that the disease is cured. Therefore, adult patients with suspected ITP should be examined for H. pylori infection, and eradication therapy is recommended if the infection is present. Notably, however, the efficacy of H. pylori eradication therapy in ITP patients varies widely among countries, with a higher response rate in Japan compared with the United States and European countries other than Italy. The pathogenesis of H. pylori -associated ITP is still uncertain, although the mechanisms are known to involve multiple factors. H. pylori may modulate the Fcγ- receptor balance of monocytes/macrophages in favor of activating Fcγ receptors, and H. pylori components may mimic the molecular makeup of platelet antigens. Further studies of the pathogenic process of H. pylori - associated ITP may be useful for the development of new therapeutic strategies for ITP. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Diefenbach A.,University of Mainz Medical Center | Colonna M.,University of Washington | Koyasu S.,RIKEN | Koyasu S.,Keio University
Immunity | Year: 2014

Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILCs). ILCs are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILCs has been linked to the pathogenesis of inflammatory and autoimmune disorders. Recent evidence suggests that ILCs can be grouped into two separate lineages, cytotoxic ILCs represented by conventional natural killer (cNK) cells and cytokine-producing helper-like ILCs (i.e., ILC1s, ILC2s, ILC3s). We will focus here on current work in humans and mice that has identified core transcriptional circuitry required for the commitment of lymphoid progenitors to the ILC lineage. The striking similarities in transcriptional control of ILC and Tcell lineages reveal important insights into the evolution of transcriptional programs required to protect multicellular organisms against infections and to fortify barrier surfaces. Innate lymphoid cells (ILCs) are important for protection against pathogens and for maintenance of organ homeostasis. Diefenbach and colleagues examine the core transcriptional circuitry required for commitment to the ILC lineage, as well as the transcriptional programs that drive differentiation into distinct ILC populations. © 2014 Elsevier Inc.

Nitta M.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We show that when a topological defect with extended world volume annihilates with an antidefect, there arise topological defects with dimensions less than those of the original defects by one. Domain wall annihilations create vortices while monopole-string annihilations result in instantons. We find that twisted domain wall rings are vortices, whereas twisted monopole rings are instantons. © 2012 American Physical Society.

Akimoto T.,Keio University
Physical Review Letters | Year: 2012

We report on a novel response to biases in deterministic superdiffusion. For its reduced map, we show using infinite ergodic theory that the time-averaged velocity (TAV) is intrinsically random and its distribution obeys the generalized arcsine distribution. A distributional limit theorem indicates that the TAV response to a bias appears in the distribution, which is an example of what we term a distributional response induced by a bias. Although this response in single trajectories is intrinsically random, the ensemble-averaged TAV response is linear. Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

Saito Y.,Keio University | Saito Y.,CNRS Physics Laboratory of Condensed Matter and Nanostructure | Dufay M.,CNRS Physics Laboratory of Condensed Matter and Nanostructure | Pierre-Louis O.,CNRS Physics Laboratory of Condensed Matter and Nanostructure
Physical Review Letters | Year: 2012

The diffusion of growing or evaporating two-dimensional clusters is investigated. At equilibrium, it is well known that the mean square displacement (MSD) of the cluster center of mass is linear in time. In nonequilibrium conditions, we find that the MSD exhibits a nonlinear time dependence, leading to three regimes: (i) during curvature-driven evaporation, the MSD shows a square-root singularity close to the collapse time; (ii) in slow growth or evaporation, the dynamics is in the Edwards-Wilkinson universality class, and the MSD shows a logarithmic behavior; (iii) far from equilibrium, the dynamics belongs to the Kardar-Parisi-Zhang universality class and the MSD shows a power-law behavior with a characteristic exponent 1/3. These results agree with kinetic Monte Carlo simulations, and can be generalized to other universality classes. © 2012 American Physical Society.

Shinjoh M.,Keio University
Kansenshōgaku zasshi. The Journal of the Japanese Association for Infectious Diseases | Year: 2012

We conducted a pediatric survey of bacterial meningitis epidemiology from January 2009 to December 2010 in Japan, and obtained the following results for 314 cases (186 boys, 124 girls, and 4 with gender not reported). Children younger than one year old accounted for the majority of cases (51.2%, 161/314), and the incidence decreased with increasing age. Haemophilus influenzae (in children aged 1 month to 5 years old) was the most common cause of infection (53.2%), followed by Streptococcus pneumoniae (1 month to 12 years, 24.2%), Streptococcus agalactiae (0-4 months, 7.6%), and Escherichia coli (0-3 months, 3.2%). Susceptibility tests showed that 50.1% (78/153) of the H. influenzae isolates and 63.0% (46/73) of the S. pneumoniae isolates were drug-resistant. Combinations of ampicillin and cephem or carbapenem and other beta-lactams were mainly used as the initial antibiotics for patients under 4 months of age (77.8%, 42/54), and a carbapenem and other beta-lactam combination was used for patients aged 4 months and older (76.4%, 198/259). The final antibiotics for H. influenzae and S. pneumoniae were mainly cefotaxime (CTX) or ceftriaxone (CTRX) and carbapenem, respectively. The overall fatality rate was 2.0% (6/305). Since the Haemophilus influenzae type b vaccine (Hib vaccine) and the 7 valent pneumococcal conjugate vaccine (PCV7) are not widely used in Japan, only 5 patients in our cohort (all with meningitis not caused by H. influenzae) had been immunized with the Hib vaccine, and none had been immunized with the PCV7 vaccine. No remarkable changes in the characteristics of pediatric meningitis have been observed for several years in Japan.

To investigate the relationship between fasting and 2-h postprandial plasma glucose concentrations and vascular complications in type 2 diabetes. METHODS: Consecutive patients with type 2 diabetes admitted for blood glucose control were grouped according to their fasting and 2-h postprandial plasma glucose levels. Frequency and severity of diabetic retinopathy and nephropathy, number of carotid artery plaques, coefficient of variation of R-R intervals (CVRR), brachial-ankle pulse wave velocity (baPWV), intima-media thickness, brain natriuretic peptide level, ankle-brachial index, and high-sensitivity C-reactive protein levels were compared. RESULTS: In the 206 patients studied, mean ± SD age, glycosylated haemoglobin and duration of diabetes were 63.4 ± 13.7 years, 9.8 ± 1.8% and 13.4 ± 8.9 years, respectively. Patients with high fasting plasma glucose levels had a higher frequency of proliferative retinopathy than those with low fasting levels. Patients with medium or high 2-h postprandial plasma glucose levels had higher baPWV and lower CVRR, respectively, than those with low 2-h levels. There was an inverse correlation between baPWV and CVRR. CONCLUSION: Elevated fasting and postprandial plasma glucose levels are risk factors for vascular complications in type 2 diabetes mellitus. ©2012 Field House Publishing LLP.

Itoh K.M.,Keio University
Nature Nanotechnology | Year: 2015

Bell's theorem proves the existence of entangled quantum states with no classical counterpart. An experimental violation of Bell's inequality demands simultaneously high fidelities in the preparation, manipulation and measurement of multipartite quantum entangled states, and provides a single-number benchmark for the performance of devices that use such states for quantum computing. We demonstrate a Bell/ Clauser–Horne–Shimony–Holt inequality violation with Bell signals up to 2.70(9), using the electron and the nuclear spins of a single phosphorus atom embedded in a silicon nanoelectronic device. Two-qubit state tomography reveals that our prepared states match the target maximally entangled Bell states with >96% fidelity. These experiments demonstrate complete control of the two-qubit Hilbert space of a phosphorus atom and highlight the important function of the nuclear qubit to expand the computational basis and maximize the readout fidelity. © 2015 Nature Publishing Group

Vinci W.,University of Pisa | Cipriani M.,University of Pisa | Nitta M.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

When a color superconductor of high density QCD is rotating, superfluid vortices are inevitably created along the rotation axis. In the color-flavor locked phase realized at the asymptotically large chemical potential, there appear non-Abelian vortices carrying both circulations of superfluid and color magnetic fluxes. A family of solutions has a degeneracy characterized by the Nambu-Goldstone modes CP2, associated with the color-flavor locked symmetry spontaneously broken in the vicinity of the vortex. In this paper, we study electromagnetic coupling of the non-Abelian vortices and find that the degeneracy is removed with the induced effective potential. We obtain one stable vortex solution and a family of metastable vortex solutions, both of which carry ordinary magnetic fluxes in addition to color magnetic fluxes. We discuss quantum mechanical decay of the metastable vortices by quantum tunneling and compare the effective potential with the other known potentials, the quantum mechanically induced potential and the potential induced by the strange quark mass. © 2012 American Physical Society.

Nitta M.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

A pair of a domain wall and an antidomain wall is unstable to decay. We show that when a vortex string is stretched between the walls, there remains a knot soliton (Hopfion) after the pair annihilation. © 2012 American Physical Society.

Hirono Y.,University of Tokyo | Nitta M.,Keio University
Physical Review Letters | Year: 2012

Quantum vortices in the color-flavor locked phase of QCD have bosonic degrees of freedom, called the orientational zero modes, localized on them. We show that the orientational zero modes are electromagnetically charged. As a result, a vortex in the color-flavor locked phase nontrivially interacts with photons. We show that a lattice of vortices acts as a polarizer of photons with wavelengths larger than some critical length. © 2012 American Physical Society.

Fujitani Y.,Keio University
Journal of the Physical Society of Japan | Year: 2012

Utilizing the recent analytical result, we numerically study the drag coefficient of a circular liquid domain in a flat fluid membrane, surrounded by three-dimensional fluids. Its derivative with respect to the domain viscosity is evaluated when the domain viscosity is the same as the membrane viscosity outside the domain. We show that the drag coefficient is smaller when the domain is more viscous, unlike that of a liquid droplet in a three-dimensional fluid. © 2012 The Physical Society of Japan.

Kawakami T.,Okayama University | Mizushima T.,Okayama University | Nitta M.,Keio University | MacHida K.,Okayama University
Physical Review Letters | Year: 2012

We demonstrate that the three-dimensional Skyrmion, which has remained elusive so far, spontaneously appears as the ground state of SU(2) symmetric Bose-Einstein condensates coupled with a non-Abelian gauge field. The gauge field is a three-dimensional analogue of the Rashba spin-orbit coupling. Upon squashing the SO(3) symmetric gauge field to one- or two-dimensional shapes, we find that the ground state continuously undergoes a change from a three-dimensional to a one- or two-dimensional Skyrmion, which is identified by estimating winding numbers and helicity. All of the emerged Skyrmions are physically understandable with the concept of the helical modulation in a unified way. These topological objects might potentially be realizable in two-component Bose-Einstein condensates experimentally. © 2012 American Physical Society.

Nitta M.,Keio University
Journal of High Energy Physics | Year: 2015

Abstract: Recently, multiple fractional instanton configurations with zero instanton charge, called bions, have been revealed to play important roles in quantum field theories on compactified spacetime. In two dimensions, fractional instantons and bions have been extensively studied in the ℂPN−1 model and the Grassmann sigma model on ℝ1 × S1 with the ℤN symmetric twisted boundary condition. Fractional instantons in these models are domain walls with a localized U(1) modulus twisted half along their world volume. In this paper, we classify fractional instantons and bions in the O(N) nonlinear sigma model on ℝN−2 × S1 with more general twisted boundary conditions in which arbitrary number of fields change sign. We find that fractional instantons have more general composite structures, that is, a global vortex with an Ising spin (or a half-lump vortex), a half sine-Gordon kink on a domain wall, or a half lump on a “space-filling brane” in the O(3) model (ℂP1 model) on ℝ1 × S1, and a global monopole with an Ising spin (or a half-Skyrmion monopole), a half sine-Gordon kink on a global vortex, a half lump on a domain wall, or a half Skyrmion on a “space-filling brane” in the O(4) model (principal chiral model or Skyrme model) on ℝ2 × S1. We also construct bion configurations in these models. © 2015, The Author(s).

Sato T.,Keio University | Sato T.,Hubrecht Institute | Clevers H.,Hubrecht Institute
Methods in Molecular Biology | Year: 2013

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently shown that Lgr5 (Leucine-rich repeat-containing G protein-coupled receptor) is expressed in intestinal stem cells by an in vivo genetic lineage tracing strategy. In the past, extensive efforts have been made to establish primary small intestinal culture systems. However, no defined, reproducible and robust culture system had been developed. To establish such a system, we screened for optimal growth factor combinations based on genetic evidence of self-renewal regulation, differentiation, and carcinogenesis of intestinal stem cells. Here, we describe methods that we have established for the isolation and culture of primary small intestinal epithelial stem cells. In this culture system, isolated crypts form organoid structures with a histological hierarchy recapitulating in vivo small intestinal epithelium. Single isolated Lgr5+ intestinal stem cells also form these organoid structures, in which stem cells are maintained by self-renewal and give rise to all lineages of the intestinal epithelium. This culture system is particularly useful for studying the regulation of intestinal stem cell self-renewal and differentiation. © 2013 Springer Science+Business Media, LLC.

Hariharan N.,Rutgers University | Maejima Y.,Rutgers University | Nakae J.,Keio University | Paik J.,Belfer Institute for Applied Cancer Science | And 2 more authors.
Circulation Research | Year: 2010

Rationale: Autophagy, a bulk degradation process of cytosolic proteins and organelles, is protective during nutrient starvation in cardiomyocytes (CMs). However, the underlying signaling mechanism mediating autophagy is not well understood. Objective: We investigated the role of FoxOs and its posttranslational modification in mediating starvation-induced autophagy. Methods and results: Glucose deprivation (GD) increased autophagic flux in cultured CMs, as evidenced by increased mRFP-GFP-LC3 puncta and decreases in p62, which was accompanied by upregulation of Sirt1 and FoxO1. Overexpression of either Sirt1 or FoxO1 was sufficient for inducing autophagic flux, whereas both Sirt1 and FoxO1 were required for GD-induced autophagy. GD increased deacetylation of FoxO1, and Sirt1 was required for GD-induced deacetylation of FoxO1. Overexpression of FoxO1(3A/LXXAA), which cannot interact with Sirt1, or p300, a histone acetylase, increased acetylation of FoxO1 and inhibited GD-induced autophagy. FoxO1 increased expression of Rab7, a small GTP-binding protein that mediates late autophagosome-lysosome fusion, which was both necessary and sufficient for mediating FoxO1-induced increases in autophagic flux. Although cardiac function was maintained in control mice after 48 hours of food starvation, it was significantly deteriorated in mice with cardiac-specific overexpression of FoxO1(3A/LXXAA), those with cardiac-specific homozygous deletion of FoxO1 (c-FoxO1), and beclin1 mice, in which autophagy is significantly inhibited. Conclusions: These results suggest that Sirt1-mediated deacetylation of FoxO1 and upregulation of Rab7 play an important role in mediating starvation-induced increases in autophagic flux, which in turn plays an essential role in maintaining left ventricular function during starvation. © 2010 American Heart Association, Inc.

Ishii Y.,Keio University
Asian journal of endoscopic surgery | Year: 2013

We report our experience of a reduced-port laparoscopic surgery as an advanced laparoscopic surgery for rectal cancer. Twelve selected patients with clinical T1-2 and N0 rectal cancer (clinical stage I) underwent low anterior resection of the rectum. The procedures were performed with one port plus a multiple-instrument access port with three channels. The multiple-instrument access port was placed at the umbilicus or the site of diverting stoma, and another port was placed in the right abdomen or in the opposite abdomen of ostomy. The median operative time and intraoperative bleeding were 280 min and 15 mL, respectively. The median number of harvested lymph nodes was 20. No major perioperative morbidities occurred in this series. The median postoperative hospital stay was 10 days. Low anterior resection performed by reduced-port laparoscopic surgery is feasible as multiport laparoscopic surgery, and it is a reliable surgical option in selected patients with rectal cancer. © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.

Birds have visual cognition as well developed as humans. Sometimes, the birds show visual discrimination similar to humans, but the birds may use different cues. Previous reports suggest that global configuration cues are salient for humans, whereas local elemental cues are salient for pigeons. I analyzed the discriminative behavior of pigeons with scrambled images because scrambled images keep the local elemental cues of the original images but lose the global configuration cues. If pigeons use local elemental cues, then, they should show transfer of discrimination from the original images to their scrambled images and also transfer from the scrambled images to their original images. In Experiment I, I trained pigeons on painting style discrimination (Japanese paintings vs. Western impressionist paintings) using either the original or scrambled images and found that the pigeons showed bidirectional transfer. In Experiment II, I trained pigeons on discrimination of "good" versus "bad" paintings using children's paintings. The birds showed poor transfer from the original images to their scrambled images and vise versa. Thus, the pigeons discriminated good and bad paintings based mostly on global configuration cues in this case. These results suggest that the pigeons use different cues for different discriminations. © 2011 Springer-Verlag.

Hachisu I.,University of Tokyo | Kato M.,Keio University | Nomoto K.,University of Tokyo
Astrophysical Journal Letters | Year: 2012

Taking into account the rotation of mass-accreting white dwarfs (WDs) whose masses exceed the Chandrasekhar mass, we extend our new single degenerate model for the progenitors of Type Ia supernovae (SNe Ia), accounting for two types of binary systems: those with a main-sequence companion and those with a red-giant (RG) companion. We present a mass distribution of WDs exploding as SNe Ia, where the WD mass ranges from 1.38 to 2.3 M ⊙. These progenitor models are assigned to various types of SNe Ia. A lower mass range of WDs (1.38 M ⊙ < M WD ≲ 1.5 M ⊙), which are supported by rigid rotation, corresponds to normal SNe Ia. A variety of spin-down time may lead to a variation of brightness. A higher mass range of WDs (M WD ≳ 1.5 M ⊙), which are supported by differential rotation, corresponds to brighter SNe Ia such as SN 1991T. In this case, a variety of the WD mass may lead to a variation of brightness. We also show the evolutionary states of the companion stars at SN Ia explosions and pose constraints on the unseen companions. In the WD+RG systems, in particular, most of the RG companions have evolved to helium/carbon-oxygen WDs in the spin-down phase before the SN Ia explosions. In such a case, we do not expect any prominent signature of the companion immediately before and after the explosion. We also compare our new models with the recent stringent constraints on the unseen progenitors of SNe Ia such as SN 2011fe. © © 2012. The American Astronomical Society. All rights reserved.

Fukushima K.,Keio University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We investigate the phase transition in cold and dense quark matter in an intuitive way that shares common features of the effective model approaches. We first express the quasiparticle contribution to the thermodynamic potential with the dynamical mass M and then discuss how we can understand the possible first-order phase transition with and without the vector interaction from the saturation curve on the plane of the energy per particle and the density. We next extend our analysis including inhomogeneity and discuss the relation between the order of the phase transition and the saturation curve. We emphasize that the saturation curve is useful to infer qualitative nature of the phase transition even without knowing the explicit solution of the ground state. © 2012 American Physical Society.

Takeuchi H.,Hiroshima University | Kasamatsu K.,Kinki University | Tsubota M.,Osaka City University | Nitta M.,Keio University
Physical Review Letters | Year: 2012

We show theoretically that a domain-wall annihilation in two-component Bose-Einstein condensates causes tachyon condensation accompanied by spontaneous symmetry breaking in a two-dimensional subspace. Three-dimensional vortex formation from domain-wall annihilations is considered a kink formation in subspace. Numerical experiments reveal that the subspatial dynamics obey the dynamic scaling law of phase-ordering kinetics. This model is experimentally feasible and provides insights into how the extra dimensions influence subspatial phase transition in higher-dimensional space. © 2012 American Physical Society.

Sasaki E.,Keio University | Sasaki E.,Central Institute for Experimental Animals
Neuroscience Research | Year: 2015

Genetically modified mice have contributed much to studies in the life sciences. In some research fields, however, mouse models are insufficient for analyzing the molecular mechanisms of pathology or as disease models. Often, genetically modified non-human primate (NHP) models are desired, as they are more similar to human physiology, morphology, and anatomy. Recent progress in studies of the reproductive biology in NHPs has enabled the introduction of exogenous genes into NHP genomes or the alteration of endogenous NHP genes. This review summarizes recent progress in the production of genetically modified NHPs, including the common marmoset, and future perspectives for realizing genetically modified NHP models for use in life sciences research. © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society.

Fujishima S.,Keio University
Journal of Intensive Care | Year: 2014

Acute respiratory distress syndrome (ARDS) is defined as an acute-onset, progressive, hypoxic condition with radiographic bilateral lung infiltration, which develops after several diseases or injuries, and is not derived from hydrostatic pulmonary edema. One specific pathological finding of ARDS is diffuse alveolar damage. In 2012, in an effort to increase diagnostic specificity, a revised definition of ARDS was published in JAMA. However, no new parameters or biomarkers were adopted by the revised definition. Discriminating between ARDS and other similar diseases is critically important; however, only a few biomarkers are currently available for diagnostic purposes. Furthermore, predicting the severity, response to therapy, or outcome of the illness is also important for developing treatment strategies for each patient. However, the PaO2/FIO2 ratio is currently the sole clinical parameter used for this purpose. In parallel with progress in understanding the pathophysiology of ARDS, various humoral factors induced by inflammation and molecules derived from activated cells or injured tissues have been shown as potential biomarkers that may be applied in clinical practice. In this review, the current understanding of the basic pathophysiology of ARDS and associated candidate biomarkers will be discussed. © 2014 Fujishima;

Nakamura S.,Keio University
[Nihon kōshū eisei zasshi] Japanese journal of public health | Year: 2012

The purpose of this study is to analyze the influence of sensitivity to cold or hiesho in pregnant Japanese women and to examine the relationship between hiesho and premature labor. In this retrospective cohort study in Japanese women after delivery, information for the approximately 12 months between October 19, 2009 and October 8, 2010 was obtained using questionnaire surveys and medical records at 6 hospitals with obstetric and pediatric departments in the Greater Tokyo Metropolitan Area. Further, in this analysis, confounding factors were adjusted by performing analysis of covariance and stratified analysis using propensity scores. The Research Ethics Review Committee of St. Luke's College of Nursing (09-057) approved this study. Analysis of data from 2,810 women was performed. Regarding the correlation between hiesho and premature labor, the incidence of premature labor was 3.38 times higher (analysis of covariance) or 3.47 times higher (stratified analysis) among pregnant women with hiesho than among those without hiesho (P < 0.001). The results of this study proved the existing discussions that there is a correlation between hiesho during the latter stages of pregnancy and incidence of premature labor.

Sado M.,Keio University
Cochrane database of systematic reviews (Online) | Year: 2012

The morbidity caused by postnatal depression is enormous. Several psychological or psychosocial interventions have appeared to be effective for treating the disorder although they have not shown a clear benefit in preventing the development of PND. As yet however, the effectiveness of hypnosis has not been evaluated in relation to this. To assess the effect of hypnosis for preventing postnatal depression compared with usual antenatal, intranatal, or postnatal care. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2011). Randomised controlled trials comparing hypnosis with usual antenatal, intranatal, or postnatal care, where the primary or secondary objective is to assess whether there is a reduced risk of developing postnatal depression. Two review authors independently assessed trials for inclusion and assessed the one included study for risk of bias. The included study did not contribute any data for analysis. There was one included study (involving 63 women). However, as it did not include the outcomes of interest, no data were available for analysis for this review. There was no evidence available from randomised controlled trials to assess the effectiveness of hypnosis during pregnancy, childbirth, and the postnatal period for preventing postnatal depression. Evidence from randomised controlled trials is needed to evaluate the use and effects of hypnosis during the perinatal period to prevent postnatal depression. Two trials are currently underway which may provide further information in the future.

Susa Y.,Tokyo Institute of Technology | Tanaka S.,Keio University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2015

We study the detection capability of the weak-value amplification on the basis of the statistical hypothesis testing. We propose a reasonable testing method in the physical and statistical senses to find that the weak measurement with the large weak value has the advantage to increase the detection power and to reduce the possibility of missing the presence of interaction. We enhance the physical understanding of the weak value and mathematically establish the significance of the weak-value amplification. Our present work overcomes the critical dilemma of the weak-value amplification that the larger the amplification is, the smaller the number of data becomes, because the statistical hypothesis testing works even for a small number of data. This is contrasted with the parameter estimation by the weak-value amplification in the literature which requires a large number of data. © 2015 American Physical Society. ©2015 American Physical Society.

Hasegawa T.,Keio University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2015

The nonlinear absorption process and associated phase shift in coupled optical cavities are studied experimentally by observing optical resonance properties. In the coupled cavity configuration, two optical cavities, one for a fundamental beam and the other for a second-harmonic (SH) beam, are coupled by a nonlinear crystal for the second-harmonic generation (SHG). The cavity for the SH beam effectively extends the nonlinear crystal length so that the frequency-conversion efficiency of the SHG, which is proportional to the square of the crystal length, is enhanced. In the observation, power reduction of the fundamental beam at resonance is observed as a small dip in the resonance curve. According to a model calculation, it is found that this power reduction is caused by blue-induced infrared absorption. © 2015 American Physical Society.

Hachisu I.,University of Tokyo | Kato M.,Keio University
Astrophysical Journal | Year: 2010

On the basis of the recently developed universal decline law of classical novae, we propose prediction formulae for supersoft X-ray on and off times, i.e., t X-on = (10 ± 1.8)t 3days and t X-off = (5.3 ± 1.4)(t 3)1.5days for 8 ≲ t 3 ≲ 80days. Here t 3 is the newly proposed "intrinsic" decay time during which the brightness drops by 3mag from optical maximum along our universal decline law fitted with observation. We have determined the absolute magnitude of our free-free emission model light curves and derived maximum magnitude versus rate of decline (MMRD) relations. Our theoretical MMRD relations are governed by two parameters, one is the white dwarf (WD) mass and the other is the initial envelope mass at a nova outburst; this second parameter explains the scatter of MMRD points of individual novae. Our theoretical MMRD relations are also in good agreement with the well-known empirical formulae. We also show another empirical relation of MV (15)∼ -5.7 0.3 based on the absolute magnitude of our model light curves, i.e., the absolute magnitude at 15 days after optical maximum is almost common among various novae. We analyzed 10 nova light curves, in which a supersoft X-ray phase was detected, and estimated their WD masses. The models best simultaneously reproducing the optical and supersoft X-ray observations are ONeMg WDs with 1.28 ± 0.04 M ⊙ (V598 Pup), 1.23 ± 0.05 M ⊙ (V382 Vel), 1.15 ± 0.06 M ⊙ (V4743 Sgr), 1.13 ± 0.06 M ⊙ (V1281 Sco), 1.2 ± 0.05 M ⊙ (V597 Pup), 1.06 ± 0.07 M ⊙ (V1494 Aql), 1.04 ± 0.07 M ⊙ (V2467Cyg), 1.07 ± 0.07 M ⊙ (V5116 Sgr), 1.05 ± 0.05 M ⊙ (V574 Pup), and a CO WD with 0.93 ± 0.08 M ⊙ (V458 Vul). The newly proposed relationships are consistent with the emergence or decay epoch of the supersoft X-ray phase of these 10 novae. Finally, we discuss the mechanism of shock-origin hard X-ray component in relation to the emergence of companion star from the WD envelope. © 2010. The American Astronomical Society. All rights reserved.

Abstract.: We consider the two-time correlation of the shape fluctuation of a fluid membrane immersed in a near-critical binary fluid mixture. Usually one component of the mixture is preferably attracted by the membrane. Adsorption layers, where the preferred component is more concentrated, are generated on both sides of the membrane significantly because of the near-criticality. The resultant gradient of the local mass-density difference between the two components generates additional stress, including the osmotic pressure, to influence the membrane motion. Assuming the mixture to be in the homogeneous phase near, but not too close to, the demixing critical point, we use the Gaussian free-energy functional to calculate the relaxation rate for a wavelength much longer than the correlation length of the mixture. Our calculation supposes weak preferential attraction and weak dependence of the mixture viscosity on the mass-density difference, and is performed within the linear approximation with respect to the undulation amplitude. It is shown for small wave number that the additional stress makes the relaxation more rapid independently of whether the preferred component is more viscous or not and that the relaxation rate can be regarded as proportional to the wave number even for a tensionless membrane. This linear dependence comes from the balance between the frictional force due to the mixture viscosity and the restoring force of the adsorption layer. Graphical abstract: [Figure not available: see fulltext.] © 2016, EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg.

Although segmentectomy is attempted for small non-small cell lung cancer (NSCLC) tumors, no reports have so far described how many of these tumors can be candidates for a successful resection by single segmentectomy. In all, 135 patients with peripheral p-T1N0M0 NSCLC were examined. The tumors were classified into five groups divided by every 0.5-cm increase in size. Tumor locations were classified into two groups - limited to within one segment and extended beyond one segment - based on the identification of whether pulmonary vessels and the bronchi were involved in the tumors on high-resolution computed tomography. Differences in the proportion of tumors limited within one segment between tumors smaller and larger than each class of tumor size were assessed. The tumor sizes were 0-1.0 cm in 8 tumors, 1.1-1.5 cm in 27, 1.6-2.0 cm in 35, 2.1-2.5 cm in 34, and 2.6-3.0 cm in 31 tumors. Of these 135 tumors, 92 (65%) were limited to one segment, whereas 48 (35%) had extended beyond one segment. When the tumor size was less than 30 mm, the proportion of tumor limited within one segment did not show any significant difference depending on the size of the tumor. More than one-third of p-T1N0M0 NSCLC tumors extended beyond one segment, irrespective of size. It is therefore noteworthy that resection of up to two segments or lobectomy should be undertaken for prevention of local recurrence in patients with p-T1N0M0 peripheral NSCLC.

Hasegawa T.,Keio University
Optics Communications | Year: 2012

Frequency quadrupling of a continuous-wave laser is carried out in coupled cavities with the stabilization to the resonance. The fourth harmonic generation in the coupled cavities is expected to be more efficient than in the two build-up cavity configuration in tandem, because input couplers, which increase the optical loss of the cavity, are not required. The cavity length is stabilized by the feedback of the error signal obtained by the cavity length modulation. In the present demonstration, the ultraviolet beam of 6μW at 238 nm is obtained by the fourth harmonic generation of the near infrared laser of 180 mW at 952 nm. This output power is expected to become higher (∼1.7mW) when the cavity setup is optimized. © 2012 Elsevier B.V. All rights reserved.

Hachisu I.,University of Tokyo | Kato M.,Keio University | Nomoto K.,University of Tokyo
Astrophysical Journal Letters | Year: 2010

In the single degenerate (SD) scenario for Type Ia supernova (SN Ia) progenitors, an accreting white dwarf (WD) is expected to undergo a supersoft X-ray source (SSS) phase. Recently, Gilfanov & Bogdán (hereafter GB10) claimed that observed X-ray fluxes of early-type galaxies would be too low to be consistent with the prediction of the SD scenario based on rather simple assumptions. We present realistic evolutionary models of SD systems and calculate durations of SSS phases. In most cases, accreting WDs spenda large fraction of time in the optically thick wind phase and the recurrent nova phase rather than the SSS phase. Thus, the SSS phase lasts only for a few hundred thousand years. This is by a factor of ∼10 shorter than those adopted by GB10 where the SN Ia progenitor WD was assumed to spend most of its life as an SSS. The theoretical X-ray luminosity of the SSS has a large uncertainty because of the uncertain atmospheric model of mass-accreting WDs and absorption of soft X-rays by the companion star's cool wind material. Wethus adopt an average of the observed fluxes of existing symbiotic SSSs, i.e., ∼0.4 × 10 36 erg s-1 for 0.3-0.7 keV. Using these SSS duration and soft X-ray luminosity, we show that the observed X-ray flux obtained by GB10 is rather consistentwith our estimated flux in early-type galaxies based on the SD scenario. This provides strong support for the SD scenario as a main contributor of SNe Ia in early-type galaxies. © 2010. The American Astronomical Society. All rights reserved.

Yokokura Y.,Nagaoka University of Technology | Ohishi K.,Nagaoka University of Technology | Katsura S.,Keio University
IEEE Transactions on Industrial Electronics | Year: 2014

This paper proposes a new motion-copying system that is capable of preserving and reproducing the motion of human operators. In conventional motion-copying systems, when the operator moves quickly, the reproduced force does not correspond to the stored force, owing to the large accelerations. Therefore, the motion-copying system proposed in this paper uses acceleration responses provided by acceleration observers, so the force is reproduced more accurately. The acceleration observer is based on a disturbance observer; it estimates the acceleration of an actuator without acceleration sensors. Furthermore, the estimation performance is not affected by the mechanical impedance of the target environment. In this article, the proposed motion-copying system is compared with current methods, and the validity of the method is demonstrated. © 1982-2012 IEEE.

Nguyen H.-T.,University of Malaya | Dawal S.Z.M.,University of Malaya | Nukman Y.,University of Malaya | Aoyama H.,Keio University
Expert Systems with Applications | Year: 2014

Global economic competition has spurred the manufacturing sector to improve and invest in modern equipment to satisfy the needs of the market. In particular, machine tool selection is the most important problem; it plays a primary role in the improvement of productivity and flexibility in the manufacturing environment and involves the imprecise, vague and uncertain information. This paper presents the hybrid approach of the fuzzy ANP (Analytic Network Process) and COPRAS-G (COmplex PRoportional ASsessment of alternatives with Grey relations) for fuzzy multi-attribute decision-making in evaluating machine tools with consideration of the interactions of the attributes. The fuzzy ANP is used to handle the imprecise, vague and uncertain information from expert judgments and model the interaction, feedback relationships and interdependence among the attributes to determine the weights of the attributes. COPRAS-G is employed to present the preference ratio of the alternatives in interval values with respect to each attribute and calculate the weighted priorities of the machine alternatives. Alternatives are ranked in ascending order by priority. As a demonstration of the proposed model, a numerical example is implemented based on the collected data and the literature. The result is then compared with the rankings provided by other methods such as TOPSIS-G, SAW-G and GRA. Moreover, a sensitivity analysis is conducted to verify the robustness of the ranking. The result highlights that the hybrid approach of the fuzzy ANP and COPRAS-G is a highly flexible tool and reaches an effective decision in machine tool selection. © 2013 Elsevier Ltd. All rights reserved.

Yamamoto N.,Keio University
IEEE Transactions on Automatic Control | Year: 2014

This paper provides a general theory for characterizing and constructing a decoherence-free (DF) subsystem for an infinite dimensional linear open quantum system. The main idea is that, based on the Heisenberg picture of the dynamics rather than the commonly-taken Schrödinger picture, the notions of controllability and observability in control theory are employed to characterize a DF subsystem. A particularly useful result is a general if and only if condition for a linear system to have a DF component; this condition is used to demonstrate how to actually construct a DF dynamics in some specific examples. It is also shown that, as in the finite dimensional case, we are able to do coherent manipulation and preservation of a state of a DF subsystem. © 1963-2012 IEEE.

Tanaka K.F.,National Institute for Physiological science | Samuels B.A.,Keio University | Hen R.,Columbia University
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2012

Using in situ hybridization, we describe, for the first time, the profiles of expression of serotonin receptors (Htr/5-HTR) along the dorsal-ventral axis of mouse hippocampus. cRNA probes for most Htrs, excluding Htr6, were used. All hippocampal subregions and the entorhinal cortex cells providing input into the hippocampus were examined. The study shows that some, but not all, Htrs are expressed in the cells of the hippocampal circuitry. At both the subfield and the cell type levels, a somewhat overlapping pattern is observed. Four serotonin receptors, Htr1a, Htr2a, Htr2c and Htr7, display an expression pattern that changes along the dorsal-ventral axis of the hippocampus. Given the proposed functional differentiation of the hippocampus along its long axis, with the dorsal pole more involved in cognitive functions and the ventral pole more involved in mood and anxiety, our results suggest that serotonin receptors enriched in the ventral pole probably contribute to mood- and anxiety-related behaviours. © 2012 The Royal Society.

Hasobe T.,Keio University
Physical Chemistry Chemical Physics | Year: 2012

Recent developments in supramolecular strategies have enabled us to construct novel well-defined assemblies of dye molecules. These fundamental researches of such organic materials also entail the synthetic and photophysical processes of molecular aggregates at the nano- and micro-meter scale, since their optical properties significantly differ from those of monomeric species. One of the promising candidates for such functional molecules is a porphyrin dye, which acts as an electron donor as well as a sensitizer. In this perspective, the focus is on the recent advances in the construction of optically and electronically functionalized molecular architectures of porphyrins for light energy conversion and electronics. First, porphyrin aggregates with morphologies such as cube, rod and fiber, which are prepared by three different supramolecular techniques, are reported. Then, we discuss composite molecular nanoarchitectures of porphyrins and carbon nanotubes such as single-wall carbon nanotubes (SWCNTs), stacked-cup carbon nanotubes (SCCNTs) and carbon nanohorns (CNHs). Finally, the structural and photophysical properties of the composite assemblies of porphyrins and graphenes including polycyclic aromatic hydrocarbons (PAH) are presented. © 2012 the Owner Societies.

Kato M.,Keio University
Astronomische Nachrichten | Year: 2010

I review various phenomena associated with mass-accreting white dwarfs (WDs) in the view of supersoft X-ray sources. When the mass-accretion rate is low (Macc < afew×10-7 MȮyr-1), hydrogen nuclear burning is unstable and nova outbursts occur. A nova is a transient supersoft X-ray source (SSS) in its later phase which timescale depends strongly on the WD mass. The X-ray turn on/off time is a good indicator of the WD mass. At an intermediate mass-accretion rate an accreting WD becomes a persistent SSS with steady hydrogen burning. For a higher mass-accretion rate, the WD undergoes "accretion wind evolution" in which the WD accretes matter from the equatorial plane and loses mass by optically thick winds from the other directions. Two SSS, namely RXJ0513-6951 and V Sge, are corresponding objects to this accretion wind evolution. We can specify mass increasing WDs from light-curve analysis based on the optically thick wind theory using multiwavelength observational data including optical, IR, and supersoft X-rays. Mass estimates of individual objects give important information for the binary evolution scenario of type Ia supernovae. © 2010 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim.

Kishida K.,Keio University
Journal of the American Society for Information Science and Technology | Year: 2010

Document clustering is an important tool, but it is not yet widely used in practice probably because of its high computational complexity. This article explores techniques of high-speed rough clustering of documents, assuming that it is sometimes necessary to obtain a clustering result in a shorter time, although the result is just an approximate outline of document clusters. A promising approach for such clustering is to reduce the number of documents to be checked for generating cluster vectors in the leader-follower clustering algorithm. Based on this idea, the present article proposes a modified Crouch algorithm and incomplete single-pass leaderfollower algorithm. Also, a two-stage grouping technique, in which the first stage attempts to decrease the number of documents to be processed in the second stage by applying a quick merging technique, is developed. An experiment using a part of the Reuters corpus RCV1 showed empirically that both the modified Crouch and the incomplete single-pass leader-follower algorithms achieve clustering results more efficiently than the original methods, and also improved the effectiveness of clustering results. On the other hand, the two-stage grouping technique did not reduce the processing time in this experiment. © 2010 ASIS&T.

Yashiro D.,Mie University | Yakoh T.,Keio University
IEEE Transactions on Industrial Electronics | Year: 2014

This paper proposes a novel traffic shaping algorithm for jitter buffers. Jitter buffers are effective in reducing jitter and therefore constitute an important technique used to improve the quality of real-time communication. Traffic shaping regulates the interval between packets received at the destination. Although the well-known dynamic jitter buffer needs to identify the maximum one-way delay and current one-way delays in the network, it is not necessary for our proposed approach to supply this information. Our algorithm utilizes a feedback controller to adjust the queuing delay in the jitter buffer to avoid packet overrun and underrun. In addition, a constant packet-receiving interval is achieved by employing a low-pass filter. The validity of our proposed method is confirmed through experiments of position control over a network. © 1982-2012 IEEE.

Chida N.,Keio University
Topics in Current Chemistry | Year: 2011

Morphine, an alkaloid isolated from the opium poppy, has been widely used as an analgesic, and has been a fascinating synthetic target of organic chemists. After the first total synthesis reported in 1952, a number of synthetic studies toward morphine have been reported, and findings obtained in such studies have greatly contributed to the progress of synthetic organic chemistry as well as medicinal chemistry. This review provides an overview of recent studies toward the total synthesis of morphine and related alkaloids. Work reported in the literature since 2004 will be reviewed. © 2010 Springer-Verlag Berlin Heidelberg.

Uematsu M.,Keio University
Journal of Applied Physics | Year: 2012

Diffusion of co-implanted carbon (C) and boron (B) in silicon (Si) and its effect on excess Si self-interstitials (I's) after annealing at 800 and 1000°C were investigated by means of secondary ion mass spectrometry. The experimental results showed that C diffusion was not significant at 800 and 1000°C but later became visible for longer annealing times at 1000°C. B diffusion was reduced by the presence of C when no significant C diffusion was observed, but it was enhanced when C diffusion was observed. These results indicate that all implanted C atoms form immobile CI clusters with excess I in the amount of implanted C and that these CI clusters are stable and trap I to reduce B diffusion. On the contrary, CI clusters are dissolved to emit I for longer annealing times at 1000°C and both B and C diffusion are enhanced. Diffusion simulation based on these models fits the experimental profiles of B and C. © 2012 American Institute of Physics.

Abraham C.,College of William and Mary | Nishihara E.,Japanese Association of Healthcare Information Systems Industry JAHIS | Akiyama M.,Keio University
International Journal of Medical Informatics | Year: 2011

Purpose: Healthcare reform as part of the economic recovery plan in Japan is placing emphasis on the use of healthcare information technology (HIT). This research mainly focuses on the HIT efforts in Japan with reference to the US for context. The purpose is to: (a) provide detail on governmental policy impacting promotion of HIT adoption to provide services to the people of Japan, (b) describe the outcomes of past and present policy impacting progress based on a case study of HIT use in the Kyoto Yamashina area, and (c) discuss issues for refinement of current policy. Methods: The method is case study, and data collection techniques include: (a) interviews of people involved in policy making for HIT in Japan (Japanese healthcare professionals, government officials, and academics involved in HIT research in Japan) and use in the medical community of HIT in the Kyoto Yamashina area, (b) archived document analysis of reports regarding government policy for HIT policy and user assessment for HIT mainly in the case study site, and (c) the literature review about HIT progression and effectiveness assessments to explore and describe issues concerning the transformation with HIT in Japan. Results: This study reveals the aspects of governmental policy that have been effective in promoting successful HIT initiatives as well as some that have been detriments in Japan to help solve pressing social issues regarding healthcare delivery. For example, Japan has stipulated some standardized protocols and formats for HIT but does not mandate exactly how to engage in inter-organizational or intra-organizational health information exchange. This provides some desired autonomy for healthcare organizations and or governments in medical communities and allows for more advanced organizations to leverage current resources while providing a basis for lesser equipped organizations to use in planning the initiative. The insights gained from the Kyoto Yamashina area initiative reflect the success of past governmental policy efforts and the current intent to promote HIT adoption. Insights from the case study as well as other social issues facing Japan warrant some refinement of policy. The refinement concerns: (a) the necessity for leadership and IT knowledge in the medical communities, (b) provider incentives, (c) legislation regarding accountability, security, privacy and confidentiality, (d) inclusion of stakeholders in solution development, and (e) creating sustainable business models. Conclusion: The research highlights the efforts of Japan for using HIT in healthcare reform. We present outcomes from a case study of the Kyoto Yamashina area medical community as proof of concept for past and present policy in Japan that are insightful for proliferation of successful projects in Japan and adoption of HIT in general. © 2011 Elsevier Ireland Ltd.

We developed chemical methods for target-selective photodegradation of various biomacromolecules, including DNA, proteins, and carbohydrates. The DNA intercalator-carbohydrate moiety, without the enediyne structure found in the enediyne antibiotic neocarzinostatin chromophore, selectively degrades duplex DNA at guanine (G) nucleotides upon photoirradiation. Based on this finding, we designed and synthesized several artificial DNA intercalator-carbohydrate hybrids that can be photoactivated. Among them, several quinoxaline-carbohydrate hybrids were found to photodegrade duplex DNA at the G on the 5 side of 5-GG-3 sites. For protein degradation, we designed and synthesized several 2-phenylquinoline-steroid hormone hybrids and a porphyrin derivative, both of which selectively photodegrade the transcription factor estrogen receptor-α. In addition, we designed and synthesized fullerene-sugar and fullerene-sulfonic acid hybrids that selectively photodegrade HIV-1 protease and amyloid β, respectively. For carbohydrate degradation, we designed and synthesized anthraquinone-lectin hybrids and anthraquinone- and fullerene-boronic acid hybrids for selective photodegradation of target oligosaccharides having affinity for the lectin or boronic acid moiety of the hybrids. Furthermore, we successfully demonstrated practical uses for these light-activatable and molecular-targeted (LAMTA) molecules for controlling the function of DNA, proteins, and carbohydrates both in glass vessels and in cells. 1 Introduction 2 DNA Photodegrading Organic Molecules 2.1 DNA Intercalator-Carbohydrate Hybrids 2.2 Neocarzinostatin DNA Intercalator- Carbohydrate Hybrids for DNA Photodegradation 2.3 Quinoxaline-Carbohydrate Hybrids for DNA Photodegradation 3 Protein Photodegrading Organic Molecules 3.1 Quinoline-Steroid Hormone Hybrids for ER-α Photodegradation 3.2 Fullerene-Carbohydrate Hybrids for HIV-1 Protease Photodegradation 3.3 Fullerene-Sulfonic Acid Hybrid for Amyloid β Photodegradation 4 Carbohydrate-Photodegrading Organic Molecules 4.1 Small Organic Molecules for Oligosaccharide Photodegradation 4.2 Anthraquinone-Lectin Hybrids for Oligosaccharide Photodegradation 4.3 Anthraquinone-Boronic Acid Hybrids for Oligosaccharide Photodegradation 5 Conclusions © Georg Thieme Verlag Stuttgart New York.

Kawauchi T.,Japan Science and Technology Agency | Kawauchi T.,Keio University
International Journal of Molecular Sciences | Year: 2012

Cell migration is a crucial event for tissue organization during development, and its dysregulation leads to several diseases, including cancer. Cells exhibit various types of migration, such as single mesenchymal or amoeboid migration, collective migration and scaffold cell-dependent migration. The migration properties are partly dictated by cell adhesion and its endocytic regulation. While an epithelial-mesenchymal transition (EMT)-mediated mesenchymal cell migration requires the endocytic recycling of integrin-mediated adhesions after the disruption of cell-cell adhesions, an amoeboid migration is not dependent on any adhesions to extracellular matrix (ECM) or neighboring cells. In contrast, a collective migration is mediated by both cell-cell and cell-ECM adhesions, and a scaffold cell-dependent migration is regulated by the endocytosis and recycling of cell-cell adhesion molecules. Although some invasive carcinoma cells exhibit an EMT-mediated mesenchymal or amoeboid migration, other cancer cells are known to maintain cadherin-based cell-cell adhesions and epithelial morphology during metastasis. On the other hand, a scaffold cell-dependent migration is mainly utilized by migrating neurons in normal developing brains. This review will summarize the structures of cell adhesions, including adherens junctions and focal adhesions, and discuss the regulatory mechanisms for the dynamic behavior of cell adhesions by endocytic pathways in cell migration in physiological and pathological conditions, focusing particularly on neural development and cancer metastasis. © 2012 by the authors; licensee MDPI, Basel, Switzerland.

Okano H.,Keio University
Proceedings of the Japan Academy Series B: Physical and Biological Sciences | Year: 2010

The adult mammalian central nervous system (CNS), especially that of adult humans, is a representative example of organs that do not regenerate. However, increasing interest has focused on the development of innovative therapeutic methods that aim to regenerate damaged CNS tissue by taking advantage of recent advances in stem cell and neuroscience research. In fact, the recapitulation of normal neural development has become a vital strategy for CNS regeneration. Normal CNS development is initiated by the induction of stem cells in the CNS, i.e., neural stem cells (NSCs). Thus, the introduction or mobilization of NSCs could be expected to lead to CNS regeneration by recapitulating normal CNS development, in terms of the activation of the endogenous regenerative capacity and cell transplantation therapy. Here, the recent progress in basic stem cell biology, including the author's own studies, on the prospective identification of NSCs, the elucidation of the mechanisms of ontogenic changes in the differentiation potential of NSCs, the induction of neural fate and NSCs from pluripotent stem cells, and their therapeutic applications are summarized. These lines of research will, hopefully, contribute to a basic understanding of the nature of NSCs, which should in turn lead to feasible strategies for the development of ideal "stem cell therapies" for the treatment of damaged brain and spinal cord tissue. © 2010 The Japan Academy.

Yoshizawa K.,Hokkaido University | Ferreira R.L.,Federal University of Lavras | Kamimura Y.,Keio University | Lienhard C.,Natural History Museum of the City of Geneva
Current Biology | Year: 2014

Sex-specific elaborations are common in animals and have attracted the attention of many biologists, including Darwin [1]. It is accepted that sexual selection promotes the evolution of sex-specific elaborations. Due to the faster replenishment rate of gametes, males generally have higher potential reproductive and optimal mating rates than females. Therefore, sexual selection acts strongly on males [2], leading to the rapid evolution and diversification of male genitalia [3]. Male genitalia are sometimes used as devices for coercive holding of females as a result of sexual conflict over mating [4, 5]. In contrast, female genitalia are usually simple. Here we report the reversal of intromittent organs in the insect genus Neotrogla (Psocodea: Prionoglarididae) from Brazilian caves. Females have a highly elaborate, penis-like structure, the gynosome, while males lack an intromittent organ. The gynosome has species-specific elaborations, such as numerous spines that fit species-specific pouches in the simple male genital chamber. During prolonged copulation (∼40-70 hr), a large and potentially nutritious ejaculate is transferred from the male via the gynosome. The correlated genital evolution in Neotrogla is probably driven by reversed sexual selection with females competing for seminal gifts. Nothing similar is known among sex-role reversed animals. © 2014 Elsevier Ltd.

Nitta M.,Keio University
International Journal of Modern Physics A | Year: 2013

Monopoles and instantons are sheets (membranes) and strings in d = 5+1 dimension, respectively, and instanton strings can terminate on monopole sheets. We consider a pair of monopole and antimonopole sheets which is unstable to decay and results in a creation of closed instanton strings. We show that when an instanton string is stretched between the monopole sheets, there remains a new topological soliton of codimension five after the pair annihilation, i.e. a twisted closed instanton string or a knotted instanton. © 2013 World Scientific Publishing Company.

Nitta M.,Keio University
Nuclear Physics B | Year: 2013

We construct a stable Skyrmion in 3+1 dimensions as a sine-Gordon kink inside a domain wall within a domain wall in an O(4) sigma model with hierarchical mass terms without the Skyrme term. We also find that higher dimensional Skyrmions can stably exist with a help of non-Abelian domain walls in an O(N) model with hierarchical mass terms without a Skyrme term, which leads to a matryoshka structure of Skyrmions. © 2013 Elsevier B.V.

Fukushima K.,Keio University
Lecture Notes in Physics | Year: 2013

My personal views of the Chiral Magnetic Effect are presented, which starts with a story about how we came up with the electric-current formula and continues to unsettled subtleties in the formula. There are desirable features in the formula of the Chiral Magnetic Effect but some considerations would lead us to even more questions than elucidations. The interpretation of the produced current is indeed very non-trivial and it involves a lot of confusions that have not been resolved. © Springer-Verlag Berlin Heidelberg 2013.

Amagai M.,Keio University
Proceedings of the Japan Academy Series B: Physical and Biological Sciences | Year: 2010

Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, the desmogleins (Dsg) and desmocollins (Dsc), which are cadherin-type cell-cell adhesion molecules and are anchored to intermediate filaments of keratin through interactions with plakoglobin and desmoplakin. Desmosomes play an important role in maintaining the proper structure and barrier function of the epidermis and mucous epithelia. Four Dsg isoforms have been identified to date, Dsg1-Dsg4, and are involved in several skin and heart diseases. Dsg1 and Dsg3 are the two major Dsg isoforms in the skin and mucous membranes, and are targeted by IgG autoantibodies in pemphigus, an autoimmune disease of the skin and mucous membranes. Dsg1 is also targeted by exfoliative toxin (ET) released by Staphylococcus aureus in the infectious skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). ET is a unique serine protease that shows lock and key specificity to Dsg1. Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia. Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development. Recently, an active disease model for pemphigus was generated by a unique approach using autoantigen-deficient mice that do not acquire tolerance against the defective autoantigen. Adoptive transfer of Dsg3-/- lymphocytes into mice expressing Dsg3 induces stable anti-Dsg3 IgG production with development of the pemphigus phenotype. This mouse model is a valuable tool with which to investigate immunological mechanisms of harmful IgG autoantibody production in pemphigus. Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic strategies with minimal side effects. © 2010 The Japan Academy.

Kobayashi M.,Kyoto University | Nitta M.,Keio University
Journal of Low Temperature Physics | Year: 2014

We study vortex polygons and their stabilities in miscible two-component Bose-Einstein condensates, and find that vortex polygons are stable for the total circulation Q≤5, metastable for Q=6, and unstable for Q≥7. As a related model in high-energy physics, we also study the vortex polygon of the baby-Skyrme model with an anti-ferromagnetic potential term, and compare both results. © 2013 Springer Science+Business Media New York.

Nagao K.,Keio University
Blood | Year: 2014

In this issue of Blood, Sparber et al have identified that p14 is crucial for maintaining the homeostasis of epidermal Langerhans cells (LCs).1 © 2014 by The American Society of Hematology.

Kubo A.,Keio University
Journal of Investigative Dermatology | Year: 2014

Nagashima-type palmoplantar keratosis (NPPK) is an autosomal recessive diffuse non-epidermolytic palmoplantar keratosis caused by mutations in SERPINB7, a member of the serine protease inhibitor superfamily. Genetic studies suggest that NPPK is the most common palmoplantar keratosis in Japan, and probably Asia, but one that is extremely rare in Western countries. In this issue, Yin et al. report a founder effect of a SERPINB7 mutation in Chinese populations. © 2014 The Society for Investigative Darmatology.

Arakawa T.,Alliance Protein Laboratories | Kita Y.,Keio University
Current Protein and Peptide Science | Year: 2014

Arginine is widely used in such applications as protein refolding, solubilization of proteins and small molecules, protein and small molecule formulation, column chromatography and viral inactivation as summarized in this review. What makes arginine effective in these applications is largely based on its ability to suppress protein-protein interactions and protein-surface interactions. The mechanism of these widespread effects of arginine on proteins can be explained at least in part from its unique interactions with the protein surface. Here we describe the modes of the interactions of arginine with model compounds and proteins and also water molecules, and then attempt to explain the mechanism of its effect on proteins by comparing with the interactions that occur between protein and protein denaturants or stabilizers. © 2014 Bentham Science Publishers.